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g8 [tProject Info].[Display Date]= g8![tProject Info].[Activity Date]> g8![tProject Info].[End Date Year]> g8![tProject Info].[End Date Date]> g8![tProject Info].[End Date Text]> g8B@  g8B@  g8B@  g8 [tProject Info].[Keyword List]= g8P@ g8N@ g8Display Abstractl@=11 o8[tProject Info].Abstract7 g8Display Project IDb@A55 o8[tProject Info].[Project ID]; g8Display FunderP@9-- o8[tProject Info].Funder5 g8 Display StateL@7++ o8 [tProject Info].State4 g8 [tProject Info].City3 g8 [tProject Info].Institution: g8 Display PI ORG@9-- o8Display PI Name@;// o8[tProject Info].[First Name]; g8[tProject Info].[Last Name]: g8[tProject Info].Title4 g8[tProject Info].[Entry Type]; g8J@ g8[tProject Info].MarkBox6 g8[tProject Info].[Record ID]: g8tProject Info+++ 8 8 GLVAL H z , X  j nrvzr<PSELECT [tProject Keywords].[Record ID], IIf(Trim(nz([tKeywords].[Area],""))="","-N/A-",[tKeywords].[Area]) AS Area, [tKeywords].[Keyword] FROM [tProject Keywords] INNER JOIN tKeywords ON [tProject Keywords].[Keyword No]=[tKeywords].[Keyword No]; ((([tCurrent Sort Fields Temp].[Sort Field Descriptor]) Is Null))[tSort Fields].[Sort Field Descriptor]=[tCurrent Sort Fields Temp].[Sort Field Descriptor][tSort Fields].[Sort Field Descriptor][tCurrent Sort Fields Temp].[Sort Order][tCurrent Sort Fields Temp].[Compiled English Expression][tCurrent Sort Fields Temp].[Sort Order]((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType5]))[tSearch Conditionals].[Conditional Text]((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType4]))[tSearch Conditionals].[Conditional Text]((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType3]))[tSearch Conditionals].[Conditional Text]((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType2]))[tSearch Conditionals].[Conditional Text]((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType1]))[tSearch Conditionals].[Conditional Text]((([tProject Info].[Record ID]) Is Not Null))[tProject Info].[Start Date Year][tProject Info].[Start Date Date][tProject Info].[Start Date Text][tProject Info].[WG Recommendation List][tProject Info].[Breakout Session List]IIf(nz([Abstract],"")="","-not available-",[Abstract])IIf(nz([Project ID],"")="","-none-",[Project ID])IIf(nz([Funder],"")="","-N/A-",[Funder])IIf(nz([State],"")="","-N/A-",[State])IIf(nz([Last Name],"") & nz([First Name],"")="","-no PI name-",[Last Name] & IIf(nz([First Name],"")="","",", " & [First Name])) & Chr(13) & Chr(10) & [Institution] & Chr(13) & Chr(10) & IIf(IsNull([City]),"",[City] & ", ") & [State]IIf(nz([Last Name],"") & nz([First Name],"")="","-no PI name-",[Last Name] & IIf(nz([First Name],"")="","",", " & [First Name]))[tProject Info].[Project/Activity ID]8F?5 v + l ! L " \ n D B~J,iK@"Pf%]M HdqBrowseDB.City- gHd qBrowseDB.Institution4 gHd qBrowseDB.[Display PI ORG]9 gHd qBrowseDB.[Display PI Name]: gHd qBrowseDB.[First Name]5 gHd qBrowseDB.[Last Name]4 gHdqBrowseDB.Title. gHdqBrowseDB.[Entry Type]5 gHd!qBrowseDB.[Project/Activity ID]> gHdqBrowseDB.[Record ID]4 gHdMode1gglSelectionMode(); oHdOrder1ggsSortStringEnglish()A oHdWhere1ggsEnglishQueryWhereClause()G oHd [tPrint Records].[Print Order]= gHdtPrint Records--- HdqBrowseDB### Hd Hd GGd([__Record ID] = [Record ID])< 'GdrWTC Projects and Activities Detail@cW 7G d GGd__Record ID''' OGd Gd GFd([__Record ID] = [Record ID])< 'FdrSub Detail Recs and Keys@OC 7F d GFd__Record ID''' OFd Fd GEd[tProject Info].State4 gEd[tProject Info].[Last Name]: gEd[tProject Info].[Record ID]: gEdtProject Info+++ Ed Ed GD d[tSort Fields].[Sort Order]: 'Dd@ 'DdtSort FieldstCurrent Sort Fields Temp@g[) DdL@ gDdtCurrent Sort Fields TempCCC DdtSort Fields))) Dd Dd GC dP@ 'Cdr@ gCdP@ gCdtCurrent Sort Fields TempCCC Cd Cd GB d[tSearch Fields].[Sort Order]< 'Bd![tSearch Fields].[Search Field]> gBdtSearch Fields--- Bd Bd GA d[tSearch Fields].[Sort Order]< 'Ad![tSearch Fields].[Search Field]> gAdtSearch Fields--- Ad Ad G@ d[tSearch Fields].[Sort Order]< '@d![tSearch Fields].[Search Field]> g@dtSearch Fields--- @d @d G? d[tSearch Fields].[Sort Order]< '?d![tSearch Fields].[Search Field]> g?dtSearch Fields--- ?d ?d GtLVAL6 & f > T 8:0j(IIf(nz([Last Name],"") & nz([First Name],"")="","No PI Entered-",[Last Name] & IIf(IsNull([First Name]),"",", " & [First Name])) & Chr(13) & Chr(10) & IIf(nz([Institution],"")="","-No Institution Entered-",[Institution]) & Chr(13) & Chr(10) & IIf(IsNull([City]),"",[City] & ", ") & [State]IIf(nz([tProject Info]!Funder,"")="","-none-",[tProject Info]!Funder)IIf(nz([Project ID],"")="","-none-",[Project ID])[tControl Sizes].[Updated Control][tControl Sizes].[Scale in Steps][tProject Info].[Start Date Year][tProject Info].[Start Date Date][tProject Info].[Start Date Text][tProject Info].[WG Recommendation List][tProject Info].[Breakout Session List]IIf(nz([Abstract],"")="","-not available-",[Abstract])IIf(nz([Project ID],"")="","-none-",[Project ID])IIf(nz([Funder],"")="","-N/A-",[Funder])IIf(nz([State],"")="","-N/A-",[State])IIf(nz([Last Name],"") & nz([First Name],"")="","-no PI name-",[Last Name] & IIf(nz([First Name],"")="","",", " & [First Name])) & Chr(13) & Chr(10) & [Institution] & Chr(13) & Chr(10) & IIf(IsNull([City]),"",[City] & ", ") & [State]IIf(nz([Last Name],"") & nz([First Name],"")="","-no PI name-",[Last Name] & IIf(nz([First Name],"")="","",", " & [First Name]))[tProject Info].[Project/Activity ID]qBrowseDB.[Record ID]=[tPrint Records].[Record ID]qBrowseDB.[WG Recommendation List]qBrowseDB.[Breakout Session List]qBrowseDB.[Record ID]=[tPrint Records].[Record ID]IIf(Trim(nz(qBrowseDB.[WG Recommendation List],""))="","-N/A-",qBrowseDB.[WG Recommendation List])IIf(Trim(nz(qBrowseDB.[Breakout Session List],""))="","-N/A-",qBrowseDB.[Breakout Session List])IIf(Trim(nz(qBrowseDB.[Project ID],""))="","-N/A-",qBrowseDB.[Project ID])IIf(Trim(nz(qBrowseDB.Funder,""))="","-N/A-",qBrowseDB.Funder)SELECT [tProject Info].[Record ID], IIf(Trim(nz([tProject Info].[WG Recommendation List],""))="","-N/A-",[tProject Info].[WG Recommendation List]) AS [WG Recommendation List], [tProject Info].[Keyword List] FROM [tProject Info]; O'1-O3 W L; A Jm  >:HDtEGcuqBXms@ps@tSort Fields88888888888&n@ hR@tSort Fields @FFF:::::::8 @wHϗ@;ϗ@tSearch Fields with Review Date @lll```````^ @qƹ%n@ ]9N@tSearch Fields @JJJ>>>>>>>< @l%$n@ }E3@tSearch Conditionals@VVVJJJJJJJH @Pw#n@ 1n@tProject WG RecommendationsC@dddXXXXXXXV @'l!n@վ0n@tProject Keywords@PPPDDDDDDDB @n@ڙU@tProject Info/p.HHH<<<<<<<: @cn@]7/n@tProject Breakout Sessions=@bbbVVVVVVVT @n@.n@tPrint Records@JJJ>>>>>>>< @\&|t@X@tModal Forms@FFF:::::::8 @{n@Q.n@tIMPAC Activity Types Available@lll```````^ @n@-n@tIMPAC Activity Types@XXXLLLLLLLJ @LP@cI@tForm Sizesp/p.DDD88888886 @7n@-n@tEntry Types@FFF:::::::8 @n@[?@tDocument ObjectsQ@PPPDDDDDDDB @n@}Kj@tDefaults and ConstantsX@\\\PPPPPPPN @{yn@D,n@tCurrent Sort Fields Temp@```TTTTTTTR @q n@E2@tCurrent Search Temp+/p.VVVJJJJJJJH @lMn@)U2@tCurrent Search!/p.LLL@@@@@@@> @gM@8:@tControl Sizes/p.JJJ>>>>>>>< @aR@@5R@tBrowse Child Sort Fields/p.```TTTTTTTR @]_n@ +n@tBreakout Sessions@RRRFFFFFFFD @$9@3 h@tBlobs3@:::......., @Q0@g0@0qUnmarkAllRecords*@|@\PPDDDDDDDB @Pdn@ n@qSimple Project Display@|@h\\PPPPPPPN @Oco@-do@qSho project id@|@XLL@@@@@@@> @NHa߱@.@qSearch and Sort Fields and Propertiesm@|@zznnnnnnnl @L@mtzN@qDetail DisplayO@|@XLL@@@@@@@> @KBIr@0G@qControl Sizes@|@VJJ>>>>>>>< @JJB/@v-@qBrowseDB @|@L@@44444442 @\&|t@&|t@MSysAccessXML4MR2KeepLocal  T|||<<<<<<<: @ (As@3Gs@MSysAccessObjectsDDDDDDDDDDB Hy@y@~sq_rrWTC Projects and Activities Detail4MR2KeepLocal Trrrrrrrp @;J|( 6 d  N  < | ^ . V4v4f,p*`9f!Id qBrowseDB.[Activity Date]8 gIdqBrowseDB.[End Date Year]8 gIdqBrowseDB.[End Date Date]8 gIdqBrowseDB.[End Date Text]8 gIdqBrowseDB.[Start Date Year]: gIdqBrowseDB.[Start Date Date]: gIdqBrowseDB.[Start Date Text]: gIdqBrowseDB.[Keyword List]7 gIdD@ gIdB@ gIdqBrowseDB.[Display Abstract]; gIdqBrowseDB.Abstract1 gId qBrowseDB.[Display Project ID]= gIdqBrowseDB.[Project ID]5 gIdqBrowseDB.[Display Funder]9 gIdqBrowseDB.Funder/ gIdqBrowseDB.[Display State]8 gIdqBrowseDB.State. gIdqBrowseDB.City- gId qBrowseDB.Institution4 gId qBrowseDB.[Display PI ORG]9 gId qBrowseDB.[Display PI Name]: gId qBrowseDB.[First Name]5 gId qBrowseDB.[Last Name]4 gIdqBrowseDB.Title. gIdqBrowseDB.[Entry Type]5 gId!qBrowseDB.[Project/Activity ID]> gIdqBrowseDB.[Record ID]4 gIdMode1gglSelectionMode(); oIdOrder1ggsSortStringEnglish()A oIdWhere1ggsEnglishQueryWhereClause()G oId [tPrint Records].[Print Order]= gIdtPrint Records--- IdqBrowseDB### Id Id GH d [tPrint Records].[Print Order]= 'HdqBrowseDBtPrint Recordsd@K?# Hd#qBrowseDB.[Review Date]6 gHd"qBrowseDB.[Date Exception]9 gHd!qBrowseDB.[Display Date]7 gHd qBrowseDB.[Activity Date]8 gHdqBrowseDB.[End Date Year]8 gHdqBrowseDB.[End Date Date]8 gHdqBrowseDB.[End Date Text]8 gHdqBrowseDB.[Start Date Year]: gHdqBrowseDB.[Start Date Date]: gHdqBrowseDB.[Start Date Text]: gHdqBrowseDB.[Keyword List]7 gHdWG Recommendation List@I== oHdBreakout Session List@G;; oHdqBrowseDB.[Display Abstract]; gHdAbstractTrim(qBrowseDB!Abstract)G!! oHd qBrowseDB.[Display Project ID]= gHdProject ID@1%% oHdqBrowseDB.[Display Funder]9 gHdFunder|@) oHdqBrowseDB.[Display State]8 gHdqBrowseDB.State. g!>v3sU g  M  v 4 i # G _5 Kk|^$g'a<eK [tControl Sizes].[Form Name]; 'KD@ gK[tControl Sizes].[Font Temp]; gK[tControl Sizes].[Font Group]< gK [tControl Sizes].[Font Max]: gK [tControl Sizes].[Font Min]: gK "[tControl Sizes].[Font Autosize]? gK [tControl Sizes].[Font Resize]= gK [tControl Sizes].[Font Base]; gK[tControl Sizes].[Has Font]: gK[tControl Sizes].Width5 gK[tControl Sizes].Height6 gK[tControl Sizes].Left4 gK[tControl Sizes].Top3 gKB@ gK![tControl Sizes].[Control Name]> gK[tControl Sizes].[Form Name]; gKtControl Sizes--- K GK GK K GJ [tProject Info].[Review Date]< gJ"[tProject Info].[Date Exception]? gJ [tProject Info].[Display Date]= gJ![tProject Info].[Activity Date]> gJ![tProject Info].[End Date Year]> gJ![tProject Info].[End Date Date]> gJ![tProject Info].[End Date Text]> gJB@ gJB@ gJB@ gJ [tProject Info].[Keyword List]= gJP@ gJN@ gJDisplay Abstractl@=11 oJ[tProject Info].[Abstract]9 gJDisplay Project IDb@A55 oJ[tProject Info].[Project ID]; gJDisplay FunderP@ 9-- oJ[tProject Info].[Funder]7 gJ Display StateL@ 7++ oJ [tProject Info].[State]6 gJ [tProject Info].[City]5 gJ [tProject Info].[Institution]< gJ Display PI ORG@ 9-- oJDisplay PI Name@ ;// oJ[tProject Info].[First Name]; gJ[tProject Info].[Last Name]: gJ[tProject Info].[Title]6 gJ[tProject Info].[Entry Type]; gJJ@  gJProject Info].[MarkBox]8 gJ[tProject Info].[Record ID]: gJtProject Info+++ J J GI d [tPrint Records].[Print Order]= 'IdqBrowseDBtPrint Recordsd@K?# Id#qBrowseDB.[Review Date]6 gId"qBrowseDB.[Date Exception]9 gId!qBrowseDB.[Display Date]7 g YxQk*SidNY Y DataIDColYAOIndexv1K[FFN03DTw `8yw< 8 H X h x  w$Alyzxy 8yhzwMLj@yyyyqGet Startup Values@ d8|@ d|@  }ult Page Folder6Use Defaul{ec@il~ {w}Kj@{DtDefaults and Constants ||| <[tDefaults and Constants].Item|||| >[tDefaults and Constants].Data1r |}} D[tDefaults and Constants].DataMemol}(~|}  <[tDefaults and Constants].Item} x}}"StartupValue",~x}}<~ (~L~ 8~ d  d    x L 8cS@~c0fpe cdԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄԄph0jfgP dMSysAccounts   L K[ࡱ> l{d*/0  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~Root Entry-fVBAԗfVBAProjectԗfVBA#ԗ__SRP_0~__SRP_10__SRP_2<__SRP_3 !K*m`      !!""##&&''      $$%%rU;~~~~~~~~~~~~~~~~~~~~~~~~~~~~~1~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. a dDACF  ((a 0QXa !Aa9i 9Ya Q!1a Q !IYa Iqa 2a ٪)K[a 1Yya 1Y!a 4 9ia  ٪)YYa 6 a AIqY 9a 8 Aq1Yyqa qA1a : 9a a Q11a Qp yydAc_Y1Yyya <ia QxYyѭ1a > a @ia IqY Aa 11IY٪qA AqQ a aJ1YHYYyHHyHH1IyIIIJAJa BiS da Deee!a Q kpqa Fa Hvyvva "a Ji} Aq1Yy9a $i~Yia L a &Qp bc_ydie9ffg h9hqhhha (1Y a *Qi~Yia Nqa PSىa ,Qi)iAiYia .qN AyIyّ 9iɒI٪1YyAiɓ AyAqѕ1a)aї 9iɘ)Y1Qɚ!Iiɛ1Q) iqDataPreparationProceduresGlobal Vars and SubsInitializations KeyClickStuffForm_fPrint Or Save MasterForm_fAAA StartupForm_fBrowse Master (Report_rWTC Projects and Activities List #Form_fData Preparation List SettingForm_fDetail Display AForm_fTestRemoteFormK[_fPrint SelectionForm_fTitle Page Good Copy #Form_fSort and Search Debug DisplayForm_fSetModesForm_fSort and Search DisplayTextHeightWidthForm_fTest Child BlobStuffForm_fTestBars Form_fTestDblForm_fPrint Options for DetailForm_fSet Sort OrderForm_fBrowse ChildForm_fBlob Input "Form_fData Prep Gather Project IDsSaveFileDialogForm_fSave ReportForm_fRecord Form/Control Sizes FormResizingXForm_fTitle PageForm_fPrint Or Save Report OldForm_fShowClasses PositionForms *Report_rWTC Projects and Activities DetailForm_fPrint Or Save ReportForm_fWrap Error Form_Form1TitlePageLogoSizesForm_fSearch Criteria WTC Data11 GC $@^$ +*$# ; Not sorted Browse All Search Results Z((([tProject Info].[Record ID]) Is Not Null)) ,, [Last Name] AS Sort1VBA Sort1 PI Last Name BrWTC Projects and Activities List FrWTC Projects and Activities Detail My Documents 4WTCDefinitionsInfoFile.htm &WTCHelpInfoFile.htmF /C:\PROGRA~1\COMMON~1\MICROS~1\VBA\VBA6\VBE6.DLL   0J_N?Option31 3C:\Program Files\Microsoft Office\Office\MSACC9.OLBAccess  y@0FC:\WINDOWS\System32\STDOLE2.TLBstdole YPm.4C:\Program Files\Common Files\System\ado\msado21.tlbADODB i`L-[DR?C:\Program Files\Common Files\Microsoft Shared\OFFICE11\MSO.DLLOffice pDAO*0[ C:\WINDOWS\SYSTEM\SHDOCVW.DLLSHDocVw 1y^F=C:\Program Files\Common Files\Microsoft Shared\DAO\DAO360.DLL RestartInitializeStartupInitialize  CompileBreakoutSessionsCompileRecommendationsCompileKeywordsɤs h)aN?!I`GXGP OpenReport)fsE"' UPDATE [tProject Info] SET [tProject Info].[Breakout Session List] = Null; 448 8, $(,0  GenerateSQL GetDirectory FormState ReportState DblQuotes SelectData BrowseAllggsEnglishQueryWhereClauseggsSortStringEnglishgglSelectionModeCloseOutSetCQR ModalFormsUnCQRCloseOpenReportsLinearKeywordList InitBrowserSetBrowserDataUnCRLF OpenDetail4  $(,048<@DHT i |8l p t x        XI tProject Infoqm.1m. ^SELECT [tBreakout Sessions].[Breakout Session] RequeryLabel22 ,FROM ([tProject Info]  VINNER JOIN [tProject Breakout Sessions] ON & [tProjecK[t Info].[Record ID] = [tProject Breakout Sessions].[Record ID])  FINNER JOIN [tBreakout Sessions] ON Breakout SessionQm.    OrderBy optAscDesc2 [tProject Breakout Sessions].[Breakout Session No] = [tBreakout Sessions].[Breakout Session No]  PWHERE ((([tProject Info].[Record ID]) =  Record IDSm. ))  hORDER BY [tBreakout Sessions].[Breakout Session No];OrderByOnLabel23 *Breakout Session List!VBE6.DLL (e  (  (i ' UPDATE [tProject Info] SET [tProject Info].[WG Recommendation List] = Null; (x  Sort English bSELECT [tWG Recommendations].[WG Recommendation]  XINNER JOIN [tProject WG Recommendations] ON & [tProject Info].[Record ID] = [tProject WG Recommendations].[Record ID])  HINNER JOIN [tWG Recommendations] ON *Cannot Find Path Name4 [tProject WG Recommendations].[WG Recommendation No] = [tWG Recommendations].[WG Recommendation No]  lORDER BY [tWG Recommendations].[WG Recommendation No]; "WG Recommendation ,WG Recommendation List 4INNER JOIN [tKeywords] ON Option33" UPDATE [tProject Info] SET [tProject Info].[Keyword List] = Null; bSELECT [tKeywords].[Keyword], [tKeywords].[Area]  DINNER JOIN [tProject Keywords] ON ! ~[tProject Info].[Record ID] = [tProject Keywords].[Record ID]) RecordSource boxSimple x[tProject Keywords].[Keyword No] = [tKeywords].[Keyword No]  DORDER BY [tKeywords].[Keyword No]; Area   Keyword Keyword List    WHERE  \ : Filename " B" includes no path specification. Data (S ( Closed Open(aN?]协N? Design " LqSearch and Sort Fields and Properties Form Name Type Search English Sub Form Control Field NametpY? ValueFormControls Requery fBrowse MastersubChildRecordsetCloneRecordsetBookmark Search Indicator (V H ( h# DELETE [tDefaults and Constants].*, [tDefaults and CK[onstants].Item  PopUp<I / FROM [tDefaults and Constants] WHERE ((([tDefaults and Constants].Item)="SearchEnglish"));- FROM [tDefaults and Constants] WHERE ((([tDefaults and Constants].Item)="SearchSQL")); HSELECT "SearchIndicator" AS Expr1, " &StartUpShowDBWindow0 FROM [tDefaults and Constants] WHERE ((([tDefaults and Constants].Item)="SearchIndicator")); rINSERT INTO [tDefaults and Constants] ( Item, DataMemo )  DSELECT "SearchEnglish" AS Expr1, " " AS Expr2; <SELECT "SearchSQL" AS Expr1, " dDELETE [tCurrent Search].* FROM [tCurrent Search]; tCurrent Search Line No Log Opt [Record ID] 0 $ records retrieved 4 records displayed out of ( k>N? High Medium Modal optContains3 DELETE [tDefaults and Constants].*, [tDefaults and Constants].Item FROM [tDefaults and Constants]  pWHERE ((([tDefaults and Constants].Item)="CloseQuit"));  lINSERT INTO [tDefaults and Constants] ( Item, Data1 ) &AllowToolbarChangesLabel20 <SELECT "CloseQuit" AS Expr1, " True False pWHERE ((([tDefaults and Constants].Item)="ShowMenus"));  <SELECT "ShowMenus" AS Expr1, " $AllowShortcutMenus m.)m.'m. AllowFullMenus (AllowBuiltInToolbars AllowSpecialKeys $AllowBreakIntoCodefĤIx8<m.  :  >Error loading database settings AllowBypassKey (  (  (  tModal Forms Modal Form Name BorderStyle \SELECT "CloseQuit" AS Expr1, "False" AS Expr2; ZSELECT "ShowMenus" AS Expr1, "Skip" AS Expr2; Menu Bar F F7R(aN? "fDetail Display A *fPrint Or Save Report bcH apiReleaseDC optSimple vUPDATE [tProject Info] SET [tProject Info].MarkBox = False; txtIndicator txtSort   txtSearch31?BorderStyle ( apiGetWindowRect user32 GetWindowRect bc(apiGetDC GetDC ReleaseDC bchapiGetDeviceCaps gdi32 GetDeviceCaps ddapiGetActiveWindow GetActiveWindow beK[ apiGetParent GetParent bifapiGetClassName GetClassNameA b)gFindReportPositionLabel19GetFormDimensionsConvertPIXELSToTWIPSGetScreenResolutionGetWindowClassPositionDetailDisplayASizeTitleLogosSetItGetIt GetItForm [Data1] .tDefaults and Constants 2[Item] = "MaximizeOnOpen" ([Item] = "ShowMenus" Skip ([Item] = "SearchSQL" 4[Item] = "SearchIndicator"6 INSERT INTO [tDefaults and Constants] ( Item, Data1 ) SELECT "MaximizeOnOpen" AS Expr1, "False" AS Expr2; ([Item] = "CloseQuit"3 INSERT INTO [tDefaults and Constants] ( Item, Data1 ) SELECT "CloseQuit" AS Expr1, "True" AS Expr2; ImgIcoNCI3 INSERT INTO [tDefaults and Constants] ( Item, Data1 ) SELECT "ShowMenus" AS Expr1, "True" AS Expr2; [DataMemo] 2[Item] = "OrderByEnglish" *[Item] = "OrderBySQL" ,[Item] = "OrderByList" 0[Item] = "SearchEnglish" [Line No] boxAscDesc [Line No] =  lSELECT [Record ID], [MarkBox], [Project/Activity ID],  `[Entry Type], Title, [Last Name], [First Name], ( IIf(nz([Last Name],"") & nz([First Name],"")="","-no PI name-",[Last Name] &  BoxHdr BoxIco BoxCenterIco' IIf(nz([First Name],"")="","",", " & [First Name])) AS [Display PI Name], ' IIf(nz([First Name],"")="","",", " & [First Name])) & Chr(13) & Chr(10) & ' [Institution] & Chr(13) & Chr(10) & IIf(IsNull([City]),"",[City] & ", ") &  fTitle Page `[State] AS [Display PI ORG], Institution, City, # State, IIf(nz([State],"")="","-N/A-",[State]) AS [Display State], % Funder, IIf(nz([Funder],"")="","-N/A-",[Funder]) AS [Display Funder],  F[Keyword List], [Start Date Text],  LinHdr# [Project ID], IIf(nz([Project ID],"")="","-none-",[Project ID]) AS  @[Display Project ID], Abstract, ) IIf(nz([Abstract],"")="","-not available-",[Abstract]) AS [Display Abstract],  f[Breakout Session List], [WG Recommendation List], boxCond L[Start Date Date], [Start Date Year],  D[End Date Text], [End Date Date],  D[End Date Year], [Activity Date],  D[Display Date], [Date Exception], K[ xDELETE [tCurrent Sort Fields].* FROM [tCurrent Sort Fields]; ImgTagline Width. [Review Date], ggsEnglishQueryWhereClause() AS Where1, ggsSortStringEnglish() AS Order1,  6gglSelectionMode() AS Mode1 * FROM [tProject Info] &qGet Startup Values Data1 [Item] = " Item DataMemo BoxHDR BoxCenterHdr- INSERT INTO [tCurrent Sort Fields] ( [Sort Field Descriptor], [Sort Field Expression], 1 [Sort Field English], [Sort Order], Ascending, [Conditional Used], [Compiled Sort Expression],  lblSubTitle Top ImgLogoType ImgSpacer Left. [Compiled English Expression] ) SELECT "PI Last Name" AS Expr1, "[Last Name]" AS Expr2, , "PI Last Name" AS Expr3, 0 AS Expr4, 1 AS Expr5, 1 AS Expr6, "[Last Name]" AS Expr7,  D"PI Last Name-Ascending" AS Expr8; lblHdr Height ImgIcoNCI ImgIcoHHS ImgIcoNIH ImgIcoFG 0UPDATE [tControl Sizes] ,Set [tControl Sizes].[ ] =  #### tWHERE ((([tControl Sizes].[Form Name])="fTitle Page") AND  H(([tControl Sizes].[Control Name])=" ")); [ ] lblSubTitle [tControl Sizes] j([Form Name] = "fTitle Page") AND ([Control Name] = " ") [tForm Sizes] ([Form Name] = "hWnd (^  (h NoKeyOK NumericKeyOK NoKeysAtAll ( c/IG+=+?CnETudEAC7? lblOptionsEC7? cmdCancelcmdOKHC7?ogRangeogWhat31?FormSC7?Detail[C7?Option5Option7Option13Option15cmdCancel_Click cmdOK_Click Form_OpenSetUpPrintTableForBrowseMaster hV;|? List Detail [Print Order] L tPrint Records &You have chosen to & a Detail report of > records that will run al least > pages. Do you really want to " this many pages? Large Document ( (  OptionsH;|?  Range: Form_Load all of the rows " marked rows only ...P;|? What:  a list & detailed summaries MarkBox `DELETE [tPrint Records].* FROM [tPrint Records]; Print OrderX]B,.Wn?HcE3ëg9UV;|LyZbl (6 MCwEDC7?ImageK[22Label1@FrM_=)hYRD8\bU]DF;^lE7׫E)v cmdBackExitcmdHelp cmdGoInfo@C7? txtIndicatorcmdSorttxtSortPC7?subChild txtSearchLabel45cmdSAVEcmdPrintcmdMarkPrimarycmdMarkSecondaryLabel8cmdBackExit_ClickcmdGoInfo_Click cmdHelp_ClickcmdMarkPrimary_ClickcmdMarkSecondary_Click cmdSave_ClickcmdPrint_ClicktxtPIORG cmdSort_Click Form_Activate Form_Close Form_ResizeSizeSubMarkSelectedBoxes | fSearch Criteria OpenInfoDoc OpenHelpDoc OpenBLOBDocOpenIEOpenLinkReadBLOB WriteBLOBCopyFile Mark Save *fPrint Or Save Master Print fSet Sort OrderReSizer   leftLabel21 0fSort and Search Display cbosearch1SetFocusF;|?d;|? tBlobs &[Blob Nickname] = " Blob Content (  8InternetExplorer.Applicationa ӯ>OnF*0[ (  lblHyperlabelHyperlinkAddress Follow Reading BLOB (  (:   BLOB Blob $Finished reading " ..   bytes read. Copy File $Finished writing "  bytes written. ( 0  [Form Name] tForm Sizes [Form Name] = " tControl Sizes .SELECT [tForm Sizes].* &FROM [tForm Sizes]  JWHERE ((([tForm Sizes].[Form Name])=" 4SELECT [tControl Sizes].*  ,FROM [tControl Sizes]  PWHERE ((([tControl Sizes].[Form Name])=" [Left]left [Top]top N([Scale in Steps]) AND ([Form Name] = "! ~WHERE (([Scale in Steps]) AND (([tControl Sizes].[Form Name])=" Scale at Once Control Name@e&N? top txtRecordID Height Width Recenter On 4") AND ([Control Name] = " Has Font Font ResizeControlType Font AutosizeCaption Font BaseFontSize \<4 @  88GetTextMetrics GetTextMetricsA d!P apiCreateFontIndirecttxtBars CreateFontIndirectA dp apiSelectObject SelectObject d apiDeleteObject DeleteObject d  apiMulDiv kernel32 MulDiv i  apiDrawText DrawTextA bA  CreateDCbyNum CreateDCA d  apiDeleteDC DeleteDC d0 GetProfileString GetProfileStringA iP  RectFontSize fK[TextHeight fTextWidthfTextWidthOrHeightGetDefaultPrintersName Font Max Font Min Font Temp SELECT  txtProjectID" [tControl Sizes].[Font Group], Min([tControl Sizes].[Font Temp]) (AS [MinOfFont Temp]  TWHERE ((([tControl Sizes].[Form Name]) = " "))  NGROUP BY [tControl Sizes].[Font Group]; MinOfFont Temp (Datasheet Row HeighttxtDisplayDate `SELECT [tControl Sizes].* FROM [tControl Sizes]  ") AND  B(([tControl Sizes].[Font Group])= Font Group )); Resize Datasheet NWHERE ((([tForm Sizes].[Parent Form])=" "parent subcontrol 6Datasheet Row Height Resize txtFunder ,Datasheet Width Resize 8FROM [tControl Sizes] WHERE  D((([tControl Sizes].[Form Name])="ColumnWidthTag WINSPOOL $fTextWidthOrHeight 0Cannot Create Printer DCFontNameFontWeightFontItalicFontUnderlinetxtTitle $Cannot Create Font windows device , (  |fH58& wLY=Y{H}6'&eTfBE¤z?PageHeaderSectionWC7?ReportPageFooterSectionaC7? ReportFooter ReportHeaderReport_Activate Report_CloseReport_Deactivate Report_Open TLabel24 WTC Form View "WTC Print Preview PrintNow%'+# EnsRDxy6Dz!N0kY#G3tL 'l,B}MKcmdRecommendation cmdKeywordsLabel0 cmdBreakoutcmdBreakout_ClickcmdKeywords_ClickcmdRecommendation_Click\P7kDJ G ɫJ(POȿ5uC<]s\@?5(4 txtAbstracttxtBreakoutSessionListtxtWGRecommendationListtxtKeywordListcmdPrintDetail txtReviewDatecmdClose txtEntryType cmdSaveDetailcmdClose_ClickcmdPrintDetail_ClickcmdSaveDetail_Click Form_CurrentPrintSaveDetail I~CfIDLbF~ZMyY]bŎECcW|5CCv" Ds8cmdStatecmdPIpЇ2FPxWEOhIGH}s:I@Y>qmLJ2JڝehOption4Option2Label7Option9Option11 ogSelection ogPreviewogPreview_AfterUpdate l4 VYou have chosen to print a Detail report of j pages. Do you really want to print this many pages? Large Printout .[Item] = "PrintPreview" xxxT hZ4Cb^ cmdSearchlblHdr ImgLogoType cmdBackgroundLabel46cmdQuit lblHyperlabelcmdBars. FROM [tDefaults and Constants] WHERE ((([tDefaults and Constants].Item)="PrintPreview")); `SELECT "PrintPreview" AS Expr1, K["True" AS Expr2; 0Print Selected Records ( ) BSELECT "PrintPreview" AS Expr1, " +KeHax KfT)k1"1SN2RBC7?BoxHdr ImgIcoHHS imgIcoNIHImgIco1GGC7?chkMax ImgSpacer ImgTaglineBoxIcochkMax_AfterUpdatecmdBackground_Click cmdQuit_ClickcmdSearch_Click Form_Timer T;|? BUPDATE [tDefaults and Constants]  NSET [tDefaults and Constants].Data1 = " " ogCQR cmdCQR_Click xWHERE ((([tDefaults and Constants].Item)="MaximizeOnOpen")); cboSearch1Ȱ̈́EZqfSkΔEX5vK֘G`MVUz&!͝C҂"QLabel4 cmdRefreshLabel3cmdRefresh_Click \Cx1LiiX N= KHp_\C#+ )8 y۰D%9j| cmdSetModalBox14cmdUnCQR cmdUnsetModalcmdCQROption8Option10cmdSetModal_ClickcmdUnCQR_ClickcmdUnsetModal_Click Low-+zDQ*a%=K1(F!OxzδBX dmqG"4 XWFB'w>=?͵fO F>6`D-=E9x;#U^Db,State Record_ID Last_Name P f([State] is not null) and ([Last Name] is not null) yspBF>n46Z?DKDIG<DwM햧 cmdBars_Click (` vN K6O*GH9!7IlMXlHXHH\ wM3:/K JWWqtxtINCommand4txtOUTCommand4_Click%誖FEw FsHK)4YOFE\OvmՁSetUpPrintTableForDetail `4jiA[Aܡ gn3I񯀙+Csp~ 1Ep=& yFfc cmdAdd cmdRemovecmdUpcmdDownlblCond1lblCond2 txtEnglishLC7?cboValueOption42txtListcmdClearOption51Option40KC7? lstSortFieldsOption53cmdResetBox59lstCurrentOrder Command62cboValue_AfterUpdate cmdAdd_ClickcmdClear_Click cmdDown_ClickcmdRemove_ClickcmdReset_Click cmdUp_ClickCommand62_ClicklstCurrentOrder_AfterUpdatelstCurrentOrder_GotFocuslstSortFields_AfterUpdatelstSortFields_GotFocusBlankCurrentOrderSetAdd SetRemoveDefineCurrentSortEntryoptAscDesc_AfterUpdateoptContains_AfterUpdateoptSimple_AfterUpdate MoveUpDownSetConditionalFieldsCompileOrderBy BlankOrderBy 48<@D Value addZ;|? .[Sort Field Descriptor] 2tCurrent Sort Fields Temp blank [Sort Order] PINSERT INTO [tCurrent Sort Fields Temp] ' ( [Sort Field Descriptor], [Sort Field Expression], [Sort Field English], ' [Sort Order], [Conditional Possible], [Sort Field Conditional Expression], $Sort Field EnglishOption934 [Sort Combo Query],[Sort Combo Limit], [Ascending], [Conditional Use K[d], [Compiled Sort Expression],  @[compiled English Expression] ) 0 SELECT [tSort Fields].[Sort Field Sent Descriptor], [tSort Fields].[Sort Field Expression],   is not  J[tSort Fields].[Sort Field English],   AS Expr1, / [tSort Fields].[Conditional Possible], [tSort Fields].[Sort Field Conditional Expression], 2 [tSort Fields].[Sort Combo Query], [tSort Fields].[Sort Combo Limit], 1 AS Expr2, 1 AS Expr3, / [tSort Fields].[Sort Field Expression], [tSort Fields].[Sort Field English] & "-Ascending" (FROM [tSort Fields]  dWHERE ((([tSort Fields].[Sort Field Descriptor])=" (0 8  Null 0Compiled Sort Expression  is % DELETE [tCurrent Sort Fields Temp].* FROM [tCurrent Sort Fields Temp];0 INSERT INTO [tCurrent Sort Fields Temp] ( [Sort Field Descriptor], [Sort Field Expression],  FINSERT INTO [tCurrent Sort Fields] *Sort Field Expression  IscboOper4. ( [Sort Field Descriptor], [Sort Field Expression], [Sort Field English], [Sort Order], * [Conditional Possible], [Sort Field Conditional Expression], [Sort Combo Query], " [tCurrent Sort Fields Temp].[Sort Field Conditional Expression], . [Sort Combo Limit], Ascending, [Conditional Used], [Value], [Compiled Sort Expression],  @[Compiled English Expression] ) xSELECT [tCurrent Sort Fields Temp].[Sort Field Descriptor],  fWHERE ((([tCurrent Sort Fields Temp].[Sort Order])>5 [tCurrent Sort Fields Temp].[Sort Field Expression], [tCurrent Sort Fields Temp].[Sort Field English], 1 [tCurrent Sort Fields Temp].[Sort Order], [tCurrent Sort Fields Temp].[Conditional Possible],  V[tCurrent Sort Fields Temp]![Sort Order]-1 2 [tCurrent Sort Fields Temp].[Sort Combo Query], [tCurrent Sort Fields Temp].[Sort Combo Limit], - [tCurrent Sort Fields Temp].Ascending, [tCurrent Sort Fields Temp].[Conditional Used],  ^SET [tCurrent Sort Fields Temp].[Sort Order] =  open/ [tCurrent Sort Fields Temp].Value, [tCurrent Sort Fields Temp].[Compiled Sort Expression], K[  t[tCurrent Sort Fields Temp].[Compiled English Expression]  BFROM [tCurrent Sort Fields Temp]; >SELECT "OrderBySQL" AS Expr1, " subChild Option102/ FROM [tDefaults and Constants] WHERE ((([tDefaults and Constants].Item)="OrderByEnglish"));- FROM [tDefaults and Constants] WHERE ((([tDefaults and Constants].Item)="OrderBySQL")); FSELECT "OrderByEnglish" AS Expr1, " Conditional Used) DELETE [tCurrent Sort Fields Temp].*, [tCurrent Sort Fields Temp].[Sort Order]  BFROM [tCurrent Sort Fields Temp]  fWHERE ((([tCurrent Sort Fields Temp].[Sort Order])= ));  FUPDATE [tCurrent Sort Fields Temp]  remove ,  Option100 nSELECT [tCurrent Sort Fields].[Sort Field Descriptor], 0 [tCurrent Sort Fields].[Sort Field Expression], [tCurrent Sort Fields].[Sort Field English], , [tCurrent Sort Fields].[Sort Order], [tCurrent Sort Fields].[Conditional Possible],  cboValue4 x[tCurrent Sort Fields].[Sort Field Conditional Expression], - [tCurrent Sort Fields].[Sort Combo Query], [tCurrent Sort Fields].[Sort Combo Limit], ( [tCurrent Sort Fields].Ascending, [tCurrent Sort Fields].[Conditional Used],  Not * [tCurrent Sort Fields].Value, [tCurrent Sort Fields].[Compiled Sort Expression],  j[tCurrent Sort Fields].[Compiled English Expression]  8FROM [tCurrent Sort Fields]; currentJ;|?\;|? (Conditional Possible Ascending 6Compiled English Expression BSort Field conditional Expression <>0 =0 4  includes $ does not include  ' -Ascending -Descending lSET [tCurrent Sort Fields Temp].[Sort Order] = 100000 txtInstitutiontxtStateOption91 zWHERE ((([tCurrent Sort Fields Temp].[Sort Order])= 100000)); move [Sort Order] = Sort Combo Query Sort Combo Limit Order By: [Sort Order] = Sort  AS  DescӖ:LMW.YI T L-@kQFSᙑUF{N"eo  txtPINameog1txtPerformancePeriodCheck14 Form_Click Form_DblClick Form_MouseUptxtFunder_DblClicktxtInstitution_DblClicktxtPerformancePeriod_DblClicktxtPIName_DblClicktxtProjectID K[_DblClicktxtState_DblClicktxtTitle_DblClick GoToDetail l8ColumnOrderName 2tBrowse Child Sort Fields [Field name] = "  AS Sort0Command2 Sort0 lbl  v  ^ Sort0 Desc* [Sort Combo Query], [Sort Combo Limit], Ascending, [Conditional Used], [Value], x[Compiled Sort Expression], [Compiled English Expression] )  N[tBrowse Child Sort Fields].Ascending, Ma X( xSELECT [tBrowse Child Sort Fields].[Sort Field Descriptor],  j[tBrowse Child Sort Fields].[Sort Field Expression],  d[tBrowse Child Sort Fields].[Sort Field English],  T[tBrowse Child Sort Fields].[Sort Order],  cmdShoDeftxtName cmdGo_Click h[tBrowse Child Sort Fields].[Conditional Possible], " [tBrowse Child Sort Fields].[Sort Field Conditional Expression],  `[tBrowse Child Sort Fields].[Sort Combo Query],  `[tBrowse Child Sort Fields].[Sort Combo Limit], `IB~ 0PcmdGoog4 `[tBrowse Child Sort Fields].[Conditional Used],  F[tBrowse Child Sort Fields].Value,  p[tBrowse Child Sort Fields].[Compiled Sort Expression],  t[tBrowse Child Sort Fields].[Compiled English Expression] ControlTipText [Parent Form] BFROM [tBrowse Child Sort Fields]  hWHERE ((([tBrowse Child Sort Fields].[Field Name])=" (k X cmdMarkSecondaryVisible cmdMarkPrimary *Mark Highlighted Rows NMark the checkboxes of highlighted rowsZE@5 Z 0Un-Mark Highlighted Rows VRemove checkbox marks from highlighted rows <SET [tControl Sizes].[Width] = 2UPDATE [tForm Sizes] SET  L[tForm Sizes].[Datasheet Row Height] = 2[Parent SubControl Width] &[Parent SubControl]sIvnG 'ʓog5cmdShoDef_Click Blob Nickname Blob FilenameG?CB@G'2X6mJ) ^6Nı=JjFB$Command0cmdGo2 cmdGo2_ClickCommand0_Click d48@H $tTrial Project IDs Project ID *Initial digit removed - .Trailing number removed Comma inserted ,[IMPAC Activity Types] .[tIMPAC Activity Types] 4[IMPAC Activity Types] = " Trial ID >None - no Project Type match $$ K[Editing (1 *tIMPAC Activity Types (IMPAC Activity Types ,GetOpenFileName% INSERT INTO [tTrial Project IDs Dup OK] ( [Record ID], [Project ID] ) " SELECT [tProject Info].[Record ID], [tProject Info].[Project ID] *FROM [tProject Info]  >WHERE (((InStr(1,[Project ID]," "))>0)); ,,LL, $,0<HHdB|U7A comdlg32.dll GetOpenFileNameA pAp SaveFileDialogBox .Rich Text Files (*.RTF) *.RTF C:\ >Save Report to a Rich Text File (_ 0 `۪sC:y[EncB MJ`cU A,aMBox2 .rtf . rtf퍈J A, ROverwrite existing file of the same name? &File Already Exists 0Rich Text Format (*.rtf)Ҳ@~ 7Nү@dzLabel16cmdRecordFormscmdRecordForms_ClickRecordControls `48<@D Parent Form .Parent SubControl Width6'HE᫠og3 6DELETE [tControl Sizes].*,  <[tControl Sizes].[Form Name],  F[tControl Sizes].[Updated Control]  j") AND (([tControl Sizes].[Updated Control])=False)); ^SET [tControl Sizes].[Updated Control] = False  4") And ([Control Name] = " Updated Control$_m#M*_j=ޔm*>^OE@|u(} {E[xԄ|IdImgIcoFG BoxCenterHdr BoxCenterIco IHM0>Iڴ KJN|l}HIkBd"MH0@ VJ;RlblRTFcmdPrintOrSavecmdPrintOrSave_Click cmdPrintOrSave Send to printer "Save as .RTF File Save to file  Huihf An error occurred while attempting to print. The printer may have been busy, disconected or otherwise unavailable. If you are sure your printer settings are correct, then try again in a few minutes. Print Error ( txt0Command2_Click  -- RD,[w#&BU>(=v[sOAw55Z ODAP$ xHqa4 O mmվ%wBsA($uEnJ  cmdWrapErrorcmdWrapError_Click$ Can't overwrite existing file: File is marked as In Use or Read Only. Can't Overwrite fWrap Error cmdOK Box2og2 cmdWrapError lblRTF!3Gy@MCh,uNEQ[K}V  RFC"O(D C$V>ڼ"@Iŧxdf7xHyz̢-԰;JPo #M[ fcmdSize cmdSize_ClickN;|?^Kk( nu6Ee<Q8C"9;Og&ڵB ROption21K[Option19Option73Option75cboOper2 cboValue2Option82Option84cboOper3 cboValue3cboOper5 cboValue5 cboSearch1 cboSearch2 cboSearch3 cboSearch4 Option158 cboSearch5 Option160 cboValue1 cmdClearAlltxtType1txtType2txtWarn1txtWarn2txtType3txtWarn4txtType4txtType5txtWarn3txtWarn5Label193 cmdBrowseogLogicalHierarchylblTop1lblTop2lblTop3cboOper1cboSearch1_LostFocuscboSearch2_LostFocuscboSearch3_LostFocuscboSearch4_LostFocuscboSearch5_LostFocuscboValue1_AfterUpdatecboValue1_ChangecboValue2_ChangecboValue3_ChangecboValue4_ChangecboValue5_ChangecboValue1_LostFocuscboValue2_LostFocuscboValue3_LostFocuscboValue4_LostFocuscboValue5_LostFocuscmdBrowse_Clickog2_AfterUpdateog3_AfterUpdateog4_AfterUpdateog5_AfterUpdatecboOper1_AfterUpdatecboOper2_AfterUpdatecboOper3_AfterUpdatecboOper4_AfterUpdatecboOper5_AfterUpdatecboOper1_GotFocuscboSearch1_GotFocuscboSearch2_GotFocuscboSearch3_GotFocuscboSearch4_GotFocuscboSearch5_GotFocuscboValue1_GotFocuscboOper1_KeyDowncboOper2_KeyDowncboOper3_KeyDowncboOper4_KeyDowncboOper5_KeyDowncboSearch1_AfterUpdatecboSearch2_AfterUpdatecboSearch3_AfterUpdatecboSearch4_AfterUpdatecboSearch5_AfterUpdatecboSearch1_KeyDowncboSearch2_KeyDowncboSearch3_KeyDowncboSearch4_KeyDowncboSearch5_KeyDowncboValue1_KeyDowncboValue2_KeyDowncboValue3_KeyDowncboValue4_KeyDowncboValue5_KeyDowncmdClearAll_ClickClearNClearAllogLogicalHierarchy_AfterUpdateValueFieldKeyDownAfterSearchUpdateAfterOperUpdateValueLostFocus BuildWhere AfterOgUpdateBuildCompositeClause SetHierarchySetLineL;|? SetSearches ValueChange ,,@48<@HLPT &WTC Database Access &WTC Database Lockup Active cboValueBackColor' Cannot search on a null field. Please enter something in the search field. $Empty Search Field& No search criteria entered. Enter at least one row or click "Browse all". $No Search Criteria* Query criteria result in zero hits. Please choose other criteria and try again. "No Search Results <Query results in retreival of  & records. Proceed?  Search Results <INSERT INTO [tCurrent Search] ) ( [Line No], Active, [Search Field], [Search Expression], [Conditional Text], - [Conditional Expression], [Use Predicate], [Value], [Value Restriction], [Log Opt], / [Where String], [Open Parenthesis], [Close Parenthesis], [And Or String], [Hierarchy On],  4[Previous Hierarchy On] )K[ & SELECT [tCurrent Search Temp].[Line No], [tCurrent Search Temp].Active, (tCurrent Search Temp txtType none+ [tCurrent Search Temp].[Search Field], [tCurrent Search Temp].[Search Expression], 0 [tCurrent Search Temp].[Conditional Text], [tCurrent Search Temp].[Conditional Expression], Conditional Text cboOperEnabled og% [tCurrent Search Temp].[Use Predicate], [tCurrent Search Temp].Value, ) [tCurrent Search Temp].[Value Restriction], [tCurrent Search Temp].[Log Opt], + [tCurrent Search Temp].[Where String], [tCurrent Search Temp].[Open Parenthesis], , [tCurrent Search Temp].[Close Parenthesis], [tCurrent Search Temp].[And Or String], - [tCurrent Search Temp].[Hierarchy On], [tCurrent Search Temp].[Previous Hierarchy On]  8FROM [tCurrent Search Temp]; Search Field cboSearch xDELETE [tCurrent Search Temp].* FROM [tCurrent Search Temp]; FINSERT INTO [tCurrent Search Temp] * ( [Line No], [Active], [Search Field], [Search Expression], [Conditional Text],  "YYYY" $[Search Field] = " Conditional Type& [Conditional Expression], [Use Predicate], [Value], [Value Restriction], , [Log Opt], [Where String], [Open Parenthesis], [Close Parenthesis], [And Or String],  T[Hierarchy On], [Previous Hierarchy On] ) "Value Restriction strict" SELECT [tCurrent Search].[Line No], [tCurrent Search].[Active], & [tCurrent Search].[Search Field], [tCurrent Search].[Search Expression], + [tCurrent Search].[Conditional Text], [tCurrent Search].[Conditional Expression],  txtWarn x[tCurrent Search].[Use Predicate], [tCurrent Search].Value, $ [tCurrent Search].[Value Restriction], [tCurrent Search].[Log Opt], & [tCurrent Search].[Where String], [tCurrent Search].[Open Parenthesis],  linHBorderColor linV' [tCurrent Search].[Close Parenthesis], [tCurrent Search].[And Or String], ( [tCurrent Search].[Hierarchy On], [tCurrent Search].[Previous Hierarchy On] .FROM [tCurrent SearchK[]; tSearch Fields (tSearch ConditionalsForeColor $Search Combo QueryRowSource Format .([Conditional Type] = " 2") And ([List Order] = 0) Use Predicate <Conditional Search Combo QueryLimitToList Field Expression "Search Expression Conditional Code   ,Conditional Expression .([Conditional Text] = " <") And ([Conditional Type] = " :Value must be a 4-digit year. Invalid Year Or And And Or String Where String 2Search for entries where: *Previous Hierarchy On Open Parenthesis "Close Parenthesis  '  Hierarchy On ( [Line No] =TextJ  "#$%&'()*+,-./013456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnpqrtuvwxyz{|}~K!7rU~~~~~~~~~~~~~~~~~~~~W 1    3 5  7  9  ;   =  ? A    C E ! 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513, TitlePageLogoSizes=45, 156, 888, 680, Form_fTitle Page Good Copy=0, 0, 0, 0, C DataPreparationProceduresDataPreparationProceduresGlobal Vars and SubsGlobal Vars andPROJECTwmn X AcessVBAData Forms  f0ph SubsInitializationsInitializationsKeyClickStuffKeyClickStuffForm_fAAA StartupForm_fAAA StartupForm_fBrowse ChildForm_fBrowse ChildForm_fBrowse MasterForm_fBrowse MasterForm_fData Preparation List SettingForm_fData Preparation List SettingForm_fDetail Display AForm_fDetail Display AForm_fPrint Options for DetailForm_fPrint Options for DetailForm_fPrint SelectionForm_fPrint SelectionForm_fSearch CriteriaForm_fSearch CriteriaForm_fSet Sort OrderForm_fSet Sort OrderForm_fSetModesForm_fSetModesForm_fSort and Search DisplayForm_fSort and Search DisplayForm_fTest ChildForm_fTest ChildForm_fTestBarsForm_fTestBarsForm_fTestDblForm_fTestDblForm_fTestRemoteForm_fTestRemoteForm_fTitle PageForm_fTitle PageForm_fSort and Search Debug DisplayForm_fSort and Search Debug DisplayForm_fData Prep Gather Project IDsForm_fData Prep Gather Project IDsSaveFileDialogSaveFileDialogForm_fSave ReportForm_fSave ReportK[FormResizingXFormResizingXTextHeightWidthTextHeightWidthBlobStuffBlobStuffForm_fBlob InputForm_fBlob InputForm_fPrint Or Save MasterForm_fPrint Or Save MasterForm_fPrint Or Save Report OldForm_fPrint Or Save Report OldForm_fRecord Form/Control SizesForm_fRecord Form/Control SizesPositionFormsPositionFormsForm_fShowClassesForm_fShowClassesReport_rWTC Projects and Activities ListReport_rWTC Projects and Activities ListReport_rWTC Projects and Activities DetailReport_rWTC Projects and Activities DetailForm_fPrint Or Save ReportForm_fPrint Or Save ReportForm_fWrap ErrorForm_fWrap ErrorForm_Form1Form_Form1TitlePageLogoSizesTitlePageLogoSizesForm_fTitle Page Good CopyForm_fTitle Page Good CopyͬUV;|LyZblDetailgImage22d Label1dggdͬ5FSᙑޘDetailmtxtPINamed lblPINamemtxtTitled lblTitlemBlob kPropData TypeInfo QBlobDelta 0 02389=BabcLe ghXiPj!k5^@O:FsH\V. 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For proper operation, the database must be copied fully onto the hard drive. To do this, drag the database icon from the CD-ROM to any folder on the hard drive (or the desktop) while holding down the "control" key. To open the database, double-click on the copied database file0^n+K,3bF1phphBlob O#PropData TypeInfo  03=Babc(#dghij/kDg@v˘QOE2 U{59ǺJL:אڙU@tProject Info{BA3{59ǺJL:אRecord ID6x$OZZ{59ǺJL:אMarkBoxD CwK|{59ǺJL:אProject/Activity IDeEnDe@]ځ{59ǺJL:אEntry TypetK!Eg&Ap{59ǺJL:אTitle:^D. I)go{59ǺJL:אLast NameZ^rO9lr{59ǺJL:אFirst Namez E Qh{59ǺJL:אInstitution!¤D "HD9.{59ǺJL:אCity߷ospJ]3/{59ǺJL:אState1qހ@Zg{59ǺJL:אFundergӒIP'{59ǺJL:אProject IDM.yGQ {59ǺJL:אAbstract̃R9N0={59ǺJL:אBreakout Session ListӢq'G>{59ǺJL:אWG Recommendation Listo; C+Br=RU{59ǺJL:אKeyword List[9SRE{W[Y{59ǺJL:אStart Date TextxkMQQ&{59ǺJL:אStart Date Date] deD<>{59ǺJL:אStart Date Year<;UxvA99{59ǺJL:אEnd Date Text0N%8\FGÀ{59ǺJL:אEnd Date DateU0;F+uښv{59ǺJL:אEnd Date Year9IO@xC{K[59ǺJL:אActivity Date9x#F$PU{59ǺJL:אDisplay Date ͓K"i÷{59ǺJL:אDate Exception)kuM(7{59ǺJL:אReview Date*>Ͳ@LZ_Display PI NameaN}+Display State*BI"Display Funder] Bxc,Display Project ID Z SELECT [tProject Info].[Record ID], [tProject Info].MarkBox, [tProject Info].[Project/Activity ID], [tProject Info].[Entry Type], [tProject Info].Title, [tProject Info].[Last Name], [tProject Info].[First Name], IIf(nz([Last Name],"") & nz([First Name],"")="","-no PI name-",[Last Name] & IIf(nz([First Name],"")="","",", " & [First Name])) AS [Display PI Name], IIf(nz([Last Name],"") & nz([First Name],"")="","-no PI name-",[Last Name] & IIf(nz([First Name],"")="","",", " & [First Name])) & Chr(13) & Chr(10) & [Institution] & Chr(13) & Chr(10) & IIf(IsNull([City]),"",[City] & ", ") & [State] AS [Display PI ORG], [tProject Info].Institution, [tProject Info].City, [tProject Info].State, IIf(nz([State],"")="","-N/A-",[State]) AS [Display State], [tProject Info].Funder, IIf(nz([Funder],"")="","-N/A-",[Funder]) AS [Display Funder], [tProject Info].[Project ID], IIf(nz([Project ID],"")="","-none-",[Project ID]) AS [Display Project ID], [tProject Info].Abstract, IIf(nz([Abstract],"")="","-not available-",[Abstract]) AS [Display Abstract], [tProject Info].[Breakout Session List], [tProject Info].[WG Recommendation List], [tProject Info].[Keyword List], [tProject Info].[Start Date Text], [tProject Info].[Start Date Date], [tProject Info].[Start Date Year], [tProject Info].[End Date Text], [tProject Info].[End Date Date], [tProject Info].[End Date Year], [tProject Info].[Activity Date], [tProject Info].[Display Date], [tProject Info].[Date Exception], [tProject Info].[Review Date], ggsEnglishQueryWhereClause() AS Where1, ggsSortStringEnglish() AS Order1, gglSelectionMode() AS Mode1, [tProject Info].[Last Name] AS Sort1 FROM [tProject Info] WHERE ((([tProject Info].[Record ID]) Is Not Null));K[ "[Event Procedure]"[Event Procedure]"[Event Procedure] Arial8(#<hh? odXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9&TIP_10.42.86.36"[Event Procedure]"[Event Procedure]"[Event Procedure]"[Event Procedure]"[Event Procedure]"[Event Procedure]d2 Tahomahgh Tahomaj1ghm45 Tahoma`< Detail2lA_Ѯm7UF`taefktxtPINameDisplay PI Name"[Event Procedure]wvY3NIREd5U`xabuclblPINamePI Name vPI Name\MKx 4Qm 27UF`l acei fktxtTitle Title"[Event Procedure]|LV\|d5U`P abclblTitle Title TitleOG9ڧ fm7UF`$aefktxtInstitutionInstitution"[Event Procedure]=j@FEJ6d5U`abfclblInstitutionInstitutionInstitution]?Bl]4m7U;F`$aefktxtStateDisplay State"[Event Procedure]+A>G[5d5U7`ab clblState State StateA5 EtZm7U;F`ae3fktxtFunderDisplay Funder"[Event Procedure]h0/GRAͽd5U7`abclblFunder Funder Funderý 0BxSm7UF`a efktxtProjectID$Display Project ID"[Event Procedure]ݔZKxP1d5U`a bWclblProjectIDProject IDProject IDt4FN9)m7UF`$a ek(txtPerformancePeriodDisplay Date"[Event Procedure]g/M}> d5U`a bc(lblPerformancePeriod$Performance Period$Performance Period3B?BG{`bj2U`abefCheck14MarkBox_d'nL9M8d5U`ab|cLabel15Markis BFYBfjtxtInstitutiond lblInstitutionmtxtStated lblStatem txtFunderd  lblFunderm txtProjectIDd  lblProjectIDm txtPerformancePeriodd lblPerformancePeriodjCheck14d Label15Record IDMarkBoxProject/Activity IDEntry TypeTitleLast NameFirK[st NameDisplay PI NameDisplay PI ORGInstitutionCityStateDisplay StateFunderDisplay Funder Project ID!Display Project ID"Abstract#Display Abstract$Breakout Session List%WG Recommendation List&Keyword List'Start Date Text(Start Date Date)Start Date Year*End Date Text+End Date Date,End Date Year-Activity Date.Display Date/Date Exception0Review Date1Where12Order13Mode14Sort1dhjmmdmdmdmdmdmdmdjdͬ]DF;^lDetailmtxtIndicBlobDelta PropDataCopy 2phphBlob e/ 02389=Babc+e g0hi<j 3knRT@YMH Uv˘QOE c6@tWf0fBrowse ChildPBrowse WTC Project and Activity Database"[Event Procedure]"[Event Procedure] Arial8 h?dXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9&TIP_10.42.86.36"[Event Procedure]"[Event Procedure]d2 Tahomag237hgh Tahomam45 Tahomap5r35`| Detail//IMZkm 2457U;CF`xaDb +chjktxtSort: dGrm 2457U;CF`xa(b +cjk txtSearchߺ [8HBm 47];CF`xa<bc,i jktxtIndicator ArialuqK;Zd5U`ab cd e Label8݌Click on column heading to sort. Double-click on any roK[w for details.PZtOCLU-h1U`&abcXg hicmdBackExitBack"[Event Procedure].Return to previous pageE߂lCK)h1U`P abcXg hicmdPrintPrint Entries"[Event Procedure]&^DӑDVh1U`abcXg hicmdHelpHelp"[Event Procedure]View help file dCLUyh1U`xabcXg hcmdSort*Advanced Sort Options"[Event Procedure]@Create a advanced sorting schemenȩ٫Jn!f~56h1U`xabcXg hicmdSaveSave Entries"[Event Procedure]lO-h0p3U`xab\+cdsubChild$Form.fBrowse ChildhMǿR^:h1U`abcXg hicmdGoInfo View Definitions"[Event Procedure]View definitions of workgroups, workgroup recommendations, and keywordsXsOVd5W`xahbc,d eLabel45fUse the "Mark" box to mark a row for print or save.|2@{vh1U`ahbc,hi cmdMarkPrimary*Mark Highlighted Rows"[Event Procedure]NMark the checkboxes of highlighted rowsw lGfh1U`a<bc,hi cmdMarkSecondary0Un-Mark Highlighted Rows"[Event Procedure]VRemove checkbox marks from highlighted rowsWHD22PropData TypeInfo <BlobDelta 3phphatord Label8h cmdBackExith cmdHelph cmdSortmtxtSortp subChildh cmdGoInfom txtSearchd Label45h cmdMarkPrimaryh cmdMarkSecondaryh cmdSAVEh cmdPrintdghmprmmmdhhhhhphdhhBlob qePropData TypeInfo BlobDelta 038=Babe ghijk sU@[OT͜o. U Set Lists Arial8K[ hP? odXXLetter DINU"4[tIUPHdLetter [none] [none]Arial4Pd?TERBORGJ<Automatic>P    K[YJIP_10.42.86.35d2 Tahomahgh Tahoma`@ DetailmY#&cH'q)qd15U7`abcd e Label0݊Front End for Breakout-, Recommendation-, and Keyword-setting modules Arial6GDeEIZNngMWh1U`abcghcmdBreakout&Go BreakoutSessions"[Event Procedure]ƫgEbdS h1U` abcghi"cmdRecommendation"Go Recommendation"[Event Procedure]K ?͕A*d]h1U`abcghicmdKeywordsGo Keywords"[Event Procedure]sSD='hͬY#G3tLDetaild Label0h cmdBreakouth cmdRecommendationh cmdKeywordsdhdhhh4phphBlob PropData TypeInfo p  02389=Babc(e g*hQ ij(2kUZl`@Zr"L­h3 U^8D{ HĤ.v-@qBrowseDBP@G^8D{ HĤ.Display Abstract̃R9N0=^8D{ HĤ.Breakout Session ListӢq'G>^8D{ HĤ.WG Recommendation Listo; C+Br=RU^8D{ HĤ.Keyword ListtK[K!Eg&Ap^8D{ HĤ.Title9x#F$PU^8D{ HĤ.Display Date"FZ7(CG c^8D{ HĤ.Display FunderUCeOUts^8D{ HĤ.Display Project ID{BA3^8D{ HĤ.Record ID5Ap^8D{ HĤ.Display PI ORG)kuM(7^8D{ HĤ.Review DateeEnDe@]ځ^8D{ HĤ.Entry TypeqBrowseDB6WTC Project/Activity Detail"[Event Procedure]"[Event Procedure]"[Event Procedure] Arial8 hT? odXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9c&TIP_10.42.86.36d2 Tahomag237hgh Tahomam45 Tahomap5` Detail CfIP_m 2457_`<a bc ktxtAbstract Display AbstractNClick for vertical scroll bar if needed\9gAvؗd5]7`<a bcd eLabel15Abstract:q)CQm 2457W`abci k,txtBreakoutSessionList*Breakout Session ListNClick for vertical scroll bar if needednSKfimd5]7abcd eLabel21Work Group:E9w$VIF 7m 2457W`La,b c(i k.txtWGRecommendationList,WG Recommendation ListNClick for vertical scroll bar if needed@\+DM1ͳr˞d5]`La<b cd eLabel27&WG Recommendations:lS]Gam 2457W`Lab c i ktxtKeywordListKeyword ListNClick for vertical scroll bar if neededVy<`8|I+Rd5]`Labcd eLabel29WTC Keywords:bM:)O@sm 2457_`abci ktxtTitle TitleNClick for vertical scroll bar if neededvfV[IC ۩d5]7`<abcd eLabel25 Title:ܖE'Em 457W`a bP i ktxtDisplayDateDisplay Date7KܳI d5_7` a bcd eLabel10&Performance Period:[* A*hÆvm 457_`abP i ktxtFunderDisplay FunderЇucDު?d5]7`abcd elblFunderFunder: DћLEm 457W`a8bP i k txtProjectID$Display Project ID[wU.L}!id5_7`aHbdcK[d elblProjectIDProject ID:*.HJ:[vm 457W`abi k txtRecordIDRecord IDN ua";@ʖ)MP^d5_``ab,cd elblRecordID RecID#lچ-Cy^~m 2457U`ab,ci k txtPIORGDisplay PI ORGNClick for vertical scroll bar if needed8{G06[d5U7abcd eLabel20PI/ Org:ALwiڬd45U7`<a<bc8d eLabel24PROJECT DETAIL ArialQilJǴS6\h1U`abc,g hcmdPrintDetailPrint Detail"[Event Procedure]gY Om=Ofrh1U` abc,g hicmdClose Close"[Event Procedure].Return to previous pagebhPxMͫvy` m 467U;CF`` a<bc,i jk txtIndicator Arial|eC# ^-m 457;`ta bi k txtReviewDateReview Dategv N$w`Mh1U`xabc,g hicmdHelpHelp"[Event Procedure]View help fileCr A,h1U`abDc,g hicmdGoInfo View Definitions"[Event Procedure]View definitions of workgroups, workgroup recommendations, and keywordsEr A,ͬ@uC<]ɘDetailmtxtAbstractd Label15mtxtBreakoutSessionListd Label21mtxtWGRecommendationListd Label27mtxtKeywordListd Label29m txtTitled Label25m txtDisplayDated Label10m txtFunderd lblFundermtxtProjectIDd lblProjectIDmtxtRecordIDd lblRecordIDmtxtPIORGd Label20d Label24h cmdPrintDetailh cmdClosemtxtIndicatormtxtReviewDated Label38mtxtEntryTyped Label40h cmdSaveDetailRecord IDMarkBox Project/Activity ID!Entry Type"Title#Last Name$First Name%Display PI Name&Display PI ORG'Institution(City)State*Display State+Funder,Display Funder-Project ID.Display Project ID/Abstract0Display Abstract1Breakout Session List2WG Recommendation List3Keyword List4Start Date Text5Start Date Date6Start Date Year7End Date Text8End Date Date9End Date Year:Activity Date;Display Date<Date Exception=Review Dateh >cmdHelph ?cmdGoInfodghmBlobDelta O5phphBlobK[  PropData pmdmdmdmdmdmdmdmdmdmddhhmmdmdhhh 023809=Babc| e ghi j> k*@wr2l@E U.Print Content Selection"[Event Procedure] Arial8 hT                        ! " # $ % & ' ( ) * + , - . / 0 1 2 3 4 5 6 7 8 9 < = > ? A B C F J K L M N O P Q R S T U V W X Y Z [ \ ] ^ ` a b c d e f g h k l m n o p q r s t u v w y z { | } ~  ?dXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9c&TIP_10.42.86.36d2 Tahomahgh Tahomai1ghk1` Detail~$@d5U7`xaxb c,d e Label7"Choose Print Mode Arial{dvJKV*k45U`xabP cogPreview"[Event Procedure]:7Ak"i2W`a4bcOption9'D<d5`abceLabel10.Preview Before Printing/`FN;+wPi2W`albcOption11|PtEG5I#jd5`aHbceLabel12*Print without Previewy.-K=4Yh1U`abc,hi cmdOKOK"[Event Procedure]ÈVM00"h1U`abc,hicmdCancel Cancel"[Event Procedure]u'rM}ͬ 4YOFEDetaild Label7kogPreviewiOption9d Label10iOption11d Label12h cmdOKh cmdCanceldhikdkididhh 023809=Babc| e ghi jXkTypeInfo BlobDeltaK[ 6phphBlob  *@AU$DQfr U.Print Content Selection"[Event Procedure]"[Event Procedure] Arial8 hT?dXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9l&TIP_10.42.86.36d2 Tahomahgh Tahomai1ghk1` Detaild!>CHW"{k45]`xabP cogSelectionLb)KR8 i2W`a@bcOption4k4KǴ Ad5`abcelblPrintAll$Print all recordsc-Ci2W`a`bcOption2MpI5+d5`aHbce"lblPrintSelection,Print selected records u/c"FhzEWd5U7`xaxbP c,d e Label7"Choose Print Mode Arial(LAk45W`xatbP ciogPreview"[Event Procedure]gB i2W`abcOption9P٢/Ih:=d5`abceLabel10.Preview Before Printing-h5& @i2W`abcOption11AQE{7k}d5`abceLabel12*Print without Preview߱-@ 0qDetailkogSelectioniOption4d lblPrintAlliOption2d lblPrintSelectiond Label7kogPreviewiOption9d Label10i Option11d Label12h cmdOKh cmdCancelPropData: TypeInfo; !BlobDelta@ 7phphK[dhikkididdkididhhͬ5KD%tDetaild Label0gImage1d Label2dgdgdBlob w$PropDataD TypeInfoE `BlobDeltaG 608=BabcL,e gh i jX,k@nRT@1ȢFרMS. U  Arial8 hT? odXXLetter.HP LaserJet 4100 PCL 62xeOKQ7fQjbhC-̅"m0ZiY6-7_)"A xsZ+;B{-/ߓ7 o`h'={ʫsRbe+)l6eq]c|'Mc@8f,c i#DhM&WyYCG?`b.C`-0F a%E~J6:߱YG<ќEsD~^q";+hՇguOWjQ:W͵z+-?XXNL}To֌i5dq ޮlNVXDK!V+`1n=цc8[X\MIP_10.42.86.33d2 Tahomag237`4 DetaillT_F"y O d5]`` aDb,cP d Label0DThe Proper size is 7 7/8 by 4 1 /8 $OH:MWg` a<bc  Image1 <  &  " ^--8 ({5{4}+})21)&$({({=85877789:;<<<=<<;;998877641558'#DDFGHHIIIHHHGGFECB@@>=<;;;;<<<==>?ABDDDEEFFFFEDCCBBA@@?>>>>>>?@@@ABCDDEEEE8BMOOOOPQSTTUVWWWWXY[\\]^__``_]Z\\]]\\\[[ZYXXWWTRTTTTTTSSSRPPOONLIMM8htttt~t~s}s}r}q}q}p}o}o}n~m~mmllllmmnoqsttuuuuuttsqpomlljihgggggjjiijjklmmnoopqqrrrrrqqpomlkjjiiiijjk~k}l|n{o{qzqzszt{u{v|w}w~wwtt8GK[~~}}|{{zzzzzzz{||}~~~}{{zyxwwwwwwxxyz{|~8{{~~{{88Q8&8G88E8 ||||8'#8h~~}}}}}}}}~~~}|{{zzz{{|}~8'#8 { { { {Q8&     E8 |#|"%$!  "!!  | |8'*&$''({+{+~(~({({8'#335678888777665431//.,++**++++,-./0133355555544332100//..---../00122334555Q8&<?>>>?@BCCDFFGGGFDADDDDDCCBBA??>>>;8<<8bQQRRQQQPPPONMMLLLLLLMNPPQRRSSSSSSRQQPOMLLJIHGGGGJJJJJJKLLLMOOPPPPPPPONMMKJJIIIIIJJKLMNOPPRSTTTTTQQ<8 YK[VV]\ZYWYYeeaa__^]^`aegedee!8ttolige c b `!8j++'$"   ejj88N8^h`h`daddhehcdcddcdcebeaeae`e_d_c_b^^^^h^h``b`b`b`c`d`dadadbcbbbbb`b````8''YcYcYeZf[h\i]j^k`kbkbkckekfjgihhifiejcjciai`h^g]f\e\c[b[b[`[^\]\\][^Z`YaYcYcYchchchdgfggfheidicjbjbj`j_i^i]h\g[f[d[c[c[b[`\_]^^]_]`]b\b\c]d]e]f^g_g`hbhchchc8Ho[7[0ktktkwkzj}igeba_^\\XXkk[[XXkkXXkkXXXZ]_ ` b d efhhijjkkkOkW[W[$[$[#[![ [ZYXYXYV(V'XwXwXuYsZq[o[o[o[G8!zSSSGGSSLLGGSSGGSSG G GSSGbGcE2E1GGG}MzSzSzS98HZZXnp  %%&&yzHHH;8"''""''"k"i'T'T'V"C"D v u"$"$'''" " ''""S8'>,R,R,Q.Q/Q1Q22210/..-,,,22,,22,,22 ,,,2"2#,p,q*?*>,>,i8288S8S8T9U:W;Y>??@AAA?<:88AA88AA88AA8 8 8 AA!8j8k696888858K]]\bb}~LKKhC:\My Documents\Greg\WTC\WTC DB\WTC DB\saicblack.wmf>)@W C}d5`a0 b cd e Label2>The correct ratio is 5 W : 2 H \5>EX8phphBlob =PropDataH TypeInfoI t02389=?Babc(e gh ij1knRT@5 2c϶HqO Ud?JKiA#Q< ]9N@`\tSearch Fields T*nB.%d?JKiA#Q.H/bQ5 2c϶HqOtxtType4YBiJ{R5 2c϶HqOtxtType5>Search Project/Activity Records"[Event Procedure]"[Event Procedure] Arial8 hT?dXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9c&TIP_10.42.86.36"[Event Procedure]"[Event Procedure]"[Event Procedure]d2 Tahomag237hgh Tahomai1ghk1m45 Tahomao2 Tahoma` Detail$IWk4m 7]F` a bktxtType5 "Text"YBiJ{Rk45]`@axb ci$ogLogicalHierarchy"[Event Procedure]1srLjLCB ~d5`|axbcelblEval1Evaluate:Zl f7P@[7Qi2_`abcOption158DEvaluate all OR's before any AND's$)e-JRyd5`laxbcelblEval2&OR's first (normal)XL,;fri2W`ab8cOption160DEvaluate all AND's before any OR's%d[H3N d5`nahbcelblEval3AND's first`5NVJK+o5]Dachdepl "";"";"10";"100"FJL$BVcboSearch1Table/QuerySELECT [tSearch Fields].[Search Field] FROM [tSearch Fields] ORDER BY [tSearch Fields].[Sort Order]; "[Event Procedure]"[Event Procedure]"[Event Procedure]"[Event Procedure]>Specify what field to search ino5]Dc\ deTl n "";"";"10";"100"W1C5x3cboOper1Table/QueryTSELECT [tSearch Conditionals].[Conditional Text] FROM [tSearch Conditionals] WHERE ((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType1])); "[Event Procedure]"contains""[Event Procedure]"[Event Procedure]bChoose a logical operator from the drop-down listd57`\ab|cd elblTop1Search in...`RF{qAd57`P ab`cd elblTop2 to see if it ...IJo~IAlo5]Dcdel npt>E>cboValue1TablK[e/Query"[Event Procedure]"contains""[Event Procedure]"[Event Procedure]"[Event Procedure]"[Event Procedure]^Enter the value to be found or choose from listd57`abcd elblTop3 Value :UOF ;^k135_`habc&iog11%oyJl i2W`abcOption21Specify what field to search ino5]Dc\ deTl n "";"";"10";"100"`ЭL9GpcboOper2Table/QueryTSELECT [tSearch Conditionals].[Conditional Text] FROM [tSearch Conditionals] WHERE ((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType2])); "[Event Procedure]"contains""[Event Procedure]bChoose a logical operator from the drop-down listo5]Dcdel ncKGnH *"cboValue2Table/Query"contains""[Event Procedure]"[Event Procedure]"[Event Procedure]^Enter the value to be found or choose from listk135_`habc&iog3"[Event Procedure]1IIsAN]@t;i2W`abcOption82Specify what field to search ino5]Dc\ deTl n "";"";"10";"100" ŭ@UQcboOper3Table/QueryTSELECT [tSearch Conditionals].[Conditional Text] FROM [tSearch Conditionals] WHK[ERE ((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType3])); "[Event Procedure]"contains""[Event Procedure]bChoose a logical operator from the drop-down listo5]Dcdel n Dx;=sDS]|'"cboValue3Table/Query"contains""[Event Procedure]"[Event Procedure]"[Event Procedure]^Enter the value to be found or choose from listk135_`habc&i og4"[Event Procedure]11YA}+m,+i2W`a.bcOption91Specify what field to search ino5]Dc\ d$ eTl n "";"";"10";"100" +MW;cboOper4Table/QueryTSELECT [tSearch Conditionals].[Conditional Text] FROM [tSearch Conditionals] WHERE ((([tSearch Conditionals].[Conditional Type])=[Forms]![fSearch Criteria]![txtType4])); "[Event Procedure]"contains""[Event Procedure]bChoose a logical operator from the drop-down listo5]Dcd$ el nW`FyKe[cboValue4Table/Query"contains""[Event Procedure]"[Event Procedure]"[Event Procedure]^Enter the value to be found or choose from listk135_`ha bc&iog5"[Event Procedure]1%LEQi2W`aJ bcOption100ьFG$>Qd5`aP btc lblOR5ORu^nbJ uYo5_Dchd@ epl n "";"";"10";"100"J$vd@]&cboSearch5Table/QuerySELECT [tSearch Fields].[Search Field] FROM [tSearch Fields] ORDER BY [tSearch Fields].[Sort Order]; "[Event Procedure]"[Event Procedure]"[Event Procedure]"[Event Procedure]>Specify what field to search ino5Dc\ d@ eTl n "";"";"10";"100"G%lZKTϸ!cboOper5Table/QueryTSELECT [tSearch Conditionals].[Conditional Text] FROM [tSearch Conditionals] WHERE ((([tSearch Conditionals].[Conditional Type])=[FK[orms]![fSearch Criteria]![txtType5])); "[Event Procedure]"contains""[Event Procedure]o5]Dcd@ el nXm Z*LK-cboValue5Table/Query"contains""[Event Procedure]"[Event Procedure]"[Event Procedure]^Enter the value to be found or choose from listf23`xaHb linH1tm\I7,"+f23`xadb linH2 9ZN3~<͟cf23`xab linH3!B &f23`xa b linH4Ƌc'kGe-f23`xa b linH5C-B,f23`xaHbc linV2\D^T<BZf23`xadbc linV3,˅8eG#Џf23`xabc linV49s.AM'f23w`xa bc linV5TƿB1JQf23w`xabch linV1!OH{LK$Ah1U`8"abdcg hicmdClearAll Clear"[Event Procedure]2Clear all search criteriaqiS?E9?$m 7WF`\ abktxtType1 "Text"ۧ@yrm 7WF`\ abktxtType2 "Text""rLzqm 7WF`\ abktxtType3 "Text"+.K%i^@=m 7WF`\ a bktxtType4 "Text">.H/bQh1`8"abdcg hicmdSearchOK/Search"[Event Procedure].Execute search strategy:#(GGS^ m 47;CF`abTi jktxtWarn1 "Text"tCqCJOȇlm 47;CF`abTi jktxtWarn2 "Text"h>@!S"Em 47;CF`abTi jktxtWarn3 "Text"%+MeP8m 47;CF`a4bTi jktxtWarn4 "Text"A_s,?cJ mm 47;CF`aP bTi jk txtWarn5 "Text"bIt!O|ؚ Ih1U`8"a bdcg hi!cmdCancelBack"[Event Procedure].Return to previous pageIvKKK/4d35W7`xaxb chd eLabel193&SEARCH WTC DATABASE ArialmAGmNd^Hh1U`ab4c,hi"cmdReset Reset"[Event Procedure]JReset all criteria to starting valuesAD~@ەax1h1U`8"aDbdcg hi#cmdBrowseBrowse All"[Event Procedure]*Go to Browse All pagea @Aln6h1`a bDcg hi$cmdGoInfo View Definitions"[Event Procedure]View definitions of workgroups, workgroup recommendations, and keywords[_PN~ }kh1U`,a b(cg hi%cmdHelpHelp"[Event Procedure]View help filepCE䑮=ͬN8C"9;ODetailocboSearch1ocboOper1ocboValue1kog1iOption21i Option19k og2i Option73iOption75ocboSearch2ocboOper2ocboValue2kog3iOption82iOption84ocboSearch3ocboOper3ocboValue3kog4iOption91iOption93o!cboSearch4o"cboOper4o#cboValue4k$og5i%Option100i'Option102o)cboSearch5o*cboOper5o+cboValue5f=linH1f>linH2f?linH3f@linH4fAlinH5fClinV2fDlinV3fElinV4fFlinV5fIlinV1kJogLogicalHierarchyiLOption158iNOption160h ZcmdCK[learAllmctxtType1mdtxtType2metxtType3mftxtType4mgtxtType5h kcmdSearchmltxtWarn1mmtxtWarn2mntxtWarn3motxtWarn4mptxtWarn5h tcmdCanceld uLabel193h vcmdReseth wcmdBrowseh xcmdGoInfoh ycmdHelpd lblOR1d lblOR2d lblOR3d lblOR4d (lblOR5d &lblAND5d lblAND4d lblAND3d lblAND2d lblAND1d KlblEval1d MlblEval2d OlblEval3d lblTop1d lblTop2d lblTop3BlobDelta_ {9phphBlob -PropDatai dghikmo4mkdididooddodkididkididoookididoookididoookididoooffffffffffhmmmmhmmmmmhdhhhhͬ-~ 1Ep=DetailnlstCurrentOrderd Label2nlstSortFieldsd Label14h cmdDownh cmdUph cmdAddh cmdRemoved Label19d Label20d Label21d Label22d Label23h cmdOKh cmdCanceld lblCond1koptContainsiOption31d Labe02389=Babc\+e g?hi j1kROر@lDfU& UIЋ]C&Cĝ=D,n@\tCurrent Sort Fields Temp3rH!ҏBpwIЋ]C&Cĝ=Sort Order\OɩDI2d RIЋ]C&Cĝ=Compiled English Expression] AAikIЋ]C&Cĝ=Sort Field DescriptorcΜ_Ma hR@\tSort FieldscYUzD-fcΜ_MaSort Field DescriptorUg9E Qk cΜ_MaSort Order"[Event Procedure] Arial8 h`? odXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; 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" # $ % & ' ( ) * + , - . / 0 1 2 3 4 5 6 7 : < = > ? @ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z [ \ ] ^ a d e i j k l m n o p q r s t u v w x y z { | } ~  ͬ퍈J A,Detailmtxt0d Label1h Command208g=Babe gh@ij`k +}@<a X(. U  Ariald2 Tahomahgh Tahomam45 Tahoma`@  Detail=a X(m27W`ab c,txtName>a X(d5]`ab c Label1ZFile Name must reside in CurrentDB directory:Ba X(h1U`abcXi cmdGogo"[Event Procedure]Ca X(h1U`abcicmdShoDefSHo Definition"[EK[vent Procedure]]a X(ͬMa X(DetailmtxtNamePropData TypeInfo sBlobDelta U24d Label1h cmdGoh cmdShoDefdhmmdhh 0238=Babc<e gh ijk?]@^Ν( A, U Arial8 h\?dXXLetterBlob  = PropData8 TypeInfo9 Y25.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9l&TIP_10.42.86.36d2 Tahomae12hgh Tahoman2 Tahoma` Detail_Ν( A,h1U`abc cmdRecordForms Record All Forms"[Event Procedure]bΝ( A,d5U`a,b0 cLabel16At first, record the forms, then turn off datasheet resize in tForm Sizes for forms that contain a datasheet. Open the datasheet forms and be sure to adjust the rowheight and *every* column width. This adjustment will cause the values to be entered into the tables. Then turn the datasheet resize for the parent form back on.Ν( A,ͬXΝ( A,Detailh cmdRecordFormsd Label16K[ 02389=Babc e ghXi3jkV"&_f@#7/G320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9l&TIP_10.42.86.36d2 Tahomae12hgh Tahoma`T DetailU{ M'Pfd15U7`<ab ce lblRTFݖAn .RTF file can be read by many word processing programs including MS WordD~9 A,e5]`<a<b c Box2UD|,PMp5Vh1`xaxbcg hcmdPrintOrSave"Save to .RTF File"[Event Procedure]rSame as Selecting File>Print... from the screen menu bar.oSIQO Jh1`axbcg hicmdClose Close"[Event Procedure]2Close the current report.TzX\@Bv{ͬl}HIkBd"MDetaileBox2h cmdCloseh cmdPrintOrSaved lblRTFdehehh089=Babe hqijD%kY@V@퍈J A, U Arial`@  Detail퍈J A,ͬ퍈J A,Detail26Blob c PropDataf TypeInfog 027 K[Blob h PropData   TypeInfo   02389=Babc e g hiXjk&_f@?.C %T. U 4Save Print or Close Report"[Event Procedure]"[Event Procedure] Arial8hT߀dXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9c&TIP_10.42.86.36d2 Tahomae12hgh Tahoma`$ Detail LJo`d15]7`<ab ce lblRTFݖAn .RTF file can be read by many word processing programs including MS WordʦG\"e5]`<a<b c Box2뎤IHr*h1`xaxbcg hcmdPrintOrSave"Save to .RTF File"[Event Procedure]rSame as Selecting File>Print... from the screen menu bar.Mo܄~NO(r&h1`axbcg hicmdClose Close"[Event Procedure]2Close the current report.n$Fp~6h1`<ab cicmdWrapErrorݢWhy does the text in the RTF file wrap incorrectly when I open it using MS Word?"[Event Procedure]rSame as Selecting File>Print... from the screen menu bar.'z*G ؔ ͬվ%wBsA(Detaild lblRTFeBox2h cmdPrintOrSaveh cmdCloseh cmdWrapErrordehdK[ehhBlobDelta H28Blob  PropData h02389=Babce ghUij%k +I;,@ՠFK ѧ. U ,Access Word-Wrap Error Arial8hT?dXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9c&TIP_10.42.86.36d2 Tahomahgh Tahoma` DetailR9"&Cl&dd5U`abce Label0On some computers, reports saved as RTF files exhibit minor word-wrapping errors. This is due to a known issue with some versions of MS Access. On occasion this can be remedied simply by using the "Search for Updates" of the Microsoft Office website to identify and install current Microsoft Office updates and patches. The problem can also be fixed easily by decreasing the font size in MS Word: ->After saving the RTF file, open it using MS Word and press Control+A to select all of the text. ->Next, press Control+Shift+< (the  less than symbol on the same key as the comma) to reduce the font size by one point. # JCR{헞h1U`a<bcg h cmdOKOK"[Event Procedure]j%-\Bb_>)ͬ RFC"ODetaild Label0h cmdOKdhdhͬK["1SN2RDetailgImgSpacergImgTaglineeBoxIcod lblHdrh cTypeInfo OBlobDelta |29 uBlob 1':9      !"#$%&'()*+,-./012345678B;<=?m@ADCEFHGIJNKLMOPQRSTXUVWkoZ[\]^_`abcdefghijlnpwqrstuvxyz{|}~ 02389=Babc-e gDhij1k"L@SܤdMf^X . U fWomen, Tobacco and Cancer Project/Activity Database"[Event Procedure] Arial8-hT? odXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9c&TIP_10.42.86.36"[Event Procedure]"[Event Procedure]"[Event Procedure]"[Event Procedure] d2 Tahomae12g237hgh Tahomaj1ghl2m45 Tahomar35` DetailPYIOuN{g6`ahbcImgSpaceraj Fl} EMFa|6`F00GDIC ߸x0 < %'  %' &_FMRIB t&_FMRFS0!P0 H# " $!P; ,& U!0; 4& N! = ,' " $!P; ,& U!0; 4& N! = ,' " $!P; ,& U!0; 4& N! = ,' F\l9 EMF(|6`F GDICw~~  ? '  ' &_FMRIT0 &_FMRIB f&_FMRFS%!P0 H# " $!P; ,& U!0; 4& N! = ,' " $!P; ,& U!0; 4& N! = ,' " $!P; ,& U!0; 4& N! = ,' " $!P; ,& U!0; 4& N! = ,' ' E!@+ <& I!@9 & _FMRPI  C %%(% )qqAA                                                                                                                                                                                                                                                                                                                              K[                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       K[                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          K[                  %  %   Q-%P(x ) %(% )qqAA                                                                                                                                                                                                                                                                                                                                                                    K[                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              K[                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 K[          % % 0 KC:\Documents and Settings\ColeG\My Documents\My Pictures\WTC\From NCI\logotype.gif,http://www.cancer.gov/{+a|J0TPe5`ahb%c BoxHdr}:L<0]~f23W5`ab% LinHdr V@jGCPropData TypeInfo BlobDelta 30uumdHelph cmdSearchh cmdBackgroundh cmdQuitj chkMaxd  Label42d  lblHyperlabeld  Label46d  lblSubTitlegImgIcoNCIgImgIcoHHSgimgIcoNIHgImgIco1GgImgLogoTypeeBoxHdrfLinHdr deghjlmrggedhhhhjddddgggggefͬ-԰;JPo Detaild Label3mtxt0h cmdGogImgLogoTypeh cmdSizedghmhmdghBlob ePropData TypeInfo BlobDelta a08=Babe ghXij$k<@i-AEKFD. U  Arial8 hT?dXXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9K[c&TIP_10.42.86.36d2 Tahomag237hgh Tahomam45 Tahoma`@  Detailw&ReEk`Bh1U`aTc cmdGoCommand0"[Event Procedure],I`Xvm7]F`Datb(cktxt0imaIY:_d5]`atbc Label3 Text2:ǖGSv]g36`ab,cImgLogoType] F lf EMF]|6`F..GDICvq. b %  % &_FMRIB x&_FMRFS3!P0 H# " $!P; ,& U!0; 4& N! = ,' ' E!@+ <& I!@9 & _FMRPI  C %%(% )qqAA                                                                                                                                                                                                                                                       K[                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    K[                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       K[                                              %  %   Q-%P(x ) %(% )qqAA                                                                                                                                                                                                                                                                                   K[                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          K[                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     K[                           % % 0 KC:\Documents and Settings\ColeG\My Documents\My Pictures\WTC\From NCI\logotype.gif L?h1U` aXbcicmdSizesize"[Event Procedure]lߎH6)DirData PropData DirDataCopy PropDataCopy Form1fPopUpfShowClasses8fRecord Form/Control Sizes.fPrint Or Save Master@fSort and Search Debug Display fAAA StartupfBrowse Child fBrowse Master@fData Preparation List Setting&fDetail Display A6fPrint Options for Detail$fPrint SelectionfProper Size$fSearch Criteria"fSet Sort Order fSetModes 4fSort and Search Display fTest Child fTest MasterfTestBarsfTestDblfTestRemotefTitle Page>fData Prep Gather Project IDsfSave ReportfBlob Input6fPrint Or Save Report Old.fPrint Or Save ReportfWrap Error.fTitle Page Good Copy 30CB0 26CB0 22CB0 24CB0 15CB0 12CB0 0CB0 1CB0 2CB0 3CB0 4CB0 5CB0 6CB0 7CB0 8CB0 9CB0 10CB0 11CB0 13CB0 14CB0 16CB0 17CB0 18CB0 19CB0 20CB0 21CB0 23CB0 25CB0 27CB0 28CB0 29CB0"fTitle Page OldfWrap Error.fPrint Or Save Report6fPrint Or Save Report OldfBlob InputfSave Report>fData Prep Gather Project IDsfTitle PagefTestRemotefTestDblfTest                       ! " # % & ' ( * + , . / 0 < = > ? @ B D E F G H J L M N O P Q R S T K[U V W X Y Z [ \ ] ^ _ ` a b c d e h k l m n o p q r s t u v w x y z { | } ~  BarsfTest MasterfTest Child 4fSort and Search Display fSetModes "fSet Sort Order $fSearch CriteriafProper Size$fPrint Selection6fPrint Options for Detail&fDetail Display A@fData Preparation List Setting fBrowse MasterfBrowse ChildfAAA Startup@fSort and Search Debug Display .fPrint Or Save Master8fRecord Form/Control SizesfShowClassesfPopUpForm1 29CB0 28CB0 27CB0 25CB0 23CB0 21CB0 20CB0 19CB0 18CB0 17CB0 16CB0 14CB0 13CB0 11CB0 10CB0 9CB0 8CB0 7CB0 6CB0 5CB0 4CB0 3CB0 2CB0 1CB0 0CB0 12CB0 15CB0 24CB0 22CB0 26CB0 30CB0 WTC Menu Bar{25f h&FileCustom Popup 6280390 h&EditCustom Popup 6304234 :u`J0Cmdbars#uf0"u$Blob  1!'$uuBlob  2&uuBlob  3%+(uu Custom Popup 6280390JJ qS m`r"0A"r- Custom Popup 6304234> d 0 0 0 } 2"ql 1"0 :qBlob  4*uuBlob $ 9DirData),)  WTC Form View{2  ` m`r"0 0 0"0 :pK[" WTC Print Preview qU  `"p ` ` 2"b r:S&Setup"7`|"WTC Form ViewWTC Menu Bar,Custom Popup 6280390,Custom Popup 6304234&WTC Print Preview,Custom Popup 6304234,Custom Popup 6280390WTC Menu BarWTC Form View(WTC Report PreviDirDataCopy- Modulesc4uf0/uuPropData1 ew1.21uuPropData2 23uuPropData3 30<5uuPropData4 47uuPropData5 56:9uuPropData6 6;uuPropData7 78@=uuPropData8 8?uuPropData9 K[BlobStuff SaveFileDialogKeyClickStuff"Initializations,Global Vars and Subs6DataPreparationProceduresFormResizingX"TextHeightWidthPositionF10>CAuuPropData: DirData; vPropDataBDA torms(TitlePageLogoSizes  8CB0 5CB0 3CB0 2CB0 1CB0 0CB0 4CB0 6CB0 7CB0 10CB0PositionForms"TextHeightWidthFormResizingX6DataPreparationProcedures,Global Vars and Subs"InitializationsKeyClickStuff SaveFileDialogBlobSDirDataCopyEC `PropDataCopyI FReportsVuf2IuutuffModule1  4CB0 0CB0 1CB0 2CB0 3CB0 5CB008:<=Babe ghij&k#zMFV@퍈J A, U Arial8 hhp deskjet 960c series!@8߀f dBlob K PropDataHJf TypeInfog v3GPMuu@RLdBeںںUSB/DeskJet_960C/MX1391T0CCROK[H(winspoolhp deskjet 960c series\\BX62\HP 960Cd28 Arial`h"PageHeaderSection퍈J A,d` a<bc Label0 Report퍈J A,`@ Detail퍈J A,`h"PageFooterSection퍈J A,ͬ퍈J A,PageHeaderSectionDetailPageFooterSectiondLabel0ͬ:Y{H}6'әReportHeaderdLabel16mtxtSearchmtxtSortmtxtSelectedPageHeaderSectiondLast_Name_LabelLast Name_LabeldTitle_LabeldInstitution_Labeld State_Labeld Funder_Labeld Project_ID_LabelProject ID_Labeld Start_Date_Date_LabelStart Date Date_LabelfBlob Y#PropDataLNi TypeInfoOj KBlobDelta 08:<=Babc4e g$h i j2k)~s@"unEW6K.DA U^8D{ HĤ.|c~@qBrowseDB2BH .n@tPrint Recordsǥ*[*VMA 4<2BH Print Order{BA3^8D{ HĤ.Record IDD CwK|^8D{ HĤ.Project/Activity IDeEnDe@]ځ^8D{ HĤ.Entry TypetK!Eg&Ap^8D{ HĤ.Title:^D. I)go^8D{ HĤ.Last NameZ^rO9lr^8D{ HĤ.First Name? ALZBj~^8D{ HĤ.Display PI Name5Ap^8D{ HĤ.Display PI ORGz E Qh^8D{ HĤ.Institution!¤D "HD9.^8D{ HĤ.City߷ospJ]3/^8D{ HĤ.State,&$Nl6^8D{ HĤ.Display State1qހ@Zg^8D{ HĤ.Funder"FZ7(CG c^8D{ HĤ.Display FundergӒIP'^8D{ HĤ.Project IDUCeOUts^8D{ HĤ.Display Project IDM.yGQ ^8D{ HĤ.AbstractP@G^8D{ HĤ.Display Abstract̃R9N0=^8D{ HĤ.Breakout Session ListӢq'G>^8D{ HĤ.WG Recommendation Listo; C+Br=RU^8D{ HĤ.Keyword List[9SRE{W[Y^8D{ HĤ.Start Date TextxkMQQ&^8D{ HĤ.Start Date Date] deD<>^8D{ HĤ.Start Date Year<;UxvA99^8D{ HĤ.End Date Text0N%8\FGÀ^8D{ HĤ.End Date DateU0;F+uښv^8D{ HĤ.End Date Year9IO@xC^8D{ HĤ.Activity Date9x#F$PU^8D{ HĤ.Display Date ͓K"i÷^8D{ HĤ.Date Exception)kuM(7^8D{ HĤ.Review DatepeEA2BH Record IDUt>p9J5?xWhere1K[%&I@TOrder1`yFEy5Mode1 |SELECT [tPrint Records].[Print Order], ggsEnglishQueryWhereClause() AS Where1, ggsSortStringEnglish() AS Order1, gglSelectionMode() AS Mode1, qBrowseDB.[Record ID], qBrowseDB.[Project/Activity ID], qBrowseDB.[Entry Type], qBrowseDB.Title, qBrowseDB.[Last Name], qBrowseDB.[First Name], qBrowseDB.[Display PI Name], qBrowseDB.[Display PI ORG], qBrowseDB.Institution, qBrowseDB.City, qBrowseDB.State, qBrowseDB.[Display State], qBrowseDB.Funder, qBrowseDB.[Display Funder], qBrowseDB.[Project ID], qBrowseDB.[Display Project ID], qBrowseDB.Abstract, qBrowseDB.[Display Abstract], qBrowseDB.[Breakout Session List], qBrowseDB.[WG Recommendation List], qBrowseDB.[Keyword List], qBrowseDB.[Start Date Text], qBrowseDB.[Start Date Date], qBrowseDB.[Start Date Year], qBrowseDB.[End Date Text], qBrowseDB.[End Date Date], qBrowseDB.[End Date Year], qBrowseDB.[Activity Date], qBrowseDB.[Display Date], qBrowseDB.[Date Exception], qBrowseDB.[Review Date] FROM qBrowseDB INNER JOIN [tPrint Records] ON qBrowseDB.[Record ID]=[tPrint Records].[Record ID] ORDER BY [tPrint Records].[Print Order]; 6WTC Projects and Activities"[Event Procedure]"[Event Procedure] Arial8884hT߀dXLetter.HP LaserJet 4050 Series PCL 62xe.DA>320Dq`,x; AN̆,Y0OZ|%#DB-^ EEaG/h ml8rJKE9gzoqϣh?,)Go3؋ػBDZYldWtk\6,8#ܧN&N%>IdN~fuVۿVJ^eT:oD䛔CSlD1QFߕ9c&TIP_10.42.86.36"[Event Procedure]"[Event Procedure]d27d Haettenschweilere24g37jghm5Ci Arialnj Arialo3Al Arialp4Print Order`HReportHeK[ader+TN#ZR3d`<bcdLabel166WTC Projects and ActivitiesdKRh=m;F` a<b,ctxtSearch Where1G:5APEJWm;F`d#a<bcktxtSort Order1D>HMb*ZJp%L.Pd`ab cYdTitle_Label TitleDetachedLabelEl*@z7@d`ab cYd"Institution_LabelInstitutionDetachedLabel~sC'.C,”2Md7`hab cYdState_Label StateDetachedLabel_cчMr)P d7`"abcYdFunder_Label FunderDetachedLabelBMAId`&abcYd Project ID_LabelProject IDDetachedLabel Project_ID_LabelEIKd7`-abc\d*Start Date Date_LabelPerf PeriodDetachedLabel*Start_Date_Date_LabelFú|D}5Zf2`<aXb3 Line19N]TDA^q|e[d37`P(abc\dLabel32Rev DateDetachedLabel&7, A,֮m;Fbci Text34 =Now()Long Date}νC>Ҩ:=m;F` bcik Text35H="Page " & [Page] & " of " & [Pages] pn^)Lɒc` DetailxB[I+HO-*(c mFbTcLast NameDisplay PI NameLast_Name PC؎mF`b ce k Title Title)G^NI0c mF`bcekInstitutionInstitutionVKVr:Bm;F`hbcek StateDisplay State`YC&(Cm;F`"b ck Funder FunderUţB&BAmF`&bckProject ID$Display Project IDProject_IDfSd6HYYBAm;F`-bckStart Date DateDisplay DateStart_Date_DateuNvJB@af2`<ab(2 Line26+!M~|F)m5;F`\(b ck Text33Review DateFH<*Rc`"PageFooterSectionY=ykB6RWf2`<b(2 Line20Q*0At`ReportFooteraίF^LFÝM; Line19dLabel32mText34mText35DetailmLast_NameLast NamemTitlemInstitutionmStatemFundermProject_IDProject IDmStart_Date_DateStart Date DatefLine26mText33PageFooterSectionfLine20ReportFooterPrint OrderWhere1 Order1!Mode1"Record ID#Project/Activity ID$Entry Type%First Name&Display PI Name'Display PI ORG(City)Display State*Display Funder+Display Project ID,Abstract-Display Abstract.Breakout Session List/WG Recommendation List0Keyword List1Start Date Text2Start Date Year3End Date Text4End Date Date5End Date Year6Activity Date7Display Date8Date Exception9Review Dateˁ K[ degjmnopdmmm dddddddfdmm mmmmmmmfmf08:<=Babc| e ghbij@8kSr@\RCgS_m.4 U{59ǺJL:אڙU@tProject Info{BA3{59ǺJ4RuuBlob  PropDataQT TypeInfo L:אRecord IDӢq'G>{59ǺJL:אWG Recommendation Listo; C+Br=RU{59ǺJL:אKeyword List}~?GH&xVܗ@%rSub Keywordsa 9@X}2Yվ0n@tProject KeywordsVܠ0M3szc@tKeywords[/ǎNIyM!a 9@X}2YRecord IDsDѣ\E_Pr{\gVܠ0M3sArea߱1C0cVܠ0M3sKeywordW?pM>$;Ya 9@X}2YKeyword No[ڽw'CuE vmNq Z lm *Gڔ]9z]wQ֏xǞE?&!:~%tI"{C6Le\sS3>g ߓQOչiܫJv=MRY(6(" toh@c&TIP_10.42.86.32d28 Arialm5< Arial` Detailnlt9MFŴs?) m 2<"b| i .txtWGRecommendationList,WG Recommendation List TahomawDOtK[&mp4ab| cd Child0(Report.rSub KeywordsRecord IDRecord IDr jLOld8"abcd e Label1WTC Keywords: TahomaG BU1Rͬy-@TD@.xrpDetailmtxtWGRecommendationListpChild0dLabel1Record IDWG Recommendation ListKeyword Listdmmpd08:<=Babc| e ghij$;Ya 9@X}2YKeyword No[ڽw'Ceںں@RLd\\DAD700\\\BX62\HP 960C,LocalOnly,DrvConvertK[>e? winspool\\BX62\HP 960C\\BX62\HP 960Cd28 Arialm5< ArialArea`GroupHeader0g$w]C0E"m 2<"b| i Text1Area Tahoma4=1JT` DetailPb3K1m 2<"`b i txtKeywordListKeyword TahomaQOMkPͬ,K&zGroupHeader0mText1DetailmtxtKeywordListRecord IDAreaKeywordͬG=v[sOAwReportHeaderdLabel16mtxtSearchmtxtSortmtxtSelectedPropDataWY TypeInfo 7\uPBlob )08:<=Babc%e g;h iHj$k$Ay@ GZX U^8D{ HĤ.|c~@qBrowseDB2BH .n@tPrint Recordsǥ*[*VMA 4<2BH Print Order{BA3^8D{ HĤ.Record IDD CwK|^8D{ HĤ.Project/Activity IDeEnDe@]ځ^8D{ HĤ.Entry TypetK!Eg&Ap^8D{ HĤ.Title:^D. 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ALZBj~^8D{ HĤ.Display PI Name5Ap^8D{ HĤ.Display PI ORGz E Qh^8D{ HĤ.Institution!¤D "HD9.^8D{ HĤ.City߷ospJ]3/^8D{ HĤ.State,&$Nl6^8D{ HĤ.Display State1qހ@Zg^8D{ HĤ.Funder"FZ7(CG c^8D{ HĤ.Display FundergӒIP'^8D{ HĤ.Project IDUCeOUts^8D{ HĤ.Display Project IDM.yGQ ^8D{ HĤ.AbstractP@G^8D{ HĤ.Display Abstract̃R9N0=^8D{ HĤ.Breakout Session ListӢq'G>^8D{ HĤ.WG Recommendation Listo; C+Br=RU^8D{ HĤ.Keyword List[9SRE{W[Y^8D{ HĤ.Start Date TextxkMQQ&^8D{ HĤ.Start Date Date] deD<>^8D{ HĤ.Start Date Year<;UxvA99^8D{ HĤ.End Date TextK[0N%8\FGÀ^8D{ HĤ.End Date DateU0;F+uښv^8D{ HĤ.End Date Year9IO@xC^8D{ HĤ.Activity Date9x#F$PU^8D{ HĤ.Display Date ͓K"i÷^8D{ HĤ.Date Exception)kuM(7^8D{ HĤ.Review DatepeEA2BH Record ID\RCgS_m.yy@rSub Detail Recs and Keys{59ǺJL:אڙU@tProject Info{BA3{59ǺJL:אRecord IDӢq'G>{59ǺJL:אWG Recommendation Listo; C+Br=RU{59ǺJL:אKeyword Listˍ4D0q<{Where1b`cúnCB+-׋Order1\Nc},LqﯚMode1  SELECT [tPrint Records].[Print Order], ggsEnglishQueryWhereClause() AS Where1, ggsSortStringEnglish() AS Order1, gglSelectionMode() AS Mode1, qBrowseDB.[Record ID], qBrowseDB.[Project/Activity ID], qBrowseDB.[Entry Type], qBrowseDB.Title, qBrowseDB.[Last Name], qBrowseDB.[First Name], qBrowseDB.[Display PI Name], qBrowseDB.[Display PI ORG], qBrowseDB.Institution, qBrowseDB.City, qBrowseDB.State, qBrowseDB.[Display State], IIf(Trim(nz(qBrowseDB.Funder,""))="","-N/A-",qBrowseDB.Funder) AS Funder, qBrowseDB.[Display Funder], IIf(Trim(nz(qBrowseDB.[Project ID],""))="","-N/A-",qBrowseDB.[Project ID]) AS [Project ID], qBrowseDB.[Display Project ID], Trim(qBrowseDB!Abstract) AS Abstract, qBrowseDB.[Display Abstract], IIf(Trim(nz(qBrowseDB.[Breakout Session List],""))="","-N/A-",qBrowseDB.[Breakout Session List]) AS [Breakout Session List], IIf(Trim(nz(qBrowseDB.[WG Recommendation List],""))="","-N/A-",qBrowseDB.[WG Recommendation List]) AS [WG Recommendation List], qBrowseDB.[Keyword List], qBrowseDB.[Start Date Text], qBrowseDB.[Start Date Date], qBrowseDB.[Start Date Year], qBrowseDB.[End Date Text], qBrowseDB.[End Date Date], qBrowseDB.[End Date Year], qBrowseDB.[Activity Date], qBrowseDB.[Display Date], qBrowseDB.[Date Exception], qBrowseDB.[Review Date] FROM qBrowseDB INNER JOIN [tPrint Records] ON qBrowseDB.[Record ID]=[tPrint Records].[Record ID] ORDER BY [tPrint Records].[Print Order]; 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</span></span>Smokeless </p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Non-specified tobacco use</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Environmental tobacco smoke</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Nicotine</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Miscellaneous</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Knowledge/attitudes/risk perception</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Weight gain/exercise</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol;text-transform:uppercase'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Sex/gender differences</p> <p class=MsoNormal><b><span style='font-size:14.0pt;text-transform:uppercase'>&nbsp;</span></b></p> <b><span style='font-size:14.0pt;font-family:"Times New Roman";text-transform: uppercase'><br clear=all style='page-break-before:always'> </span></b> <p class=MsoNormal><a name=Check8><b><span style='font-size:14.0pLVALt;text-transform: uppercase'>Funding Organizations</span></b></a></p> <p class=MsoNormal>&nbsp;</p> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 width=656 style='width:492.0pt;margin-left:-12.6pt;border-collapse:collapse'> <tr style='height:20.6pt'> <td width=416 nowrap style='width:312.0pt;border:solid windowtext 1.0pt; background:#E0E0E0;padding:0in 5.4pt 0in 5.4pt;height:20.6pt'> <p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:11.0pt'>Organization</span></b></p> </td> <td width=104 style='width:78.0pt;border:solid windowtext 1.0pt;border-left: none;background:#E0E0E0;padding:0in 5.4pt 0in 5.4pt;height:20.6pt'> <p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:11.0pt'>Acronym</span></b></p> </td> <td width=136 style='width:102.0pt;border:solid windowtext 1.0pt;border-left: none;background:#E0E0E0;padding:0in 5.4pt 0in 5.4pt;height:20.6pt'> <p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:11.0pt'>Category</span></b></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>American Cancer Society</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>ACS</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span sLVAL8tyle='font-size:11.0pt'>Private</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Agency for Health Care Research and Quality</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>AHRQ</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>Other HHS</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Congressionally Directed Medical Research Programs</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>CDMRP</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>Other Fed</span></p> D @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ! 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gR [tControl Sizes].[Font Resize]= gR [tControl Sizes].[Font Base]; gR [tControl Sizes].[Has Font]: gR[tControl Sizes].Width5 gR[tControl Sizes].Height6 gR[tControl Sizes].Left4 gR[tControl Sizes].Top3 gRB@! gR [tControl Sizes].[Recenter On]= gR![tControl Sizes].[Control Name]> gR[tControl Sizes].[Form Name]; gRtControl Sizes--- R GR GR R GQ[tProject Info].MarkBoxFalseR? wQtProject Info+++ Q GQ GQ Q GP"[tProject Info].[Date Exception]? gP [tProject Info].[Display Date]= gP![tProject Info].[End Date Year]> gPB@! gP [tProject Info].[Keyword List]= gPP@! gPN@! gP[tProject Info].Abstract7 gP [tProject Info].[Project ID]; gP [tProject Info].Funder5 gP PIORG@!' oP [tProject Info].State4 gP [tProject Info].City3 gP[tProject Info].Institution: gP[tProject Info].[First Name]; gP[tProject Info].[Last Name]: gYN%% Y  Y  Y Blob FilenameBlob NicknameBlob Content%%%%Hv1bLVAL\*p.'<html> <head> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <meta name=Generator content="Microsoft Word 11 (filtered)"> <title>WTC Keywords</title> <style> <!-- /* Font Definitions */ @font-face {font-family:Wingdings; panose-1:5 0 0 0 0 0 0 0 0 0;} @font-face {font-family:Batang; panose-1:2 3 6 0 0 1 1 1 1 1;} @font-face {font-family:Tahoma; panose-1:2 11 6 4 3 5 4 4 2 4;} @font-face {font-family:"\@Batang"; panose-1:0 0 0 0 0 0 0 0 0 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {margin:0in; margin-bottom:.0001pt; font-size:12.0pt; font-family:"Times New Roman";} p.MsoHeader, li.MsoHeader, div.MsoHeader {margin:0in; margin-bottom:.0001pt; font-size:12.0pt; font-family:"Times New Roman";} p.MsoFooter, li.MsoFooter, div.MsoFooter {margin:0in; margin-bottom:.0001pt; font-size:12.0pt; font-family:"Times New Roman";} a:link, span.MsoHyperlink {color:blue; text-decoration:underline;} a:visited, span.MsoHyperlinkFollowed {color:purple; text-decoration:underline;} p.MsoAcetate, li.MsoAcetate, div.MsoAcetate {margin:0in; margin-bottom:.0001pt; font-size:8.0pt; font-family:Tahoma;} /* Page Definitions */ @page Section1 {size:8.5in 11.0in; margin:.5in 1.0in 1.0in 1.1in;} div.Section1 {page:Section1;} @page Section2 {size:8.5in 11.0in; margin:.5in 1.0in 1.0in 1.1in;} div.Section2 {page:Section2;} /* List Definitions */ ol {margin-bottom:0in;} ul {margin-bottom:0in;} --> </style> </head> <body lang=EN-US link=blue vlink=purple> <div class=Section1> <p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:16.0pt;text-transform:uppercase'>Women Tobacco and Cancer</span></b></p> <p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:14.0pt;text-transform:uppercase'>Background Information</span></b></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNLVAL(ormal>This is a searchable database, produced for the National Cancer Institute s Office of Women s Health and the Tobacco Control Research Branch by Science Applications International Corporation. It houses research projects, initiatives, and activities related to women, tobacco, and cancer. This database is meant to serve as a resource for those working to reduce and ultimately eliminate tobacco-related diseases in women, including researchers, planning and policymakers, and state and local advocates. The research projects and related activities included were funded by federal and non-federal organizations and active between 2000 and 2004. This database may be used to identify of areas of ongoing research, gaps in research, and opportunities for collaborations and partnerships.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The original portfolio analysis, which is the basis for this resource, was developed to support the work of the Women, Tobacco, and Cancer (WTC) Working Group. The report from the working group,  <i>Women, Tobacco, and Cancer: An Agenda for the 21<sup>st</sup> Century </i>(available at: <a href="http://women.cancer.gov/reports/wtobacco.shtml">http://women.cancer.gov/reports/wtobacco.shtml</a>) was published in August 2004. </p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The strategy for identifying the projects and activities was a search of project databases of relevant organizations as follows:&nbsp; <u>Search terms</u>:&nbsp; [tobacco OR nicotine OR smoking OR smoke OR cigarette OR cigar] AND [female OR woman OR women OR girl OR pregnant OR pregnancy].&nbsp; A second search used gender in place of the female/woman/women/girl/ pregnant/pregnancy search group.&nbsp; Projects have been coded so that the database can be searched and sorted by broad areas of research or by project identifies such as: author, title, working group, or by specific key words. A list of these codes can be accessed conveniently on all pages by selectLVAL)ing the  View Definitions button. </p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal><b><span style='font-size:14.0pt;text-transform:uppercase'>Table of Contents</span></b></p> <p class=MsoNormal><span style='font-size:14.0pt'>&nbsp;</span></p> <p class=MsoNormal><a href="#Check10">Breakout groups</a></p> <p class=MsoNormal><a href="#Check11">Recommendations</a></p> <p class=MsoNormal><a href="#Check9">Key words</a></p> <p class=MsoNormal><a href="#Check8">Funding Organizations</a></p> <span style='font-size:12.0pt;font-family:"Times New Roman"'><br clear=all style='page-break-before:always'> </span> <p class=MsoNormal><a name=Check10><b><span style='font-size:14.0pt;text-transform: uppercase'>Breakout Groups</span></b></a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Biology &amp; Cancer</b> <b> </b> Addressing tobacco toxicology, cancer susceptibility, and biological gender differences related to tobacco and cancer.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Addiction</b> <b> </b> Addressing the biology and behavior of addiction.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Epidemiology &amp; National Surveillance</b> <b> </b> Addressing the surveillance of tobacco use and control efforts.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Interventions for Prevention &amp; Treatment</b> <b> </b> Addressing tobacco control interventions to prevent tobacco use and to treat tobacco addiction.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Awareness, Risk Perception &amp; Communications</b> <b> </b> Addressing public knowledge of tobacco addition, health and addiction risks and interventions for tobacco control as well as strategies for communication with the public about tobacco issues.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Community &ampLVAL*; Policy Interventions</b> <b> </b> Addressing population-based, policy, community, legal and regulatory interventions in tobacco control.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Global Issues</b> <b> </b> Addressing tobacco use and control internationally with recommendations in each of the 6 other breakout session topic areas.</p> <p class=MsoNormal><span style='font-size:10.0pt'>&nbsp;</span></p> <p class=MsoNormal><span style='font-size:10.0pt'>&nbsp;</span></p> <p class=MsoNormal><span style='font-size:10.0pt'>&nbsp;</span></p> <p class=MsoNormal><a name=Check11><b><span style='font-size:14.0pt;text-transform: uppercase'>Recommendations</span></b></a></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>I. </span>Discovery</b></p> <p class=MsoNormal><i>Overall Goal:</i><b><span style='text-transform:uppercase'> </span></b>Increase our understanding of sex and gender differences across the broad range of research on women, tobacco, and cancer.</p> <p class=MsoNormal><i>Individual Goals:</i> A better understanding of sex and gender differences is critical to eliminating tobacco use and tobacco-related cancer morbidity and mortality in men and women.</p> <p class=MsoNormal><span style='font-size:10.0pt'>&nbsp;</span></p> <p class=MsoNormal><u>Goal 1</u>: Multidisciplinary research is needed on sex differences in the mechanisms and processes associated with:</p> <p class=MsoNormal style='margin-left:.5in'><i>1A</i>  All phases of tobacco addiction--from experimentation to regular use and addiction to cessation--including the natural history of the progression between phases and the effects of environmental tobacco smoke (ETS) exposure. This includes genetic, molecular, cellular, neurobiological, biobehavioral, and hormonal factors that play a criticLVAL+al role in tobacco addiction and in the etiology of cancers and other diseases caused by tobacco.</p> <p class=MsoNormal style='margin-left:.5in'><i>1B</i>  The etiology of cancers caused by tobacco, especially those related to gene-hormone-environment interactions involved in carcinogenic and other disease pathways.</p> <p class=MsoNormal style='margin-left:.5in'><i>1C</i>  Methods of prevention and treatment of tobacco addiction.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 2</u>: Multidisciplinary research is needed on gender-specific factors in tobacco use and the components of effective prevention and treatment interventions for women and girls, especially in populations at greatest risk, to:</p> <p class=MsoNormal style='margin-left:.5in'><i>2A </i> Identify behavioral, psychosocial, sociocultural, and environmental influences on tobacco use, exposure to ETS and disease risk, and prevention and treatment interventions.</p> <p class=MsoNormal style='margin-left:.5in'><i>2B</i>  Assess women s and girls knowledge of the harms of tobacco use and ETS exposure and the benefits of quitting.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 3</u>: Multidisciplinary research is needed to validate and standardize sex- and gender-appropriate definitions and measures of addiction, ETS exposure, tissue injury, and recovery.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>II. Development</b></p> <p class=MsoNormal><i>Overall Goal:</i><b><span style='text-transform:uppercase'> </span></b>Develop new and more effective interventions to prevent and treat tobacco use and ETS exposure among women and girls, especially in populations at greatest risk.</p> <p class=MsoNormal><i>Individual Goals:</i> Translating basic and applied research into effective, evidence-based prevention and treatment programs and broad public health tobacco control policies will require:</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormLVAL,al><u>Goal 1</u>: Using evidence from animal studies, pilot projects, and small-scale clinical and community-based studies to develop, refine, and evaluate promising sex- and gender-appropriate interventions for prevention, cessation, and treatment.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 2</u>: Using or modifying existing infrastructures to rapidly evaluate the efficacy of promising treatments and the effectiveness and cost-effectiveness of proven small-scale interventions, programs, and policies.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 3</u>: Developing and disseminating evidence-based cessation, prevention, and advocacy messages targeted to women using state-of-the-art, audience-tailored communication strategies.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 4</u>: Conducting research to explore and strengthen the positive health impacts of public and private tobacco control policies on women and girls, especially in populations at greatest risk, and improving the adoption of evidence-based policies and strategies by policy and decision makers.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 5</u>: Monitoring the harmful effects of tobacco marketing targeted to diverse populations of women and girls domestically and globally.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>III. Delivery</b></p> <p class=MsoNormal><i>Overall Goal:</i><b><span style='text-transform:uppercase'> </span></b>Ensure the widespread delivery of effective interventions to prevent and treat tobacco use and ETS exposure among women and girls.</p> <p class=MsoNormal><i>Individual Goals:</i> Expanding the reach and impact of evidence-based tobacco control programs and policies will require:</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 1</u>: Increasing the appeal, access, affordability, and use of effective interventions, particularly among women and girls in populatioLVAL-ns at greatest risk.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 2</u>: Identifying and using targeted messages and strategies to involve and activate individuals and organizations in effective, sustained advocacy for evidence-based tobacco control programs and policies.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 3</u>: Making data from surveillance and policy research, as well as social, economic, and cultural studies, available to the health care community, policy makers, and the general public in a timely and effective fashion.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 4</u>: Supporting research and demonstration projects to better understand how to convert women s broad-based support for tobacco control policies and programs into more active involvement in their communities.</p> <p class=MsoNormal><b>&nbsp;</b></p> <p class=MsoNormal><b>IV. Partnership</b></p> <p class=MsoNormal><i>Overall Goal:</i><b><span style='text-transform:uppercase'> </span></b>Harness and expand partnerships, networks, and innovative research platforms to design and launch broad-based strategies to eliminate the harms of tobacco use and ETS exposure among women and girls.</p> <p class=MsoNormal><i>Individual Goals:</i> Successfully implementing the discovery, development, and delivery recommendations will require capitalizing on existing collaborations and developing new partnerships. To maximize the development and dissemination of effective interventions, partners must be involved from the beginning, and knowledge gained from practice should be used to inform future research. Partnerships are especially needed between:</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 1</u>: Established networks of clinical and translational researchers that can provide the resources and infrastructure needed to foster cross-disciplinary interactions and rapidly evaluate treatments and interventions.</p> <p clLVAL.ass=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 2</u>: Research institutions and community-based organizations that serve populations at greatest risk to conduct community-based participatory research. These partners must be committed to joint decision making in designing research, sharing ownership of the products of research, and disseminating and implementing research results.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 3</u>: Research institutions and tribal colleges, tribal health departments, and/or American Indian health care and community settings to develop effective, culturally appropriate individual, family, and community-level tobacco prevention and cessation initiatives.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u>Goal 4</u>: Public and private funding agencies to fully and efficiently support the implementation of successful interventions.</p> <p class=MsoNormal><b>&nbsp;</b></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>V. </span>Evaluation and Surveillance</b></p> <p class=MsoNormal><i>Overall Goal:</i><b><span style='text-transform:uppercase'> </span></b>Improve national and global evaluation and surveillance of the harms of tobacco use and ETS exposure, and of women s and girls knowledge, attitudes, and behaviors related to tobacco use and harms.</p> <p class=MsoNormal><i>Individual Goals:</i> It is essential to monitor and evaluate progress toward reducing tobacco use, ETS exposure, and the impact of tobacco-related cancers on women and to make midcourse adjustments as needed. This will require further development of standardized measures and surveillance systems to ensure that data are comparable within and across countries.</p> <p class=MsoNormal><span style='font-size:10.0pt'>&nbsp;</span></p> <p class=MsoNormal><u>Goal 1</u>: Improve national and global evaluation and surveillance of:</p> <p class=MsoNormal style='margin-left:.5in'><i>1A</i>*  The patterns, extent, aLVAL/nd trends in morbidity, mortality, and tobacco use, and the impact of policies on these data.</p> <p class=MsoNormal style='margin-left:.5in'><i>1B</i>*  The biological effects of tobacco and ETS.</p> <p class=MsoNormal style='margin-left:.5in'><i>1C</i>*  Women s and girls knowledge, attitudes, and behaviors related to tobacco use and harms, and the effectiveness of policies in changing knowledge, attitudes, and behaviors.</p> <p class=MsoNormal><b><span style='font-size:10.0pt'>&nbsp;</span></b></p> <p class=MsoNormal><b><span style='font-size:10.0pt'>*Note: Wording for Goals 1a, 1b, and 1c was derived from information in the Working Group Report</span></b></p> <b><span style='font-size:12.0pt;font-family:"Times New Roman";text-transform: uppercase'><br clear=all style='page-break-before:always'> </span></b> <p class=MsoNormal><a name=Check9><b><span style='font-size:14.0pt;text-transform: uppercase'>Key Words</span></b></a></p> <p class=MsoNormal><b>&nbsp;</b></p> <p class=MsoNormal><b>&nbsp;</b></p> <p class=MsoNormal><b>Addiction </b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Initiation</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Maintenance</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Cessation</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbLVAL0sp; </span></span>Withdrawal</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Relapse</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt'><b>Age</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Child (&lt;18)</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Young adult (18  24)</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Adult</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Older adult</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Fetus/prenatal</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt'><b>Community</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Women s groups</p> <p class=MsoNormal style='margin-left:.25in;text-indent:LVAL1-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>General partnerships</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Health care provider</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Other</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt'><b>Disease/Biology</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Cardiovascular/Pulmonary</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Cancer Mechanisms</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Other</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt'><b>Economics</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>SES</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='LVAL2font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Medicaid/Medicare</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Insurance coverage</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Cost of intervention/treatment</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Cost of smoking</p> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-12.0pt'>&nbsp;</p> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt'><b>Epidemiology/Surveillance</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Data collection (small, &lt;100)</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Data collection (large, &#8805;100)</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Education Level</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Less than High school</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:SymboLVAL3l'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>High school</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>College and above</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Location</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Urban</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Rural</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>National</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>International</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Marketing</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Industry</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Counter-marketing</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><LVAL4span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Media-websites/pamphlets/radio</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Other</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Policy</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Excise tax</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Guidelines/best practices</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Regulatory intervention</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>FCTC</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Other</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Psychological</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>DepresLVAL5sion/Mood/Anxiety</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Social factors</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Cultural factors</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Other</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Research</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Animal studies</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Human studies</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>In vitro studies</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Clinical research</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Study Population</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "LVAL6Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>African American</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>AI/AN</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Asian Pacific Islander</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Caucasian</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Hispanic</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>LGBT</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Prevention/Treatment</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Counseling/behavioral therapy</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Support group</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.LVAL70pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Interview/focus group</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Quitline</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Educational materials</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Biochemical assessment</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Bupropion</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>NRT</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Other pharmacological</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Women</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Pregnancy</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pLVALt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Postpartum</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Parent/mother</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Partner/spouse</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Menstrual cycle</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Menopause</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Hormones</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>HRT</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b>Tobacco</b></p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Cigarette/Other smoking</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"LVAL9 </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Canadian Tobacco Control Research Initiative</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>CTCRI</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>Int'l</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>California</span><span style='font-size:11.0pt'> Tobacco-Related Disease Research Program </span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>CTRDRP</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>State Government</span></p>LVAL: </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Fogarty</span><span style='font-size:11.0pt'> International Center</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>FIC</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:13.5pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:13.5pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Florida</span><span style='font-size:11.0pt'> Tobacco Control Program </span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.5pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>FTCP</span></p> </td> <td width=136 nowrap valign=top style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.5pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>State Government</span></p> </tdLVAL;> </tr> <tr style='height:13.5pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:13.5pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Minnesota</span><span style='font-size:11.0pt'> Partnership for Action Against Tobacco </span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.5pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>MPAAT</span></p> </td> <td width=136 nowrap valign=top style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.5pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>State Government</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Cancer Institute </span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NCI</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.7LVAL<5pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Cancer Institute of Canada </span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NCIC</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>Int'l</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National</span><span style='font-size:11.0pt'> Center</span><span style='font-size:11.0pt'> on Minority Health and Health Disparities</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NCMHD</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </trLVAL=> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National</span><span style='font-size:11.0pt'> Center</span><span style='font-size:11.0pt'> for Research Resources</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NCRR</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Eye Institute</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NEI</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style=LVAL>'height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Human Genome Research Institute</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NHGRI</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Heart, Lung, and Blood Institute </span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NHLBI</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='widLVAL?th:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute on Aging</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIA</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute on Alcohol Abuse and Alcoholism </span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIAAA</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.LVAL@4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute of Allergy and Infectious Diseases</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIAID</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute of Child Health &amp; Human Development</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NICHD</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=LVALAMsoNormal><span style='font-size:11.0pt'>National Institute on Drug Abuse</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIDA</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute on Deafness and Other Communication Disorders</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIDCD</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:14.25pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:14.25pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National InsLVALBtitute of Dental and Craniofacial Research</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.25pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIDCR</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.25pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute of Diabetes and Digestive and Kidney Diseases</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIDDK</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute of Environmental HealthLVALC Sciences</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIEHS</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute of General Medical Sciences</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIGMS</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute of Mental Health</span></p> </td> <td width=104 nowrap valign=bottom stLVALDyle='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIMH</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute of Neurological Disorders and Stroke</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NINDS</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute of Nursing Research</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;bordLVALEer-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NINR</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Institute for Occupational Safety and Health</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIOSH</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>Other HHS</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>National Library of Medicine</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtextLVALF 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NLM</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>NIH</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Rockefeller Foundation</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>&nbsp;</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>Private</span></p> </td> </tr> <tr style='height:15.0pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Robert Wood Johnson Foundation</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:15.0pt'> <p class=MsoNormal align=center style='tLVALext-align:center'><span style='font-size:11.0pt'>RWJF</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:15.0pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>Private</span></p> </td> </tr> <tr style='height:12.75pt'> <td width=416 nowrap valign=bottom style='width:312.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal><span style='font-size:11.0pt'>Smoke-Free Families</span></p> </td> <td width=104 nowrap valign=bottom style='width:78.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>SFF</span></p> </td> <td width=136 nowrap valign=bottom style='width:102.0pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.75pt'> <p class=MsoNormal align=center style='text-align:center'><span style='font-size:11.0pt'>Private</span></p> </td> </tr> </table> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>&nbsp;</p> </div> <span style='font-size:12.0pt;font-family:"Times New Roman"'><br clear=all style='page-break-before:auto'> </span> <div class=Section2> <p class=MsoNormal>&nbsp;</p> </div> </body> </html> LVAL^C:\Documents and Settings\ColeG\My Documents\WTC\V1.28.1\WTCHelpFile V1.28.htmC:\Documents and Settings\ColeG\My Documents\WTC\V1.26\DefinitionInfoFile.JET.htms$@GWTCHelpInfoFile.htm;I\*p./#@GWTCDefinitionsInfoFile.htm9&\*p.6*LVAL\*p.J<html> <head> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <meta name=Generator content="Microsoft Word 11 (filtered)"> <title>TABLE OF CONTENTS</title> <style> <!-- /* Font Definitions */ @font-face {font-family:Wingdings; panose-1:5 0 0 0 0 0 0 0 0 0;} @font-face {font-family:Tahoma; panose-1:2 11 6 4 3 5 4 4 2 4;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {margin:0in; margin-bottom:.0001pt; font-size:12.0pt; font-family:"Times New Roman";} p.MsoCommentText, li.MsoCommentText, div.MsoCommentText {margin:0in; margin-bottom:.0001pt; font-size:10.0pt; font-family:"Times New Roman";} a:link, span.MsoHyperlink {color:blue; text-decoration:underline;} a:visited, span.MsoHyperlinkFollowed {color:purple; text-decoration:underline;} p.MsoDocumentMap, li.MsoDocumentMap, div.MsoDocumentMap {margin:0in; margin-bottom:.0001pt; background:navy; font-size:10.0pt; font-family:Tahoma;} p.MsoCommentSubject, li.MsoCommentSubject, div.MsoCommentSubject {margin:0in; margin-bottom:.0001pt; font-size:10.0pt; font-family:"Times New Roman"; font-weight:bold;} p.MsoAcetate, li.MsoAcetate, div.MsoAcetate {margin:0in; margin-bottom:.0001pt; font-size:8.0pt; font-family:Tahoma;} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in;} div.Section1 {page:Section1;} /* List Definitions */ ol {margin-bottom:0in;} ul {margin-bottom:0in;} --> </style> </head> <body lang=EN-US link=blue vlink=purple> <div class=Section1> <p class=MsoNormal align=center style='text-align:center'><b><span style='text-transform:uppercase'>TABLE OF cONTENTS</span></b></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal><u><span style='color:blue'><a href="#Started">GETTING STARTED</a></span></u></p> <p class=MsoNormal><u><span style='color:blue;text-transform:uppercase'><a href="#SysReq"> <span style='text-tranLVALKsform:none'>System Requirements/Downloading the Database</span></a></span></u></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u><span style='color:blue;text-transform:uppercase'><a href="#Intro">INTRODUCTION</a></span></u></p> <p class=MsoNormal><u><span style='color:blue;text-transform:uppercase'><a href="#WhatAccess"> <span style='text-transform:none'>What Is Access?</span></a></span></u></p> <p class=MsoNormal><u><span style='color:blue'><a href="#WhatDB"> What Is in This Database?</a></span></u></p> <p class=MsoNormal><u><span style='color:blue;text-transform:uppercase'><a href="#DBStruc"> <span style='text-transform:none'>Database Structure</span></a></span></u></p> <p class=MsoNormal><u><span style='color:blue'><a href="#Navigate"> How to Navigate the Database</a></span></u></p> <p class=MsoNormal><u><span style='color:blue'><a href="#ObtainHelp"> How to Obtain Help</a></span></u></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u><span style='color:blue'><a href="#SearchMain">SEARCH THE DATABASE</a></span></u></p> <p class=MsoNormal><u><span style='color:blue'><a href="#SearchSub"> Search Database</a></span></u></p> <p class=MsoNormal><u><span style='color:blue'><a href="#SortSub"> Sorting Findings</a></span></u></p> <p class=MsoNormal><u><span style='color:blue'><a href="#BrowseSub"> Browse Database</a></span></u></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u><span style='color:blue'><a href="#SaveMain">SAVING AND PRINTING</a></span></u></p> <p class=MsoNormal><u><span style='color:blue'><a href="#SaveSub"> How to Save Reports</a></span></u></p> <p class=MsoNormal><u><span style='color:blue'><a href="#PrintSub"> How to Print Reports</a></span></u></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u><span style='color:blue'><a href="#Exit">EXITING THE DATABASE</a></span></u></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><u><span style='coloLVALLr:blue'><a href="#Feedback">SENDING FEEDBACK</a></span></u></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><span style='text-transform:uppercase'>&nbsp;</span></p> <p class=MsoNormal><a name=Started><b><u><span style='text-transform:uppercase'>Getting Started</span></u></b></a></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal><a name=SysReq><b><span style='text-transform:uppercase'>System Requirements and Database files</span></b></a></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <ul style='margin-top:0in' type=disc> <li class=MsoNormal>In order to run this database, you must have Microsoft Access 2000 (MS Office Professional 2000) or higher installed on your computer. </li> <li class=MsoNormal>An internet browser (any type) is required to view the WTC Database Definitions file and the help file but an internet connection is not necessary once the database has been downloaded. </li> <li class=MsoNormal>If you obtained a copy of this database on CD or other portable media, you must copy the database file (NCI WTC DB V1.28.mde) from the CD to your hard disk before it can run properly. You can do this by dragging the Access database icon from the CD to a folder on the hard disk while holding down the &quot;control&quot; key. Remove the CD from the CD drive. [If you do not hold down the control key, you might create a &quot;shortcut&quot; to the CD copy instead of a new copy on the hard disk. A &quot;shortcut&quot; will not run properly.] </li> <li class=MsoNormal>If you wish to download a copy of this database to CD, first download the files to your hard drive, then follow the instructions for using your CD-burner software to copy the &quot;NCI WTC DB V1.28.mde&quot; file to the CD. Though it is not necessary, it is still a good idea to copy the file &quot;Installing and RunninLVALMg.txt&quot; to the CD as well. Be aware that the database will not run correctly directly from a CD. It must be copied to a computer hard drive in order to operate properly.</li> <li class=MsoNormal>The database can be saved anywhere on the hard drive but it is recommended that you create a separate folder specifically for the database and save it there.</li> <li class=MsoNormal>To run the database, double-click the icon of the copy you just created on the hard disk. </li> <li class=MsoNormal>Files: During the course of running the database, the following three files may be created on the hard disk in the same folder the database was copied to: </li> </ul> <p class=MsoNormal> </p> <p class=MsoNormal> NCI WTC DB V1.28.mdl</p> <p class=MsoNormal> WTCHelpInfoFile.htm</p> <p class=MsoNormal> WTCDefinitionsInfoFile.htm</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal style='margin-left:.5in'>These files are created by the database as needed. If you delete them, the database will simply re-create them the next time they are needed.</p> <p class=MsoNormal><b>&nbsp;</b></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal><a name=Intro><b><u><span style='text-transform:uppercase'>Introduction</span></u></b></a></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal><a name=WhatAccess><b><span style='text-transform:uppercase'>What is Access?</span></b></a></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal>Access is a Microsoft database program that allows for the collection and organization of data and information. A database is much more than just a list or table. It gives you great control of your data, enabling you to retrieve it, sort it, analyze it, LVALNsummarize it, and report results quickly and accurately. Using Microsoft Access, we have been able to manage a large amount of related data/information.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=WhatDB><b><span style='text-transform:uppercase'>What is in this database?</span></b></a></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal>The Women, Tobacco, and Cancer: Current Research and Activities database (WTC database) was produced by Science Applications International Corporation for the National Cancer Institute s (NCI s) Office of Women s Health and the Tobacco Control Research Branch. The database houses research projects, initiatives, and activities related to women, tobacco, and cancer. The research projects and related activities included were funded by federal and non-federal organizations and were active between 2000 and 2004. Projects have been coded so that the database can be searched and sorted by broad areas of research; by project identifiers such as author, title, and working group; or by specific keywords. A list of these codes, and a short description, can be accessed conveniently on all pages by selecting the <i>View Definitions</i> button. </p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=DBStruc><b><span style='text-transform:uppercase'>Database Structure</span></b></a></p> <p class=MsoNormal><b>&nbsp;</b></p> <p class=MsoNormal>The WTC Database is designed to guide you through a search of the WTC projects and allow you to print and/or save your search results. The following is a description of the WTC Database pages and their capabilities. </p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>From the <b>Home</b> page you may enter the database by selecting <i>Search Database</i>. The <i>View Definitions</i> and <i>Help</i> buttons bring up separate files that contain database descriptions and guidance. The database may be opened withLVALO screens maximized by checking the available box on the <b>Home</b> page. Select the <i>Quit</i> button when you are prepared to end your session. Please note that searches performed during each session will not be automatically saved by the database; however, you are able to save individual searches as .RTF files (described later in this section) as you work in the database.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The <b>Search WTC Database</b> page allows you to create a specific search to meet your research criteria. You have five rows to capture your search strategy. If you would like to start a new search, select the <i>Clear</i> button at any time. The <i>Browse All</i> button will take you to the <b>Browse All</b> page, which provides a full listing of information available in the database. Use the <i>Back</i> button to return to the <b>Home</b> page and the <i>Help</i> and <i>View Definition</i> buttons to view the support files.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>Once you have executed your search, by selecting the <i>OK/Search</i> button, a pop-up window will appear revealing the number of search results retrieved. Select <i>OK</i> to continue to the <b>Search Results</b> page. The order of results on this page may be altered by clicking the column headings (ascending/descending). For more advanced sorting, press the <i>Advanced Sort Options</i> button to set the sort order and listing view of all of the entries. Once completed, your search criteria and selected order will appear at the bottom of the screen. To retrieve a more detailed view of each entry, double click a row and the <b>Project Detail</b> page will appear for that specific entry. To select specific entry rows, use the check boxes in the column titled  Mark. You may use the buttons that appear at the top of the page to mark or un-mark the selected rows. Saving and printing are also available from this page. Use the <i>Back</i> button to return to LVALPthe <b>Search WTC Database </b>page and the <i>Help</i> and <i>View Definition</i> buttons to view the support files.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The <b>Browse All</b> page, indicated by the blue background, allows you to view all database entries. From this page, you may sort the data and save/print all entries, as well as view the help and definition files. Press the <i>Advanced Sort Options</i> button to set the sort order and listing view of all of the entries. The <i>Mark Highlighted</i> <i>Rows</i> and <i>Un-Mark Highlighted Rows </i>buttons and search criteria description are also available on this page. Use the <i>Back</i> button to return to the <b>Search WTC Database </b>page and the <i>Help</i> and <i>View Definition</i> buttons to view the support files.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The <b>Project Detail</b> page (accessed by double-clicking an entry row) can be printed or saved. The <i>Close</i> button will close the <b>Project Detail</b> page and return you to your search results. Once again, you may also use the <i>Help</i> and <i>View Definition</i> buttons to view the support files from this page.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The <b>Set Record Sort Order</b> page is available from the <b>Browse All</b> and <b>Search Results</b> pages. If you would like to start your sort selection over, select the <i>Clear</i> button at any time. The <i>Cancel</i> button will return you to the previous page. A step-by-step description of creating an advanced sort can be found in the Search the Database section of this guide.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=Navigate><b><span style='text-transform:uppercase'>How to navigate the database</span></b></a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The database is set up so that you may utilize the provided buttons to navigate through the available pages. From the <b>Home</b> page, you mLVALQay move to the <b>Search Database</b> page, or view the Definitions, or Help files (the <i>Quit</i> button will allow you to exit the program). The <i>Back</i> button on each page will return you to the previously viewed page. A list of pages and buttons can be viewed in the previous section.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=ObtainHelp><b><span style='text-transform:uppercase'>How to obtain help</span></b></a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>You may access the Help file from almost every screen of the database. Simply click the <i>Help</i> button at the bottom of each page. The <i>View Definitions</i> button is also available on most pages. (NOTE: Informational text will appear when the cursor is held over most buttons.)</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=SearchMain><b><u><span style='text-transform:uppercase'>Search the Database</span></u></b></a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=SearchSub><b><span style='text-transform:uppercase'>Search Database</span></b></a></p> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=1 type=1> <li class=MsoNormal>Click the <i>Search Database</i> button on the <b>Home</b> page. </li> </ol> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <ol style='margin-top:0in' start=2 type=1> <li class=MsoNormal>The <b>Search WTC Database</b> page will appear. </li> </ol> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <ol style='margin-top:0in' start=3 type=1> <li class=MsoNormal>From the first pull-down column,  Search in& , select what information you would like to search. </li> </ol> <p class=MsoNormal style='margin-left:.75in'>&nbsp;</p> <p class=MsoNormal style='margin-left:.75in'>Choose from: </p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='fontLVALR:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Title</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>PI Last Name</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Institution</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>City</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>State</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Keywords</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Abstract</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Performance Period</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Project Type</p> <p class=MsoNormal style='margin-left:1.25in;text-indLVALSent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Project ID</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Funder</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Working Group (WG)</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>WG Recommendations</p> <p class=MsoNormal style='margin-left:.75in'>&nbsp;</p> <ol style='margin-top:0in' start=4 type=1> <li class=MsoNormal>From the second pull-down column,  to see if& , select a qualifier for your search statement. </li> </ol> <p class=MsoNormal style='margin-left:.75in'>&nbsp;</p> <p class=MsoNormal style='margin-left:.75in'>Choose from: </p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Contains</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Does not contain</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Equals (exactly)</p> <p class=MsoNormal style='margin-left:1.25in;textLVALT-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Is empty</p> <p class=MsoNormal style='margin-left:.75in'><span style='text-transform:uppercase'>&nbsp;</span></p> <ol style='margin-top:0in' start=5 type=1> <li class=MsoNormal>Finally, use the third pull-down column to enter specific search terms. </li> </ol> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <p class=MsoNormal style='margin-left:.5in'>(NOTE: Many of the  Search in&  fields provide you with a drop-down list of search terms in the third column to query the database. Fields such as Title and Abstract will allow you to type in your own search terms.)</p> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=6 type=1> <li class=MsoNormal>You may clear your selections at any time and start over by clicking the <i>Clear</i> button. </li> </ol> <p class=MsoNormal style='margin-left:.25in;text-indent:.25in'>&nbsp;</p> <p class=MsoNormal style='margin-left:.5in'>(NOTE: You are provided five lines for your search. Once you enter a second line of search parameters, &quot;AND/OR&quot; check boxes appear and let you specify how to perform the search.)</p> <p class=MsoNormal style='margin-left:.5in'>&nbsp;</p> <ol style='margin-top:0in' start=7 type=1> <li class=MsoNormal>Click the <i>OK/Search</i> button to run the search. </li> </ol> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <ol style='margin-top:0in' start=8 type=1> <li class=MsoNormal>A pop-up box will appear listing the number of results you may view. </li> </ol> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <ol style='margin-top:0in' start=9 type=1> <li class=MsoNormal>Click <i>OK</i>. </li> </ol> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <ol style='margin-top:0in' start=10 type=1> <li class=MsoNormal>The <b>Search Results</b> pagLVALUe will appear with the listed data. On this page you will find: </li> </ol> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Search Results in a table format</p> <p class=MsoNormal style='margin-left:1.75in;text-indent:-.25in'><span style='font-family:"Courier New"'>o<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Navigate through the results using the left and right arrows below the table.</p> <p class=MsoNormal style='margin-left:1.75in;text-indent:-.25in'><span style='font-family:"Courier New"'>o<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>You may adjust the width of each column by dragging the sections larger or smaller.</p> <p class=MsoNormal style='margin-left:1.75in;text-indent:-.25in'><span style='font-family:"Courier New"'>o<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Columns may be sorted (ascending/descending) by clicking the heading.</p> <p class=MsoNormal style='margin-left:1.75in;text-indent:-.25in'><span style='font-family:"Courier New"'>o<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Mark columns for printing or saving by using the check boxes on the left.</p> <p class=MsoNormal style='margin-left:1.75in;text-indent:-.25in'><span style='font-family:"Courier New"'>o<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>The <i>Un-Mark Highlighted Rows</i> and <i>Mark Highlighted Rows</i> buttons will appear near the top of the page once you select several data rows.</p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></spaLVALVn>A summary of your search strategy, below the listed entries and above the available buttons, detailing your search criteria and sort order. </p> <p class=MsoNormal style='margin-left:1.0in'>&nbsp;</p> <p class=MsoNormal style='margin-left:1.25in'>(NOTE: Sort order is also indicated by up or down arrow heads in the column headings.)</p> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <ol style='margin-top:0in' start=11 type=1> <li class=MsoNormal>Double-click an individual line to access the <b>Detail View</b> page for each entry. </li> </ol> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=SortSub><b><span style='text-transform:uppercase'>Sorting Findings</span></b></a></p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal>From the <b>Search Results</b> page, you may organize your results by clicking the column headings or by selecting the <i>Advanced Sort Options</i> button. To sort your results by multiple columns, use the following steps:</p> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=1 type=1> <li class=MsoNormal>Click the <i>Advanced Sort Options</i> button. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=2 type=1> <li class=MsoNormal>The <b>Set Record Sort Order</b> page will appear. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=3 type=1> <li class=MsoNormal>Add  Order by choices by selecting the column heading (i.e., PI Last Name, Keywords, Start Date, etc.) and clicking the <i>Add</i> button. Choices may be deleted by clicking the <i>Remove</i> button.</li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=4 type=1> <li class=MsoNormal>You may further refine your search by ordering your selection. </li> </ol> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span sLVALWtyle='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Select the column heading you wish to change and click the <i>Move Up</i> or <i>Move Down</i> buttons to change the priority (column headings near the top will be listed in your search results before column headings near the bottom). </p> <p class=MsoNormal style='margin-left:1.25in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Additionally, you may select the order within the column heading by ascending/descending using the check boxes on the right.</p> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <ol style='margin-top:0in' start=5 type=1> <li class=MsoNormal>Remove fields by selecting the column heading in the  Order by column and clicking the <i>Remove</i> button. </li> </ol> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <ol style='margin-top:0in' start=6 type=1> <li class=MsoNormal>When your selection is complete, click the <i>OK/Sort</i> button. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=7 type=1> <li class=MsoNormal>You will return to the <b>Search Results</b> page. </li> </ol> <p class=MsoNormal style='text-indent:.25in'>&nbsp;</p> <p class=MsoNormal style='margin-left:27.0pt'>(NOTE: Additional sorting options are available and will be discussed in future versions of the Help Guide.)</p> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <p class=MsoNormal><a name=BrowseSub><b><span style='text-transform:uppercase'>Browse Database</span></b></a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>From the <b>Search Results</b> page, you may view all of the database entries.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal style='margin-left:.5in;text-indent:-.25in'>1.<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp; </spaLVALXn>Click the <i>Browse All</i> button.</p> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in'>&nbsp;</p> <p class=MsoNormal style='margin-left:.5in;text-indent:-.25in'>2.<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp; </span>The <b>Browse All</b> page will appear (distinguished by a blue background).</p> <p class=MsoNormal style='margin-left:.25in'>&nbsp;</p> <p class=MsoNormal style='margin-left:.5in;text-indent:-.25in'>3.<span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp; </span>You may sort all entries in the same manner as mentioned above (clicking the column header or by clicking <i>Advanced Sort Options</i>).</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=SaveMain><b><u><span style='text-transform:uppercase'>Saving and Printing</span></u></b></a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>You may save or print any of your searches by clicking the <i>Print Entries</i> or <i>Save Entries</i> buttons at the bottom of the <b>Search Results</b> or <b>Browse All</b> pages. Results may be saved or printed in two formats, List View or Detail View. </p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The List View will provide a limited amount of data in a spreadsheet format (similar to that seen on the <b>Search Results</b> and <b>Browse All</b> pages) including: </p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>PI Name</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Title</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&LVALYnbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Institution</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>State</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Funder</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Project Type</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Performance Period</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>The Detail View will provide greater detail including:</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Title</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>PI Name</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Organization</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></LVALZspan>Project ID</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Funder</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Project Type</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Performance Period</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Working Group (WG)</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Abstract</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>WG Recommendations</p> <p class=MsoNormal style='margin-left:.75in;text-indent:-.25in'><span style='font-size:10.0pt;font-family:Symbol'><span style='font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span></span>Keywords</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><a name=SaveSub><b><span style='text-transform:uppercase'>How to save reports</span></b></a></p> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=1 type=1> <li class=MsoNormal>Click the <i>Save Entries</i> button. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='mLVAL[argin-top:0in' start=2 type=1> <li class=MsoNormal>Select whether you would like to save the results in List View or Detail View. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=3 type=1> <li class=MsoNormal>Select the range of rows you would like to save (all rows or marked rows only). </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=4 type=1> <li class=MsoNormal>Click the <i>Save</i> button. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=5 type=1> <li class=MsoNormal>A dialogue box will give the options to save as an .RTF file or cancel the save request. An .RTF file can be read by most word processing programs, including Microsoft Word. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=6 type=1> <li class=MsoNormal>Select the location on your computer where you would like to save your search results. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=7 type=1> <li class=MsoNormal>Click the <i>Close</i> button to return to you the <b>Search Results</b> page. </li> </ol> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b><i>Potential problem with reports saved as .RTF files:</i></b></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>On some computers, reports saved as .RTF files may exhibit incorrect word-wrapping when opened in MS Word. This originates with a long-standing problem in MS Access and is dependent upon the configuration of the machine running the database.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>On occasion the problem as been remedied simply by applying current MS Office updates and patches available from the MS Office web site:</p> <p class=MsoNormal><a href="http://office.microsoft.com/en-us/officeupdate/default.aspx" title="http://office.microsoft.com/en-us/officeupdate/default.aspx">http://office.microsoft.com/en-us/officeupdLVAL\ate/default.aspx</a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>For a quick fix that doesn't require updating Office, select all the text in the file and reduce the font size or condense the existing font.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>To fix specific instances in MS Word:</p> <p class=MsoNormal>Inspect the .RTF output carefully in Word to locate specific fields&nbsp;that contain too much text and overrun their right-hand boundaries.&nbsp; Select the text within the offending fields, and use the Formatting Menu or toolbar to either (1) reduce the font size (Format&gt;Font&gt;Font&gt;Size) by 1-3 points, or (2) &quot;condense&quot; the existing font size by 1-3 points (Format&gt;Font&gt;Character Spacing&gt;Condensed&gt;By).</p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</span></b></p> <p class=MsoNormal><a name=PrintSub><b><span style='text-transform:uppercase'>How to print reports</span></b></a></p> <p class=MsoNormal> </p> <ol style='margin-top:0in' start=1 type=1> <li class=MsoNormal>Click the <i>Print Entries</i> button. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=2 type=1> <li class=MsoNormal>Select whether you would like to print the results in List View or Detail View. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=3 type=1> <li class=MsoNormal>Select the range of rows you would like to print (all rows or marked rows only). </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=4 type=1> <li class=MsoNormal>Click the <i>Print</i> button. </li> </ol> <p class=MsoNormal>&nbsp;</p> <ol style='margin-top:0in' start=5 type=1> <li class=MsoNormal>In the pop-up window that appears, click either the <i>Print</i> button or the <i>Cancel</i> button. </li> </ol> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><b><span style='text-transform:uppercase'>&nbsp;</spaLVALn></b></p> <p class=MsoNormal><a name=Exit><b><u><span style='text-transform:uppercase'>Exiting the Database</span></u></b></a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>You may exit the program at any time by closing the program or navigating to the <b>Home</b> page and selecting <i>Quit</i>. If you wish to save any of your searches, you must save either the List View or the Detail View of your results as an .RTF file (Saving and Printing section above). Once you exit the program, your searches will no longer be available, but all of the database information will remain for future searches.</p> <p class=MsoNormal><b>&nbsp;</b></p> <p class=MsoNormal>If, after clicking the <i>Quit</i> button, the Microsoft Access window remains open, go to File menu and select Exit.</p> <p class=MsoNormal><b>&nbsp;</b></p> <p class=MsoNormal><a name=Feedback><b><u><span style='text-transform:uppercase'>SENDING FEEDBACK</span></u></b></a></p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal>Your help will be a key factor in determining the future of the WTC Portfolio Database. Please tell us how you are using this tool and how it will be useful in the future. Your input will be used to decide whether to support regular updates and improvements to this database. Questions, comments, or suggestions are also welcome.</p> <p class=MsoNormal>&nbsp;</p> <p class=MsoNormal><span style='color:black'>Contact us at: &nbsp;NCI Women s Health, </span><a href="mailto:nciospw_health-r@mail.nih.gov" title="mailto:nciospw_health-r@mail.nih.gov"><span style='color:#333399'>nciospw_health-r@mail.nih.gov</span></a></p> </div> </body> </html> +YxQk*SidN^^Y  Y &Breakout Session No Breakout SessionAn^`YRecordIDv1 ]W@FGlobal Issues <Community and Policy InterventionsJ2Awareness Risk Perception and Communications^(Interventions for Prevention and TreatmentZEpidemiology and National SurveillanceRAddiction Biology and Cancer* ] @ ___(_2_<_F_O YN bb Y d Y d Y  Y 0Y Y  Y  Y Y Y  Y   Y  d Y  V Y  VField Name*Sort Field Descriptor*Sort Field Expression$Sort Field EnglishSort Order(Conditional PossibleBSort Field Conditional Expression Sort Combo Query Sort Combo LimitAscending Conditional Used Value0Compiled Sort Expression6Compiled English ExpressionVVbeVVV bfVYYPrimaryKeySort Orderbb bb bb, v1b N @  a4 X TitleTitle[Title]TitleInstr(1,nz([Title],""),"$@^$") [Title]Title-Ascending~aLLL,% 6StateInstitution State[State]State [State]State-AscendingjM88881( 6ProjectIDProject ID[Project ID]Project IDInstr(1,nz([Project ID], ""),"$@^$")@d[Project ID]Project ID-Ascendingqqe?3% 6PINamePI Last Name[Last Name]PI Last Name [Last Name]PI Last Name-Descending}X????1$ 6PerformancePeriodStart Date[Start Date Date]Start Date[Start Date Date]Start Date-DescendingkLLLL@-! 6InstitutionInstitution Name[Institution]Institution Name[Institution]Institution Name-AscendingiNNNN<- 6FunderFunder[Funder]Funder [Funder]Funder-DescendingeF0000( 6CLVALSSELECT [tIMPAC Activity Types Available].[IMPAC Activity Types] FROM [tIMPAC ActivitSELECT [tIMPAC Activity Types Available].[IMPAC Activity Types] FROM [tIMPAC Activity Types Available] ORDER BY [tIMPAC Activity Types Available].[IMPAC Activity Types]; a SobOQicYbkmYmomYdbcfQiSdi`JbMQfQiYdOcfYbJ`Qcfid[QMmYOckmJmQcmYm^Qc a @ccccccc BYNhh Y  d Y dY Y Y Y Y  Y Y Y  Y  Y  Y  Y  Y  Y  Y 4Form NameControl NameScale in StepsTopLeft Height WidthHas FontFont BaseFont ResizeFont AutosizeFont MinFont MaxFont GroupFont TempUpdated ControlRecenter OndvCg2f1 L g  1 ? 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'&Q&Xi2mTq0 ri&4v&4vmQ(bhWomen Tobacco and Cancer Background Information Table of Contents  HYPERLINK \l "Check10" Breakout groups  HYPERLINK \l "Check11" Recommendations  HYPERLINK \l "Check9" Key words  HYPERLINK \l "Check8" Funding Organizations Breakout Groups Biology & Cancer Addressing tobacco toxicology, cancer susceptibility, and biological gender differences related to tobacco and cancer. Addiction Addressing the biology and behavior of addiction. Epidemiology & National Surveillance Addressing the surveillance of tobacco use and control efforts. Interventions for Prevention & Treatment Addressing tobacco control interventions to prevent tobacco use and to treat tobacco addiction. Awareness, Risk Perception & Communications Addressing public knowledge of tobacco addition, health and addiction risks and interventions for tobacco control as well as strategies for communication with the public about tobacco issues. Community & Policy Interventions Addressing population-based, policy, community, legal and regulatory interventions in tobacco control. Global Issues Addressing tobacco use and control internationally with recommendations in each of the 6 other breakout session topic areas. Recommendations I. Discovery Overall Goal: Increase our understanding of sex and gender differences across the broad range of research on women, tobacco, and cancer. Individual Goals: A better understanding of sex and gender differences is critical to eliminating tobacco use and tobacco-related cancer morbidity and mortality in men and women. Goal 1: Multidisciplinary research is needed on sex differences in the mechanisms and processes associated with: 1A All phases of tobacco addiction--from experimentation to regular use and addiction to cessation--including the natural history of the progression between phases and the effects of environmental tobacco smoke (ETS) exposure. This includes genetic, molecular, cellular, neurobiological, biobehavioral, and hormonal factors that play a critical role in tobacco addiction and in the etiology of cancers and other diseases caused by tobacco. 1B The etiology of cancers caused by tobacco, especially those related to gene-hormone-environment interactions involved in carcinogenic and other disease pathways. 1C Methods of prevention and treatment of tobacco addiction. Goal 2: Multidisciplinary research is needed on gender-specific factors in tobacco use and the components of effective prevention and treatment interventions for women and girls, especially in populations at greatest risk, to: 2A Identify behavioral, psychosocial, sociocultural, and environmental influences on tobacco use, exposure to ETS and disease risk, and prevention and treatment interventions. 2B Assess womens and girls knowledge of the harms of tobacco use and ETS exposure and the benefits of quitting. Goal 3: Multidisciplinary research is needed to validate and standardize sex- and gender-appropriate definitions and measures of addiction, ETS exposure, tissue injury, and recovery. II. Development Overall Goal: Develop new and more effective interventions to prevent and treat tobacco use and ETS exposure among women and girls, especiaLVALlly in populations at greatest risk. Individual Goals: Translating basic and applied research into effective, evidence-based prevention and treatment programs and broad public health tobacco control policies will require: Goal 1: Using evidence from animal studies, pilot projects, and small-scale clinical and community-based studies to develop, refine, and evaluate promising sex- and gender-appropriate interventions for prevention, cessation, and treatment. Goal 2: Using or modifying existing infrastructures to rapidly evaluate the efficacy of promising treatments and the effectiveness and cost-effectiveness of proven small-scale interventions, programs, and policies. Goal 3: Developing and disseminating evidence-based cessation, prevention, and advocacy messages targeted to women using state-of-the-art, audience-tailored communication strategies. Goal 4: Conducting research to explore and strengthen the positive health impacts of public and private tobacco control policies on women and girls, especially in populations at greatest risk, and improving the adoption of evidence-based policies and strategies by policy and decision makers. Goal 5: Monitoring the harmful effects of tobacco marketing targeted to diverse populations of women and girls domestically and globally. III. Delivery Overall Goal: Ensure the widespread delivery of effective interventions to prevent and treat tobacco use and ETS exposure among women and girls. Individual Goals: Expanding the reach and impact of evidence-based tobacco control programs and policies will require: Goal 1: Increasing the appeal, access, affordability, and use of effective interventions, particularly among women and girls in populations at greatest risk. Goal 2: Identifying and using targeted messages and strategies to involve and activate individuals and organizations in effective, sustained advocacy for evidence-based tobacco control programs and policies. Goal 3: Making data from surveillance and policy research, as well as social, economic, and cultural studies, available to the health care community, policy makers, and the general public in a timely and effective fashion. Goal 4: Supporting research and demonstration projects to better understand how to convert womens broad-based support for tobacco control policies and programs into more active involvement in their communities. IV. Partnership Overall Goal: Harness and expand partnerships, networks, and innovative research platforms to design and launch broad-based strategies to eliminate the harms of tobacco use and ETS exposure among women and girls. Individual Goals: Successfully implementing the discovery, development, and delivery recommendations will require capitalizing on existing collaborations and developing new partnerships. To maximize the development and dissemination of effective interventions, partners must be involved from the beginning, and knowledge gained from practice should be used to inform future research. Partnerships are especially needed between: Goal 1: Established networks of clinical and translational researchers that can provide the resources and infrastructure needed to foster cross-disciplinary interactions and rapidly evaluate treatments and interventions. Goal 2: Research institutions and community-based organizations that serve populations at greatest risk to conduct community-based participatory research. These partners must be committed to joint decision making in designing research, sharing ownership of the products of research, and disseminating and implementing research results. Goal 3: Research institutions and tribal colleges, tribal health departments, and/or American Indian health care and community settings to develop effective, culturally appropriate individual, family, and community-level tobacco prevention and cessation initiatives. Goal 4: Public and private funding agencies to fully and efficiently support the implementation of successful interventions. V. Evaluation and Surveillance Overall Goal: Improve nationLVALal and global evaluation and surveillance of the harms of tobacco use and ETS exposure, and of womens and girls knowledge, attitudes, and behaviors related to tobacco use and harms. Individual Goals: It is essential to monitor and evaluate progress toward reducing tobacco use, ETS exposure, and the impact of tobacco-related cancers on women and to make midcourse adjustments as needed. This will require further development of standardized measures and surveillance systems to ensure that data are comparable within and across countries. Goal 1: Improve national and global evaluation and surveillance of: 1A* The patterns, extent, and trends in morbidity, mortality, and tobacco use, and the impact of policies on these data. 1B* The biological effects of tobacco and ETS. 1C* Womens and girls knowledge, attitudes, and behaviors related to tobacco use and harms, and the effectiveness of policies in changing knowledge, attitudes, and behaviors. *Note: Wording for Goals 1a, 1b, and 1c was derived from information in the Working Group Report Key Words Addiction Initiation Maintenance Cessation Withdrawal Relapse Age Child (<18) Young adult (18 24) Adult Older adult Fetus/prenatal Community Womens groups General partnerships Health care provider Other Disease/Biology Cardiovascular/Pulmonary Cancer Mechanisms Other Economics SES Medicaid/Medicare Insurance coverage Cost of intervention/treatment Cost of smoking Epidemiology/Surveillance Data collection (small, <100) Data collection (large, e"100) Education Level Less than High school High school College and above Location Urban Rural National International Marketing Industry Counter-marketing Media-websites/pamphlets/radio Other Policy Excise tax Guidelines/best practices Regulatory intervention FCTC Other Psychological Depression/Mood/Anxiety Social factors Cultural factors Other Research Animal studies Human studies In vitro studies Clinical research Study Population African American AI/AN Asian Pacific Islander Caucasian Hispanic LGBT Prevention/Treatment Counseling/behavioral therapy Support group Interview/focus group Quitline Educational materials Biochemical assessment Bupropion NRT Other pharmacological Women Pregnancy Postpartum Parent/mother Partner/spouse Menstrual cycle Menopause Hormones HRT Tobacco Cigarette/Other smoking Smokeless Non-specified tobacco use Environmental tobacco smoke Nicotine Miscellaneous Knowledge/attitudes/risk perception Weight gain/exercise Sex/gender differences Funding Organizations OrganizationAcronymCategoryAmerican 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While the health benefits of an active lifestyle are well documented in adults, the prevalence of inactivity in the US adult population remains high. It is widely believed that the prevention of physical activity in adults is best accomplished by establishing a physically active lifestyle during youth that will persist into adulthood. However, there is a paucity of data on the relationship between childhood and adult physical activity and no evidence that an active child becomes an active adult. The overall goal of this study is to examine the relationship between physical activity in adolescence and physical activity in young adulthood. This proposal is a follow-up study of 1245 young adults aged 21-25 years, who represent a biracial population-based cohort initially recruited in 1990 to participate in a NIH funded longitudinal study of the incidence and determinants of injury in adolescents, the Asolescent injury Control Study (AICS).The baseline age of the participants was 12- 16 years of age. Extensive physical activity data were collected during the four years of AICS. Physical activity will be assessed in the current study using a standardized questionnaire identical to that used in the adolescent study. Additional data to be collected include sociodemographic (i.e., education, marital status, occupation), lifestyle factors (i.e., cigarette and alcohol use), and psychosocial factors (i.e., self- efficacy, social support, barriers), as well as health information. Data collected in this proposed study and data from AICS will be combined, allowing for longitudinal analyses of the same subjects from ages 12-16 (AICS bseline) to ages 25-29 (final year of proposed study). The primary objectives of this study are to: 1) determine changes in the amount of PA from adolescence to young adulthood and to evaluate possible gender and racial differences; 2) evaluate the degree of tracking of P LVAL0A from adolescence to young adulthood; and 3) evaluate adolescent predictors of PA in young adulthood.LVAL PAGE Fetus/Prenatal RESEARCH1 Animal Studies TOBACCO NicotineTOBACCO Cigarette/Other Smoking WOMEN Pregnancy Partner/SpouseLOCATION National PSYCHOLOGICAL Cultural Factors RESEARCH Human Studies STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use NicotineADDICTION Relapse ECONOMICS Socio-Economic Status Insurance Coverage Cost of Intervention/Prevention Cost of Smoking LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Menopause Hormones MISCELLANEOUS Weight Gain/ExerciseLOCATION National International POLICY Guidelines/Best Practices Regulatory Intervention PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionADDICTION Cessation ECONOMICS Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials PSYCHOLOGICAL Social Factors RESEARCH Human Studies TOBACCO Cigarette/Other SmokingAGE Child Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Social Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExercisebLVAL(F h T  ` j@.>HRDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Partnerships 3 Evaluation 1aDiscovery 1b Discovery 1c Discovery 2a Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1a Evaluation 1bDiscovery 1b Discovery 1c Discovery 2a Development 1 Evaluation 1bDiscovery 2a Development 3 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1aDiscovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 1c Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Development 1 Delivery 2 Partnerships 2Discovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 1c Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Development 1 Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Discovery 2a Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 2a Development 4 Evaluation 1a Evaluation 1cDiscovery 1c Development 2 Development 3 Delivery 1 Delivery 2Discovery 2a Evaluation 1a Evaluation 1cLVAL `T  |  V f"Z|(J2HAddiction Interventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Interventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentEpidemiology and National Surveillance Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentInterventions for Prevention and TreatmentAddiction Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National Surveillance Interventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceCommunity and Policy InterventionsEpidemiology and National Surveillance Interventions for Prevention and TreatmentEpidemiology and National SurveillanceAddiction Epidemiology and National Surveillance Interventions for Prevention and TreatmentEpidemiology and National Surveillance Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentEpidemiology and National Surveillance Awareness Risk Perception and CommunicationsEpidemiology and National SurveillanceBiology and Cancer Interventions for Prevention and TreatmentInterventions for Prevention and Treatment Community and Policy InterventionsBiology and Cancer Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceInterventions for Prevention and TreatmentEpidemiology and National SurveillanceLVAL#2:| @ n  L @ h2`j.h XGENETIC SUSCEPTIBILITY TO CARCINOGENSHUMAN NEUROPHYSIOLOGY OF NICOTINE ANALGESIA: SEX DIFFERENCESSMOKING CESSATION FOR MOTHERS AND OTHER HOUSEHOLD MEMBERS OF BABIES BEING TREATED IN THE SPECIAL CARE NURSERYCHRONIC STRESSORS AND DRUG ABUSE IN TWO INDIAN POPULATIONSSMOKING, STRESS, AND IMMUNE FUNCTIONSPORTS, GENDER AND ADOLESCENT SUBSTANCE USEPAF ACETYL-HYDROLASE IN LOCALIZED JUVENILE PERIODONTITISHORMONE REPLACEMENT THERAPY, SMOKING, AND LIPOPROTEIN OXIDATIONPHYTOESTROGENS, ALCOHOL, AND ENDOMETRIAL CANCER RISKTOBACCO DEPENDENCE: TREATMENT AND OUTCOMESREPRODUCTIVE HORMONES AND PRE-CLINICAL CVD IN WOMENENVIRONMENTAL EFFECTS ON FERTILITYLUNG HEALTH STUDY--LONG TERM FOLLOW UPPILOT--SOCIAL RESOURCES AND SMOKING AMONG HISPANIC YOUTHBRIEF INTERVENTIONS FOR NICOTINE AND CANNABIS USESEXUAL ORIENTATION AND HEALTH DISPARITIES IN ADOLESCENCECOMMUNITY SURVEILLANCE OF CARDIOVASCULAR DISEASE-RISK FACTORSLUNG HEALTH STUDY--LONG TERM FOLLOW UPBIOBEHAVIORAL MARKERS OF RISK FOR NICOTINE ADDICTIONSISTER TO SISTER: HELPING LOW-INCOME WOMEN QUIT SMOKINGLUNG CANCER MOLECULAR MARKERS BY SEX: INTERGROUP STUDYLUNG HEALTH STUDY--LONG TERM FOLLOW UPTOBACCO CESSATION IN POSTMENOPAUSAL WOMENMENSTRUAL PHASE EFFECTS ON SMOKING RELAPSEPSYCHOBIOLOGICAL MECHANISMS OF STRESS AND SMOKING RELAPSEPSYCHOBIOLOGICAL MECHANISMS OF SMOKING RELAPSENICOTINE WITHDRAWAL AND RESPONSES TO PSYCHOLOGICAL STRESSBIOBEHAVIORAL NICOTINE DEPENDENCE IN BLACK WOMENCIGARETTE SMOKING TOPOGRAPHY AMONG AFRICAN AMERICA WOMENESTABLISHING A CULTURALLY APPROPRIATE PRENATAL CARE EDUCATION PROGRAM FOR HISPANIC WOMEN IN NEW JERSEYEVALUATING THE CHARACTERISTICS, COSTS, AND POTENTIAL FOR RELAPSE IN LOW-INCOME PREGNANT SMOKERSA PROSPECTIVE STUDY OF ACRYLAMIDE CONTAMINATED FOOD AND BREAST CANCER RISKASSIMILATION AND TOBACCO USE AMONG U.S. IMMIGRANTSINTERNET AND TELEPHONE TREATMENT FOR SMOKING CESSATIONEPI OF PHYSICAL ACTIVITY: TEENAGE TO ADULT YEARS  k Q;T @K@ResearchR@ ALLENSHARONUNIVERSITY OF MINNESOTAMINNEAPOLISMNNIDAR01, DA008075\*p.Biology and Cancer Addiction@ n@3/1/19937/31/20023/1/1993 to 7/31/20024/2005 wqm`G?88," @@ResearchT@ ALLENSHARONUNIVERSITY OF MINNESOTAMINNEAPOLISMNNIDAR01, DA008075\*p.Biology and Cancer Addiction@ @3/1/19934/30/20053/1/1993 to 4/30/20054/2005 wqm`G?88," @+@Researchr@ AL'ABSIMUSTAFAUNIVERSITY OF MINNESOTAMINNEAPOLISMNNIDAR01, DA016351*p.Biology and Cancer Addiction@@9/30/20036/30/20079/30/2003 to 6/30/20074/2005ztpcJA88," @@u@Research\@ AL'ABSIMUSTAFAUNIVERSITY OF MINNESOTAMINNEAPOLISMNNIDAR21, CA088272*p.Biology and Cancer Addiction@8@7/1/20006/30/20037/1/2000 to 6/30/20034/2005 ztpcJA88," @C@Researchr@AL'ABSIMUSTAFAUNIVERSITY OF MINNESOTAMINNEAPOLISMNNIDAR03, DA013435*p.Biology and Cancer Addiction@f@6/1/20005/31/20026/1/2000 to 5/31/20024/2005 ztpcJA88,"P@ @Research`@AHIJEVYCHKARENOHIO STATE UNIVERSITYCOLUMBUSOHNIDAR29, DA010809*p.t@@@2/1/19971/31/20042/1/1997 to 1/31/20044/2005uokaJC88,"o@ -@Researchp@AHIJEVYCHKARENOHIO STATE UNIVERSITYCOLUMBUSOHNCRRM01, RR000034@L@@@12/1/197611/30/200112/1/1976 to 11/30/20014/2005uokaJC88," W@@Research@AHERNSHARONMARCH OF DIMES BIRTH DEFECTS NATIONAL FOUNDATION, NEW JERSEY CHAPTERCRANBURYNJRWJF47077Not available11/1/200212/31/200511/1/2002 to 12/31/20054/2005G?88,"?~@@Research@ADAMSE.EMORY UNIVERSITY, ROLLINS SCHOOL OF PUBLIC HEALTHATLANTAGARWJF51797N@L@Evaluation 1a@9/1/20048/31/20069/1/2004 to 8/31/20064/2005vC?88," 1@@Research@ADAMIHANS-OLOVKAROLINSKA INSTITUTESWEDENCDMRPBC020201@t@p@@200220052002 to 20054/2005yoh``J?88,"@@Researchd@ACEVEDO-GARCIADOLORESHARVARD UNIVERSITYBOSTONMANCIR03, CA093198`*p.L@r@F@8/1/20017/31/20048/1/2001 to 7/31/20044/2005vqmeQH88,"@ @Researchl@ABRAMSDAVIDBROWN UNIVERSITYPROVIDENCERINCIR01, CA104836<*p.T@@@8/25/20047/31/20098/25/2004 to 7/31/20094/2005}nieYG@88,"@@Researchb@AARONDEBORAHUNIVERSITY OF PITTSBURGHPITTSBURGHPANICHDR01, HD035607*p.L@T@@2/1/19991/31/20052/1/1999 to 1/31/20054/2005yrnbH?88,"LVAL*p.Tobacco use is the major preventable cause of cancer and disease burden in the U.S. While effective treatments exist, innovative means of efficient delivery are needed to accelerate reduction in smoking prevalence. Telephone counseling and tailored self-change programs have an evidence-base of efficacy and the capability to make an impact on population prevalence. There is a growing movement to provide comprehensive tobacco control services, both through telephone quit lines and tailored self-change via the Internet. Scientists, policy makers and the public need to know if these programs work, for whom, by what mechanisms, and at what cost. There are no rigorous evaluations of the efficacy of Internet-driven cessation services or of combined telephone and Internet treatment At the same time, Internet-based programs are already available to the public and are being used at a very high volume without any evidence that they are effective. This study aims to extend existing theory and application by comparing the efficacy of a popular, full service, Internet intervention (Premium Internet) alone or in conjunction with proactive telephone counseling (Premium Internet plus Telephone) against a standard Internet control (Basic Interact). This study will recruit motivated smokers (N=2,055) who use an Internet search engine to find smoking cessation programs. A subset will be directed to a Web page that will describe the study and enrollment procedures. Using a 3-condition randomized design with repeated measures at baseline, 3, 6, 12, and 18-months post-randomization, consented smokers will be assigned to: 1) Basic Internet; 2) Premium Internet; and 3) Premium Internet plus Proactive Telephone Counseling. The hypotheses tested are that Premium Interact plus Telephone will outperform Premium Internet alone and both will outperform Basic Internet on 7-day point prevalence abstinence measured at 12 months post-randomization (6-months post treatment). Cost-effectiveness will also be examined along with explorator LVAL y analyses of theory-driven hypotheses about the mediators and moderators of outcome (e.g., gender, amount and frequency of service use, type of content used, and behavior change variables including self-efficacy, social support, and motivation). Market demand and State health departments are stimulating delivery of Interact and telephone cessation services. There is an urgent need for science to fill the gap and evaluate their efficacy. If effective, such treatments can be widely disseminated and can make a significant impact on population health.LVAL*p.Recent immigrants to the U.S. constitute an increasingly significant demographic group and overall have lower socioeconomic status (SES) than the native-born. It is known that tobacco use is a major health risk for groups with low SES. On the other hand, there is some evidence that within certain ethnic/racial groups in the U.S., tobacco use is lower among the foreign-born than among the US-born, and that tobacco use is positively correlated with measures of immigrant assimilation. Previous analyses of tobacco use among immigrants have been fragmentary, i.e. have focused on a single state/community, a single national origin/ethnic group, and/or convenience samples. Research on tobacco use among immigrants is urgently needed, given its implications for preventative action and cancer incidence reduction. We seek to examine tobacco outcomes among immigrants to the United States, and to investigate the role of assimilation in these outcomes, using the Tobacco Use Supplement of the Current Population Survey (CPS, 1995-96), a data set that is representative at the national and state level. The combination of information on tobacco outcomes and immigrant status makes the CPS a uniquely valuable resource for studying tobacco outcomes among the U.S. immigrant population. To the best of our knowledge, there is no previous national-level study of tobacco outcomes among immigrants. The specific aims of this study are to assess the role of assimilation in tobacco use; attitudes towards tobacco; and household, workplace, and community tobacco control among immigrants to the U.S. We will also examine whether age, gender, race/ethnicity, SES, state-level tobacco control policy, and smoking prevalence and tobacco control in the country of origin mediate (moderate) the effect of assimilation on tobacco outcomes. The proposed multilevel logistic regression analyses are grounded on the segmented assimilation theory and the context of reception framework.rLVALp ",<A series of guides tailored to quitting smoking during pregnancy were used in this study.To develop a model to explain the process of how men influence the smoking cessation of their partners during pregnancy.To examine the pharmacokinetics of menthol in venous plasma following dosing via cigarette smoking women cigarette smokers.The Foundation's program, Smoke-Free Families: Innovations to Stop Smoking During and Beyond Pregnancy, is a multi-component strategy to improve current clinical practice and advance the field into the next generation of smoking cessation techniques for childbearing women. The purpose of this project is to provide current statistics on maternal smokers, derive updated estimates of the costs attributable to smoking during pregnancy, and estimate the number of quits that will need to be achieved by smoking cessation interventions of varying cost. The specific goals of this study are (1) to compare high and low intake of specific food items found to cinatin elevated acrylamide on risk of breast cancer in women; (2) to quantify total acrylamide exposure from diet for each individual using data from the Swedish National Food Administration and correlate it with cancer risk; and (3) to assess whether traditional breast cancer risk factors modify the association between acrylamide and breast cancer.LVAL*p.More African Americans die from diseases caused by cigarette smoking than from AIDS, homicide, drugs and accidents combined. In addition, smoking intensifies a number of serious health problems that disproportionately affect African Americans including heart disease, cancer, stroke, low birth weight, and infant mortality. African Americans report smoking fewer cigarettes per day, prefer high nicotine, mentholated brands, and are noted to be highly dependent on nicotine. Higher cotinine levels, the major metabolite of nicotine, have been described in black women, in comparison to other race-gender groups, in spite of smoking fewer cigarettes per day. Furthermore, there is a lower smoking cessation quit rate among African American women compared to Caucasian women. Alternative explanations for increased exposure as indicated by elevated cotinine levels in African American women are warranted. The overall aim of the FIRST award proposal is to examine effects of selected biobehavioral and contextual factors on smoke constituent exposure and nicotine dependence in African American and Caucasian women. Three separate studies to be conducted in the General Clinical Research Center (GCRC) with black and white women are proposed. 1) To characterize cotinine elimination trends, subjects will be admitted for a 7-day inpatient study of smoking abstinence during which plasma cotinine levels will be obtained. The effect of race, body composition, and menthol preference on cotinine trends will be analyzed. 2) During a 4 hr study, the effects of smoking topography (e.g. puff duration and volume and lung retention time), race, menthol preference, and body composition on plasma nicotine trends post-cigarette will be analyzed. Menthol exposure will be examined. 3) During a 6-day inpatient study with a counterbalanced design, smoke constituent exposure as measured by plasma nicotine and carbon monoxide increases pre to post-cigarette, as well as puff duration and volume, and lung retention time, will be contrasted across LVAL three conditions of nicotine availability of usual, increased and restricted smoking rates. Information about metabolic and behavioral issues concerning nicotine will add to a limited knowledge base about nicotine dependence in African American women and provide scientific support for specific targeted smoking cessation interventions, in conjunction with or separate from nicotine replacement.LVAL` DISEASE/BIOLOGY Cancer Mechanisms RESEARCH1 Animal Studies RESEARCH In Vitro StudiesDISEASE/BIOLOGY Cancer Mechanisms RESEARCH In Vitro StudiesADDICTION Cessation Withdrawal Relapse DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Hormones MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesADDICTION Cessation Withdrawal Relapse DISEASE/BIOLOGY Other Disease/Biology LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Hormones MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse DISEASE/BIOLOGY Other Disease/Biology PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Hormones MISCELLANEOUS Sex/Gender DifferencesADDICTION Withdrawal DISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking NicotineLVAL*p.Abstinence from cigarette smoking is associated with negative affect symptoms, such as anxiety, irritability, depression and craving. These symptoms present a major obstacle in cessation, and they are intensified under acute stressful situations. Mechanisms responsible for the stress- induced exacerbation of withdrawal symptoms are not known. Without specific knowledge of the biobehavioral mechanisms responsible for the effects of stress in smoking, targeted efforts to stress-precipitated smoking will remain limited. The long-term goal of this research is to determine how psychobiological responses to behavioral stress influence smoking behavior. The specific goal of this project is to evaluate cortisol responses to behavioral stress and to assess the extent to which smoking abstinence alters these responses in dependent cigarette smokers. Smokers and non-smokers will participate in two counter-balanced laboratory sessions conducted on two separate days (rest session and stress session). Smokers will be randomly assigned to one of two conditions: abstinence from smoking for 24 hours prior to each lab session or ad libitum smoking. During the laboratory stress session, behavioral stress will be modeled by work on an extended, interpersonally demanding stress (public-speaking) with an emphasis on social evaluation. Salivatory cortisol and self-report measures of withdrawal symptoms will be obtained during the two laboratory sessions and during the 24-hour period prior to each session. During lab sessions, we will also monitor heart rate, systolic and diastolic blood pressure, and measure stroke volume using impedance cardiography. Calculated valuables will include cardiac output, systemic vascular resistance, and rate-pressure product. The project will include men and women, and will explore gender differences in responses to abstinence from nicotine and to behavioral stress. Ultimately this work should lead to a better understanding of the biobehavioral mechanisms responsible for the increased desire tLVALo smoke under stressful situations, and to development of more effective intervention techniques for smoking cessation and relapse prevention.LVAL*p.Cigarette smoking is the leading preventable cause of cancer and cardiovascular diseases. Although the decades have witnessed accelerated efforts to develop effective smoking cessation strategies, the long-term success rates have been disappointing. The majority of smokers relapse within two weeks of a cessation attempt, and little is known about the nature of this early relapse. Smoking cessation is associated with negative affect symptoms. These symptoms are intensified in stressful situations, possibly accelerating the progression towards a full relapse. Mechanisms responsible for this stress effect are not known. Without specific knowledge of the stress-related biobehavioral changes, targeted efforts to reduce smoking and relapse will remain limited. The long-term goal of this research is to determine the psycho biological mechanisms responsible for smoking relapse. The specific goal of this project is to evaluate hormonal changes during early abstinence and in response to behavioral stress, and to assess the extent to which these changes predict early relapse. Our central hypothesis is that exaggerated responses to behavioral stress predict a shorter time to relapse. This hypothesis is based on the well-established observation that stressful events, characterized by negative emotions, are associated with rises in adrenocorticotropic hormone (ACTH) and cortisol concentrations. It is also based on the observation that environmental stressors increase the risk for smoking relapse. We will specifically determine the extent to which basal cortisol activity during early smoking abstinence predicts relapse, examine endocrine and cardiovascular responses to stress as predictors of smoking relapse, and evaluate gender differences in psycho biological changes during smoking abstinence and in response to behavioral stress. This research focuses on the pituitary-adrenocortical axis, an important stress-related biological system recently implicated in addiction. We will integrate hormonal, autonomic and psych LVAL ological indices to gain an accurate profile of the stress response patterning among smokers and use this information in a prospective fashion to predict relapse in men and women. The results will provide a base of knowledge concerning psycho biological changes associated with quitting and risk for relapse. This information will facilitate efforts towards improving methods to identify and assist individuals at high risk for relapse. Reducing relapse rates will contribute significantly towards reducing smoking and its harmful effects.LVAL*p.Tobacco addiction is the leading preventable cause of cancer and cardiovascular diseases. Although the last two decades have witnessed accelerated efforts to develop effective smoking cessation strategies, the long-term success rates have been disappointing. The majority of smokers relapse within two weeks of a cessation attempt. Stress is one of the most commonly reported precipitants of smoking relapse. Mechanisms responsible for the stress-precipitated relapse are not known. Without specific knowledge of the stress-related psychobiological changes in smokers, targeted efforts to reduce smoking relapse will remain limited. The long-term goal of our research is to determine the psychobiological mechanisms responsible for smoking relapse. The specific goal of this project is to determine the extent to which changes in the pituitaryadrenocortical activity during early abstinence and in response to acute stress predict relapse in smokers attempting to quit. Our central hypothesis is that exaggerated adrenocorticotropic hormone (ACTH) and cortisol changes during early abstinence, as measured during ambulatory monitoring and in response to stress, predict time to relapse. This hypothesis is based on our previous studies and on the observation that psychosocial stressors increase the risk for smoking relapse. The proposed study will include ambulatory measurement of diurnal cortisol levels and awakening rise in cortisol during 24 hours while participants are still smoking at their normal rates (baseline), and during the period of 24-48 hours of abstinence. The study will also include measurement of plasma ACTH, cortisol, blood pressure, and withdrawal symptoms during two laboratory stress sessions (during ad libitum smoking and after 48 hours of abstinence). During each session participants will perform three stressful challenges (public speaking, math, and cold pressor). This research focuses on the hypothalamic-pituitary-adrenocortical axis, an important biological system recently implicated in addiction LVAL . The research integrates hormonal, hemodynamic, and psychological indices to determine stress response patterning among smokers during this critical period of a quit attempt, and uses this information in a prospective fashion to identify specific biobehavioral markers of relapse over a 12-month period. An important goal for this research is to determine differences in psychobiological changes between men and women, and establish the extent to which these differences predict relapse. The results will be important in the development of optimal diagnostic and intervention strategies for smokers interested in cessation and at high risk for relapse. Reducing relapse rates will contribute significantly towards decreasing tobacco use and its devastating effects.LVAL*p.In spite of the negative health effects of cigarette smoking, if current trends continue, smoking rates for women will surpass men by the year 2000. Studies show that women have a greater fear of weight gain after quitting, as well as, they tend to gain more weight to suggest gender specific cessation strategies are needed. Animal and clinical studies suggest that estrogen could decrease appetite behavior and minimize weight gain, as well as, affect mood and therefore could attenuate withdrawal symptoms. However, no study has systematically and comprehensively investigated the different effects of estrogen replacement therapy (ERT) in smoking cessation in postmenopause where the estrogen level is low. This renewal application will address this area in a randomized double blind nontreatment study conducted in 2 parts over 4 years. Part I investigates if there is a differential effect of ERT on appetitive behavior and withdrawal symptoms in postmenopausal women during short term smoking cessation, i.e., to decrease appetite behavior and minimize weight gain, and affect mood and attenuate withdrawal symptoms. Eligible subjects are randomized to smoking and non-smoking status, and enter a 3-week period of scheduled measurements. Week 1 is baseline with smoking ad lib, and in weeks 2 and 3 some subjects stop smoking while others continue smoking. During these 3 weeks weight, caloric intake, RMR and tobacco withdrawal symptom measurements will be done. Part II is also a short term nontreatment study investigating the additive effects of ERT on the same parameters in postmenopausal women on nicotine replacement. Subjects are randomized to ERT and placebo and monitored for 1 month, then randomized to placebo or active patch. The study design and measurements are identical to Part I. The results of this research will increase our understanding of the functional relationships between ERT and appetitive behavior and withdrawal symptoms in smoking cessation in postmenopausal women. This research will provide new xLVALinformation which will be important and useful in assessing direction for specific and more effective treatment strategies for smoking cessation in women during the postmenopausal years.LVAL*p.In spite of the negative health effects of cigarette smoking, if current trends continue, smoking rates for women will surpass men by the year 2000. Studies show that women have a greater fear of weight gain after quitting, as well as, they tend to gain more weight to suggest gender specific cessation strategies are needed. Animal and clinical studies suggest that estrogen could decrease appetite behavior and minimize weight gain, as well as, affect mood and therefore could attenuate withdrawal symptoms. However, no study has systematically and comprehensively investigated the different effects of estrogen replacement therapy (ERT) in smoking cessation in postmenopause where the estrogen level is low. This renewal application will address this area in a randomized double blind nontreatment study conducted in 2 parts over 4 years. Part I investigates if there is a differential effect of ERT on appetitive behavior and withdrawal symptoms in postmenopausal women during short term smoking cessation, i.e., to decrease appetite behavior and minimize weight gain, and affect mood and attenuate withdrawal symptoms. Eligible subjects are randomized to smoking and non-smoking status, and enter a 3-week period of scheduled measurements. Week 1 is baseline with smoking ad lib, and in weeks 2 and 3 some subjects stop smoking while others continue smoking. During these 3 weeks weight, caloric intake, RMR and tobacco withdrawal symptom measurements will be done. Part II is also a short term nontreatment study investigating the additive effects of ERT on the same parameters in postmenopausal women on nicotine replacement. Subjects are randomized to ERT and placebo and monitored for 1 month, then randomized to placebo or active patch. The study design and measurements are identical to Part I. The results of this research will increase our understanding of the functional relationships between ERT and appetitive behavior and withdrawal symptoms in smoking cessation in postmenopausal women. This research will provide new xLVALinformation which will be important and useful in assessing direction for specific and more effective treatment strategies for smoking cessation in women during the postmenopausal years.LVAL  DISEASE/BIOLOGY Cancer Mechanisms RESEARCH1 Animal Studies TOBACCO Non-Specified Tobacco UseDISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation COMMUNITY General Partnerships ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Support Group PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION African American TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesAGE Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesADDICTION Cessation Withdrawal AGE Adult Older Adult LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menopause Hormones Hormone Replacement Therapy MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesLVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long- term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors (gender, airways reactivity, weight gain, and co- morbidities) in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600.  ~ I / ;:`@`@Researchf@BAIREY MERZC. NOELCEDARS-SINAI MEDICAL CENTERLOS ANGELESCANHLBIR01, HL073108*p.Biology and CancerDiscovery 1b Evaluation 1b\@9/19/20038/31/20059/19/2003 to 8/31/20054/2005)!  |xkNE88,"g@p@4ResearchD@BAIRDDONNANIEHSRESEARCH TRIANGLE PARKNCNIEHSZ01, ES0490033*p.Biology and CancerDiscovery 1b Evaluation 1b>@Not GivenNot GivenUncertain4/2005 pieMF?88,"`~@b@ResearchL@BAILEYWILLIAMUNIVERSITY OF ALABAMA AT BIRMINGHAMBIRMINGHAMALNHLBIU10, HL059291@Biology and Cancer@@2/1/19981/31/20032/1/1998 to 1/31/20034/2005 ~znI@88,"g@@@Researchp@BAEZCONDE-GARBANATILOURDESUNIVERSITY OF SOUTHERN CALIFORNIA, KECK SCHOOL OF MEDICINELOS ANGELESCANCIP50, CA084735*p.@ @@Not Given2003? to 20034/2005 VM88,"M@@Research"MATERNAL LIFESTYLE STUDY PHASE 4BADAHENRIETTAUNIVERSITY OF TENNESSEE HEALTH SCIENCES CENTERMEMPHISTNNICHDU01, HD042638*p.Biology and Cancer@@8/19/20023/31/20068/19/2002 to 3/31/20064/200580 k`ZZ,"@@`a@Researchb@BABORTHOMASUNIVERSITY OF CONNECTICUT SCHOOL OF MEDICINEFARMINGTONCTNIDAR01, DA018949 @T@ Discovery 1c Discovery 34@9/20/20048/31/20089/20/2004 to 8/31/20084/2005uG?88," @R@Researchp@AUSTINS. BRYNBRIGHAM AND WOMEN'S HOSPITALBOSTON MANICHD1RO1HD045763-01A1*p.@ l@<@7/1/20044/30/20087/1/2004 to 4/30/20084/2005{tpgI@88,"L@@Researchz@ARNETTDONNAUNIVERSITY OF MINNESOTA TWIN CITIESMINNEAPOLISMNNHLBIR01, HL023727B*p.L@ T@b@5/1/19792/28/20045/1/1979 to 2/28/20044/2005}ylG@88,"g@^@ResearchL@ANTHONISENNICHOLASUNIVERSITY OF MANITOBAWINNIPEGMANITOBA, CANADANHLBIU10, HL0592926@|@ @D@Not Given2002? to 20024/2005pfND88," @@@Researchh@ANOKHINANDREYWASHINGTON UNIVERSITYST. LOUISMONIDAK01, DA000421*p.Biology and Cancer Addiction@@7/1/20016/30/20067/1/2001 to 6/30/20064/2005uok`IA88,"@:@ @Researchp@ANDREWSJEANNETTEUNIVERSITY OF S. CAROLINA-COLUMBIACOLUMBIASCNINRF31, NR008065*p.@@ @3/15/20023/14/20053/15/2002 to 3/14/20054/2005~zpLA88,"@{@Researchn@AMROSONECHRISTINEROSWELL PARK CANCER INSTITUTE CORP.BUFFALONYNCIR01, CA106815*p.Biology and Cancerl@ @4/15/20043/31/20094/15/2004 to 3/31/20094/2005 {rMB88,"`~@b@ResearchL@ ALTOSEMURRAYCASE WESTERN RESERVE UNIVERSITYCLEVELANDOHNHLBIU01, HL0592778@|@@ z@2/1/19981/31/20032/1/1998 to 1/31/20034/2005xtiH@88,"LVAL*p.We propose to conduct a case-series study in men and women with lung cancer, investigating molecular markers of susceptibility, biologically effective dose, and tumor tissue alterations. These markers will be evaluated in relation to exposure data on active and passive smoke exposure, occupational exposures and reproductive and hormonal factors, in order to elucidate reasons for the increase in lung cancer, particularly adenocarcinoma, in both smoking and non-smoking women. To optimize our capabilities to enroll nonsmokers with lung cancer, we will work with the Lung Committee investigators of the Southwest Oncology Group and collaborating members of the NCI lung intergroup to identify large numbers of patients with lung cancer, enrolling 120 never-smoking women with lung cancer and an equal number of males, as well as 200 each of ever smoking females and males. We have two primary hypotheses: that women are at higher risk due to susceptibility to tobacco-smoke carcinogens, based on metabolic variability. We propose that markers of the interactions of environmental and genetic risk factors for lung cancer (DNA adducts), as well as genetic alterations in tumor tissue (p53 and kras mutations), will reflect differences in exposures and susceptibility between men and women, smokers and non-smokers, and will elucidate the disproportionate variability in risk by gender and smoking status. Our second hypothesis is that steroid hormones, which appear to play a role in lung carcinogeneis, will have a greater effect in women than in men and in never smokers rather than smokers. We predict that tumor HER2 amplification and estrogen receptors will vary by gender and smoking status, particularly in relation to environmental and genetic (SNPs in carcinogen and steroid hormone metabolism pathways) risk factors. Biomarkers of exposure, susceptibility, and effect will be assayed in the blood and tumor tissue of these women men with lung cancer and evaluated in relation to questionnaire data to test the proposed hypoth(LVAL8eses. Results from this study, the largest to date to evaluate biomarkers of susceptibility and effect, will likely elucidate reasons for the rise in lung cancer, particularly adenocarcinomas, in smoking and non-smoking women.DLVAL*p.TTobacco use is strongly linked to coronary heart disease (CHD), the leading cause of death in women. African American women of lower socioeconomic status are known to have high smoking rates, disparities in smoking related diseases, and difficulty with cessation. Despite these inequities, sparse data exist describing effective interventions targeted to this population. Although not evaluated in African American women, research supports that intensive group tobacco cessation interventions produce the highest quit rates (24 - 48 percent) over self help (7 - 11 percent) and brief interventions (13 - 16 percent) with other populations. Social support and informal extended kin network, particularly with lay health advisors (LHA), are beneficial in targeted behavioral interventions to African American women for other risk reduction measures such as breast cancer screening; however this approach has not been effectively evaluated with tobacco cessation. With further exploration and knowledge, the investigator's goal is to develop and implement a nurse/LHA-managed smoking cessation intervention tentatively entitled, Sister To Sister: Helping Low-Income Women Quit Smoking. The proposed intervention will target mediating variables of social support, self-efficacy, and adaptive coping mechanisms utilizing an intensive group intervention managed by a nurse and LHA. A community advisory group consisting of informal and formal community leaders will be formed to assist with the recruitment and retention of LHAs. Community partnership(s) with businesses, health agencies, churches, and other organizations will provide a representative to the advisory group and resources such as physical space and incentives for LHA. A mid-range theory of self care behaviors in low-income African American women will be developed to provide a framework the study, and Prochaska's Transtheoretical Model of Change will be used to guide the development and implementation of the nurse/LHA intervention.LVAL*p.This Mentored Research Scientist Development award (KO1) resubmission requests 5 years of support for research and advanced research training on the genetic and biobehavioral etiology of substance use disorders, using nicotine addiction as a model system. Although a strong genetic contribution to smoking behavior has been well documented by recent studies, little is known about biobehavioral mechanisms that might mediate increased genetic risk. The overall goal of the proposed research is to identify electrophysiological trait markers of genetic susceptibility to nicotine addiction and to differentiate them from the long-term impact of smoking on brain function. This goal will be achieved through the integration of genetic and experimental psychophysiological methods. Epidemiological and behavioral research strongly implicates disinhibition (deficits of inhibitory selfregulation of behavior) as a potential mediator of susceptibility to smoking and other substance use behaviors. The proposed study will use an extended co-twin control design to delineate genetic and environmental causes of differences between smokers and nonsmokers on psychophysiological traits pertinent to disinhibition. Young adult MZ female twins and their siblings (total n=300) concordant and discordant for lifetime regular smoking will be recruited from an ongoing study of 3000 female twins and their parents. Assessments will include a diagnostic interview, questionnaires, and a battery of laboratory psychophysiological tests. The focus will be on electrophysiological traits theoretically and empirically linked to cognitive and behavioral disinhibition: ERPs elicited in classical oddball and Go-No Go tasks and prepulse inhibition of startle response (PPI). Specific aims are to identify genetically transmitted characteristics of CNS functioning indicative of increased vulnerability to nicotine addiction and to assess the long-term impact of smoking on brain function. Significantly elevated MZ compared to full sib correlations will l LVAL ead to a future ROI proposal to study DZ pairs, to confirm genetic etiology. It is expected that the proposed study will advance our understanding of biobehavioral mechanisms mediating vulnerability to nicotine addiction and provide useful end phenotypes for future genetic linkage or association studies of smoking and other substance use disorders. The training component will include supervised research, formal course work and tutorials in advanced methods of genetic analysis, and lab training in experimental psychopharmacology. The acquired expertise will allow the candidate to better integrate genetic and psychophysiological approaches in order to establish a program of interdisciplinary research in the neurobehavioral genetics of addiction.LVAL Z AGE Child EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National International PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionAGE Child DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN Parent/Mother MISCELLANEOUS Sex/Gender DifferencesAGE Young Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION Lesbian Gay Bisexual Transgender TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Child Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology LOCATION National International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesLVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular disease and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long-term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12 to 15-year period of following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors (gender, airways reactivity, weight gain, and co-morbidities) in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600.LVAL*p.Data from the most recent survey (1995-97) of the Minnesota Heart Survey (MHS) indicate that previously favorable trends in cardiovascular risk factor levels are attenuating. While cigarette smoking and self-reported dietary fat intake continued to decline, mean body weight rose substantially and rapidly, physical activity decreased, and the previous decline in serum total cholesterol was no longer apparent. These trends may or may not continue in the future. As part of the Minnesota Heart Survey, we propose to conduct another population survey of 4,000 adults, ages 25-84 years in 2000-02, to detect current trends in cardiovascular disease risk factors, including serum lipids, blood pressure, cigarette smoking prevalence, dietary fat intake, obesity, diabetes, physical inactivity, fibrinogen, and serum vitamin E. The proposed survey will build upon four previous, independent cross-sectional surveys conducted in 1980-82, 1985-87, 1990-92, and 1995-97, which collectively examined 23,000 adults in the metropolitan Minneapolis-St. Paul (2.3 million residents in 1990). Using a sampling strategy identical to that of prior surveys, households will be randomly selected by a two-stage cluster design. A wide range of risk factors for cardiovascular disease will be measured using previously employed methods. Cohort and ecological analyses will link secular trends in risk factors to morbidity and mortality from coronary heart disease, congestive heart failure, and stroke within the same population. To estimate risk factor levels in children and adolescents, 1,000 youth ages 8-17, offspring of selected adults, will also be recruited and examined using youth-specific measurement instruments where appropriate (e.g., physical activity and smoking). New methodological studies are proposed to understand trends in reported dietary intake which are irreconcilable with trends in body weight and serum cholesterol. New information will be collected on measures of leisure time physical inactivity and diet validation. Serial  LVAL ascertainment of risk factor levels in populations is crucial to understanding, predicting, and controlling population trends in cardiovascular disease. The Minnesota Heart Survey has been, and continues to offer, a powerful resource to examine long-term trends in cardiovascular disease risk factors.LVAL*p.Healthy People 2010, the nation's essential document for setting the national agenda for health, identifies the persistence of health disparities across communities to be among the leading health challenges of our era. Recent studies suggest that the health of the nation's adolescent population may be patterned in important ways by sexual orientation group disparities. Depressive symptoms and low self-esteem have been proposed as underlying vulnerabilities driving elevated rates of risk behaviors in sexual minority adolescents. Rosario et al. propose a psychosocial Coming Out Process (COP) Model for adolescents in which dimensions of the process are linked with health behaviors. Additionally, drawing on Bandura's Social Cognitive Theory (SCT), we propose that social norms in lesbian/bisexual female (LB) and gay/bisexual male (GB) communities also influence both positively and negatively health behaviors of sexual minority youth through processes of social learning. Family environment, an adolescent's age at the time of coming out, and presence or absence of preexisting psychosocial distress may be important factors influencing a young person's resiliency or risk and their experience with the coming out process. Research is needed to explore important predictors of the process of coming out and how this process relates to health behavior. We will examine sexual orientation in association with weight concerns, disordered weight control behaviors, binge eating, and tobacco and alcohol use in adolescent girls and boys in the Growing Up Today Study (GUTS), a longitudinal cohort study of 16,882 adolescents living across the U.S. In addition, we will examine factors that underlie the coming out process in adolescence, leading some to be more resilient while others have greater difficulties. Our specific aims are to compare the prevalence and severity over 4 years of follow-up of weight concerns and tobacco and alcohol use across sexual orientation groups among adolescent girls and boys and to empirically tes: LVALJ t the application of the COP Model and SCT to understand sexual orientation group disparities in health. We will examine prospectively the contribution of components of the COP Model and SCT in their relation to psychological distress and factors linked with LB and GB community social norms and orientation group differences in health outcomes.LVALThe six-year period between 18 and 24 years of age is critical in terms of the development of addictive behaviors. Marijuana use is particularly prevalent among young adults who smoke cigarettes, and there is reason to believe that the two behaviors should be approached concomitantly. This protocol describes a 4-year study that will investigate the effectiveness of two types of Brief Intervention (BI) for tobacco and marijuana use as linked to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), a new screening test developed by the World Health Organization. Following initial exposure to smoking cessation therapy, 300 young adult cigarette smokers who are also marijuana users will be randomized to three conditions: 1) a wait list control group; 2) a group receiving one session of brief intervention for their marijuana use; and 3) a group receiving the same one session of MET along with a referral to an additional two sessions of brief therapy. Participants will be reinterviewed at 2, 4 and 6 months post randomization. The specific aims of the study are to answer the following questions: 1) Does exposure to smoking cessation therapy reduce marijuana smoking? 2) Does a marijuana-specific BI reduce marijuana use following smoking cessation therapy? 3) Does the more intensive three-session intervention reduce marijuana use more than one session? And 4) Are these interventions equally effective across groups defined by gender and ethnicity? The long-term objectives of the study are to develop screening and brief intervention procedures that will be feasible and effective in primary health care settings for the young adult population.LVAL*p.Prenatal substance exposure continues to be a major public health problem that affects millions of children and places enormous financial and social burdens on society. The Maternal Lifestyle Study (MLS) is an interagency collaboration involving the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the Administration on Children, Youth and Families, and the Center for Substance Abuse Treatment. MLS is being conducted in four University sites: Miami, Tennessee at Memphis, Wayne State, and Brown; and it is the largest clinical prospective longitudinal study to date of prenatal drug exposure and child outcome. The follow-up cohort includes 658 exposed and 730 comparison children who have been studied through 7 years of age with 71% retention. This application is to continue the follow-up through age 11. One aim is to study the effects of prenatal cocaine/opiate exposure on immediate child outcomes that start in infancy (e.g. attention, relationship to parent, neuromotor, physiologic reactivity, arousal/regulation, and medical status) as well as latent effects on domains of function that emerge later and become salient as children reach school age (e.g. cognition, antisocial behavior, substance use onset, psychopathology, neuroendocrine function, and health disorders). This includes determining the effects of heavy cocaine exposure and controlling for exposure to other drugs (alcohol, marijuana, and tobacco), medical (e.g. physical growth) and environmental factors, gender, minority status, and study site. The second aim is to study a broader conceptualization of the consequences of maternal drug use that includes determining how drug effects, and the effects of the postnatal environment combine to affect child outcome, including specific aspects of the environment unique to the drug culture. As a major longitudinal study, MLS is important to the field of developmental science by contributing to our understanding of developmental processes in normal and at-ris LVALk children. MLS will also contribute to the field by addressing health indicators related to Healthy People 2010. Understanding the consequences of prenatal cocaine exposure and risky environments is crucial for treatment and public policy.LVAL*p.This developmental research project investigates the availability and use of social resources as communicators and reinforcers of smoking-related cultural normal and values among Hispanic youth at risk for smoking. Social resources include: social networks of adult family members and familial peers, the integration into those networks and the perceived support from these to experiment with tobacco products. Social resources are particularly important among Hispanics because they exercise an influence in deterring or promoting youth smoking. The study of these factors is particularly important for understanding some of the social sources of tobacco as well as cultural reasons behind the increases in Hispanic youth prevalence. This project will be conducted in three phases. Phase I will consist of eight focus groups (8) with 8-12 adolescent Hispanic smokers and non-smokers, ages 12-15. Sixty four to ninety six (64-96) U.S. born and foreign-born Hispanic youth from Central American (Nicaragua, El Salvador) and Mexico will be recruited through schools we are currently working with in the greater Los Angeles area. youth will discuss in Spanish, English or both, smoking-related cultural factors and the functional value of social resources in influencing youth smoking. Phase II consists of performing content and thematic analyses of focus group data and the development of a scale, the Hispanic Youth Cultural Protection Against Smoking Survey (HYCPASS) that assesses the existence and functional value of culturally-based protective factors and social resources in preventing Hispanic adolescents from engaging in smoking. Based on focus group data, items will also be developed for the Multiethnic Cultural Values Scale proposed in another TTURC project. The HYCPASS will be transplanted using an anthropological method called "decentering", by which the survey is translated and back translated favoring the agreement in cultural meaning and context rather than language equivalency, and the proper use of youth-based * LVAL: Spanish idiomatic expressions easily understood by Mexican and Central American adolescents. They survey will be pre-tested in a sample of 16 adolescents to ensure cultural significance and concordance with the theoretical framework. In Phase III, the survey will be administered to a sample of 40 Hispanic youth smokers and non-smokers to assess their endorsement of those social resources, norms and values that protect youth from smoking. Within group analyses will be made focusing on levels of acculturation, age, gender, number of years in the U.S., and national origin. Findings will form the basis for the submission of large scale studies and will be disseminated for program planning purposes through the Hispanic/Latino Tobacco Education Network, a California- based network of over 700 researchers, providers and tobacco control advocates housed at USC.LVAL H ZDISEASE/BIOLOGY Cardiovascular/Pulmonary RESEARCH1 Animal Studies TOBACCO Environmental Tobacco Smoke WOMEN Menopause Hormone Replacement TherapyAGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Hispanic TOBACCO Cigarette/Other Smoking WOMEN Hormones Hormone Replacement Therapy MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesADDICTION Cessation Withdrawal DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Buproprion Nicotine Replacement Therapy Other Pharmacological PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies Clinical Research STUDY POPULATION African American TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Hormones Hormone Replacement Therapy MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use WOMEN Pregnancy Menstral Cycle MISCELLANEOUS Weight Gain/ExerciseAGE Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesLVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A lung function test 11 to 12 years after entry into the LHS is also proposed to determine long-term effects of smoking cessation on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airways, reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600.LVAL*p.Most people take their ability to reproduce for granted, but when couples can't have a baby they want, it can be devastating. Fecundability, defined as the per cycle probability of conceiving, involves a series of complex biological processes in both male and female partners. Environmental factors that interfere with any of these can result in reproductive failure in any given menstrual cycle. Identifying such factors has become an active area of research internationally, and the biological processes involved are studied both clinically and as subjects of basic research. I am particularly interested in using time-to-pregnancy data to evaluate fecundability, and in the biological processes involved in achieving a viable pregnancy. I contribute to the field through consulting, collaborations, reviews, commentaries, and continuing analysis of data from the North Carolina Early Pregnancy Study. The aim of this project is to learn more about environmental effects on fertility by developing methods for studying fertility in human populations, and analyzing data that describe aspects of human fertility and factors affecting it. Assessing human fertility. For identifying the day of ovulation, we proposed a semi-parametric mixture model that uses multiple independent markers of ovulation to account for measurement error. The model assigns each method of assessing ovulation a distinct non-parametric error distribution, and corrects bias in estimates of day-specific fecundability. We used a Monte Carlo EM algorithm for joint estimation of (i) the error distribution for the markers, (ii) the error-corrected fertility parameters, and (iii) the couple-specific random effects. We appied the methods to data from a North Carolina fertility study to assess the magnitude of error in measures of ovulation based on urinary luteinizing hormone and metabolites of ovarian hormones, and estimated the corrected day-specific probabilities of clinical pregnancy. Menopause status. We assessed associations with menopausal status bLVALased on either menstrual cycle or elevated (more than 20+ IU/L) FSH. Higher body mass index was associated with a lower likelihood of elevated FSH, but not with menstrual-based menopause. Exercise (3 times per week) was associated with a lower likelihood of being postmenopausal. Alcohol use also tended to be moderately associated with postmenopausal status by either measure. There was little evidence of associations with ethnicity, education, age at menarche, number of live births, and oral contraceptive use. Menstrual-based definitions of menopause can be misclassified for women with menstrual irregularity. Conception. Emergency post-coital contraceptives effectively reduce the risk of pregnancy, but their degree of efficacy depends on the pregnancy rate without treatment, which cannot be measured directly. We provided indirect estimates of such pregnancy rates. We estimated the probability of pregnancy relative to intercourse on a given cycle day. We found that the possibility of late ovulation produces a persistent risk of pregnancy even into the sixth week of the cycle. Post-coital contraceptives may be indicated even when intercourse has occurred late in the cycle. Pregnancy Testing. We estimated the maximum screening sensitivity of pregnancy tests when used on the first day of the expected period, taking into account the natural variability of ovulation and implantation. We conducted a community-based prospective cohort study of women who were planning to conceive. Main outcome measures were day of implantation, defined by the serial assay of first morning urine samples using an extremely sensitive immunoradiometric assay for hCG, relative to the first day of the missed period, based on self-reported usual cycle length. Data were available for 136 clinical pregnancies conceived during the study, 14 (10%) of which had not yet implanted by the first day of the missed period. The highest possible screening sensitivity for an hCG-based pregnancy test therefore is estimated to be 90% on the first dayLVAL of the missed period. By 1 week after the first day of the missed period, the highest possible screening sensitivity is estimated to be 97%. In this study, using an extremely sensitive assay for hCG, 10% of clinical pregnancies were undetectable on the first day of missed menses. In practice, an even larger percentage of clinical pregnancies may be undetected by current test kits on this day, given their reported assay properties and other practical limitations. Onset of symptoms of pregnancy. 221 women attempting pregnancy made daily records of the presence or absence of symptoms of pregnancy during cycles of attempting pregnancy and during the 8 weeks following the LMP. Among 136 women delivering live infants, 89% had onset of symptoms by the end of the 8th week (median day 36). Women who smoked tobacco or marijuana, or who had clinical miscarriages had later onset of symptoms. Among 48 who lost their pregnancies before 6 weeks LMP, 21% reported symptom onset. Nearly 90% of women with successful pregnancies experience symptoms within 8 weeks LMP. Very early losses (before 6 weeks) are unlikely to be confirmed clinically, but they are sometimes recognized as symptomatic by women themselves. Age and fertility. Most analyses of age-related changes in fertility cannot separate effects due to reduced frequency of sexual intercourse v. those related to ageing. Information on intercourse collected daily through each menstrual cycle provides the data for estimating day-specific probabilities of pregnancy for specific days relative to ovulation, and these estimates allow unconfounded analysis of ageing effects. 782 healthy couples using natural family planning methods contributed prospective data on 5 860 menstrual cycles. Day of ovulation was based on basal body temperature measurements. Estimates of day-specific probabilities of pregnancy and the length of the fertile window were compared across age groups. Nearly all pregnancies occurred within a 6 day fertile window. There was no evidence for a shorter  LVAL fertile window in older men or women. On average, the day-specific probabilities of pregnancy declined with age for women from the late 20s onward. Controlling for age of the woman, fertility was significantly reduced for men aged 35+ years. Women's fertility begins to decline in the late 20s with substantial decreases by the late 30s. Fertility for men is less affected by age, but shows significant decline by the late 30s.LVAL*p.Cardiovascular disease is the leading killer of women, yet prior research has failed to provide any clear understanding of the gender gap wherein women appear to be relatively protected from CVD while premenopausal, compared to men. Recent randomized trials of hormone replacement therapy (HRT), described below, have failed to demonstrate CVD benefit, and call into question the "estrogen protection" hypothesis. Alternative explanations for the gender gap, e.g., androgen exposure, have not been explored. This application, developed in response to the NHLBI's Innovative Research Grant Program Request for Application HL-01-016 and using existing data sets and biological specimens, is designed to support collaborative feasibility research in an innovative and high impact area relevant to CVD in women. The overall aim of this application is to use the existing data and stored blood samples from the NHLBI-sponsored Los Angeles Atherosclerosis Study (LAAS, HL-490-10) to explore new and innovative hypotheses with regard to reproductive hormones and progression of pre-clinical cardiovascular disease (CVD), measured by carotid intima-media thickness (IMT), in the 269 women (45% minority) in the Los Angeles Atherosclerosis Study (LAAS), an ongoing NHLBI-sponsored study of employed utility workers in Southern California without CVD at study entry. Hormonal assays will be performed on stored samples by a NHLBI Reproductive Hormone Core Laboratory, and subsequent analyses will characterize relationships to carotid IMT measured by the LAAS Ultrasound Core Laboratory. The following hypotheses will be test ed: 1) Reproductive hormonal profiles characterized by a relative estrogen deficiency and/or relative androgen excess will be directly correlated with increased baseline carotid IMT and predict greater carotid IMT progression over time in women; 2) Reproductive hormone effects on carotid IMT progression will be observed dominantly in situations of intimal injury, e.g. cigarette smoking, hypercholesterolemia, hyperten& LVAL6 sion or diabetes in women. Innovative aspects of this application include evaluation of reproductive hormones repeatedly and prospectively in women across the spectrum of menopause (pre-, peri- and post-) using innovative methodologies including the sensitive reproductive hormonal assays used in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) core laboratory, and a newer quantitative carotid intimal media thickness (carotid IMT) protocol from the NHLBI-sponsored LAAS. The current application represents an opportunity to gain feasibility pilot data in the area of the role of reproductive hormones and CVD in women using novel measures and a collaborative approach in order to plan further investigation, if warranted.LVAL*p.There are multiple efficacious pharmacotherapies for tobacco dependence, yet we still do not know: which medications work best, how best to match individuals to medications, how to combine medications, and how medications achieve their effects. These knowledge gaps are due, in part, to a lack of head-to-head comparisons of pharmacotherapies, including newer pharmacotherapies (e.g., the nicotine lozenge) and combinations of pharmacotherapies. In addition, clinicians and smokers have no scientifically based algorithms to guide the use of these medications because of the limited knowledge about which medications are most efficacious in particular populations of smokers. Also lacking are data that reveal how pharmacotherapies work, making it difficult to develop new pharmacotherapies on a rational basis. Participants (n = 1,520) will be randomly assigned to one of five medication conditions: nicotine patch, nicotine lozenge, bupropion, nicotine patch + nicotine lozenge, and bupropion + nicotine lozenge (n= 264/condition) and a placebo control condition (n=200). An extensive set of assessments will be collected from participants including: genotypes, personality, psychiatric symptoms and diagnoses, physiologic and medical status, diet, alcohol use/abuse, social relations, quality of life, exercise, smoking, withdrawal symptoms, stress, and nicotine dependence. These constructs will be assessed using psychometrically sound questionnaires, structured interviews, physical tests, and ecological momentary assessment (EMA). Assessments wilt serve three vital purposes: 1) to measure treatment outcomes (e.g., abstinence, withdrawal symptoms, weight gain); 2) to develop treatment matching algorithms based on individual differences (e.g., gender, level of dependence); and 3) to assess mechanisms of treatment effects (e.g., withdrawal suppression), tn sum, Project I will produce the best evidence to date on relative efficacies and mechanisms of action of cessation pharmacotherapies, and will provide algorithms to guiLVALde medication use.6  R  ]N^''g@p@4Researchl@BENOWITZNEALUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCANCRRM01, RR000083@Biology and CancerP@@Not GivenNot GivenUncertain4/2005sHB88,"&&m@@Researcht@BENNETTWILLIAMBECKMAN RESEARCH INSTITUTECITY OF HOPECANCIR21, CA098827@Biology and CancerP@l@5/1/20034/30/20055/1/2003 to 4/30/20054/2005}xtfJA88,"%%g@p@4ResearchJ@"BELLDOUGLASNot GivenNot GivenN/ANIEHSZ01, ES046008J @Biology and CancerDiscovery 1b Evaluation 1b`@Not GivenNot GivenUncertain4/2005xib]RG>88,"$$@@u@Researchz@!BECKERDAVIDUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP9RT-0142*p.Biology and CancerDiscovery 1a Discovery 3@7/1/20006/30/20037/1/2000 to 6/30/20034/2005*"  rG@88,"##@@Research@ BECKERBRUCERHODE ISLAND HOSPITALPROVIDENCERIRWJF40671@@V@@ 10/1/20003/31/200410/1/2000 to 3/31/20044/2005{tnj^G@88,"""@@$@Researcht@BEALSJANETTEUNIVERSITY OF COLORADO HEALTH SCIENCES CENTERAURORACONIDAR01, DA017803*p. Addiction@@ 5/1/20044/30/20075/1/2004 to 4/30/20074/2005wH?88,"!! S@4@ResearchH@BAUMANDREWUNIVERSITY OF PITTSBURGHPITTSBURGHPANIDAR01, DA010887*p.Biology and Cancer@@ 2/20/19971/31/20022/20/1997 to 1/31/20024/2005vpl`F>88," ` @@@ResearchTASTE PSYCHOPHYSICSBARTOSHUKLINDAYALE UNIVERSITYNEW HAVENCTNIDCDR01, DC000283 *p.Biology and CancerP@@ 12/1/19896/30/200912/1/1989 to 6/30/20094/2005{p_XMM,"@@ResearchV@BARNESGRACESTATE UNIV. OF NEW YORK AT BUFFALOBUFFALONYNIDAR21, DA013570 *p.L@@@ 9/30/20008/31/20049/30/2000 to 8/31/20044/2005~xtkG@88,"@@Researchp@BARBOURSUZANNEVIRGINIA COMMONWEALTH UNIVERSITYRICHMONDVANIDCRU19, DE13102*p.Biology and CancerP@@ 7/1/20006/30/20047/1/2000 to 6/30/20044/2005zvlJA88,"@@Research~@BANKACAROLELA JOLLA INSTITUTE FOR MOLECULAR MEDICINELA JOLLACACTRDRP7RT-0101A*p.Biology and CancerP@Z@9/15/20006/30/20019/15/2000 to 6/30/20014/2005 |rG?88,"{@]@Researchh@BANDERAELISAUNIVERSITY OF MEDICINE AND DENTISTRY-RW JOHNSON MED. SCHOOLPISCATAWAYNJNCIK07, CA095666V*p.Biology and CancerP@<@8/22/20037/31/20088/22/2003 to 7/31/20084/2005#HA88," @@ResearchV@BAKERTIMOTHYUNIVERSITY OF WISCONSIN AT MADISONMADISONWINIDAP50, DA019706 *p.@@@9/30/19998/31/20099/30/1999 to 8/31/20094/2005yulH?88,"LVAL*p.This is an Academic Career Award application to support a training and research program for Dr. Elisa V. Bandera, an Associate Research Scientist in the Department of Nutritional Sciences, Rutgers University. The goals of this program are: 1) to complement her previous training in medicine and epidemiology by providing a strong theoretical foundation in nutrition, nutritional epidemiology, molecular epidemiology, and cancer epidemiology; and, 2) to apply this theoretical training in a case-control study of endometrial cancer. The proposed educational plan includes mentoring, structured courses, seminars, conferences, and guided readings. A highly qualified team of experts in the relevant areas will mentor the candidate through these activities and help her achieve her goals. The research proposed in this application builds upon a five-year population-based case-control study (Dr. Sara OIson, PI; R01CA83918), with a funding start date of July 1, 2001. The case-control study that provides the context for the proposed research includes 600 cases with endometrioid tumors, 200 with serous or clear cell tumors, and 600 controls. The cases will be women older than 21 years, residents of six counties in New Jersey, with newly diagnosed, histologically confirmed epithelial endometrial cancer. The controls will be frequency matched to the cases (+5years) and selected by random digit dialing (for those under 65) or from HCFA files (for those older than 65 years). The proposed project expands the objectives of the parent grant, whose main goals are to evaluate the role of estrogens, genetics, and dietary fat. The specific aims of the proposed project are to investigate the association between phytoestrogen and alcohol consumption and endometrial cancer risk. Possible effect modification by body mass index, estrogen replacement therapy, fat and total energy intake, smoking, genotypes for enzymes involved in estrogen metabolism, and histologic type will be investigated. Interactions between alcohol and phytoestroge~ LVAL n intakes will also be examined. An additional component of the proposed research is a feasibility study to evaluate an innovative multi-media web-based dietary assessment method, the Computer-Assisted Self-Interview Diet History, in the context of the case-control study of endometrial cancer. This award will provide the support and training the Candidate needs to develop an independent career in the nutritional epidemiology of cancer.LVAL*p.When women reach menopause, their risk for heart disease increases, in part, because of the aging process and, in part, because their ovaries no longer make estrogen and progesterone. Estrogen is known to reduce cardiovascular risk significantly. Cigarette smoking constitutes a third significant risk factor in postmenopausal women and environmental tobacco smoke (ETS) also contributes to cardiovascular risk in "passive" smokers. Therefore, it appears that the lack of ovarian hormones associated with menopause and exposure to cigarette smoke (passive or active) constitute the two most important risk factors for heart disease in otherwise healthy women. Hormone replacement therapy (HRT), the replacement of estrogen (or estrogen and progesterone) through medication, reduces the risk of heart disease by as much as 50% in postmenopausal women. Yet physicians are hesitant to prescribe HRT for women smokers, due to the historical (albeit rare) occurrence of blood clotting (and the resulting risk of blood vessel occlusion and/or stroke) in women who smoke and take contraceptive pills that contain estrogen. However, the risk of clotting associated with HRT is minimal and increases only slightly in HRT-treated women who smoke. Although the ideal approach to management of heart disease risk in postmenopausal women would include smoking cessation, for those women who chose to continue smoking, or who live in a situation associated with exposure to environmental tobacco smoke, HRT may be an especially important intervention. It is my goal to develop a small animal model for the first rigorous studies of the interactions between environmental tobacco smoke, postmenopausal status and hormone replacement therapy as they relate to heart disease. To this end, I have designed this proposal to accomplish the following specific aims: Aim #1 To test the hypothesis that exposure to environmental tobacco smoke (ETS) will accelerate artery disease in normal mice and to a greater extent, in mice whose ovaries have been4 LVALD removed (postmenopausal mice). Aim #2: To test the hypothesis that estrogen, and estrogen + progesterone, will partially reverse the acceleration in artery plaque formation resulting from removal of the ovaries and from ETS exposure. Aim #3: To test the hypothesis that factors involved in ETS-induced acceleration of artery disease include oxidant stress in addition to increases in cholesterol levels, and that cholesterol levels and oxidant stress are reduced as a result of HRT. The successful completion of these aims will yield valuable information concerning 1) the extent and mechanisms of ETS-mediated acceleration of arterial disease; 2) the additive effects of ETS and postmenopausal status on risk of heart disease; 3) the mechanisms underlying protective effects of estrogens; and 4) the interactions of ETS and hormone replacement therapy.LVAL*p.Project 4: PAF acetyhydrolase in localized juvenile periodontitis. Localized Juvenile Periodontitis (LJP) has a circumpurbertal onset and is characterized by severe destruction of the periodontal tissues surrounding the first molars and incisors. Although LJP has some of the clinical characterization of other periodontal diseases, it is clearly unique in terms of its mechanisms of pathogenesis and inheritance patterns. Among the immunological anomalies associated with LJP are the elevated levels of IgG 2 that are commonly found in the sera of LJP patients. Recent experiments suggest that IgG2 production is regulated by macrophage- derived lipid cytokines. Platelet activating factor (PAF), in particular stimulates IgG2 production, but has minimal effects on other isotypes of IgG. Preliminary data suggest that mononuclear cells from LJP patients express lower levels of PAF acetylhydrolase (PAF-AH), the enzyme that catabolizes PAF, then cells from periodontally healthy subjects. The decrease in PAF-AH activity could increase the availability of PAF and thereby stimulate IgG2 production in LJP patients. Hence, the goal of this research effort is elucidate the role of PAF-AH in the regulation of IgG2 production in LJP patients. Hence, the goal of this research effort is elucidate the role of PAF-AH in the regulation of IgG2 production in LJP patients. Experiments will be performed to determine whether mononuclear cells from LJP patients secrete less PAF-AH than cells from periodontally health subjects and if this enzyme is a negative regulator of IgG2 production. As preliminary studies indicate that mononuclear cells from LJP patients are predisposed to differentiate into dendritic cells, experiments will be performed to determine if dendritic cells express less PAF-AH than macrophages. Several lines of evidence indicate that both LJP and PAF-AH levels are heritable. Therefore, PAF-AH levels will be measured in the sera of LJP probands and their family members to determine if PAF-AH correlates with the inc LVAL$ idence of the disease. Some cigarette smokers exhibit lower levels of serum IgG2 than non-smokers. This effect varies with the race and periodontal health status of the subject. Preliminary experiments indicate that there are higher levels of PAF-AH in the plasma of smokers than in non-smokers. Therefore, experiments will be performed to determine if PAF-AH is related to the reduction in serum IgG2 that is observed in cigarette smokers. Together, these studies should elucidate the role of PAF-AH in the regulation of IgG2 production. In addition, these experiments may yield insights into the genetic mature of LJP.*LVALRZ  DADDICTION Cessation Relapse COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy RESEARCH Human Studies STUDY POPULATION African American American Indian/Alaskan Native Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother Partner/SpouseLOCATION Rural National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION American Indian/Alaskan Native TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesADDICTION Cessation DISEASE/BIOLOGY Other Disease/Biology LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Child EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesAGE Child DISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesLVAL*p. Recent research findings have shown strong associations between participation in sports and reduced sexual risk-taking, especially among adolescent girls. The present R21 application will extend this research to explore the effects of sports and other extracurricular activities on substance use and other risky behaviors among female and male adolescents. Cost-effective, secondary data analysis is proposed using two large data sets. The Family and Adolescent Study, a six-year longitudinal study of Western New York adolescents and their families (N=699), includes self-report data on alcohol, tobacco, marijuana and other substance use, sexual activity, and a variety of delinquent behaviors, as well as questions regarding recent participation in extracurricular activities. The 1997 school-based Youth Risk Behavior Survey (YRBS), generated by the Centers for Disease Control and Prevention, is a nationally representative cross-sectional survey of priority health-risk behaviors in American high school students (N=l 6,262). The YRBS includes data on tobacco, alcohol, marijuana, steroids, and other illicit drug use, sexual activity, and behaviors resulting in unintentional and intentional injuries (e.g., drunk driving, fighting, weapons carrying), as well as questions on athletic participation. Both sources of data oversample racial/ethnic minority populations, facilitating race-specific analysis. Specific aims of the study include determination of the nature of the relationships between sports and other specific extracurricular activities and substance use and other risky adolescent behaviors. Gender and racial/ethnic differences in these relationships will be determined. This research will also serve as a basis for the development of a theory- driven R01 proposal examining factors associated with gender-specific sports participation and substance use. This research has the overall aim of establishing more effective prevention and intervention strategies for reducing adolescent substance use and other relatedLVAL risk behaviors.LVAL*p. The long-term goal of this research is to understand the influence of genetic and pathological variation in oral sensations on health and quality of life. Taste, oral burn (e.g., alcohol) and oral tactile intensity (e.g., fats) show broad genetic variation, which is linked to intake behaviors for bitter and sweet-fat foods, alcohol, and tobacco. These behaviors influence health risks for cancer and cardiovascular disease, but different risks arise for different individuals. For example, supertasters, who experience intense bitter taste from 6-npropylthiouracil (PROP), avoid bitter vegetables containing protective phytochemicals, which increases risk for certain cancers (e.g., breast, colon). On the other hand, supertasters avoid alcohol and tobacco due to their bitterness and oral burn, thereby reducing risk for craniofacial tumors. Taste input inhibits oral pain and oral tactile inputs centrally, ensuring intake during localized oral injury. However, this feedback comes at a cost, as pathology can alter oral sensation via disinhibition. Taste loss causes oral burn and oral tactile sensations to rise, and it may alter food and other behaviors (e.g., smoking, alcohol use). Some supertasters also experience phantom sensations (e.g., burning mouth syndrome); women are at special risk because they are more likely to be supertasters than are men. Recent findings suggest that taste damage compromises retronasal olfaction, altering flavor perception and food choice in ways that may promote fat intake (e.g., chronic ear infections in supertasting men). Experiments using oral anesthesia will further our knowledge of these mechanisms. Our research focuses on psychophysical comparisons of oral sensation between individuals and groups. Conventional intensity scales often distort these relationships, but our new methodology enables accurate group comparisons of sensory intensity. Recent isolation of a putative PROP taste receptor gene further extends our ability to dissociate genes from pathology. In sum, we are n&LVAL6ow equipped to uncover the full range of oral sensory variation and its effects on diet and health.LVAL*p.There is considerable evidence that behavioral factors such as smoking, drug-taking and psychological stress have an important impact on the risk of cardiovascular and immune-related diseases, including infectious and neoplastic disorders. Recent findings also suggest that these factors can promote viral infections and accelerate the development of some AlDS-related infections in HIV seropositive individuals. Given the potential health impact of these risk factors in both normal and at-risk (e.g., HIV positive) populations, there is need for more basic research on the mechanisms mediating their cardiovascular and immune actions. Moreover, these factors rarely occur individually outside of the laboratory, and a more realistic laboratory model should include their convergent, in addition to their isolated effects. Finally, considerably more research has been devoted to the effects of these variables in men and more information is needed on their consequences in women. Our research team has had considerable experience in studying the endocrine, cardiovascular and immunological effects of smoking and stress in men and women and the endocrine and immunological effects of nicotine in laboratory animals. On the basis of our research, and the findings of others, we propose that smoking and stress are convergent risk factors for cardiovascular and immune-related disease and that their convergent effects may be mediated by acute activation of the sympathetic nervous system. We now propose to extend our research to study the convergent effects in women of two of these factors, psychological stress and smoking. Specifically, we will determine: 1) how the effects of smoking and acute stress on the immune and sympathetic nervous systems converge in women and 2) how the convergent effects of smoking and stress in women are altered by smoking cessation. The first goal will be achieved by comparing the effects of acute laboratory stress on smokers, with and without concurrent smoking, to the effects of stress in non-s LVALmokers. The second will be approached by using an already planned and funded smoking treatment program to assess baseline and stress-induced changes in the function of the SNS and immune systems which accompany cessation of smoking in women.LVAL*p.American Indian (AI) reservation populations face numerous chronic stressors. Poverty, unemployment, violence, and accidents are all common, and it has been argued that the combination of historical trauma, inconsistent and disruptive governmental policies, and mandated boarding schools, have rendered many in current reservation populations especially vulnerable to both the impact of everyday chronic stressors, to substance misuse, and to PTSD. Drug use has also been documented among AIs, with AI youth often reporting greater use of drugs and tobacco than many others in the U.S. Only recently have data about the prevalence of drug disorders become available; such data suggest drug disorder rates that are comparable to other populations, but with age trends reflecting that AI youth are at increased risk for lifetime use of both drugs and tobacco compared to their elders suggesting an upward trend in drug disorders among AIs. Thus, the focus of the proposed research on the relationship between chronic stressors and drug use and disorders in this population is particularly timely. The data from the American Indian Service Utilization, Psychiatric Epidemiology; Risk and Protective Factors Project (AI-SUPERPFP) provide a unique opportunity for an epidemiological investigation of stress and drug disorders in an understudied population with a comprehensive assessment of chronic stressors (historical traumas, family history, childhood stressors, traumatic events, chronic strains, frequent lifetime events, and macro level stressors) in combination with standard measures of use and disorder for 9 drugs. The following specific aims guide this work: 1) To characterize and estimate the epidemiology of chronic stressors in these 2 reservation populations; 2) To understand and describe the relationships between chronic stressors, drug use, and DSM-defined drug abuse and dependence in these populations; 3) To investigate and portray the relationships between chronic stressors, drug use and disorders, and co-occurring LVAL problems including PTSD, other DSM-defined problems (depressive, anxiety, and alcohol disorders), and violence and antisocial behavior. Within each specific aim, the role of important demographic correlates (e.g., gender, tribe, SES, and age) and personal resources (coping, self-esteem, external locus of control, social support, spirituality, ethnic identity, and treatment history) will be investigated. The American Indian and Alaska Native Programs (AIANP) provide a distinctive multidisciplinary environment in which to conduct this work. The proposed work promises to provide the most comprehensive and focused investigation to date of chronic stressors within Al populations and of the relationship of various stressors with drug use and disorder.LVAL Z J v  f T  F @J &Discovery 1a Discovery 2a Discovery 3 Development 5 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1c Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1c Discovery 2a Discovery 2b Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 1c Discovery 3 Development 1 Evaluation 1bDiscovery 1c Discovery 2a Development 3 Delivery 1 Evaluation 1aDiscovery 1c Discovery 2a Development 3 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1b Discovery 1c Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 1c Discovery 2a Discovery 3 Evaluation 1bDiscovery 1b Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1c Discovery 3 Development 2 Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1c Development 1 Development 3Discovery 1b Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1b Discovery 1c Discovery 3 Development 2 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Development 1 Development 3 Delivery 2 Partnerships 3 Evaluation 1aDiscovery 1c Development 1 Delivery 1 Delivery 2Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDevelopment 1 Development 4 Delivery 1 Partnerships 1Discovery 1b Discovery 3 Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1aDiscovery 1b Discovery 3 Evaluation 1bDevelopment 1 Development 2 Evaluation 1aLVAL Human genetic polymorphisms in metabolic activation and detoxification pathways are a major source of inter-individual variation in susceptibility to environmentally induced disease. The group has developed genotyping assays for the "at-risk" variants of enzymes that protect against carcinogens in cigarette smoke, diet, industrial processes and environmental pollution. Following genotyping of over 15,000 individuals for these candidate susceptibility genes, it has been found that the frequency of the at-risk genotypes for glutathione transferase M1 (GSTM1), theta 1 (GSTT1), Pi (GSTP1) and N-acetyltransferase (NAT1 and NAT2), XRCC1, XPD, vary significantly between Asians, European- and African-Americans. This suggests that some of the ethnic differences in cancer incidence may be due to genetic metabolic differences as well as exposure differences. Mission: Our long-term goal is to understanding how genes and environment interact to influence risk of environmentally induced disease. To this end we are engaged in "Environmental Genomics." This encompasses: 1) identification of candidate environmental response genes, 2) discovery and functional characterization of genetic and phenotypic variation in these genes, and; 3) the analysis in population studies of environmental disease susceptibility associated with functional polymorphisms, acquired susceptibility factors and exposures; and the interactions between these factors. The major goals of this project are to define the natural history of smoking and smoking cessation for mothers and other household members of babies being treated in the Special Care Nursery and to test a smoking cessation intervention in this milieu.LVAL*p.Nicotine addiction is a powerful process that is not well understood. The ability of nicotine to reduce pain and discomfort has been proposed as a mechanism underlying smoking addiction. The majority of human studies have found pain-reducing effects, while others, especially those using women subjects, have not. Furthermore, a recent study found that nicotine reduced pain for men, but not women. These findings suggest an important gender difference in the mechanisms of smoking that lead to addiction. We will use state-of-the-art techniques for assessing pain and pain-reduction to test for the reality and magnitude of nicotine's pain-reducing effects in both smokers and nonsmokers; their possible dependence on gender; and their possible dependence on menstrual cycle phase in women. These techniques will include the use of an objective, neurophysiological measure of pain. Measures of the electrical activity of the brain that can be recorded with electrodes placed on the head have been shown to be sensitive to a number of different pain-reducing treatments. We have developed a measure that can differentiate pain from other, non-pain aspects of sensory processing. In addition, we will assess pain-reduction from nicotine with three other pain measures: the amount of painful electrical current needed to produce a just painful sensation; the amount of heat needed to produce a just painful sensation; and subject's ratings of the painfulness of electrical pulses across a range of pain intensities. Nicotine will be administered using a computer controlled intravenous infusion to produce and maintain stable target blood levels of nicotine. This will allow us to exert precise control over nicotine levels in both smokers and nonsmokers. In contrast to other methods of providing nicotine that involve multiple, small amounts of drug and rapidly changing blood levels (smoking, nasal spray) or more slowly changing blood levels (skin patch, gum), computer controlled infusions will provide the stable blood co,LVAL<ncentrations necessary for the approximately 45 minute set of tests of pain-reduction. Each subject will participate in two infusion sessions: one for nicotine and one for a non-active substance. Each session will include two sets of pain measures: a pre-drug baseline set and a drug infusion set. Procedures will be identical in each set. Specifically, we hypothesize that, using a procedure where neither the subject nor the technician running the session knows whether the drug given is nicotine or a non-active substance, intravenous nicotine will provide more pain reduction for men than for women. We will test this hypothesis separately in groups of 60 smokers and 60 nonsmokers. Furthermore, we will relate the degree of pain-reduction produced in each smoking subject to his or her own patterns of smoking behavior (using the Smoking Occasions Questionnaire) in order to evaluate whether the pain-reduction effect is associated with the use of smoking to relieve physical and emotional discomfort. In a second study, 20 women subjects will participate in nicotine sessions during each of three different phases of the menstrual cycle. We hypothesize that the pain-reducing effects of nicotine will vary across the menstrual cycle.LVALj HRCOMMUNITY Health Care Provider ECONOMICS Medicaid/Medicare Cost of Intervention/Prevention LOCATION National POLICY Guidelines/Best Practices PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN PregnancyDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology RESEARCH In Vitro Studies TOBACCO Environmental Tobacco Smoke WOMEN HormonesDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology RESEARCH Human Studies Clinical Research TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology RESEARCH Human Studies Clinical Research TOBACCO Nicotine WOMEN PregnancyDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION Caucasian TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Small (< 100) Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle MISCELLANEOUS Sex/Gender DifferencesLVALBackground. Carcinogens leave their "signatures" in tumors in the form of characteristic genetic damage. One of the best examples is a molecular "signature" of tobacco smoke in the p53 tumor suppressor gene from lung cancers. Although highly specific, this imprimatur occurs in less than 20% of tumors, so a more common marker is needed. A recent report showed that allelic deletion occurs more often in lung cancers from smokers than nonsmokers, that the distribution of damage differs in these groups, and that statistically meaningful differences could be discerned in studies of modest size. If confirmed and extended, this approach might define a useful genetic marker for tobacco carcinogens as well as a new tool for investigating cancer etiology.Principal Hypothesis. Carcinogens in tobacco smoke cause recognizable patterns of allelic deletion at characteristic chromosomal locations.Specific Aims. [I] Determine patterns and frequencies of allelic deletion in early stage, lung adenocarcinomas from forty white women including 20 smokers and 20 never-smokers. [II] Analyze data from Aim I to assess the feasibility and cost of developing a sensitive and specific signature of genetic damage caused by tobacco smoke. [III] Compare the character of allelic deletion at chromosome 9p in early stage lung adenocarcinomas from smokers and nonsmokers.Samples & Laboratory Methods. Twenty, early stage lung adenocarcinomas from smoking women will be matched by age, stage, histology, gender and ethnicity to 20 lung cancers from never-smokers. Allelic deletion will be tested at 16 chromosomal loci commonly lost in lung cancers from smokers and never-smokers.Data Analysis. Multivariate analysis will test coordinate genetic losses for power to discriminate prior exposure to tobacco smoke.LVAL# J  h : x D &V0FvXSTUDIES OF OCCUPATIONAL CANCER AMONG WOMEN AND MINORITIESTREND OF SMOKING AND PSYCHOSOCIAL PREDICTORS AMONG YOUTHSMOKING PROGRESSION AMONG CULTURALLY DIVERSE YOUTHDISSEMINATING THE BEST PRACTICE INTERVENTION FOR SMOKING CESSATION DURING PREGNANCYANABOLIC THERAPIES FOR MUSCLE DYSFUNCTION IN WOMEN WITH COPDISOTHIOCYANATES AMONG AFRICAN AMERICANS AND CAUCASIANSMULTIMEDIA SMOKING CESSATION FOR ALCOHOLIC CLIENTSPOSTMENOPAUSAL ESTROGEN AND PROGESTIN INTERVENTION (PEPI) TRIALINTENTION TO QUIT SMOKING AMONG LGBT SMOKERSSMOKING AND ATHEROSCLEROSIS: MECHANISMS AND MODULATIONSTUDYING THE INFLUENCE MALE PARTNERS HAVE ON SMOKING CESSATION AMONG PREGNANT WOMENNURSING SMOKING CESSATION INTERVENTION DURING PREGNANCYLUNG HEALTH STUDY--LONG TERM FOLLOW UPMOLECULAR GENETIC EPIDEMIOLOGY OF LEADING U.S. CANCERSGENDER AND NICOTINE WITHDRAWAL--A PLACEBO CONTROL STUDYBEHAVIORAL VULNERABILITY TO EARLY SMOKING RELAPSERISK FACTORS FOR DUCTAL CARCINOMA IN SITU (DCIS)GENETIC AND ENVIRONMENTAL RISK FACTORS FOR STROKEEVALUATING RISK REDUCTION PRODUCTS FOR SMOKERSFETAL ALCOHOL AND NICOTINE INDUCED GROWTH RETARDATIONGENE-ENVIRONMENT INTERACTION IN COMPLEX DISEASEPREVENTING SMOKING RELAPSE DURING PREGNANCY AND BEYONDNEURODEVELOPMENTAL BASIS(ES) OF NICOTINE SENSITIZATIONSLEEP, MOOD, AND POSTPARTUM SMOKING RELAPSEDNA DAMAGE IN HUMAN ENDOMETRIUM BY TAMOXIFEN TREATMENTMENTORED INVESTIGATOR AWARD IN WOMEN'S HEALTHPROMOTING HEALTH PARITY AMONG MEXICAN-AMERICAN WOMENHEALTHY FAMILIES PROMOTE HEALTHY CHILDRENEVOLUTION OF CARDIOVASCULAR RISK WITH NORMAL AGINGDESIGNING A PROVIDER INCENTIVE SYSTEM TO INCREASE ADHERENCE TO MATERNITY TOBACCO CESSATION GUIDELINESEFFECT OF ESTROGEN ON ETS-INDUCED GLYCO-OXIDATIONPHARMACOKINETICS AND PHARMACODYNAMICS OF NICOTINESTABLE ISOTOPE STUDIES OF NICOTINE AND COTININE METABOLISMMETABOLISM AND CLEARANCE OF NICOTINE IN PREGNANT WOMENALLELIC DELETION IN LUNG CANCERS OF SMOKERS AND NONSMOKERSLVAL " Although relatively modest interventions have been shown to decrease tobacco use in adults, compliance of practices and practitioners with recommended guidelines has been limited. Practitioners are often already stretched to their limits and in many states (including Illinois) tobacco settlement monies initially awarded to fund tobacco-related programs in practices and public health clinics has been reallocated to meet budget shortfalls. Due to this lack of adequate funding to support the staff time required, recommended counseling, tracking, and follow-up of smokers becomes an impossible task in a busy medical office. This pilot project examines the application of tobacco-related care within the reality of busy office-based practices and determines ways to foster the routine incorporation of systems that promote addressing family tobacco use at each prenatal and pediatric office visit. This protocol compares the disposition kinetics of natural (unlabeled cotinine) and deuterium-labeled cotinine; compares the rates of metabolism of deuterium-labeled nicotine and low doses in smokers and non-smokers; and studies the pharmacokinetics of nicotine and cotinine, making use of a combined infusion of labeled compounds in subjects of different ages and gender.The specific aims of this study are to determine: (1) metabolic renal clearance of nicotine and cotinine; (2) the plasma half-life of nicotine and cotinine; (3) fractional conversion of nicotine to cotinine; and (4) pattern of nicotine metabolism in pregnant women. Investigators will also determine alterations in tobacco use (nicotine intake) that may occur during pregnancy. s +  cT44u@ (@Research^@BRAYMOLLYUNIVERSITY OF TEXAS HEALTH SCIENCES CENTERHOUSTONTXNHLBIR01, HL073366/+p.Biology and CancerP@ T@.7/5/20035/31/20077/5/2003 to 5/31/20074/2005 ~zqE>88,"33K@/@Researchl@ BRANDONTHOMASUNIVERSITY OF S. FLORIDATAMPAFLNCIR01, CA094256,+p.T@T@ @.8/1/20027/31/20078/1/2002 to 7/31/20074/2005snjcIA88,"22R@+@Researchl@ BOOZEROSEMARIEUNIVERSITY OF SOUTH CAROLINA-COLUMBIACOLUMBIASCNIDAR01, DA0137128*+p.Biology and Cancern@ @@#9/28/20026/30/20079/28/2002 to 6/30/20074/2005{qJ?88,"11@@ResearchV@ BOERGERSJULIERHODE ISLAND HOSPITALPROVIDENCERIRWJF51799< @)b@R@ @#9/1/20048/31/20069/1/2004 to 8/31/20064/2005}vpl`IB88,"00@@`O@Researchl@ BODELLWILLIAMUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCANCIR01, CA075402l @(Biology and CancerP@ @#9/4/19988/31/20029/4/1998 to 8/31/20024/2005 tI@88,"//$@@ResearchZ@ BOARDMANLORIWOMEN AND INFANTS HOSPITALPROVIDENCERINICHDK23, HD001307&+p.@@@#9/25/20018/31/20069/25/2001 to 8/31/20064/2005{tpdHB88,"..@ @Researchh@BLUMEARTUNIVERSITY OF TEXAS AT EL PASOEL PASOTXNCMHDR24, MD000520$+p.@@@#9/30/20039/29/20069/30/2003 to 9/29/20064/2005xqmdD?88,"--@@ResearchR@BINNSHELENCHILDREN'S MEMORIAL HOSPITALCHICAGOILRWJFNot Given@T@f@$@#9/1/20048/31/20069/1/2004 to 8/31/20064/2005wqmdF?88,",,@`@Researchd@BERENSONGERALDTULANE UNIVERSITYNEW ORLEANSLANIAR01, AG016592F!*p.t@n@(@#5/15/20008/31/20055/15/2000 to 8/31/20054/2005snj]JB88,"++@-@`@Research@BENTZCHARLESPROVIDENCE HEALTH SYSTEMS, OREGON REGIONPORTLAND ORRWJF43969*p.D@p@@12/1/200111/30/200312/1/2001 to 11/30/20034/2005}rH?88,"**@@Researchb@BENTONJEANAUNIVERSITY OF CALIFORNIA AT DAVISDAVISCACTRDRP9DT-0130*p.Biology and CancerDiscovery 1b Discovery 3N@7/1/20006/30/20017/1/2000 to 6/30/20014/2005}uqjG@88,"))<@@u@Researchb@BENOWITZNEALUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCANIDAR37, DA002277*p.Biology and CancerP@@3/1/19796/30/20033/1/1979 to 6/30/20034/2005 sHB88,"((g@^@Researcht@BENOWITZNEALUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCANCRRM01, RR000083@Biology and CancerDiscovery 1b Discovery 3@@Not Given2002? to 20024/2005  sHB88,"LVAL*p.The main focus of the present proposal is to understand the pharmacologic basis for differences in individual susceptibility to tobacco addiction and adverse health consequences of smoking. We propose to continue a program combining analytical and synthetic chemistry and clinical investigation, focusing on the metabolism, pharmacokinetics and pharmacodynamics of nicotine. Chemistry studies will include (a) developing methodology for quantitative analysis of tobacco alkaloids and metabolites and applying these methods to qualitatively and quantitatively define pathways of metabolism in humans; (b) synthesis of tobacco alkaloids and stereoisomers, metabolites and deuterium-labeled analogs for pharmacologic and metabolic studies, and (c) developing GC-MS assays for nicotine metabolites for stable isotope studies of nicotine metabolic disposition. Clinical studies will pursue the observation that habitual smokers regulate body levels of nicotine, testing the hypothesis that the rate of nicotine metabolism is an important determinant of individual differences in tobacco smoking behavior. Using stable isotope methodology, the kinetics of nicotine and cotinine and its relationship to daily intake of nicotine from smoking will be compared in various population groups. These include men and women, older and younger people, different racial groups (caucasians, blacks, hispanics and asians), and in heavy vs. light vs. nonsmokers. As different patterns of metabolism yielding different levels of active metabolites could contribute to individual differences, we will study the metabolism, disposition kinetics and pharmacologic effects of nicotine metabolites. Initially, we will study trans-3'-hydroxycotinine (3-HC); in future studies, the glucuronides of nicotine, cotinine and 3-HC as well as other metabolites. Since 3-HC is the major metabolite of nicotine, we will examine the utility of 3-HC as a biomarker of nicotine intake from tobacco. Environmental factors could affect nicotine metabolism. To begin to explore .LVAL>the nature of such influences, we will study the effects of phenobarbital, known to affect nicotine metabolism in animals, on nicotine and cotinine clearance as well as self-determined intake of nicotine from tobacco. We will explore the nature and mechanisms of differential tolerance to cardiovascular and metabolic effects of nicotine observed in light vs. heavy smokers. Using a computer- controlled infusion pump, we will determine quantitative parameters of tolerance to nicotine in individuals, and examine the influence of glucocorticoids on the sensitivity and development of tolerance to nicotine. To examine the hypothesis that subjective and cardiovascular consequences of nicotine are more pronounced with a rapid vs. low rate of dosing of nicotine, we will conduct a crossover study comparing the effects of cigarette smoking, transdermal nicotine (slow release) and nicotine nasal spray (rapid release). The proposed studies will clarify factors determining individual differences in tobacco consumption and effects, and may lead to more patient-specific and effective ways of treating tobacco addiction.LVAL*p.Both diabetes and environmental tobacco smoke (ETS) are very strongly associated with arterial disease but very little is known about how these factors contribute to increased disease development. A common link between these two diverse risk factors is that each increase a modification of the arterial wall that is clearly associated with arterial disease. This modification occurs through a process termed glyco-oxidation. Glyco-oxidation increases accumulation of low-density lipoprotein (LDL) in the artery wall and is positively correlated with arterial disease in many diverse populations. While estrogen is widely believed to protect against arterial disease, mechanisms of action are poorly defined. The goal of this proposal was to evaluate the antioxidant properties of estrogen and its atheroprotective potential following ETS exposure and/or glycemic stress. To accomplish these objectives we pursued two specific aims: 1) Investigate the actions of diabetes, ETS and estrogens on vascular LDL accumulation in BALB/c mice. 2) Examine the ability of estradiol to attenuate glyco-oxidative damage to collagen in vitro as a result of glycemic stress and/or ETS exposure and to elucidate the specific reaction pathways affected by estradiol. Our first specific aim involved LDL flux measurement in control, diabetic and ETS-treated mice with and without circulating estrogen. We have completed all LDL flux measurements for non-ETS-exposed animals. Diabetes significantly increased LDL accumulation over control. The presence of estradiol had no effect on diabetes-induced LDL accumulation. Our second aim involved determining the ability of estrogen to decrease ETS and/or glycemic stress-induced glyco-oxidative damage to collagen in vitro. Pathways involved in the formation of glyco-oxidation products include classic Maillard reactions, glucose auto-oxidation, lipid oxidation, and ETS exposure. Estrogen was found to decrease lipid and glucose oxidation as well as the formation of carbohydrate-derived glyco-oxidation pNLVAL^roducts (via Maillard reactions) but was not able to decrease ETS-derived glyco-oxidation. In light of estrogen's inability to decrease ETS-induced glyco-oxidation, we examined the effects of a very potent glyco-oxidation inhibitor (aminoguanidine) on ETS-induced LDL oxidation. ETS-exposed LDL was significantly more oxidized than non-exposed LDL. Pre-incubation of LDL with 0.1 mg/ml aminoguanidine had no effect but 10 mg/ml significantly decreased ETS-induced LDL oxidation. These results suggest that only high doses of aminoguanidine inhibited LDL oxidation due to ETS-exposure. These data clearly demonstrate that ETS poses a severe glyco-oxidative stress to the vascular system that is only minimally affected by known inhibitors of glyco-oxidation. Further, we have shown that estrogen is capable of inhibiting many pathways contributing to glyco-oxidative damage but is ineffective at inhibiting ETS-induced glyco-oxidation. These in vitro findings corroborate previous in vivo experiments showing that the protective effect of estrogen on arterial permeability is eliminated in ETS-exposed animals. Our data may help to explain the particularly toxic effect ETS exposure has on the cardiovascular system and could potentially have a major positive impact on the understanding of the role of estrogen in ETS and diabetes-induced vascular disease. LVAL*p. To significantly increase adherence with the 5 A s Tobacco Cessation guidelines for pregnant smokers in Oregon through development of a comprehensive reimbursement system for obstetrical providers. Objectives: Develop a comprehensive reimbursement system for obstetrical providers. Develop a strong implementation strategy for the reimbursement system. Develop the capacity to conduct future systems-level tobacco research by establishing relationships between key Oregon entities engaged in maternity tobacco cessation. This project will significantly advance the state of the art of maternity tobacco cessation within Oregon. Since Providence hospitals have the largest volume of deliveries in Oregon, this reimbursement system applied within Providence has the potential to significantly decrease smoking rates during pregnancy in this state. The collaboration with Care Oregon will potentially extend the reimbursement system to all Medicaid pregnant smokers in Oregon, which could lead to significant reductions in the Medicaid smoking rate. The comprehensive implementation strategy will provide a compelling rationale for managed care organizations (MCOs) to adopt the reimbursement system. The implementation strategy will include a variety of tools to assist MCOs in efficiently implementing the new reimbursement system. Financial modeling is a key component of this strategy, so that MCOs can easily predict the costs of implementing the reimbursement system and can demonstrate the cost-effectiveness of the system in achieving tobacco cessation among pregnant smokers, including avoided negative outcomes for the baby. The implementation strategy will also include recommendations for reducing barriers to provider adherence with 5 A s guidelines, and materials that will aid dissemination once reimbursement is adopted (e.g., suggestions for clinic-based training materials on implementing the 5 A s with pregnant smokers, and information about how to use the new reimbursement billing codes). The statewide coa LVAL lition developed during this planning project will help direct the adoption of the reimbursement system by Oregon MCOs. A successful working partnership will be established between Providence, Care Oregon, the various Oregon agencies focusing on maternity tobacco cessation (TOFCO and the Oregon Health Division), and Oregon State University tobacco researchers who are currently studying the efficacy of patient incentives in maternity tobacco cessation. This partnership will enhance future research opportunities by creating relationships that encourage collaboration on additional shared research goals beyond the reimbursement system.LVAL*p."The cardiovascular (C-V) system is one of the organ systems most affected by the aging process. Significant differences in C-V morbidity and mortality occur by race and gender that influence longevity. The proposed research involves a biracial (black-white) population that has been followed for C-V risk factors and lifestyles in the Bogalusa Heart Study over the past 25 years. The specific aim of the research is to characterize traits (intrinsic aging vs. The risk factor burden) in a population reaching middle age that influence the subclinical C-V disease process in normal aging. The extensive data base collected since childhood provides information related to silent underlying C-V disease and aging. The study cohort includes 1,200 individuals born between 1959 and 1969, who were examined at least four times since childhood. The cohort will be examined for: 1) C-V risk factor variables comprising obesity measures, blood pressure, lipids, lipoproteins, apoliproproteins, homocysteine, glucose, insulin, fibrinogen, plasminogen activator inhibitor 1, intercellular adhesion molecules -1, C-reactive protein, lipid peroxides and microalbuminuria; 2) lifestyle and psychosocial variables such as tobacco and alcohol use, physical activity, diet, and life change events; 3) subclinical changes of the heart and vasculature (outcome variables) observed by echo-Doppler measurements of cardiac-carotid structure and function and brachial and radial artery compliance; and 4) selected longevity-associated allele markers, like apoE. These variables (except for the allele markers) will be measured at two points in time, with a 3-year interval. In addition, a family history of longevity and health history information on study subjects and their parents and grandparents will be obtained to evaluate familial risk characteristics of the cohort. The proposed studies will provide insights into the interaction of normal aging and predisposing factors that influence the subclinical C-V disease process in a black-white populationLVAL reaching middle age. Understanding the evolution of C-V risk in normal aging can lead to more rational programs for successful aging and longevity and C-V disease prevention.LVAL DJAGE Fetus/Prenatal TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Other Disease/Biology RESEARCH1 Animal Studies TOBACCO Nicotine WOMEN Hormones MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PostpartumDISEASE/BIOLOGY Cancer Mechanisms LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use WOMEN Menopause Hormones Hormone Replacement TherapyADDICTION Cessation DISEASE/BIOLOGY Cancer LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Biochemical Assessments Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco UseECONOMICS Socio-Economic Status LOCATION Urban PSYCHOLOGICAL Cultural Factors RESEARCH Human Studies STUDY POPULATION Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Health Care Provider LOCATION National PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Other Psychological RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN Pregnancy Postpartum Parent/MotherDISEASE/BIOLOGY Cardiovascular/Pulmonary EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesLVAL+p.%This revised application, "Promoting health parity among Mexican-American women," is submitted in response to RFA-MD-03-001. The University of Texas, E1 Paso (UTEP), a Hispanic-serving institution in a metropolitan statistical area with 78% Hispanic density, 27% poverty rate, and comprised of census tracts designated as Health Professional Shortage Areas, has developed this proposal to further our capacities to understand and reduce health disparities among Mexican-American women. UTEP proposes a partnership with established Hispanic healthy disparity researchers at the University of Arizona (UA) (recipients of a Project EXPORT P60 Comprehensive Center grant) to facilitate the development of UTEP's institutional capacity to conduct healthy disparity research. We will pursue integrated research, outreach, and training objectives that are theory- and hypothesis-driven; the pilot research projects proposed address health issues that disproportionately affect Mexican-American women. Moreover, the focus is on potentially modifiable behavioral health issues, i.e., use of tobacco and alcohol, food choices and methods of preparation, and pursing recommended screening tests such as Pap smears and human papillomavirus tests. All projects share a common focus on understanding health disparities and promoting health parity among Mexican-American women. The four pilot research projects will: (1) examine alcohol use and related risks among impoverished Mexican-American women of childbearing age living in colonias along the Texas-Mexico border. (2) Test the effects of a culturally sensitive nutrition intervention on maternal health outcomes among pregnant Mexican-American women; (3) Develop and test the efficacy of a linguistically and culturally appropriate web-based smoking cessation intervention for young Hispanic women. (4) Develop and test the efficacy of an intervention to increase knowledge and intentions to engage in Pap and HPV tests. The results of our research will inform and enhance our outreach activiti LVAL es. In addition, a multifaceted training program will support the professional development of minority and female junior faculty pursuing health disparities research. This proposal is supported by UTEP and UA investigators knowledgeable in women's health, community outreach, and work with the Mexican-American population, and an ethnically diverse Project Advisory Committee that includes both expert scientists and members of the communities that are the focus of the proposed research and outreach efforts.LVAL+p.'The purpose of this award is to provide support for Dr. Lori Boardman to pursue formal training in the fields of biostatistics, epidemiology and public health, thereby attaining the necessary theoretical and methodological background to further a career in patient- oriented research. The final three years of the award will be devoted to the design, implementation, analysis of data and preparation of the results of a randomized controlled trial of two smoking cessation interventions in a cohort of women referred for the evaluation of abnormal Papanicolaou smears. The primary aims of this study are to evaluate smoking cessation rates between the two groups and to confirm self-reports of cessation through measurement of cervical mucus cotinine. The secondary aims are to determine the regression rate of cervical neoplasia in women who quit smoking compared to those who continue and to assess the independent and combined contribution of human papillomavirus and smoking on the natural history of atypical or low-grade cervical neoplasia (includes cytology and/or histology). This trial will be conducted with the guidance of a multidisciplinary and experienced team including experienced women's health and behavioral health researchers, epidemiologists, an oncologist, and a statistician. Immediate Career Objectives: Pursue formal training in research design and analysis by obtaining a master's degree in public health; Improve abilities to design, perform, analyze and communicate research findings through the preparation of a master's thesis and formal presentations of ongoing research stemming from clinical work in cervical neoplasia; Implement and complete a randomized trial of two smoking cessation interventions in women with cervical neoplasia. Lone-Term Career Objectives: Become an independent and productive investigator in the field of women's health care; Secure independent grant funding for patient-oriented research; Become a leader in academic medicine and mentor more junior investigators interested in LVALwomen's health.LVALTamoxifen (TMX) is an antiestrogenic compound used in the treatment of breast and other cancers. Women treated with TMX have been reported to show up to a 6-fold increased risk for the development of uterine cancer. Studies from the applicant's laboratory suggest that TMX usage may result in the formation of DNA damage in human endometrium. In these studies the applicant proposes to: (1) collect endometrial biopsy samples from a group of women with varying TMX usage. Patient medical records will be used to asses TMX usage and a questionnaire will be used to analyze other variables including age, menopausal status, and tobacco history. (2) Measure levels of TMX metabolites and uterine peroxidase activity in the endometrial samples. These measurements will be treated as biomarkers of internal TMX dose and individual capacity to activate TMX metabolites to form DNA damage. (3) Measure levels of DNA adducts and 8-hydroxydeoxy-7,8- dihydroguanosine in the endometrial samples Attempts will be made to verify that the adducts detected in the endometrial samples are derived from TMX by direct analysis with liquid chromatography-mass spectrometry. (4) Identify the structure of the DNA adduct formed by 4-OH-TMX. (5) Develop a model to test for associations between TMX usage and the formation of DNA adducts and 8-hydroxydeoxy-7,8-dihydroguanosine in endometria samples. The applicant will seek to determine if any association is modified by either levels of TMX metabolites in endometrial samples, activity of uterine peroxidase, or tobacco smoking history. Statistical power has been considered regarding the hypothesis that administration of TMX results in the formation of DNA damage in human endometrium.LVALThis study hypothesizes that sleep problems, in conjunction with mood disturbance, are a trigger for smoking relapse during the postpartum period. Over half of women who quit during pregnancy resume smoking within the first six months postpartum. While many demographic variables are associated with an increased risk of postpartum relapse, few of these variables are appropriate targets for intervention. Attention to the unique features of the postpartum experience may provide keys to advancing the efficacy of abstinence maintenance strategies. One of the nearly universal challenges of the postpartum period is insufficient sleep. Mood problems are also frequently noted during this period, and often co-occur with sleep problems. In the general population, depressed mood is associated with smoking relapse. However, previous research has not examined the role of insufficient sleep as a trigger for smoking relapse, either in the general population or among postpartum women. If our data support these links, results will have important implications for developing innovative smoking cessation and relapse prevention programs for this population to improve upon the efficacy of existing programs. For example, interventions could include anticipatory guidance about sleep hygiene, healthy countermeasures to combat fatigue, avoidance of caffeine and alcohol, and early identification and intervention with mood problems. LVAL+p.+Gender differences in response to psychostimulants have been reported both in animals and humans; however, the biological mechanisms which underlie these gender differences to psychostimulants remain for the most part, unexplained. The common observation is that females are more sensitive to psychostimulants, such as nicotine. Our hypothesis is: Gonadal hormones in adulthood and development act on dopaminergic systems, providing the underlying basis for the gender differences in behavioral sensitization produced by repeated IV nicotine administration. First, we will determine whether pharmacokinetic differences between the sexes result in higher levels of nicotine in the female brain. We have successfully developed a technically simple, economical and practical non-tethered technique for repeatedly administering IV nicotine to freely moving, group-housed rats. Detailed pharmacokinetic analysis has demonstrated rapidly peaking nicotine levels following IV dosing in rats, which is similar to that observed in humans, as opposed to SC or PO dosing. Using this clinically relevant IV rodent dosing model, we will determine whether pharmacokinetic factors contribute to the increased sensitivity of female animals to the effects of nicotine. Second, we will determine whether gonadal hormones regulate the expression of gender differences in response to nicotine in adulthood. We will test the ability of gonadal hormones to modulate dopamine receptor responsiveness to chronic nicotine administration. Third, we will determine whether the brain organizational (neurodevelopmental) effect of the perinatal hormonal milieu mediates the gender differences in nicotine responsiveness. We have pharmacologically characterized a recently discovered unique dopamine receptor subtype (D3) which is localized to the striatum/nucleus accumbens region of the brain. We hypothesize that alterations in dopaminergic systems underlie the gender differences produced by repeated IV nicotine administration. Our long-term goal is LVAL to determine the role of the dopamine neurochemical system in gender differences following repeated IV nicotine administration. The ultimate goal of this research is to develop pharmacological interventions to assist in correcting the behavioral problems associated with chronic tobacco use in humans, and specifically to provide potential insight into effective gender-specific treatment strategies for smoking cessation.LVAL+p.-The prenatal risks of tobacco smoking motivate many women to quit smoking during pregnancy and to maintain abstinence for several months. Unfortunately, the majority of these women relapse to smoking either during their pregnancy or within the first six months postpartum. Resumption of smoking is associated with cancer and other health risks to the smokers themselves and to those exposed to their environmental tobacco smoke, including the infant and other members of the family. Because so many women are able to achieve at least short-term abstinence during their pregnancy, the pregnancy and postpartum periods are collectively viewed as a "window of opportunity for interventions designed to prevent smoking relapse. Although modest success has been achieved at aiding women in smoking cessation during pregnancy, attempts to prevent subsequent smoking relapse have been unsuccessful to date. The goal of Study I is to develop the key materials for a cost-effective minimal intervention preventing smoking relapse among pregnant/postpartum women. The intervention will be modeled after one developed by the research team that has been found to reduce smoking relapse by approximately two-thirds among a general population of recent quitters. This intervention comprises a series of eight Stay Quit booklets mailed to former smokers over a year. The booklets were developed based on theory and research on smoking relapse, and were found to be extremely cost-effective. However, because pregnant and postpartum women differ in many ways from the general population of ex-smokers, it cannot be assumed that the existing intervention would adequately meet their unique needs. The end product of Study I will be a series often Forever Free for Baby and Me booklets designed to be provided to women between their sixth month of pregnancy and eight months postpartum. The content of the booklets will be based on three sources of information: (1) the existing, validated Stay Quit booklets, (2) theory and research on smokinLVALg relapse during and after pregnancy, and (3) systematic formative research comprising focus groups, in-depth interviews, and learner verification interviews. Subjects will include pregnant and postpartum women who have maintained tobacco abstinence, as well as those who have relapsed; their partners; and relevant health professionals in the community. Study II will be a randomized, controlled trial of the intervention developed in Study I. Women who have quit smoking during pregnancy will be recruited via childbirth education classes and randomly assigned to receive the series of Forever Free booklets versus a usual care control condition. Follow up will be conducted through 12 months postpartum, and a format cost-effectiveness analysis wilt be conducted. If shown to be effective, this minimal intervention would be easy and inexpensive to disseminate to women via a variety of channels and settings.LVAL\  6 \<AGE Child Young Adult Adult DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Hormones Hormone Replacement Therapy MISCELLANEOUS Weight Gain/ExerciseAGE Adult Older Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking WOMEN Hormones MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation Withdrawal LOCATION National PREVENTION/TREATMENT Biochemical Assessments Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Nicotine WOMEN Hormones MISCELLANEOUS Sex/Gender DifferencesAGE Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION Caucasian TOBACCO Cigarette/Other Smoking WOMEN Hormones MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesADDICTION Relapse COMMUNITY Health Care Provider ECONOMICS Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Postpartum Partner/SpouseLVAL+p.0Cardiovascular disease (CVD), the number one cause of death in industrialized countries today is a complex disease with a multifactorial etiology involving many genetic and environmental factors. Public health prevention programs designed to reduce the risk and occurrence of CVD commonly focus on modifiable environments and behaviors such as diet and physical activity, with varied results among individuals. This heterogeneity in response to CVD interventions is at least in part of genetic origin. Although a number of candidate genes have been identified which appear to influence the development of CVD, little is known about how these genetic effects may vary within demographic (e.g., race and gender) and environmental (e.g., diet and exercise) contexts; thus, it is of utmost importance to determine how genes and environments interact to produce CVD. The purpose of this study is to characterize the environment-dependent effects of 87 biologic and positional candidate genes in a population-based sample of 11,625 African-American and Caucasian men and women from the Atherosclerosis Risk in Communities (ARIC) study. Candidate loci were selected based on confirmed functional significance, consistent association with CVD or its risk factors, and or identified as positional candidates in genome-wide linkage scans. Environmental contexts will focus on dietary measures (e.g., total kcals, Keys score, alcohol intake), obesity, measures of physical activity (sport, leisure, and work indices), smoking, and menopause status/hormone use (women only). Outcome variables will include measures of quantitative risk factors (e.g., total cholesterol, BMI, blood pressure), subclinical disease (carotid wall thickness), and clinical disease (incident CHD and stroke). Existing DNA samples will be used for genotyping of candidate loci, and no further contact with study participants will be necessary. The ARIC cohort, because of its large size and wealth of environmental and physiological measures, provides an ideal, timely, an LVALd efficient opportunity to evaluate the effects of modifiable environments on genetic variation which may influence CVD risk and disease outcomes with the ultimate goal of establishing more efficacious programs for the treatment and prevention of CVD.LVAL+p.2Fetal alcohol syndrome is a constellation of birth defects caused by maternal alcohol use during pregnancy, and is characterized by intrauterine and postnatal growth deficits, and CNS dysfunctions in the offspring. Tobacco use during pregnancy is also an established cause of fetal growth deficiency, although the toxicological effects of prenatal nicotine exposure on the CNS are not clear. Since tobacco use is highly correlated in women that abuse alcohol during pregnancy, exposure to the combination of these substances may exacerbate the deficiencies associated with alcohol or tobacco use alone. While intrauterine and postnatal growth deficiencies are the most common symptoms of fetal alcohol or tobacco exposure, the cause of these deficiencies unknown. Studies have shown a consistent long-term reduction of insulin-like growth factor-1 (IGF-1), a major mediator of developmental growth, in prenatally ethanol exposed offspring. The goal of this application is to investigate the actions of in utero ethanol, nicotine, and ethanol/nicotine co-exposure, on the regulation of the IGF and somatotropin gene families, and assess the relationship of changes in tissue and brain IGF and GH regulation, to that of the growth and CNS deficits observed in these offspring. The hypothesis is that fetal exposure to ethanol and nicotine inhibits fetal and neonatal IGF-1 gene expression, thereby reducing tissue availability to IGF-1, and causing or exacerbating the observed growth deficits observed in these offspring. The proposed studies to test this hypothesis include: 1) Examining the effect of fetal ethanol, nicotine and alcohol/nicotine co exposure, on plasma and somatic tissue specific IGF and GH peptide and gene regulation; 2) Assessing the effect of fetal ethanol and nicotine exposure and co-exposure on changes on CNS neurotrophic expression, with particular emphasis on the IGF and neurotrophic gene families; 3) Examining the specific actions of ethanol and nicotine exposure on growth factor induced cellular  LVAL function and second messenger systems, in organ culture systems of affected tissues; and 4) Assessing changes in gene expression by differential display PCR, to identify additional candidate genes in these disorders. These studies will provide valuable data which correlate with the endocrine and neuropathological changes seen in fetal alcohol syndrome and smoking in human populations.  r D  eIAAg@p@4Research~@BUSHTRUDYJOHNS HOPKINS UNIVERSITYBALTIMOREMDNCRRM01, RR002719Not availableBiology and CancerDiscovery 1b Evaluation 1b@DNot GivenNot GivenUncertain4/2005  tnj_E>88,"@@@v@@ResearchX@BURKHALTERJOHNSLOAN-KETTERING INSTITUTE FOR CANCER RESEARCHNEW YORKNYNCIR03, CA103485E+p.@@^@D7/8/20036/30/20057/8/2003 to 6/30/20054/2005yJD88,"?? @@@Researchn@BURKEANNEUNIVERSITY OF PENNSYLVANIAPHILADELPHIAPANCRR5K32RR016293-04B+p.|@@@D7/1/20016/30/20067/1/2001 to 6/30/20064/2005ysoaE?88,">>`@@Research@BULLOCKLINDAUNIVERSITY OF MISSOURI-COLUMBIA, CHARLES AND JOSIE SMITH SINCLAIR SCHOOL OF NURSINGCOLUMBIAMORWJF51415Not availableT@@@6/1/200411/30/20056/1/2004 to 11/30/20054/2005-%  HA88,"==@@Researchn@BULLOCKLINDAUNIVERSITY OF MISSOURI-COLUMBIACOLUMBIAMONINRR01, NR005313D@+p.T@@@:8/1/20014/30/20058/1/2001 to 4/30/20054/2005}wsiHA88,"<<`~@ @ResearchL@BUISTALINEOREGON HEALTH AND SCIENCE UNIVERSITYPORTLAND ORNHLBIU10, HL0593208@?@@@:2/1/19981/31/20042/1/1998 to 1/31/20044/2005{wlF?88,";;L@@@Researchl@BUETOWKENNETHCENTER FOR CANCER RESEARCHBETHESDAMDNCIZ01, CP010140'<+p.t@P@@:199720031997 to 20034/2005xsoeI@88,":: @p@4Researchn@BUCHHALTERAUGUSTVIRGINIA COMMONWEALTH UNIVERSITYRICHMONDVANIDAF31, DA006052;+p.Biology and Cancer Addiction@@:6/15/2001Not Given6/15/2001 to ?4/2005|xnLD88,"99@@}@Researchb@BROWNRICHARDBUTLER HOSPITALPROVIDENCERINCIR21, CA0882978+p.Biology and Cancer Addiction@@:9/1/20008/31/20039/1/2000 to 8/31/20034/2005}nieYH?88,"88@`@Research`@BRODYJULIASILENT SPRING INSTITUTENEWTONMANCIR03, CA103478 @7t@@@.9/16/20038/31/20059/16/2003 to 8/31/20054/2005pkg_F?88,"77l@C@Researchb@BRODERICKJOSEPHUNIVERSITY OF CINCINNATICINCINNATIOHNINDSR01, NS03669585+p.Biology and CancerP@ @.9/12/19975/31/20029/12/1997 to 5/31/20024/2005|uqeKC88,"66N@@Research\@BRELANDALISONVIRGINIA COMMONWEALTH UNIVERSITYRICHMONDVANIDAF31, DA015570 @4j@n@@.8/27/20028/26/20058/27/2002 to 8/26/20054/2005yukIA88,"55`@`O@Researchj@BREESECHARLESAUBURN UNIVERSITYAUBURNALNIAAAR29, AA0111641+p.Biology and CancerP@@.9/21/19988/31/20029/21/1998 to 8/31/20024/2005~ohd\I@88,"RLVALbAssessing new, potential reduced exposure products (PREPs) for smokers is essential to predict if they will increase, decrease, or fail to change the health risks of smoking. In the past, some harm reduction efforts (i.e., low-yield cigarettes) did little to reduce smoking's lethality. Smokers using these cigarettes compensated for lower yields of nicotine by taking larger, longer, or more frequent puffs, thus potentially increasing exposure to harmful smoke constituents. In addition, some research indicates that men and women differ in their response to nicotine/tobacco; thus it is important to understand differential responses to these products. To assess the effects of PREP use, male and female smokers will participate in a 4-week, within-subjects study. Each week, participants will use either one of two PREPs, their own brand, or will abstain from smoking. Smokers will use these products outside of the laboratory but will be also be assessed for behavioral changes in the laboratory. Subjective and physiological withdrawal suppression, as well as smoke constituent exposure (CO, nicotine, nitrosamines) will be measured. Measuring these factors is essential to determine if these PREPs reduce the risk associated with smoking, and to avoid past failures to evaluate products which claimed to decrease exposure to harmful smoke constituents.LVAL+p.6The primary goal of this application is to determine the important genetic and environmental risk factors for intracerebral hemorrhage (ICH) and Subarachnoid hemorrhage (SAH), which occur in over 50,000 Americans each year and yield a combined mortality of 40- 50% all cases of ICH and SAH in a racially mixed metropolitan population of 1.3 million (14% African-American) will be identified over 3 years. Two age-, gender, and race matched controls will be identified for each case by random-digit-dialing (RDD). A study nurse will perform a 1-hour interview of cases and controls including blood pressure measurements and buccal swabs for genetic testing. Data from 470 cases of ICH, 250 cases of SAH, 720 case proxies, 1440 controls, and 360 control proxies will be used to test the following hypotheses: Hypothesis 1: the ApoE4 and ApoE2 alleles are significant and independent risk factors for lobar hemorrhage in persons over the age of 50. The presence of an ApoE4 or ApoE2 allele is not significant risk factor for ganglionic or deep white matter hemorrhages. Hypothesis 2: Age, hypertension, prior cerebral infarction, current smoking, use of anticoagulants, heavy alcohol use, diabetes, and the presence of an ApoE4 or ApoE2 allele are significant and independent risk factors for ICH. Hypertension will be the modifiable risk factor with the greatest attributable risk. Hypothesis 3: the presence of a Z or S mutation of the normal M1 allele for alpha-1 antitrypsin is associated with an increased risk of aneurysmal SAH. Hypothesis 4: Age, female gender, cigarette smoking, hypertension, estrogen deficiency among women, a family history of SAH, and the presence of Z or S mutation of the normal M1 allele for alpha-1 antitrypsin are significant risk factors for SAH. Smoking will be the modifiable risk factors with the greatest attributable risk. Hypothesis 5: although the age- and sex-adjusted incidence rates of both ICH and SAH will be increased among African-Americans as compared to whites, race will not be an indepeLVALndent risk factor for either ICH or SAH.LVALAmerican Cancer Society estimates that 54,000 new cases of in situ breast cancer representing 20 percent of new breast cancers will be diagnosed in 2002. With incidence of ductal carcinoma in situ (DCIS) increasing rapidly, primarily due to greater mammography use, epidemiologic research to identify risk factors that can contribute to prevention is essential. The proposed case-control study will evaluate risk associated with teenage and adult active and passive tobacco smoking, timing and patterns of alcohol consumption, pharmaceutical hormone use, physical activity, breastfeeding duration, nonsteroidal anti-inflammatory drug use, and exposure to home and wide-area pesticide use and wastewater-infiltrated tap water. Mammography use will be assessed in order to take into account any exposure-related screening behaviors. Medical records will be reviewed for information on nuclear grade and presence of comedo necrosis. Study participants will be 224 cases diagnosed among Cape Cod residents in 1992-1998, the earliest and most recent years available from the MA Cancer Registry, and a comparison group of Cape residents similar in age. Exposures will be assessed using interviews and a geographic information system (GIS) containing environmental data, modeling tools to estimate historical exposure, and study participants' addresses dating back to 1948. The study builds on the Cape Cod Breast Cancer and Environment Study of invasive breast cancer and additional grants that currently support the proposed study of DCIS.LVAL+p.9Relapse continues to plague public health efforts to reduce the prevalence of cigarette smoking. Recent evidence suggests that a large percentage of individuals attempting smoking cessation lapse to smoking within a matter of days, and few recover to achieve and maintain smoking abstinence. Results of studies relating severity of nicotine withdrawal symptoms to short-term smoking cessation outcomes have been equivocal. Instead of focusing on severity of withdrawal symptoms, we suggest that factors surrounding how one reacts to symptoms of nicotine withdrawal is more promising. In total, biological, physiological, emotional and behavioral responses to nicotine withdrawal constitute a type of biobehavioral reactivity that may convey vulnerability to early smoking lapse, and in a broader sense, may be an important component of dependence to nicotine. The overall aim of this study is to examine biobehavioral mechanisms related to early smoking lapse in a laboratory investigation of 84 cigarette smokers making an unaided smoking cessation attempt. The sample will be stratified by gender, level of nicotine dependence and history of major depression. Additionally, subjects will be followed for four weeks after attempting cessation, and based upon a median split of time to first smoking lapse, will be grouped as either early lapsers or sustainers. Prior to self-quitting, subjects will be exposed to three laboratory procedures to investigate biobehavioral reactivity to (a) a psychological stressor, (b) physical discomfort and (c) a neuroendocrine dexamethasone/corticotropin releasing hormone (DEX/CRH) challenge test. We expect that early lapsers will have higher levels of reactivity to these procedures on biological, physiological, affective and behavioral measures. Secondarily, we hypothesize that these biobehavioral measures of reactivity will be related to lifetime recurrent MDD, elevated measures of affective vulnerability, and elevated negative mood upon initial cessation. We expect that the results of thN LVAL^ is study will increase our basic knowledge about biobehavioral vulnerability factors in early smoking lapse and subsequent relapse in smokers quitting without professional assistance, a group that is understudied yet accounts for 90 percent of all cigarette smokers. Because early lapsers represent a recalcitrant group of smokers who are at-risk for continued nicotine dependence, these research findings should hold considerable clinical and public health significance and may result in the development of novel pharmacological and cognitive- behavioral treatments for nicotine dependence.LVAL" n tp|LOCATION National MARKETING Industry Counter-Marketing TOBACCO Non-Specified Tobacco UseADDICTION Cessation DISEASE/BIOLOGY Cancer RESEARCH1 Animal Studies TOBACCO Cigarette/Other SmokingADDICTION Cessation Relapse COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status Medicaid/Medicare LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation Withdrawal DISEASE/BIOLOGY Other Disease/Biology LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation Relapse DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender Differences<LVAL+p.LUnderstanding factors that influence drug withdrawal in men and women is an essential component of successful drug abuse treatment. This within-subjects study will explore the time course of tobacco withdrawal in men and women over a 5-day period using a placebo control design. Smokers will participate in three, 5-day conditions separated by a minimum 48-hour washout period. Conditions will span Monday-Friday and subjects will attend the research facility for about one hour on each weekday for periodic monitoring on various measures (e.g., subjective, physiological, behavioral, compliance). Weekends will serve as washout periods during which subjects will smoke their usual brand of cigarettes. Conditions vary by the cigarettes to be smoked: in one condition subjects will smoke denicotinized cigarettes, in another they will smoke control (nicotinized) cigarettes, and in the third they will abstain from smoking. Smoking conditions will be double-blind and all these conditions will be ordered by Latin Square. Each condition will include periodic monitoring of subjective symptoms of tobacco withdrawal, performance measures, levels of urinary cotinine (a nicotine metabolite), expired air carbon monoxide (CO), and several physiological variables. Subjective and performance measures will be administered daily, Monday-Friday. Monitoring levels of urinary cotinine and expired CO will be done thrice weekly (i.e., Monday, Wednesday, and Friday) and will be used to assess compliance with smoking restrictions. Additionally, compliance with smoking restrictions will be reinforced monetarily twice weekly (i.e., Wednesday and Friday). Results from this study will help to determine: a) the extent to which cigarette smokers are physically dependent on nicotine, the long-term contribution of non-nicotine, tobacco-related factors in the withdrawal suppression produced by denicotinized cigarettes, and c) whether men and women differ in their response to the nicotine/tobacco withdrawal syndrome.LVAL+p.=Almost half of new cancer diagnoses in adults in the U.S. will be of three types: cancers of the lung, breast, and prostate. If significant progress is to be made in reducing total cancer incidence, it will be important to finds means of preventing these major tumors. Toward this end, basic scientists have identified a variety of genes in experimental systems that may be important in the etiology of these cancers. Concordantly, epidemiologists have identified environmental factors that are associated with increased cancer risk (e.g., smoking and lung cancer). In addition, statistical geneticists have shown that for a large number of malignancies, the risk of developing and surviving cancer is not uniformly distributed throughout the population. Given the complexity of cancer phenotypes and the dramatic disruption of cancer cells' genomic constitution, it is rational to only be cautiously optimistic about the near term success of novel therapeutic approaches to end-stage disease. A more efficacious short-term strategy may be early diagnosis or prevention. For most cancer types, therapeutic intervention in early stages of disease has demonstrated high rates of efficacy. The laboratory is attempting to identify genetic constitutional markers that distinguish individuals at high risk for developing breast cancer, or at risk of developing complications from prevention interventions. Two sample populations will be used to achieve these goals: a case only collection from a large phase 3 trial of Tamoxifen (13,388 women) and a case-control study (750 in all). Preliminary studies in the laboratory using a distinct case-control population set (493 in all) have focused on candidate breast cancer susceptibility genes, including those involved in estrogen biosynthesis and metabolism. A significant difference in allelic distribution of the aromatase gene (Cyp19) was observed between cases and controls. In addition, the laboratory has developed MALDI-TOF MS assays on an extended collection of gene markers useful inLVAL> dissecting estrogen biosynthetic and metabolic pathways, focusing specifically on functionally significant allelic variants described in the literature. Thirty-eight variants will be assessed in the case only Tamoxifen studies to address potential associations with complications from prevention intervention, and in the case-control population to identify markers indicative of high risk for breast cancer development. The laboratory is also attempting to identify genes that modify the risk of developing lung cancer by examining candidate gene variation in a case-control study. In this study, fifteen variants in fourteen genes involved in Phase I and Phase II metabolism were evaluated. When these 15 candidate susceptibility gene variants were assessed in a 756-sample subset of smokers, and the results introduced into logistic regression models (following adjustments for genetic background), only GSTA4 was significantly associated with lung cancer. The interaction among tobacco smoke, dietary intake and candidate gene variation was also determined. On stratified analysis of 329 smokers, a healthy dietary pattern (high intakes of fibers and carbohydrates and low intakes of protein and animal fat) was associated with decreased lung cancer risk among GSTM1 null individuals. This result suggests that dietary factors can influence carcinogen metabolizing enzymes effects in lung cancer risk. Pilot application of path analysis methodologies for interpreting lung cancer gene expression has been performed utilizing the G1/S checkpoint pathway. This pathway was chosen because it has been shown to play an important role in the development of lung cancer. The initial study examined whether the fitted models of correlation between genes reflect current biological knowledge about the changes that occur in this pathway in lung tumors. Gene expression data from 17 normal lung and 55 lung carcinoma cell lines was used for path analysis. Much is known about many of the key genes in the pathway, which includes TGF-b, SMALVALD4, p53, gsk3b, cdc25A, p27, p21, cdk2, cyclin E, cdk6 cdk4, cyclin D and Rb, and models were tested based on the available data. The first and simplest model examined the direct influence of upstream genes on Rb expression. In normal cells, 35% of the variation in Rb expression appeared related to the expression of cdks and cyclins. Increases in these proteins, which signal G1 to S transition, corresponded to decreases in Rb expression. Tumor samples showed lower Rb expression, and Rb expression was not strongly influenced by cdk4 and cdk6. The influence of cyclin E over Rb expression appeared to increase in tumors, but there was an apparent decoupling of cyclin E and its regulator cdk2 suggesting that these effects may be poorly regulated. This initial study is consistent with the literature concerning these genes in normal and cancer cells, and suggests that path analysis can be used to reliably test hypotheses concerning changes in the patterns of correlations occurring in the normal and disease state.LVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long- term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 10 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airways reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600.LVAL+p.AProblems related to smoking during pregnancy are entirely preventable. The imminent danger of smoking to mothers (i.e. abruptio placentae) and unborn children (i.e. low birthweight) calls for prompt and intensive intervention. Reasons for continued smoking during pregnancy vary by age and income. In this proposed study's low-income population, the most likely group to smoke throughout pregnancy, women suffer from stressful events in their lives, which they cite as difficult barriers to smoking cessation. Social support has been shown to be beneficial in general for coping with problems. AHCPR smoking guidelines call for a social support component in cessation programs that is delivered by healthcare providers. Unfortunately, the guidelines' recommendations for social support focus narrowly on smoking related problems alone. For low-income pregnant women, this tight focus means healthcare providers may not touch on the very topics that are key to their quitting smoking. Nurses' skills in assessment and providing support are extremely well matched to delivering the help women need to quit smoking during pregnancy. This study's primary aim is to determine whether a combination of an established smoking cessation educational program for pregnant women and a nurse- delivered telephone social support intervention (weekly telephone calls as well as having 24-hour pager access to research nurses) will increase pregnant womens' smoking cessation or smoking reduction rates. A sample of pregnant women who smoke will be recruited from WIC clinics in central Missouri. The outcome measure will be saliva cotinine values collected repeatedly every month from enrollment in the study until the last month of pregnancy. A secondary aim of the study will be to determine the prevalence of relapse among the women who quit smoking, when the relapse occurs, and associated stressors. A randomized controlled trial of four groups will be conducted using a repeated measures 2x2 factorial design with two levels of educ LVAL ation (Present or Absent) and two levels of nurse-delivered telephone social support (Present or Absent). To determine significant group differences in quit rates, Chi-square analysis for each month will be used. A fixed-effects repeated measure ANOVA will be used to determine significant group differences in reduction in smoking and survival analysis will detect if there are significant group differences in time to relapse.LVAL+p.CObjectives: This research is to investigate a mechanism of smoking induced atherosclerosis and to assess the impact of smoking reduction strategies on arterial injury. Improving our understanding of smoking induced atherosclerosis will increase our armamentarium against this and non-smoking induced atherosclerosis. Specific aims: 1) To address the hypothesis that nicotine substitution or buproprion reduces smoking induced thromboxane (TX) formation and consequent endothelial dysfunction. 2) To address the hypothesis that nicotine substitution or buproprion reduces the smoking induced increment in isoprostane generation and inflammatory cytokines. 3) To address the hypothesis that smoking reduction may improve endothelial function even in the absence of smoking cessation. Relationship to health: Smoking is the leading cause of preventable death in America. Smoking costs the United States approximately $1 billion per annum. Reducing the harm of smoking will have a considerable impact on the health and health care costs of the United States. Research design: Healthy endothelium displays a vasodilatory response to vasoactive stimuli, which is blunted or absent in arterial disease. Flow mediated vasodilatation (FMD) can be measured non-invasively by ultrasound and correlates closely with subsequent development of atherosclerosis. Urinary isoprostane measured by gas chromatography / mass spectrometry (GC/MS) provide a specific and sensitive means to measure oxidative stress (OS) in vivo in humans. GC/MS also allows for accurate non-invasive quantification of TX and prostacyclin (PGI2) metabolites in humans. This research will be carried out in healthy age and gender matched human volunteers. Subjects will be studied for 6 months. It will quantify FMD in non- smokers, light and heavy smokers, before and after administration of vitamin C - an antioxidant, and aspirin - an inhibitor of TX and PGI2 synthesis. It will correlate FMD and eicosanoid production, before during and after smoking cessation on nicotine  LVAL and non-nicotine smoking cessation medications. In addition, this research, in a separate experiment, will study the impact of nicotine and non nicotine assisted smoking reduction strategies on these parameters. Expected findings: We expect to find that smokers have impaired FMD and elevated OS, TX and PGI2 production. We expect that smoking reduction and cessation and the administration of antioxidants and aspirin will improve these parameters towards the levels of healthy volunteers and that the effects will be additive.,LVAL p2HDISEASE/BIOLOGY Cancer RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesECONOMICS Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesLOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use WOMEN Menopause Hormones Hormone Replacement TherapyECONOMICS Socio-Economic Status LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies STUDY POPULATION Lesbian Gay Bisexual Transgender TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology LOCATION National PREVENTION/TREATMENT Biochemical Assessments Buproprion Nicotine Replacement Therapy Other Pharmacological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesLVAL+p.FOne of Healthy People 2010's (USDHHS, 2000) overarching health priorities includes eliminating health disparities among segments of the population, including disparities related to sexual orientation. Lesbians, gay men, bisexuals, and transgender persons comprise a sexual orientation and gender identity minority known collectively as the LGBT community, or LGBT persons. Evidence strongly suggests that smoking prevalence is greater among lesbian, gay, and bisexual persons when compared to the general population. Smoking prevalence estimates are not available for transgender persons, but they share characteristics associated with higher smoking prevalence in the general population--lower socioeconomic status, high rates of depression, and high prevalence of substance abuse. High rates of smoking and the concentration of other health behaviors associated with greater cancer risk suggest that LGBT persons are at increased risk for certain cancers. The role of social-cognitive variables in understanding smoking, motivation to quit, and cessation is well-described for the general population and many special populations, but similar data are lacking for LGBT persons. Given the higher prevalence of smoking and the stigmatized social status of LGBT persons, it is likely that unique social-cognitive and contextual factors exist that are important in understanding their motivation to quit smoking and smoking patterns. Guided by the Theory of Planned Behavior and using qualitative interview and quantitative methodologies, this study will explore attitudes about quitting smoking, subjective norms (perceived social norms) for quitting, perceived behavioral control (self-efficacy) regarding quitting, and behavioral intention to quit among LGBT persons. In addition to theory-driven constructs, potentially important, LGBT-culture specific variables will be examined for their additive contribution to the variance in intention to quit smoking. Further, we will determine LGBT persons' preferences for delivery, format and LVAL provider characteristics in designing future smoking cessation interventions. If effective smoking cessation interventions are to be developed to address high smoking rates in the LGBT community, then culturally specific smoking cessation interventions should be informed by theory-driven research that supports targeting LGBT-specific factors, as well as those of general import, that are amenable to change. This application represents the beginning step toward developing a cancer control and prevention research program targeted to the LGBT community that has as its starting point a focus on tobacco control and prevention.LVAL'+p.HThis application proposes development of an interactive multimedia program called, "On the Air: A Smoking Education Program for Alcoholics," designed to reduce smoking of clients in alcohol treatment. The program will be offered through inpatient, residential and outpatient treatment programs to help those struggling with alcohol addiction to understand, reduce and stop smoking. The program utilizes multimedia technology to tailor intervention material to clients' stage of change with respect to smoking. Based on the metaphor of a television network, users are able to access their own personal "channel" broadcasting a selection of "shows," each of which represents an entertaining, educational oriented intervention tailored to the user's stage-of-change, concerns about smoking and smoking cessation, and other key variables. Phase I involved the gathering of feedback from interviews, focus groups with professionals, interviews with experts, and acceptance and satisfaction testing to develop the "On the Air" prototype. Phase II will involve the completion of the "On the Air" CD-ROM, acceptance and satisfaction testing, and implementation of a comprehensive field test of the program. If "On the Air" were shown to demonstrably increase clients' motivation to actively quit smoking, the national commercial potential would be significant. PROPOSED COMMERCIAL APPLICATION: The proposed program will provide a targeted, computer-administered intervention to facilitate smoking cessation for alcoholic clients. Despite extremely high proportions of alcoholics who smoke (as much as 90%), and the growing evidence of addictive and even synergistic health consequences of abusing both alcohol and tobacco, few alcohol treatment programs directly address client smoking. Limited financial and staff resources and a general lack of reimbursement for smoking interventions are some of the barriers to integrating smoking cessation efforts into ongoing treatment programs. If a computerized, affordable smoking cessation program caLVAL(n be shown, in field trials, to have demonstrable efficacy, the commercial potential can be extraordinary.LVAL"XH 4 ` @ H r`6NAddiction Epidemiology and National Surveillance Interventions for Prevention and TreatmentEpidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentEpidemiology and National Surveillance Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentEpidemiology and National Surveillance Interventions for Prevention and TreatmentAwareness Risk Perception and Communications Community and Policy InterventionsBiology and Cancer Epidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentEpidemiology and National Surveillance Awareness Risk Perception and Communications Community and Policy InterventionsBiology and Cancer Epidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceEpidemiology and National Surveillance Interventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentInterventions for Prevention and TreatmentEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and Treatment  s 0 r_<NNn@@Researchn@\COSTELLOELIZABETHDUKE UNIVERSITYDURHAMNCNIDAR01, DA011301a'+p.j@IR@X@]9/30/19978/31/20049/30/1997 to 8/31/20044/2005pjf^MB88,"MM`g@K@Researchp@\COONEYNEDYALE UNIVERSITYNEW HAVENCTNIAAAR01, AA0111970_'+p.T@In@XP@]8/1/19977/31/20028/1/1997 to 7/31/20024/2005{leaVE@88,"LL^@@@Research@\CONWAYTERRYSAN DIEGO STATE UNIVERSITYSAN DIEGOCACDMRPPR033058F@^L@IR@X^@]200320062003 to 20064/2005yrncG@88,"KK@Y@R@ResearchJ@\CHRISTIANIDAVIDDIV. OF CANCER CONTROL AND POPULATION SCIENCESBOSTONMANCIR01, CA074386['+p.t@Il@X@R4/10/19974/30/20084/10/1997 to 4/30/20084/2005{KD88,"JJR@@Researchr@"CHOWWONG-HODIV. OF CANCER EPIDEMIOLOGY AND GENETICSBETHESDAMDNCIZ01, CP010123 Y'+p.L@I@X,@R9/26/20029/30/20039/26/2002 to 9/30/20034/2005{qG>88,"II@y@@Researchp@!CHOUCHIH-PINGUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANCIR01, CA098763NV'+p.b@IR@X@R8/1/20037/31/20058/1/2003 to 7/31/20054/2005}ylI>88,"HHg@@@Researchd@ CHENXINGGUANGUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANCIP50, CA084735v @Ub@I@>@RNot Given2003? to 20034/2005}ylI>88,"GG @@@Research NICOTINE AND BRAIN DEVELOPMENTCHENWEI-JUNGTEXAS A&M UNIVERSITY HEALTH SCIENCES CENTERCOLLEGE STATIONTXNINDSR01, NS039899(S'+p.Biology and CancerR@8@R4/1/20003/31/20054/1/2000 to 3/31/20054/200580h^XX,"FF @`@Research@CHAPINJANETAMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTSWASHINGTON DCRWJF38611Not availableT@IDiscovery 1c Development 3@R4/1/20002/28/20054/1/2000 to 2/28/20054/2005*"  |G@88,"EE @@Researchx@CASABURIRICHARDHARBOR-UCLA RESEARCH AND EDUCATION INSTITUTELOS ANGELESCACTRDRP10RT-0046P'+p.Biology and Cancerl@Z@R7/1/20016/30/20047/1/2001 to 6/30/20044/2005 yKB88,"DDG@@@Researchl@CARPENTERCATHERINEUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECACTRDRP11IT-0082N'+p.Biology and CancerR@>@D7/1/200212/31/20037/1/2002 to 12/31/20034/2005 ~zrNC88,"CC @@ResearchPHARMACOGENETIC STUDIESCAPORASONEILNATIONAL C ANCER INSTITUTEBETHESDAMDNCIZ01, CP005804P*K'+p.Biology and Cancerl@D@D9/30/19999/30/20039/30/1999 to 9/30/20034/2005}a[QQ,"BB@@@Researchd@BUTLERSTEVEINFLEXXION, INC.NEWTON MANIDAR44, DA080460G'+p.T@I@B@D8/5/20013/31/20058/5/2001 to 3/31/20054/2005{lfbYG@88,"LVAL'+p.LPharmacogenetic Studies. Pharmacogenetics involves the study of host susceptibility and environmental exposures in cancer development. The unique contribution of this discipline is that common genes are studied, and the role of the environment is more explicit because the mechanism of the putative polymorphic gene of interest is known. The study base is the population, but family studies often complement this work. We primarily focus on molecular epidemiology studies involving lung and lymphoproliferative cancers and occasionally explore special exposures such as dioxin. The major aim is to identify and better understand genetic components that contribute to major cancers. The studies involve interdisciplinary efforts and emphasize the integration of epidemiological, genetic, and laboratory approaches. Lung Cancer: GEB has been a pioneer in studies aimed at identifying a genetic component to common cancers using epidemiological study designs and we currently have a large lung cancer case-control study in the field (see below). Early work emphasized polymorphic genes (e.g., CYP2D6, GSTM1) that are hypothesized to activate or detoxify carcinogens and thereby alter an individual's susceptibility to cancer when exposed to a specific agent. Lung cancer is a logical focus for these studies, because the environmental agent is well characterized (i.e., tobacco smoking), although only a minority of heavy smokers develop the disease. Furthermore, somatic gene mutations are well documented in lung tumors and relatives of people who develop the cancer are also at increased risk. To better understand the genetic component to smoking-related cancer we have conducted case-control studies of lung cancer with extensive biospecimen collection; studied determinants of the cancer in nonsmokers; studied cancer in different geographic, occupational, and ethnic groups; and examined tumor mutations in consecutive surgical cases. We are currently involved in studies to evaluate whether genes contribute to precursor conditioLVALMns (i.e. emphysema) or to the key exposure (i.e. smoking). Families with lung and other smoking-related cancers have been studied, although suitable large, multi generation families are challenging to accrue because of the death toll for smoking-related diseases. Integrated Studies: In our single largest study, we are investigating the genetic determinants of lung cancer and smoking in a multi-hospital, population-based case-control study of lung cancer with sufficient power to detect gene-environment interactions, biospecimen collection to allow interdisciplinary study of biomarkers from normal and neoplastic tissue, tissue collection from lung cancer surgical cases, and the planned study of genetic determinants of smoking in controls. This study is currently in the field in Milan, Italy. We also participate in NCl's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Study, which is a cohort study of 70,000 individuals in which large numbers of lung cancer cases will be identified over the next few years. Currently studies of the genetic determinants of emphysema and the genetic determinants of smoking are planned. A related component, the National Lung Cancer Screening Trial (NLST) is planning to randomize over 50,000 high risk subjects to chest x-ray or helical CT scan, a promising new imaging technique that may detect lung cancer in an early curable stage. We have proposed collection of biospecimens on the screened population so both early markers and molecular determinants of benign vs. malignant outcomes can be explored. We also plan to address the hypothesis of a genetic component to smoking itself. We have examined genetic polymorphisms affecting dopamine regulation and receptor stimulation as candidates for influencing genetic susceptibility to cigarette smoking. Preliminary findings suggest that the dopamine transporter gene (DATI), which governs the reuptake of dopamine from the neuronal synapse, and the D2 dopamine receptor gene (DRD2), which is a postsynaptic receptor, may ilLVAL|nteract to influence smoking behavior. This finding suggests that smoking may be influenced by an interplay among multiple genes affecting dopaminergic reuptake and receptor stimulation. Understanding the mechanisms of dopaminergic genes in smoking may facilitate development of improved strategies to prevent smoking and help smokers quit the habit. Other Tumors and Exposures: We collaborate in studies of genetic susceptibility for a wide variety of other tumors. We have recently described a role for GSTTI as well as NAT1/NAT2 in prostate cancer. Unusual population exposures provide an opportunity to test for the role of mechanistically plausible genes in cancer causation. One example is the industrial accident that contaminated Seveso, Italy, with the highly toxic compound 2,3,7 ,8-tetrachloro-dibenzo(p )-dioxin (TCDD). Two decades after the incident, a population-based study was designed to determine current TCDD levels in healthy individuals from the contaminated zones and surrounding areas. We previously showed that TCDD levels were significantly higher in women than in men in both the contaminated and surrounding areas. Future research will examine the relation between risk of dioxin-related chloracne and cancer to dose as well as to expression of polymorphisms of candidate genes, including CYPlAl and the Ah receptor.LVAL'+p.OSmokers have a much greater chance of developing lung cancer than non-smokers. What remains to be determined is why some smokers get lung cancer while the majority do not. Many studies of large populations have found that eating fruits and vegetables protects against lung cancer, however it is not known what part of fruits and vegetables is responsible. In the past it was thought that beta carotene protected against lung cancer, but results from large clinical trials showed that smokers who consumed large quantities of beta carotene had a greater chance of developing lung cancer than smokers who consumed lower amounts of beta carotene. Recent studies of cruciferous vegetables such as cabbage and broccoli have been shown to protect against lung cancer. A substance found in broccoli called isothiocyanate (ITC), is thought to be responsible for the protection, because administering ITC to animals reduces the ability of substances known to produce cancer from creating tumors. We recently conducted a study among Shanghai Chinese where we found that Chinese who had large amounts of ITC in their urine had a lower chance of developing lung cancer than Chinese who had smaller amounts. It is important to measure ITC in the urine because then we will have a more accurate way to determine how much ITC our study subjects consumed, rather than only relying on how well they reported what they ate. Measures of ITC in the urine also tell us about the specific action of ITC, and not other compounds such as beta-carotene. We propose to measure ITC in the urine of both African Americans and Caucasians so that we can develop a baseline measure among healthy people of both ethnic groups. We plan to determine whether there might be differences between the two groups. We also would like to see if ITC level differs according to whether our subjects currently smoke, whether our subjects are men or women, whether our subjects are exposed to passive smoke, and according to genes that are known to influence the metabolism of* LVAL: ITC as well as the metabolism of carcinogens from cigarette smoke. We collected urine specimens of lung cancer patients and healthy control subjects in the early 1990's when we conducted a population study of African Americans and Caucasians in Los Angeles. A study sample of 599 healthy individuals who previously provided urine specimens, answered our study questionnaire, and completed a dietary questionnaire will be available to the current proposed research. We will send the urine specimens to the American Health Foundation in Valhalla, New York for measurement of ITC. ITC may be a supplement people, especially smokers, can use to reduce their chances of developing lung cancer. However only a few studies have been conducted on ITC. With the present study we can further establish the role that ITC may play in protection from developing lung cancer.LVAL'+p.QThis project aims to improve the effectiveness of medical treatment for women with lung disease produced by cigarette smoking. Chronic obstructive pulmonary disease (COPD, also called emphysema or bronchitis) is a disorder affecting approximately 14 million people in the United States. It is a disabling disorder and inability to exercise is usually the foremost problem. It is becoming clear that these patients suffer not only from poorly functioning lungs but also because the muscles of ambulation perform poorly. We have recently shown that muscle function can be improved in men with COPD both by strength training and by giving supplemental testosterone, a drug known to build muscles. Until now, most research into methods to improve muscle function has involved only men. However, the number of women suffering from COPD is accelerating and is nearly equal to that of men. The body chemicals that stimulate muscle growth operate differently in women than they do in men. We will focus on two specific strategies intended to improve the muscle's ability to tolerate exercise. First, there is a growing realization that testosterone is not only a  male hormone. Though levels in women are much lower than in men, studies in healthy women suggest that testosterone supplementation increases muscle size. We have found that women with COPD have low levels of this chemical. However, the amount of testosterone that best balances the benefits of testosterone without creating troubling side effects has yet to be determined. We will determine whether administering testosterone to women with COPD will increase muscle mass and exercise tolerance. Second, we have found that women with COPD usually have a low level of activity; we will determine whether a strength conditioning program consisting of a varied group of exercises improves exercise tolerance. We will assign by chance 72 women with COPD to one of six groups. Four of the groups will receive no training, but will apply a gel to their skin daily that w LVAL0ill contain no testosterone or one of three doses of testosterone. Two of the groups will receive strength training (for one hour a day three times per week) plus either a gel with no testosterone or with the highest of the three doses of testosterone. A number of state-of-the art measurements will be made before and after the 10 week study period including 1) precise measurement of the muscle and fat mass in the body, 2) muscle strength by weight lifting and by measuring the electrical activity of the muscle, 3) exercise capacity measured on a stationary bicycle, 4) strength of the breathing muscles and 5) the overall quality of life, assessed by well designed questionnaires. In this study, a number of safeguards will be in place to assure the participants' safety. Programs are already in place to help rehabilitate patients with COPD. This study should be directly applicable to these programs and will help to decrease the suffering of patients with this smoking-related disease.LVAL V 6DISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Non-Specified Tobacco UseAGE Child Young Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National International MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION African American American Indian/Alaskan Native Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Cigarette/Other Smoking Nicotine WOMEN PregnancyPREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesLVAL'+p.TThe overall purpose of this proposal is to evaluate developmental nicotine-induced neurotoxicity. Despite the Surgeon General's warning concerning the harmful effects of smoking on the developing fetus, there is still a disturbing number of pregnant women who smoke during pregnancy. This proposal will utilize a rat model system to examine how and to what extent nicotine affects the developing brain. The proposal will test several hypotheses that are categorized into three Specific Aims. Specific Aim number 1 will test two hypotheses: 1) that nicotine exposure during all three trimesters equivalent will result in region-specific reductions in neuronal numbers in two important brain regions (hippocampus and cerebellum) in neonates and young adults; and 2) that the long-term brain deficits resulting from developmental nicotine exposure will be manifested through and correlated with specific behavioral impairments, spatial learning and parallel bars tasks, respectively. The exposure regimen used in Specific Aim number 1 is especially clinically relevant, since most pregnant women who smoke do so throughout pregnancy. Specific Aim number 2 will test two hypotheses: 1) that nicotine exposure during the third trimester equivalent (the brain growth spurt period) will lead to more severe neuronal loss than exposure restricted to first or first and second trimesters equivalent, and 2) that the cessation of nicotine exposure gestation will be beneficial to the developing brain. Specific Aim number 2 is important in addressing the questions regarding temporal vulnerability and the potential interaction between brain-regional specificity and temporal factors in mediating differential effects on nicotine-induced neuronal loss. Specific Aim number 3 will begin to address the question of mechanisms underlying nicotine-induced neuronal loss by testing the hypothesis that the application of specific neurotrophic factors (brain-derived neurotrophic factor [BDNF] and glial-derived neurotrophic factor [GDNF]) wilLVALl attenuate nicotine-induced neuronal loss in an organotypic explant culture system. Specific Aim number 3 is the fist step to identify the involvement of specific neurotrophic factors as one of the underlying mechanisms for developmental nicotine-induced neuronal loss. The proposal will incorporate innovative in vivo and in vitro approaches to evaluate nicotine's toxicity during brain development, and many of the experimental techniques (artificial-rearing for third trimester equivalent exposure, 3-D stereological cell counting, organotypic explant culture system) proposed to be implemented in this proposal are novel to developmental nicotine research. The proposed studies will contribute to and broaden our knowledge of the harmful consequences from maternal smoking during pregnancy, provide a better understanding of the potential risk that may influence the severity of nicotine-induced brain deficits during different stages of development, and lead to a focus on mechanistic issues regarding developmental nicotine-induced neurotoxicity.zLVALDespite the nationwide anti-smoking efforts, cigarette smoking has increased among adolescents across ethnicity/culture in the last decade. Although numerous studies and tobacco control programs have focused on many specific aspects of cigarette smoking among adolescents, the process by which adolescents program from never smokers to susceptible non-smokers, smoking experimenters, and regular smokers has not been sufficiently investigated. The dramatic ethnic and cultural differences in cigarette smoking among adolescents suggests the importance of acculturation, media and social influences in smoking acquisition. With longitudinal data from two cohorts, 17,500 7th graders, 12,500 from California, a state with the most ethnically diverse population in the United States, and 5,000 from Wuhan, China, a mid-level industrial provincial capital with 7 million Han population, this project seeks to understand the progression process of cigarette smoking among adolescents across culture and ethnicity. With a cross-culture and transdisciplinary approach, the progression from never smokers to susceptible non-smokers, to smoking experimentation and, finally to regular smokers including addicted and chipper smokers will be examined. In addition to pro-tobacco media, social influences (parents and peers), the role of acculturation in predicting smoking progression will be examined in detail. Cross-ethnicity, cross-country and cross- gender comparisons will also be made to gain inside into gender and ethnic differences in cigarette smoking progressions. The findings from this project will facilitate the development of effective anti-smoking interventions geared toward our increasingly multi-cultural society.LVAL'+p.WFrom the mid-1970's to 1992, the prevalence rates of cigarette smoking among youth in the United States steadily decreased. However, these rates increased from 1992 and peaked in 1997. During the past five years, a steady decline in tobacco use among youth has again been observed. A similar pattern has also been observed in California. In this study, we will use secondary analysis of archival data from two youth tobacco surveys in California to determine whether this inverted V-shaped trend applies to various smoking behaviors (e.g., 30-day and weekly smoking behaviors) among youth in California. We will also examine the trends of cigarette use across different age groups and birth cohorts. Furthermore, we will identify several risk and protective factors of tobacco use (e.g., friends' smoking, social norms) and examine their patterns of change and impacts on tobacco use in the last ten years using two newly developed statistical approaches: age-period-cohort analysis and multilevel structural equation model. The proposed data sets (California Youth Survey and California Tobacco Youth Survey) to be analyzed in this project provide a rich array of cross-sectional data from 1990 to 2000. Each cross-sectional sample provides a replicated survey of tobacco use among youth in California. This project proposes to analyze the cross-sectional data using multiple regression, logistic regression, and structural equation models. Information obtained from the replicated cross-sectional samples provides a profile of changes across time. Furthermore, they can be studied using the multilevel approach to gain a better understanding of the long-term trend of tobacco use, changes in tobacco use-related psychosocial factors, and changes in the impacts of those factors on tobacco use across time. The project is important because it will identify factors associated with recent trends in cigarette smoking, which will help in specifying critical components for tobacco use prevention programs, leading to efficient and well-tLVALargeted prevention intervention programs for youth.LVAL$f : $ d  | f"~,"Discovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1c Discovery 2a Discovery 2b Development 1 Development 3 Delivery 1 Delivery 2 Partnerships 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 2a Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Discovery 3 Development 1 Evaluation 1aDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1c Discovery 2a Development 1 Delivery 2 Evaluation 1aDiscovery 2a Discovery 2b Development 3 Development 4 Development 5 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1a Evaluation 1bDiscovery 2a Discovery 2b Development 3 Delivery 2 Delivery 4 Partnerships 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1a Discovery 1b Discovery 1c Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Discovery 3 Development 1 Delivery 1 Evaluation 1aDiscovery 1c Development 1 Delivery 1 Evaluation 1aDiscovery 1c Discovery 2a Development 2Discovery 1a Discovery 1c Development 1 Delivery 2 Evaluation 1aDiscovery 1c Discovery 2a Development 1 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 2 Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1c Discovery 3 Development 2 Evaluation 1aDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1aLVAL'+p.ZTraditionally, occupational research has focused primarily on white men, even though women comprise 46% of the U.S. civilian workforce, and minorities are often employed in jobs with hazardous exposures. The OEB has undertaken a number of epidemiologic studies with a substantial focus in occupation which include women and minorities during the past year. A multicenter case-control study of bladder cancer is launched to examine environmental and occupational risk factors for the consistently elevated incidence and mortality of this cancer in New England. A hospital-based case-control study of kidney cancer with a major focus on occupational exposures is initated in Central and Eastern Europe, while a population-based case-control study of renal cell cancer among Caucasian and African Americans in the United States was initiated last year. Currently a telephone interview survey is updating exposure information in the Agricultural Health Study, a prospective cohort study of more than 90,000 subjects, including approximately 32,000 women and 2,000 minorities. Both direct occupational exposure and indirect environmental exposure to pesticides and other exposures will be evaluated in the study. The Shanghi Women's Study is a prospective cohort study of 75,000 women conducted in collaboration with Vanderbilt University and the Shanghai Cancer Institute. Baseline data collection is completed in Spring, 2000. Blood/buccal cell and urine samples have been collected from nearly 90% of participants. This cohort will provide a valuable resource for evaluation of environmental and genetic risk factors for cancer among women. Analysis are on-going to examine the association of smoking, occupation, diet, and anthrometric measurements with risk of prevalent breast cancer and other chronic conditions. In another on-going prospective cohort study among participants in a screening trial (PLCO Study), about 50,000 women have been enrolled for follow-up studies of cancer risk factors. Other studies are also underway that fLVALocus on cancer among hairdressers, aircraft maintenance workers, and drycleaners on the relationships between occupational exposures, particularly pesticides, solvents, and dusts, and non-Hodgkin's lymphoma, multiple myeloma, and cancers of the pancreas, brain, and stomach in projects which include women and minorities. Feasibility and methodologic projects were also conducted for the study of cancer among migrant farm workers, the majority of whom are Hispanic. Questionnaires involving an innovative life events-icon method of collecting occupational histories were developed and tested as well as projects to test the ability to trace farm workers over extended periods of time, to study mortality patterns, to evaluate cancer diagnosis and treatment patterns, to assess exposures via biological measures using cord blood, and to add epidemiologic variables to a national data base of information collected from farmworkers who are applying for social services. The materials and methods developed in the feasibility projects will help NCI and others to launch full-scale studies of cancer. In addition, analyses are on-going in several case-control studies that include a large proportion of women and minorities, including a study of occupational and environmental cancer risk factors in Iowa, a 24-State death certificate study, the Swedish cancer-environment linked-registry study, a multicenter study of cancer risks among whites and African Americans, case-control studies of stomach cancer in Mexico and Poland, a case-control study of several gastrointestinal cancers in Shanghai, China, a cohort study of farmers in Xuanwei, China, and a study of oral cancer in Puerto Rico. Recent findings including similar reduction in lung cancer risks following home stove improvement in Xuanwei, and excess risks of cancers of the esophagus, larynx, and lung, and Hogkins disease among dry clearners, the majority of whom were women.PLVAL'+p.`Lung cancer is the most common cause of cancer mortality among both men and women in the United States. Although up to 90 percent of lung cancer is attributable to cigarette smoking, only 10-20 percent of smokers develop bronchogenic carcinoma over their lifetimes. This observation, along with substantial literature implicating heritable polymorphic factors, indicates that other environmental and host factors influence individual susceptibility to tobacco smoke. This proposal will take advantage of recent advances in molecular epidemiology in this competing continuation (R01 CA 74386) by expanding our original aims of evaluating six xenobiotic metabolic polymorphisms in lung cancer to include the assessment of more recently described polymorphic genes that control oxidative metabolism (Phase I) and the conjugation of reactive intermediates (Phase II). In addition, a number of other polymorphic genes that affect lung inflammatory processes, DNA repair, growth factor function, and tumor suppression (oncogenes) will be evaluated, as there is accumulating evidence supporting the role of these non-metabolism polymorphic alleles in lung cancer development. Moreover, this proposal addresses the role of smoking, diet, and genetic factors as effect modifiers for the association between polymorphisms and lung cancer risk, and the potential roles of age and gender in these associations. To assess these gene-environment and gene gene associations in this expanded group of polymorphic genes, our proposal will build on our productive R01 by increasing our sample size and including greater population diversity by increasing minority recruitment. A better understanding of these risks will lead to improved preventive strategies. The proposal directly addresses two "Extraordinary Opportunities" of the National Cancer Institute, specifically the aim to identify genetic variations that affect cancer risk in concert with environmental factors, and research on tobacco-related concerns.LVAL B & F : b tL>t"`COGNITIVE BEHAVIORAL THERAPY FOR SUBSTANCE-USING ANGRY YOUTHDETERMINANTS OF DRUG PREFERENCE IN HUMANSACTIVE AND PASSIVE SMOKING AND THE RISK OF BREAST CANCERFIRST MEDICINES RESEARCH PLANNING PROJECTTOBACCO: PRENATAL EFFECTS AND ADOLESCENT USEINFECTION AND CARDIOVASCULAR DISEASEIMPULSIVITY AND TREATMENTS FOR RELAPSE PREVENTION IN SMOKINGANOGENITAL CANCER--EPIDEMIOLOGY/BIOCHEMISTRY/IMMUNOLOGYPEDIATRIC SMOKING CESSATION STUDYCOUNTERING TOBACCO ADVERTISING IN DIVERSE POPULATIONSEPIDEMIOLOGY OF AGE RELATED HEARING LOSSSMOKING RESEARCH WITH INCARCERATED FEMALESTHE ALABAMA TOBACCO FREE FAMILIES PROGRAMEPIDEMIOLOGIC AND BIOLOGIC PREDICTORS OF IVF SUCCESSTHE EFFECT OF TOBACCO SMOKE ON IMMUNE FUNCTION IN TWINSPILOT--GENDER/BONE MINERAL DENSITY IN PULMONARY DISEASEDETERMINANTS AND TRAJECTORIES OF SMOKING CESSATION, MAINTENANCE, AND RELAPSE AMONGST PREGNANT AND POSTPARTUM ADOLESCENTS: A NATURALISTIC QUALITATIVE STUDYLUNG HEALTH STUDY--LONG TERM FOLLOW-UP DATA COORDINATION CENTERSHS TREATMENT FOR POSTPARTUM AFRICAN AMERICAN SMOKERSPOSTPARTUM SMOKING AND INFANT ETS REDUCTION TRIALEFFECTS OF NICOTINE ON BRAIN DEVELOPMENT ASSESSED BY 1H-MRSBODY IMAGE TREATMENT FOR WEIGHT CONCERNED SMOKERSAN EVALUATION OF VIDEOTAPED VIGNETTES FOR SMOKING CESSATION AND RELAPSE PREVENTIONSA MOOD MANAGEMENT INTERVENTION FOR PREGNANT SMOKERSGENETIC FACTORS IN THE MODULATION OF MOOD BY NICOTINEMOLECULAR EPIDEMIOLOGY OF ADENOCARCINOMA OF THE LUNG CANCERMAINTENANCE TREATMENT FOR PREVENTION OF SMOKING RELAPSECOLORECTAL CANCER RISK: ASSOCIATION WITH EPIDEMIOLOGIC FACTORS AND GENETIC POLYMORPHISMS IN SELECTED ENZYMES THAT ACTIVATE CARCINOGENS AND METABOLIZE ESTROGENSVULNERABILITY TO DRUG ABUSE--A TEST OF COMPETING MODELSFIELD STUDY OF SMOKING CESSATION IN ALCOHOLISM TREATMENTPREDICTING ATTRITION, PERFORMANCE, REENLISTMENT, AND HOSPITALIZATIONS FROM THE SMOKING HISTORY OF WOMEN PRIOR TO ENTERING THE NAVYGENETIC SUSCEPTIBILITY TO LUNG CANCERLVALR xDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms LOCATION National RESEARCH Human Studies TOBACCO Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse ECONOMICS Socio-Economic Status Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy Other Pharmacological RESEARCH Human Studies Clinical Research STUDY POPULATION African American Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Young Adult EPIDEMIOLOGY/SURVEILLANCE Small (< 100) Large (>=100) LOCATION Urban Rural National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors STUDY POPULATION African American American Indian/Alaskan Native Asian Pacific Islander Caucasian Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Nicotine Replacement Therapy RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking"LVAL 8To develop a theoretical framework that explains the processes and experiences of smoking cessation, maintenance, and relapse among pregnant and postpartum adolescents, and to provide a theoretical foundation for potential intervention approaches and strategies specifically targeted to this group. The effectiveness of a program to stop smoking and to prevent relapse among pregnant women smokers was examined through this study.Relevance: Colorectal cancer is caused by both inherited and environmental factors. It appears that common genetic changes called polymorphisms in a person's cells may increase that person's risk of colorectal cancer. That risk is also thought to be increased in people who eat overcooked red meat or who smoke - possibly because genetic polymorphisms affect the function of certain enzymes that activate the cancer-causing substances found in overcooked meat and tobacco products. Dr. Cotterchio's team is studying the association between colorectal cancer risk and genetic polymorphisms in a large group of Canadians. Their results will increase our understanding of how this cancer develops and may suggest new ways to prevent it. Description: Dr. Cotterchio's team plans to measure the occurrence of certain genetic polymorphisms in blood samples from more than 1200 men and women with colorectal cancer and 700 healthy men and women. They will then analyze the results to see whether certain polymorphisms appear to make a person more likely to develop colorectal cancer, and to study the links between these polymorphisms and lifestyle factors (such as smoking).The proposed study will focus specifically on women sailors and determine whether their tobacco use before entering the U.S. Navy is predictive of subsequent job performance, testing the general hypothesis that smoking at entry is related to attrition before completing the first term of enlistment, poorer career advancement, more disciplinary problems, lower reenlistment, and more hospitalizations of various types. LVAL'+p.`This study was designed to increase understanding about the alcohol-tobacco interaction processes that impact the treatment of individuals with combined alcohol and nicotine dependence. Treatment outcome methodology will be combined with sophisticated Ecological Momentary Assessment methodology in order to examine the extent to which smoking serves as a cue for alcohol craving and/or a response to alcohol craving in treated alcoholics. A secondary aim of the study will be to examine treatment outcome effects of delivering a smoking cessation intervention concurrent with ambulatory treatment for alcohol dependence. If smoking cessation treatment is found to affect alcohol outcome, further analyses will be conducted to determine the impact of possible mediators of this effect such as alcohol abstinence self-efficacy and alcohol-related coping skills. Subjects will be 112 alcoholics who have requested alcohol treatment and are willing to attempt smoking cessation. Subjects will be veterans participating in the Substance Abuse Day Programs at the Newington and West Haven campuses of the VA Connecticut Healthcare System. Non-veteran women will be recruited from the community and enrolled in the Day Program to ensure adequate gender representation. One week after admission to the Day Program, subjects will be randomly assigned to one of the following two conditions: (1) Intensive smoking cessation therapy (behavioral counseling plus nicotine replacement using nicotine patches) concurrent with alcohol treatment, or (2) Brief smoking cessation advice concurrent with alcohol treatment. Two days before completing the Day Program, subjects will be instructed in self-monitoring of moods, situations, drinking, smoking and urges to drink or smoke using a hand-held computer that will beep them for assessment at random times 4 times/day. They will also be instructed to activate the computer immediately prior to, and just following, smoking each of four cigarettes per day. After leaving treatment they will continue toLVAL self-monitor for 14 days. Outcome will be measured at 14 days, three months and six months posttreatment using interviews, questionnaires, and biological measures.LVAL'+p.bThis proposal seeks funding to continue to test two competing hypotheses about the etiology of problem drug use: H1 : Early onset drug users (before age 16) are at increased risk of later problem drug use, relative to later onset drug users; H2: Early-onset drug users are at a significantly increased risk of problem drug use, compared with later-onset users, only if they have comorbid psychiatric problems in childhood. The proposal responds to NIDA's program announcement DA-91-33, "Vulnerability to drug abuse". The proposal capitalizes on the Great Smoky Mountains Study (GSMS), a longitudinal research program on childhood predictors of alcohol, drug, and mental (ADM) disorders and comorbidity. In 1992-93 a representative population sample (N = 1,422) of 9, 11, and 13-year-olds, stratified on parent-reported behavioral and drug problems, was selected from a mixed rural-urban area of the southeastern United States. American Indians (mainly Cherokee) were over sampled so that all age-appropriate youth (N=349) were recruited. Response rate was 80% for both groups. Participants ( 50% female) and parents/caretakers have been interviewed annually for 4 years, using a highly-structured interview for ADM disorders. Data include use and abuse of tobacco, alcohol, marijuana and hard drugs, psychopathology and DSM-IV diagnoses, level of functioning at school, at home, and with peers, need for and use of services for ADM disorders, risk and protective factors including physical health and development, family functioning and family history of ADM problems and treatment, and community resources. Analyses to date show early-onset drug users (N=357) to have high rates of emotional (girls) and behavioral disorders, and a family history of drug problems. Cherokee youth have started drug use earlier and escalated faster than others. In the next 5 years we propose to reinterview each cohort at age 15 and 18, and the oldest cohort at age 21, keeping contact between interviews using computer-assisted telephone interviews. T LVAL ests of the hypotheses will use (weighted) random regression modeling to capitalize on the strengths of the longitudinal data. This is the first study capable of testing these competing hypotheses prospectively using state of-the-art assessment of ADM disorders, in a representative population sample of both sexes, with two ethnic groups to test generalizability. Support for the first hypothesis makes the case for primary (universal) prevention programs: support for the second mandates interventions targeted at high-risk groups.  G  fF!![[@@Researchn@\COVEYMARGARETUNIVERSITY OF ILLINOIS AT CHICAGOCHICAGOILNINRP20, NR007812Hx7+p.Biology and Cancerl@Xr@u8/15/20017/31/20048/15/2001 to 7/31/20044/2005yulI?88,"ZZ 1@@Research6@\CONSTANTINENORMANPUBLIC HEALTH INSTITUTEOAKLANDCARWJF40675V@^b@IR@XD@u200220042002 to 20044/2005ysofME88,"YY`~@@Research~@\CONNETTJOHNUNIVERSITY OF MINNESOTA TWIN CITIESMINNEAPOLISMNNHLBIU10, HL059275Zv7+p.@I@X@u2/1/19981/31/20052/1/1998 to 1/31/20054/2005}ylGA88,"XX@@@Researchj@ \COLLINSBRADLEYUNIVERSITY OF PENNSYLVANIAPHILADELPHIAPANCIR01, CA105183~s7+p.T@I@X@u7/16/20046/30/20097/16/2004 to 6/30/20094/2005}xtfJA88,"WW;@@@Researchb@ \COLLINSBRADLEYUNIVERSITY OF PENNSYLVANIAPHILADELPHIAPANCIK07, CA093756q7+p.T@Il@ X@j3/27/200212/31/20063/27/2002 to 12/31/20064/2005}xtfJA88,"VV@1@Researchv@ \CLOAKCHRISTINECEDARS-SINAI MEDICAL CENTERLOS ANGELESCACTRDRP8DT-0170o7+p.Biology and CancerDiscovery 1b Evaluation 1b@j1/1/200012/31/20011/1/2000 to 12/31/20014/2005!xtgJ?88,"UU!@@Researchb@ \CLARKMATTHEWMAYO CLINIC COLLEGE OF MEDICINEROCHESTERMNNCIR03, CA093183m7+p.T@ IR@ X @j9/1/20018/31/20049/1/2001 to 8/31/20044/2005}xtiH?88,"TTg@p@4Research@ \CINCIRIPINIPAULUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNot givenNot Given@^@ I@ X"@jNot GivenNot GivenUncertain4/2005zKE88,"SS@y@R@Researchf@\CINCIRIPINIPAULUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNIDAR01, DA014301k7+p.T@ Ip@ X@j8/1/20034/30/20088/1/2003 to 4/30/20084/2005zKE88,"RR@!@Researchj@\CINCIRIPINIPAULUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNCIR21, CA081649 g7+p.Biology and Cancer AddictionP@ Xn@j9/1/19998/31/20019/1/1999 to 8/31/20014/2005zKE88,"QQ`@Y@Researchv@\CHRISTIANIDAVIDDANA-FARBER CANCER INSTITUTEBOSTONMANCIP20, CA090578e7+p.t@ I@X@]9/19/20036/30/20089/19/2003 to 6/30/20084/2005zuqiKD88,"PP@@Researchn@\COVEYLIRIONEW YORK STATE PSYCHIATRIC INSTITUTENEW YORKNYNIDAR01, DA013490d7+p.j@ I@X@]8/20/20004/30/20058/20/2000 to 4/30/20054/2005zvlF?88,"OOG@ @Research@@\COTTERCHIOMICHELLECANCER CARE ONTARIOTORONTOON, CANADANCICNot Given& @^Biology and Cancerl@X@]7/1/20027/1/20047/1/2002 to 7/1/20044/2005~xlcND88,"LVAL7+p.More than one quarter of US adults are cigarette smokers and the vast majority would like to stop smoking. Among smokers unable to do so on their own, treatments that enable many of these smokers to quit in the short-term have been developed. However, whether stopping on their own or with the help of formal programs, it is clear that more than half of initial successes will return to smoking. This study will examine the problem of tobacco relapse. The primary aim of this study is to test whether, after achieving initial success, the risk of relapse during the next several months can be significantly reduced by maintenance pharmacotherapy. Seven hundred and fifty subjects (50 percent female, 50 percent white, 25 percent African American, 20 percent Hispanic, 5 percent Asian or Other) will be entered initially in an open treatment phase. Roughly 400 of the successes from this open treatment will be randomized in double- blind fashion, in a 2 x 2 factorial design to one of four treatment arms (bupropion or placebo and nicotine gum or placebo gum). The primary efficacy measure will be time to relapse according to treatment condition. Data obtained from this study will be examined further to address three additional aims: 1) to understand the effects on relapse of psychological (e.g., number of cigarettes smoked, nicotine dependence level, major depression history, personality factors, weight gain) and sociodemographic factors (e.g., age, gender, race, socioeconomic status) identifiable either before treatment begins or after initial cessation has occurred: 2 ) to conduct a cost-effectiveness analysis comparing the incremental societal costs and effects (i.e., treatment costs, smoking relapses prevented, lives saved, life-years saved, and quality of life years saved) of the active maintenance treatments compared with no maintenance treatment; and 3) collect and DNA samples for future genetic studies.LVAL7+p.fAdenocarcinoma has become the most common histologic subtype of lung cancer in North America, and the proportion of lung cancers that are adenocarcinoma continues to rise. Although up to 90% of lung cancer is attributable to cigarette smoking, only 10-15% of smokers develop bronchogenic carcinoma in their lifetime. This observation, along with substantial literature implicating heritable polymorphic factors, indicates that other environmental and host factors influence individual susceptibility to tobacco smoke. This proposal will take advantage of an existing large case-control study of lung cancer and expand recruitment to focus specifically on the molecular epidemiologic analysis of lung adenocarcinoma risk. The role of a number of polymorphic xenobiotic metabolism enzymes involved in oxidative metabolism (Phase I), and the conjugation of reactive intermediates (Phase II) in lung adenocarcinoma risk will be examined, along with polymorphisms of genes involved with growth suppression, inflammatory and DNA repair pathways (Aim 1). Clinical, epidemiology and biologic information has suggested potential roles for gender factors, age, and environmental tobacco smoke (ETS) exposure in the specific development of adenocarcinoma of the lung, compared to other histologic subtypes. To address these gene-environment, gene-gender, gene-age, gene-ETS and gene-gene associations in lung adenocarcinomas, our proposal will build on our productive existing case-control study, with a goal to expand the age, gender, and possible ethnic diversity of our adenocarcinoma sample. Specifically, aim 2 will assess the role of gender and age with regard to genetic susceptibility to lung adenocarcinoma; and Aim 3 will assess the role of genetic polymorphisms among individuals reporting environmental tobacco smoke (ETS) exposure in susceptibility to lung adenocarcinoma. A better understanding of these risks will lead to improved preventive strategies. This proposal addresses directly a major research priority of the National CanLVALcer Institute, specifically to identify genetic variations that affect cancer risk, often in concert with environmental factors.LVAL7+p.hThe specific aims of this project are to determine the effects of nicotine administration and deprivation on changes in emotional processing among smokers carrying the DRD2 A1 and A2 alleles. Data from our laboratory suggest that smokers carrying the A1 allele vs. those with only the A2, are both less likely to quit smoking and experience less consistent negative affect reduction when exposed to a treatment involving antidepressant (venlafaxine) therapy. This suggests that the A1 allele may modulate the effects of a psychotropic agent on mood while quitting, and by implication may influence the direction and magnitude of affective changes associated with nicotine exposure. Understanding the relationship between genetic factors, nicotine and mood, may help us identify the most salient properties of smoking for particular groups of individuals (e.g., positive mood enhancement, negative affect reduction), and select treatments which seek to alter this relationship in a beneficial way (e.g., reinforcement blockade and mood modulating drugs). However, procedures for studying the effects of nicotine on mood have largely been limited to self-report. While important, these methods rely heavily on cognitive appraisal and cannot assess the near instantaneous neurophysiological activity thought to precede a change in affect. In this study, we will use the startle response as an index of reactivity to affective stimuli. The startle reflex (eye blink) is an orienting response that follows an unexpected auditory stimulus (startle probe), and may reflect immediate changes in underlying cortical and subcortical processes associated with drive or motivational states (e.g., appetitive/defensive; approach/avoidance). Negative emotional cues delivered prior to the probe increase the blink response magnitude (eye muscle EMG), while positive cues reduce or inhibit the response. This startle-affect relationship provides an ideal paradigm for studying the effects of acute nicotine administration and withdrawal on mood and alLVALilows comparisons between smokers with more or less vulnerability to become nicotine dependent (e.g. A1 allele types) and/or those who may have more difficulty quitting. Using a 2x2x2x3 factorial design, we will determine if the magnitude and latency of the startle response is influenced by genotype (A1/A1 and A1/A2 or A2/A2), level of nicotine withdrawal (overnight deprived or non- deprived), acute administration of nicotine (nicotine or placebo), and the affective valance (positive, negative, neutral) of emotional stimuli. Two groups of smokers (60 with and without the A1 allele), stratified by race, gender and depression history, will be exposed to four counterbalanced laboratory assessments, completely crossing the 2 levels of pre-session nicotine withdrawal (deprivation/non-deprived) with 2 levels of within session drug administration (nasal nicotine administration or placebo). Within each session, participants will receive 2 blocks of startle probe trials, associated with exposure to emotional cues (standardized slides) selected for 3 levels of affective valence (positive, negative or neutral). The first will be preceded by placebo and the second by either nicotine nasal spray or placebo, depending on the session. Differences in startle intensity and latency between the first trial block (placebo) and the second (placebo or nicotine) will be compared across the four sessions. We hypothesize an enhanced startle response (increased magnitude/decreased latency) for negative vs positive cues, presence of the A1 allele (A1/A1 +A2/A1 greater than A2/A2); deprived vs. nondeprived; and nicotine vs. placebo conditions. A1 smokers are also expected to show significantly enhanced responding to negative stimuli and greater attenuation of responding by nicotine. In exploratory analyses, we will also assess the modulating effects of other candidate genes (DRD4 and SLC6A3) on these relationships. Confirmation of these hypotheses will provide evidence for nicotine's action as a mood modulator and the importance LVALof genetic factors related to dopamine neurotransmission in determining the direction and magnitude of these effects.LVAL 22AGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology TOBACCO Nicotine WOMEN PregnancyAGE Child COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Postpartum Parent/MotherAGE Child DISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Parent/MotherADDICTION Cessation DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseDISEASE/BIOLOGY Mechanisms Other Disease/Biology LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation LOCATION National PREVENTION/TREATMENT Educational Materials Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Cessation EPIDEMIOLOGY/SURVEILLANCE Large (>=100) PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Pregnancy PostpartumLVAL7+p.lThe majority of studies evaluating smoking cessation treatments for pregnant smokers have employed minimal intervention strategies that have achieved limited success. We believe a significant reason for this lack of efficacy is the failure of minimal treatment approaches to address symptoms of depression and stress among pregnant smokers who fail to quit on their own. Data from our recently completed trial of a videotape smoking cessation intervention for pregnant smokers indicated that significant levels of affective impairment were present in this group. Over 50 percent of the women met DSM-IV criteria for major depression on the Prime MD, or had CES-D scores > 16. Depressive symptoms were frequently chronic. In addition, research indicates that high levels of stress, poor coping resources, and low levels of social support satisfaction are predictive of depression and continued smoking during pregnancy. The proposed study will address these issues by evaluating the efficacy of an intervention designed to impact these risk factors. Approximately 375 women will be randomized to either a mood management (MM) intervention, health education (HE), or usual care (UC) control condition. The MM and HE interventions will be delivered in 7 60-minute counseling sessions that will incorporate 10 minutes of brief smoking cessation counseling based on the Clinical Practice Guidelines that will include a specific focus on smoking and pregnancy. Participants in the MM condition will receive an additional 50 minutes of counseling emphasizing the development of affect management skills. The MM protocol will be based on Cognitive Behavioral Analysis System of Psychotherapy (CBASP), a psychotherapy developed for the treatment of chronic depression that has been shown to be highly effective in reducing depression in this difficult-to-treat population. HE participants will receive an additional 50 minutes of standard pre/postnatal health education focused on non-smoking related issues relevant to maintaining a healthy preLVALgnancy. The UC condition will receive 7 3 to 5-minute Clinical Guidelines-based brief counseling sessions that will be similar in content to the smoking cessation counseling component of the MM and HE interventions. We hypothesize that cessation rates during pregnancy and at 3 and 6 months postpartum will be significantly greater for smokers in the MM versus the HE and UC control conditions. In addition, we hypothesize that smokers with significant levels of depression and/or positive histories of depression at the start of the intervention will quit significantly less often than nondepressed smokers and negative depression history smokers. We will also evaluate the role of coping, self-efficacy, social support, perceived counselor support, perceived stress, negative affect, and depression as mediators of treatment outcome. As secondary aims we will assess whether levels of depression are significantly reduced for smokers in the MM condition relative to those in the HE or UC conditions, and we will assess the role of neuroticism in the relationship between depression and nicotine dependence. We will also evaluate the extent of smoking reduction (cigarettes smoked/cotinine) among women who fail to quit, as a function of treatment, depression history, and current depression.LVAL7+p.nThis application will serve as the foundation on which the Principal Investigator will build a major line of research dedicated to the area of improving smoking abstinence rates in weight-concerned smokers. Many individuals smoke to manage their weight. This subpopulation of smokers has been classified as having weight concerns. Weight concerned smokers have lower smoking abstinence rates compared to non-weight concerned smokers, and women have higher rates of weight concern than men. Behavioral weight management interventions added to nicotine dependence treatment have not been found to be effective and pharmacological interventions have delayed rather than prevented weight gain. New avenues need to be explored for this difficult-to-treat subpopulation. A novel approach is to focus on changing the weight concerns themselves by implementing a body image intervention. Negative body image has been found to predict reduced rates of smoking abstinence. The primary aim of this study is to evaluate the efficacy of body image treatment compared to weight management intervention on improving the smoking abstinence rates in weight concerned smokers after 12 weeks of treatment and at 6-month (week 24) follow-up. A further aim is to examine the effect of body image treatment on improving body image satisfaction, and reducing weight concerns in weight concerned smokers. We hypothesize that the body image treatment will be associated with higher 7-day point-prevalence smoking abstinence rates, greater improvements in body image satisfaction scores, and decreased weight concerns at end of treatment (week 12) and at 6-month follow-up as compared to the weight management intervention. The ultimate goal is to develop effective interventions that will reduce tobacco-related morbidity and mortality in this population. This is consistent with the objectives of the National Cancer Institute to develop and test new behavioral, pharmacological, and combination therapies to treat nicotine dependence, with special emphasis on LVAL populations at high risk. Subjects will be randomly assigned to either a 12-week group cognitive-behavioral treatment for body image improvement (experimental group) (N=20) or to a 12-week group behavioral weight management treatment (contact control group) (N=20). Subjects in both conditions will receive bupropion and prescription for home-based exercise. The major assessments will occur at end-of-treatment (week 12) and at 6-month (week 24) follow-up. Dependent measures include 7-day point prevalence smoking abstinence confirmed with expired air carbon monoxide, and self-report measures of body image satisfaction and weight concerns.LVAL7+p.pMaternal cigarette smoking produces profound health effects including premature labor, low birth weight, stillbirth, and neonatal death. Postnatal growth and behavior also are affected. Despite all the public health warnings many pregnant women still smoke or are placed on nicotine replacement therapies such as the patch. Nicotine is well known as an important component of cigarette smoke and has been implicated in many of the adverse effects of smoking, on fetal development. Although data clearly show that prenatal exposure to nicotine is bad, considerably less is known about the effects of nicotine on the brain during other developmental periods, particularly during puberty. The brain is still maturing rapidly during puberty and, most likely, it remains vulnerable to the detrimental effects of nicotine during this period as well. We extended our studies to determine if the "window" of vulnerability that exists during very early development extends into adolescence. We used a relatively new imaging procedure called proton magnetic resonance spectroscopy (1 H MRS), which can be performed safely on humans. One of the brain metabolites measured by 1 H MRS is the compound n-acetyl-aspartate (NAA). In animals with brain damage or humans with neurodegenerative diseases, NAA concentrations are reduced, in a regionally specific manner. The concentration of this brain metabolite reflects the health and viability of neurons. We hypothesized that developmental nicotine exposure would result in a decrease in NAA concentrations. Our data indicated that NAA concentrations were not reduced in adult offspring exposed to nicotine during development, however other brain metabolites were affected. The primary focus of the study (long-term effects of developmental nicotine exposure) has been completed and written up as the Ph.D. dissertation for Christine Cloak. We are in the process of converting the dissertation into journal, articles for publication. Tissue has been collected but not yet analyzed for  LVAL the progressive developmental effects of nicotine exposure (early developmental time points). Although our hypotheses concerning the long-term effects of nicotine during development on NAA concentrations in the brain were not supported, other measurable metabolites were effected such as glutamate and myo-inositol. Future studies will focus more on these metabolites.LVAL7+p.rThe purpose of this proposal is to build a mentored, clinical research training experience to foster independent professional development in cancer control research. This application is being submitted from the University of Pennsylvania Cancer Center, which provides a setting with excellent opportunities to work with Dr. Caryn Lerman, the Transdisciplinary Tobacco Use Research Center (TTURC), and my co-sponsors, Drs. Charles O'Brien and J. Sanford Schwartz. Sound career development in cancer control research requires broad exposure to research methodologies and intensive research training in order to make significant, independent contributions to this field. Therefore, this K07 Career Development Award application seeks to achieve these goals in the area of tobacco control and maternal and child health. General plans for the career development program include: (a) expanding working knowledge of areas relevant to cancer/tobacco control research; (b) refining skills in the application of behavioral science to cancer/tobacco control; (c) increasing knowledge of maternal health issues related to cancer/tobacco control; (d) expanding understanding of the biobehavioral mechanisms of tobacco addiction; (e) improving skills in designing, implementing, and analyzing cancer/tobacco control interventions; and (f) learning effective ways to disseminate research findings to impact upon public health practices. Specifically, the research project aims to develop a low-cost, primary-care intervention to reduce children's Environ- mental Tobacco Smoke exposure and maternal smoking rates targeting under- served mothers with children ages 0-2. The effectiveness of this intervention will be tested by comparing it with a standard care control-group intervention using a two-group, repeated measures randomized design. The intervention will be modeled after more intensive, home-based counseling programs, the feasibility of which has been demonstrated. However, as these interventions were labor intensive and costly, the prop LVAL osed intervention presents an innovative, comprehensive, albeit streamlined primary-care approach to an emerging issue in the tobacco control field. This intervention will also set the groundwork for an eventual R01 that will test the treatment and prevention efficacy of this intervention on other populations (e.g., adolescent smokers and their younger, nonsmoking siblings).LVAL7+p.tMore than 19 million children in the U.S. are exposed to second-hand smoke (SHS) on a daily basis. Infants are the most susceptible to SHS harm, and for children under five, SHS exposure causes more deaths than all unintentional childhood injuries combined. In response to Healthy People 2010 goals and NCI priorities, this trial aims to reduce infant SHS exposure in an under-served urban African American (AA) population while simultaneously promoting smoking cessation among the postpartum (Pp) mothers. The proposed 16-week trial, "Philadelphia FRESH (Family Rules for Establishing Smoke-free Homes)," will randomize 450 Pp mothers of children up to two years old into two treatment groups. Mothers randomized to the multimodal, individualized treatment (MIT) will receive 1.) pediatrician advice, 2.) two intensive, family-centered, in-home behavioral counseling sessions, 3.) a culturally-sensitive treatment manual mailed in four sections, biweekly starting week 1, and 4.) seven follow-up phone counseling sessions. Mothers in the standard care control (SCC) group will receive pediatrician assessment, advice, and one comprehensive self-help manual with information on SHS and its reduction, smoking cessation, and relapse prevention. We predict that through 12-month follow-up, the MIT group will demonstrate better infant SHS exposure and maternal smoking outcomes (measured by self-report, infant urine cotinine, and maternal saliva cotinine) than the SCC group. Our trial will also test the mediating influence of social support, perceived infant vulnerability to SHS, and negative affect on smoking outcomes by incorporating treatment components to boost and sustain natural maternal support systems, increase knowledge of SHS risks and benefits of SHS reduction, and improve mood management. We hypothesize that improvements in these variables will positively impact treatment outcome. Finally, our trial will test the moderating effects of baseline weight concerns and depression symptoms. We hypothesize a main effect fV LVALf or baseline weight concerns and depression on outcomes, as well as an interaction: moms with greater baseline weight concern and depression will have better outcomes in MIT compared to SCC. We will use GEE analysis to test hypothesized smoking behavior changes across baseline, 8-week, 16-week (EOT), 3-mo and 12-month follow-up time points and explore the influence of moderating variables. Path analysis will test mediating variables' influence on outcomes.LVALP fDISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms Other Disease/Biology LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesAGE Young Adult Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION National RESEARCH1 Animal Studies RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Hormones MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesADDICTION Maintenance Cessation Relapse AGE Child Young Adult ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group RESEARCH Human Studies STUDY POPULATION African American Caucasian Hispanic TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumAGE Adult Older Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Child LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Quitline Educational Materials Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION African American TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Postpartum Parent/Mother MISCELLANEOUS Weight Gain/ExerciseLVAL7+p.wThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long- term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airway reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the Lung Health Study will be invited to participate (potential sample size, approximately 5600). As in the preceding Lung Health Studies, the Data Coordinating Center will be within the Diversion of Biostatistics, School of Public Health, at the University of Minnesota, and will have full acceszLVALs to all records and data from the previous LHS projects.LVAL7+p.yPatients with Chronic Obstructive Pulmonary Disease (COPD) have risk factors for the development of osteoporosis including: heavy smoking history, corticosteroid use, sedentary life style. Few studies have examined the incidence of bone loss in these patients and no studies have compared bone mass in men and women with COPD. The purpose of this study is to examine the relationship of variables that potentially influence bone mass with current bone compared between men and women with COPD, and healthy men and healthy women. The sample will consist of 45 patients with COPD, and 45 healthy subjects. In order to control for the effects of smoking history vs. disease state on BMD, the healthy group will be divided into those with a significant smoking history (>20 pack-years) versus those with minimal or no smoking history (<20 pack years). Bone mineral density will be measured using dual energy x-ray absorptiometry (DXA) at the following sites: PA lumbar spine, proximal femur, and whole body. Variables potentially influencing BMD will be measured: 1. calcium and ethanol intake as measured by the Bloc' '98 Food Frequency Questionnaire, historical and current physical activity as measured by the Historical Liesur Time Activity Questionnaire and the Physical Activity Scale for the Elderly respectively, cumulative smoking: history as measured by the number of pack-years, gonadal hormones as measured by serum testosterone and serum estradiol levels, corticosteroid use as measured by clinical questionnaire, body mass as measured by body weigh and whole body DXA scan. Statistical analysis will include: 1. univariate linear regression with lumbar spine BMI and proximal femur BMD as dependent variables and smoking history, disease state, calcium intake, ethanol intake physical activity, gonadal hormone levels, corticosteroid use, body mass as independent variables; and 2. analysis of variance with lumbar spine BMD and proximal femur BMD as dependent variables. Results of this study will provide improved understandLVALing of the nature of bone loss in COPD patients.LVAL7+p.{Environmental tobacco smoke is thought to be responsible for asthmatic episodes in millions of children each year. Children of mothers who smoke are 2-5 times more likely to be diagnosed with asthma than children of non-smoking mothers. It is not known how tobacco smoke causes asthma but an allergic pathway may be involved. Smoker have increased levels of a particular gamma globlulin, IgE. IgE is also elevated in people with allergies. IgE binds to special cells in the lining of the airways where it causes the cells to release powerful bronchoconstrictors. Cytokines are proteins that regulate the immune system and are produced by white blood cells. Two cytokines, IL-4 and IL- 13 control the production of IgE and are, therefore probably, involved in producing asthmatic reactions. A third cytokine, IL-5, controls the recruitment of the special immune cells that bind to IgE, eosinophils, into the lining of the airways, and may also be involved. One poorly designed study suggests that smokers have higher levels of LL-4 and IL-5 than non-smokers. The investigators did not evaluate other factors, such as race, age and sex, in the smokers and non-smokers which may have been responsible for the different levels. We propose to compare cytokine levels of IL-4, IL-5, IL-13 and IgE in healthy identical twin pairs, in whom one member smokes and the other does not smoke. In addition, we will compare cytokine and IgE levels in non-smoking twin pairs, in whom one member is exposed to passive smoke and the other is not. Since twins are naturally matched on genes, age, race and gender, we will be able to isolate the affects of smoking on the tobacco levels. Twins will be recruited from the California Twin Program. Smoking history information will be obtained from questionnaires previously completed and returned by the twins. Twins will obtain blood samples at their physicians' offices and mail them to us in pre-paid Federal Express mailers. Serum will then be sent to the California State Public Health Laboratories for  LVAL IgE analysis. Cytokine levels will be analyzed here in our laboratories. If we observe an association between smoking and these immunological measures, it will increase the understanding of how tobacco smoke leads to asthma and allow us to design effective interventions.  s R .  eNDhh @+@Researchp@\DE ROOLISAUNIVERSITY OF GENEVAGENEVASWITZERLANDACSPF-04-100-01-CNBfF+p.Biology and CancerR@X0@7/1/20046/30/20077/1/2004 to 6/30/20074/2005vqd\F@88,"gg`@@ResearchR@\DAYSHARONINDIGENOUS PEOPLES TASK FORCEMINNEAPOLISMNMPAATRC-2004-0008-F+p.@I@Xh@200420052004 to 20054/2005|uqdE=88,"ff @@@ResearchZ@\DAYNANCY UNIVERSITY OF PITTSBURGHPITTSBURGHPANICHDR01, HD036890\ @t@I@Xp@9/3/19985/31/20049/3/1998 to 5/31/20044/2005vok_E=88,"ee`@@ResearchH@\DAVIDSONMICHAELMEDSTAR RESEARCH INSTITUTEHYATTSVILLEMDNHLBIR01, HL062233JF+p.Biology and CancerDiscovery 1a Evaluation 1b*@4/1/19996/30/20054/1/1999 to 6/30/20054/2005#xtgKB88,"ddq@@Researchx@\DALLERYJESSEUNIVERSITY OF FLORIDAGAINESVILLEFLNIDAR03, DA015373F+p.j@I@X@6/1/20034/30/20056/1/2003 to 4/30/20054/2005vpl_HA88,"ccg@p@4Researchn@\DALINGJANETFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWANCIP01, CA042792F+p.Biology and CancerR@X@Not GivenNot GivenUncertain4/2005|xoG@88,"bbc@@ResearchB@\CURRYSUSANCENTER FOR HEALTH STUDIESSEATTLEWANHLBIR01, HL0567720 @@I@XR@7/1/19976/30/20017/1/1997 to 6/30/20014/2005unjaF?88,"aa@$@@Researchj@\CRUZTESSUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANCIP50, CA084735"F+p.@I@Xr@9/20/20018/31/20049/20/2001 to 8/31/20044/2005}xtgD>88,"``@f@ResearchP@\CRUICKSHANKSKARENUNIVERSITY OF WISCONSIN AT MADISONMADISONWINIAR01, AG011099@t@IR@X@3/1/19932/28/20033/1/1993 to 2/28/20034/2005~zqMF88,"__ S@3@ResearchT@\CROPSEYKARENVIRGINIA COMMONWEALTH UNIVERSITYRICHMONDVANIDAK23, DA015774 F+p.j@I@X@9/30/20028/31/20079/30/2002 to 8/31/20074/2005~xtjHA88,"^^@@ResearchR@\CRAWFORDMYRAUNIVERSITY OF ALABAMA AT BIRMINGHAMBIRMINGHAMALNCIR01, CA086311 F+p.@I@X@8/4/20006/30/20048/4/2000 to 6/30/20044/2005}ymHB88,"]]`@@Researchh@\CRAMERDANIELBRIGHAM AND WOMEN'S HOSPITALBOSTONMANICHDR01, HD032153}F+p.t@IDiscovery 1a Evaluation 1b@8/1/19947/31/20048/1/1994 to 7/31/20044/2005 yrnfH@88,"\\ @G@Researchn@\COZENWENDYUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP7RT-0134Hz7+p.Biology and CancerR@X@u7/1/19986/30/20027/1/1998 to 6/30/20024/2005zviF?88,"LVALF+p.~In 1994, more than 39,000 cycles involving ART were performed in the United States. Given the cost of approximately 8,000 per cycle, studies are needed which could improve the likelihood that ART will result in a successful pregnancy. In 1994, the investigators initiated a study of couples seeking ART that involved collect of baseline epidemiologic data, treatment variables, and biological specimens. The preliminary data collected on 927 couples, support published findings and suggest exciting new ones. Only 8 percent of women over the age of 39 years became pregnant other first ART cycle and the number of eggs retrieved during ART decline more rapidly after the age of 33 years. Key exposure examined in men and women included caffeine, alcohol, and tobacco. In women, smoking was the principal exposure that decreased number of eggs retrieved. The decrease occurred in both current and former smokers. In men, caffeine use decreased ART success. This association was not present if the ART cycle involved direct injection of sperm in eggs which suggests that caffeine (or tannins in coffee or tea) could be affecting ART success (or natural fertility) by interfering with sperm-egg penetration. Women with the primary diagnosis of endometriosis had fewer eggs retrieved, whereas diagnosis of hernia or varicocele was linked to decreased sperm concentration. Use of a gonadotropin releasing hormone agonist in a long or down regulation fashion prior to ovarian stimulation was associated with markedly better ART success and egg retrieval than used in the short or flare regimen. The joint effect of these female, male and treatment variables will be examined in discrete failure application, the investigators propose continuation of the study, anticipating that in increase in the sample size of 3,000 would allow them to examine important associations in diagnostic or treatment subgroups, as well as expand the power to study other intriguing preliminary findings. These include an association between endometriosis and a p LVAL olymorphic variant, known as N314D, a key gene in galactose metabolism; evidence that acetaminophen use may lower follicle stimulating hormone levels; and evidence that alcohol use in men adversely affect sperm morphology. The investigators' ability to study male factor infertility will be enhanced by collection of a blood specimen from men and retrieval of residual semen after ART. The continued goal is to assess the effect of epidemiologic and biologic markers and treatment-related variables of ART success and to address broader aspects of reproductive physiology by examining gamete number and quality as outcomes.LVAL  &AGE Child Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesAGE Adult Older Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use Environmental Tobacco SmokeADDICTION Cessation ECONOMICS Cost of Smoking PREVENTION/TREATMENT Counseling/Behavior Therapy Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Child Young Adult Adult COMMUNITY Womens Group General Partnerships Health Care Provider ECONOMICS Medicaid/Medicare LOCATION Urban Rural National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Interview/Focus Group Biochemical Assessments RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionDISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy MISCELLANEOUS Sex/Gender DifferencesLVALF+p.The objective of the Alabama Tobacco Free Families (ATOFF) Program, a multi component, multi-channel health communications and policy change program, is to reduce the smoking prevalence rate among a representative sample of pregnant females whose maternity care is supported by Medicaid. This will be achieved by reducing the rate of females of childbearing age in eight targeted counties by changes in social norms. The proposed study is an extension of two decades of public health education studies conducted by the University of Alabama at Birmingham (UAB) tobacco research team in partnership with the ADPH's Bureau of Family Health Services (BFHS). ATOFF will expand this partnership to include the ADPH Bureau of Health Promotion and Information. It is designed to enhance the capacity of the state's Tobacco Use Prevention and Control Program (TUPC), funded by CDC in 1999. UAB and ADPH will implement statewide and local partnerships targeting females of childbearing age to be tobacco-free prior to and during pregnancy. ATOFF will be evaluated using a time series design and analysis with multiple, quarterly baseline and follow-up measures of prevalence across the eight targeted counties. Process and behavioral impact evaluations will be conducted. The four specific aims to be accomplished by the proposed study will be to 1.) Identify and select a representative sample of patients from a randomly selected sample of Medicaid supported maternity care sites to serve as the ATOFF clinic population, and to recruit a representative sample of females (14-44) to participate in a telephone-based survey to serve as the ATOFF community cohort; 2.) Develop and implement a multi-component, multi-channel program focused on females of childbearing age and their families in eight target counties and consisting of (a) a mass media-health communications component, (b) a community organization component, and (c) a professional practice component; 3.) Document the implementation success (process evaluation) of the media LVAL messages and community initiatives to change beliefs, behaviors, and social norms related to tobacco use among the samples of females in Aim number 1 by conducting clinical and community assessments in Years 01, 02, 03 and 04; and 4.) Document, by self-reports and saliva continine tests, the effectiveness (impact evaluation) of ATOFF's program to reduce the prevalence among the clinic population at entry (first visit) into Medicaid maternity care, and by self-report via telephone of the females in the community population.LVALF+p.The purpose of this application for a 5-year Mentored Patient-Oriented Research Career Development Award (K23) on smoking among incarcerated females is to conduct research and training activities to advance the candidate's development as an independent clinical researcher. This includes formal classwork pertaining to research design, biostatistics, and ethics along with conference attendance and meetings with mentors. The proposed research plan includes two studies that build upon each other in the area of smoking among female prisoners. The first study is cross-sectional and is designed to investigate the smoking behavior of incarcerated females. In addition, this study will examine differences between smokers, ex-smokers, and non-smokers on measures of substance abuse and personality, with consideration to other key covariables such as criminal history, medical problems, readiness to change, and Axis I pathology as possibly differentiating between the three groups. The second study will be a clinical trial using Hall et al. 's (1994) Mood Management group smoking cessation intervention combined with nicotine patch (or no patch). The intervention group will be compared to a wait-list control group who will receive the treatment six months later. It is expected that women who successfully complete the intervention will have higher smoking cessation rates than wait-list controls. Further, it is hypothesized that women with substance abuse and psychiatric comorbidity will have poorer outcomes than those without comorbidity. These projects should add significant information to the literature which is currently devoid of research related to smoking and female prisoners. This is particularly relevant now as it has been shown that women may have more difficulty with quitting smoking than men and may also have additional concerns related to smoking (e.g., smoking as weight management) that influence their success. Testing effective smoking cessation interventions with this underserved and understud LVAL ied population is urgently needed as the medical costs associated with treating prisoners currently accounts for 11% of the Department of Corrections' budget and is expected to double over the next 10 years. Overall, these projects will provide experiences necessary for the candidate to develop an independent research program focusing on effective smoking interventions for incarcerated individuals.LVAL.The purpose of this application is to re-examine a large population- based cohort to determine the 5-year incidence and progression of hearing loss and the risk factors for each outcome. Participants (n=3753) in Beaver Dam, WI, were ages 48-92 years at baseline. The re- examinations will be conducted, using the same standardized protocols for otoscopy, screen tympanometry, pure tone audiometry, word recognition tests and distortion product otacoustic emissions. A standardized questionnaire about medical history, noise exposure, and the functional impact of hearing impairment will be administered. New protocols will build upon cross-sectional results which suggested that atherosclerosis, exposure to tobacco smoke and familial factors may be associated with hearing loss. B-mode carotid ultrasound will be used to obtain an objective marker of generalized atherosclerosis. Serum cotinine, an objective measure of exposure to tobacco smoke will be measured. Using extensive pedigree and genetic marker information obtained in the Beaver Dam Linkage Studies of Age-Related Ocular Disorders, segregation analyses and preliminary linkage studies will be performed to elucidate genetic factors for hearing loss. The prevalence of olfactory deficits will be measured using an odor identification test. Data on vision, ocular disorders and physical functioning will be available from the planned ten-year follow-up of the Beaver Dam Eye Study. A 7-year follow-up telephone interview will be used to assess prospective relations between multiple sensory deficits and function. The study is intended to provide new data about the risks of incidence and progression of hearing loss in older adults and potentially modifiable factors associated with incidence and progress of hearing loss. It will provided much-needed, population-based data on the prevalence and risk factors for olfactory deficits.LVALF+p.Phase One of this Study is designed to examine the independent and interactive effects of pro- and anti-tobacco media exposure on tobacco- related outcomes in diverse groups of adolescents and adults in California. Data will be drawn from the California Independent Evaluation in-school surveys of approximately 40,000 adolescents and phone surveys of approximately 20,000 adults, to explore the roles of ethnicity and acculturation in the exposure-outcome relationships, and to determine whether there are stronger or weaker relationships among certain populations. This phase will result in the identification of specific ethnic, are stronger or weaker relationships among certain population. This phase will result in the identification of specific ethnic, gender, acculturation level, and age specific groups that are more or less responsive to pro- and anti-tobacco media, and potential moderators of outcomes in these groups. Phase Two will involve development of culturally grounded media materials and programmatic applications for four specific groups, and testing of the effectiveness of these approaches. An experimental trial will test the effectiveness of four ethic-specific approaches, compared with established general-audience approaches. The specific aims of this study are the following: 1. Determine the relationship between exposure to the California anti- tobacco media campaign and tobacco-related outcomes, including attitudes, policy support, refusal sell-efficacy, smoking-related behaviors and ETS exposure for adolescents and adults in diverse ethnic populations. 2. Determine the relationship between exposure to pro-tobacco marketing and tobacco-related outcomes, including attitudes, policy support, refusal self-efficacy, smoking-related behaviors and ETS exposure for adolescents and adults in diverse ethnic populations. 3. Determine the interactive effects of pro- and anti-tobacco media exposure related outcomes in these same populations. 4. Determine how acculturation influences the relationships  LVAL between pro- and anti-tobacco media exposure and tobacco related outcomes in these populations. 5. Using the information from this analysis, develop culturally grounded educational materials that can be used to inoculate youth and adult groups at highest risk to the effects of tobacco marketing. 6. Conduct an experimental trial to determine whether these culturally relevant media materials are more effective in influencing tobacco-related attitudes and behaviors among difficult-to-each groups than the general- audience media materials.LLVAL  h >fLOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION American Indian/Alaskan Native TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use WOMEN PregnancyAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies STUDY POPULATION African American Caucasian TOBACCO Non-Specified Tobacco Use WOMEN Pregnancy Parent/MotherDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer Mechanisms LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingCOMMUNITY Health Care Provider ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother Partner/Spouse MISCELLANEOUS Weight Gain/ExerciseLVALIn this revised application the investigators propose to recruit 500 female smokers from two low-income urban pediatric clinics. The first aim of the study is to conduct a randomized trial comparing usual care to a smoking cessation intervention consisting of a brief motivational message from a pediatric health care provider; self-help materials developed specifically for low literacy, low income populations; a 10 to 15 minute motivational interview with a specially-trained nurse at the pediatric clinic; and three personal follow-up contacts. The primary endpoint is smoking prevalence at a 12 month follow-up. Secondary endpoints include use of the self-help materials, serious quit attempts, and short and long-term abstinence. A second aim is to conduct a prospective, longitudinal assessment of factors associated with smoking cessation in the target population. For this aim, at baseline and at three and 12 months, a variety of process variables are to be measured, including knowledge and attitudes about smoking and health, expectations and concerns about weight and weight gain following smoking cessation, motivation regarding smoking cessation, alcohol and other drug use, stress, depression, partner and household-member smoking status, and health events of the child. The investigators plan to examine the degree to which these variables predict changes in smoking status, whether time-related changes in these variables are associated with change in smoking status, and the extent to which these variables moderate the intervention effects.LVALF+p.We propose to study risk factors for multiple primary anogenital cancers and to continue our case-control studiers of cervical and vulvar cancer. Both studies have as their goal the elucidation of factors, beyond HPV, that contribute to the etiology of anogenital cancer. The new, major focus of this proposal will be risk factors for the development of multiple primary anogenital tumors. We will match each of these women to a women with one anogenital tumor who does not go on to develop a second tumor. We will interview multiple primary anogenital cancer cases and matched single primary controls about characteristics that may be related to their risk of a second primary tumor, and collect archival tumor tissue to test for HPV DNA types and non- prototype variants. Blood will be collected for serologic and genetic testing. We plan to determine whether the risk of multiple primary anogenital cancers is related to: 1) cigarette smoking, particularly continued smoking following the initial primary; 2) HLA class II alleles; 3) family history of anogenital cancers; 4) HPV type and non-prototype variant in the initial primary cancer. The data from this study may contribute to the design of clinical monitoring for anogenital cancer patients at high risk of second primary cancer, and may provide targets for behavior modification that could reduce the incidence of multiple anogenital tumors. In continuing our case-control study, we will example HPV co-factors in relation to risk cervical and vulvar carcinoma. The study will be conducted in three counties of western Washington. All women engaged 18-74 who are diagnosed from January 2000 through December 2004 with cervical or vulvar cancer will be identified through the population- based Cancer Surveillance System. Cases and population-based controls will be interviewed regarding history of sexually transmitted diseases, smoking status, family history of anogenital and other cancers, as well as known risk factors for each tumor. Tissue specimens will be obtained f LVAL rom all cases and will be assayed for HPV DNA. Blood will be collected and tested for antibodies to HPV and for HLA alleles. The data will provide sufficient power for testing important interactions among HLA alleles, and between HLA alleles and lifestyle risk factors.LVALF+p.Cigarette smoking is the largest preventable risk factor for morbidity and mortality in developed countries. There is growing evidence from questionnaire-based research that smokers are more impulsive than nonsmokers, suggesting that impulsivity could be one mechanism operating in the acquisition, maintenance, and relapse of cigarette smoking. However, the conditions that affect impulsivity in smokers are virtually unknown, and the relationship between questionnaire- and behavior-based measures of impulsivity remains unclear. In the proposed project, smokers will choose between immediate reinforcers and delayed reinforcers in a laboratory setting. This laboratory model nicely captures a central characteristic of relapse: An abstaining smoker relapses when an immediate smoke reinforcer is chosen over a delayed alternative reinforcer. The project will adapt powerful questionnaire- and behavior-based laboratory preparations and examine a treatment-relevant question: What conditions influence impulsive choice? Ongoing studies are showing that nicotine deprivation increases impulsive choices to smoke and impulsivity in general. The proposed study will examine the effects of a pharmacological intervention on impulsivity. The intervention, a nicotine patch, is expected to return impulsive choice to non-deprivation levels. The laboratory model may be enormously useful for initial testing of both pharmacological and behavioral interventions designed for relapse prevention. For instance, methods to decrease impulsive choice developed using animal models can be assessed in smokers and could lead to novel treatment strategies. More generally, the model could further our understanding about whether and how critical variables (e.g., cue exposure, contextual factors, nicotine deprivation, drugs of abuse, pharmacotherapies, stress, etc) affect the impulsive choices that lead to or prevent relapse.LVALF+p.Recent studies have associated evidence of Chlamydia pneumoniae infection with coronary and carotid atherosclerosis and evidence of increased infection with cytomegalovirus (CMV) in patients developing restenosis or with atherosclerosis. Several other common pathogens have been less consistently associated with atherosclerosis. Altered parameters of inflammation and hemostasis have been identified as prognostic factors of myocardial infarction and have been linked as possible pathogenetic mechanisms. Recent studies have indicated that peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease frequently called Chlamydia pneumoniae DNA and stimulation of PBMCs can reflect an unsuccessful host cellular immune response to CMV associated with elevated C-reactive protein (CRP). This proposed study is both a nested case-cohort study and a nested cohort analysis within the Strong Heart Study (SHS), an ongoing cohort study of 4,549 American Indians. This study will utilize previously collected specimens, baseline data, and the planned ultrasound measurement of carotid wall thickness (IMT) in SHS participants. Within the initial SHS cohort, 400 definite cases of incident myocardial infarction, coronary heart disease, and stroke will be compare with 400 control individuals with no such diagnoses and matched for age, gender, and residence. Their prior serum specimens will be analyzes for Chlamydia pneumoniae-specific IgG, IgM antibody, for cytomegalovirus-specific IgG antibody, and for CRP. In addition, assays will be performed for antibodies to Helicobacter pylori, hepatitis A virus, (HAV) and herpes simplex virus (HSV) type 1 and 2. Correlations will be made with baseline parameters of lipids, coagulation, and adjusted for potential confounding variables of tobacco use, pneumonia, and altered pulmonary function. An additional analysis of a subcohort, the above 400 controls, will be performed looking at the outcome of their carotid IMT, a parameter of subclinical atherosclerosis, in re LVAL lation to serologic results indicating a prior exposure to CMV, Chlamydia pneumoniae, and/or other pathogens approximately 8 years preceding ultrasound testing. Both case-control and cohort analysis will be stratified by levels of hemostasis and inflammation, including CRP, fibrinogen, Lp(a), and plasminogen- activator inhibitor-1. A separate nested substudy performed on PBMCs, prospectively collected from 80 cases and 80 controls, will examine the host T-cell proliferative response to CMV and other pathogens in relation to disease and also search for a chronic persistent infection with Chlamydia pneumoniae evidence by DNA detection. Thus, this study will assemble a prognostic profile of infectious, inflammatory, and hemostatic factors and provide a foundation for possible future primary prevention trials.LVALThe Maternal Health Practices and Child Development Project is a prospective study of the effects of prenatal tobacco exposure on the offspring of 755 women. We have identified significant effects of prenatal tobacco exposure on the offsprings' development of the central nervous system and on delinquent behavior and peer problems. At 10 years of age, the children have begun to experiment with tobacco and other substances. These children were more depressed and anxious, they had more attention problems, aggression, and delinquency. We will assess the long-term effects of mental and physical development, temperament, psychological status, activity levels, academic performance, behavior problems, the environment, and prenatal exposure on the adolescents' substance use at age 14 and 16 and on the development of tobacco use between the ages of 14 and 16. No prior study has been able to explore the predictors of adolescent tobacco use across time, from birth to adolescence. The cohort is a general population sample of low income women selected from a prenatal clinic. Half the women are Caucasian, half are African-American. We have assessed these mothers and their children at prenatal months 4 and 7, delivery, 8 and 18 months, 3, 6, and 10 years. We have an exceptional follow-up rate of 91% at 10 years.LVALF+p.For centuries before the arrival of Europeans, the two predominant tribes now living in Minnesota (the Ojibwe and the Dakota Sioux) used Nicotina Rustica (a different species of tobacco than used commercially) or other sacred herbs (kinnikinnik or chanshasha) for special healing and religious ceremonies. Neither group had a tradition of frequent or recreational use of tobacco, but instead considered tobacco an important "first medicine" for healing. Yet, today, a majority of American Indian adults in Minnesota report using commercial tobacco. Unfortunately, we know very little about how to help American Indian smokers quit and how to reduce the continued addiction to toacco in American Indian settings. Brief description fo type of research. The Indigenous Peoples Task Force (IPTF), along with academic and community partners, is requesting a one-year developmental Community Academic Research Award (CARA) to bring together scientific and cultural experts to designa n intervention to test smoking cessation programs for pregnant American Indian women in the Twin Cities. The developmental CARA will draw on indigenous and scientific knowledge to create a culturally and scientifically rigorous design that will provide critical information on programs to help our community motivate and support pregnant American Indian women to quit using commercial tobacco. The Co-Principal Investigators on this study are both American Indian, with one from a background in community activism and one from an academic background. How proposed research fits MPAAT funding priorities. The proposed developmental CARA falls under the MPAAT objective to reduce tobacco use among American Indian Nations and communities of color. The research will also provide information on an emerging area of concern for MPAAT - effective programs for women, especially pregnant women. Type of Research. Our research focus for the developmental CARA will be to develop a quasi-experimental or other rigorous research design that can test the effectivenessLVAL of implementing the 5As cessation program for pregnant American Indian women in a Twin Cities community setting, and compare this to implementing a community reviewed and chosen approach We will draw on both scientific and cultural experts using principles from community-based participatory research and indigenous knowledge generation. Rationale. American Indians are the only ethnic or racial group in Minnesota in which the majority of members (60.8%) report smoking cigarettes. According to our analysis of Minnesota birth certificate data, American Indian women smoke at alarmingly high rates (41%) compared to Caucasian pregnant women (12%). Recent mortality and morbidity data show a high, and increasing, rate of lung cancer and an increase in infant mortality rates among American Indians that result in at least in part from high rates of cigarette use. These statistics underscore the compelling need to bring effective programs into American Indian community settings in Minnesota. Unfortunately, very little research has been conducted to investigate patterns of tobacco use among Minnesota's pregnant American Indian women, or effective culturally-relevant programs to help them quit. Thus, the rationale underlying our proposed research is twofold: 1) to begin to fill in the gap in knowledge about "evidence based" programs because these programs have not been tested in American Indian communities, and 2) to draw on community knowledge to build and test effective interventions. Specific aims, methodology & analysis plan. Our research focus will be to develop a quasi-experimental or other rigorous research design that can test the effectiveness of implementing the 5As cessation program for pregnant American Indian women in a Twin Cities community setting, and compare this to implementing a community reviewed and chosen approach. We are reluctant to have a no treatment arm in the study, given the exceedingly high rates of smoking in American Indian settings. We propose using the 5As as a comparison treatmenLVALt, but during the developmental CARA process, the community and academic research teams will discuss methods to address control issues. We will use teams of academic and community researchers working together to design both the process and the content of research, e.g., one working group will review established curricula and programs for both mainstream and American Indian communities and decide on an intervention to test against the 5As (e.g., the Sacred Path, Sacred Ways curriculum) and the second working group will review clinical and community sites in the Twin Cities, review research designs for evaluating interventions and decide on the most culturally and scientifically appropriate way that the intervention should be tested in this community. The groups will come together as well as work separately, with the Project Coordinator and the Co-Principal Investigators serving on both groups to insure coordination and communication. Capacity for Community Research. The IPTF has assembled a group of community members, Project Staff and research consultants with an impressive list of community accomplishments and an eagerness to undertake this research project. During the past 2 years, with an MPAAT funded CART grant, the IPTF has worked with a small cadre of community women to conduct qualitative research on pregnant women's thoughts, feelings, and ideas about smoking during pregnancy. This group, the Community Research Team, will play an integral role in this developmental CARA. The research consultants on the CARA are also members of the Community Research Team and will continue their collaborative efforts. Thus, this developmental CARA will allow us to further build and strengthen the relationships needed for successful community based participatory research.LVALF+p.Breast cancer is the most common cancer among women worldwide, yet the causes of most cases are unknown. Although there is substantial evidence that smoking is related to the development of several types of cancers, the relationship between smoking and breast cancer remains uncertain. The purpose of this fellowship is to study in-depth the relationships between active and passive (second hand) smoke exposures and the development of breast cancer. Exposure to second hand smoke, in addition to active smoking, is important because second hand smoke is unfiltered and contains high concentrations of potential cancer causing chemicals. Using detailed information on women's lifetime exposures to active and passive smoking, we will study women with and without breast cancer to characterize the relationship between smoking and the risk of breast cancer, while taking into account other factors that are related to breast cancer such as age, number of pregnancies and obesity. We are also interested in determining whether the effects of smoking on breast cancer risk depend on when the exposure occurs during breast development. The female breast dramatically changes in size, shape, and function as women mature. Exposure to tobacco smoke during puberty and first pregnancy, when the breast is growing and rapid cell division is taking place, may be related to the development of breast cancer later in life. We will also study whether the relationship between smoking and breast cancer differs by how quickly women can inactivate potential cancer causing chemicals in the body, as measured by particular differences in DNA, the body's hereditary material. The studies planned for this fellowship are unique in that they will be among the first to examine smoking and breast cancer in relation to when exposures occurred during the reproductive lifecycle, and among the first to consider both passive and active smoking using a detailed lifetime smoking history. Ultimately, we would like to better understand the role of smoking inn LVAL~ the development of breast cancer so we can provide women with strategies for lowering their risk of the disease. If these studies reveal that tobacco exposures have little influence on whether or not women get breast cancer, this information will be useful in understanding the impact of tobacco chemicals in the body.^LVAL f d|DISEASE/BIOLOGY Cancer RESEARCH1 Animal Studies RESEARCH Human Studies In Vitro Studies Clinical Research WOMEN PregnancyEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation AGE Child EDUCATION LEVEL High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Nicotine Replacement Therapy RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Mechanisms Other Disease/Biology TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Young Adult EDUCATION LEVEL College and Above LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy MISCELLANEOUS Weight Gain/ExerciseLVALV+p.This project is designed to investigate interactions between acute stress and drugs of abuse, and to compare stress-drug interactions in men and women. The studies are based on preclinical research indicating that stress, through various neural and endocrine mechanisms, increases drug self-administration and alters acute responses to drugs. The studies also address clinical observations that stress increases drug use and relapse to drug use in drug-dependent individuals. The physiological and psychological effects of both stress and drugs depend on the sex, hormonal state, and drug history of the individual. The proposed laboratory studies will investigate how acute stress alters the acute responses to drugs or the propensity to use drugs. First, we propose to characterize the time course of subjective, physiological and hormonal responses to acute social stress in several groups, including men and women, women at different phases of the menstrual cycle and male smokers vs nonsmokers. Second, we will investigate the effects of acute stress on responses to two stimulant drugs, methamphetamine and nicotine, administered at varying times after (or before) stress. Our preliminary data suggest that stress dampens the stimulant-like subjective effects of drugs, but this effect is likely to depend on the interval between the stress and ingestion of the drug. Third, we will investigate the interaction between stress and methamphetamine or nicotine in men vs women, smokers vs nonsmokers, and in women at different phases of the menstrual cycle phase. Based on previous studies with humans and non-humans, we hypothesize that the psychological effects of stress will be greater in women than men, in non-smokers than smokers, and during the luteal phase compared to the follicular phase in women. Finally, we propose to investigate the effects of stress on smoking behavior and on reactions to smoking-related cues in regular cigarette smokers. Taken together, these studies will provide a critical link between preclinic LVAL al findings and clinical observations, to elucidate how stress increases drug use. The results of these studies will improve our understanding of mechanisms by which stress increases drug use, and could lead to improved methods for preventing and treating stress-related drug use.D  h A |luu@@Research@ DOESCHERMARKUNIVERSITY OF WASHINGTONSEATTLEWARWJF40664@T@l@ @10/1/20006/30/200410/1/2000 to 6/30/20044/2005|uokbHB88,"tt 1@p@ResearchH@DODSONDONALDAOREGON DEPARTMENT OF HUMAN SERVICESORRWJFNot Given@T@N@ @1/1/20024/31/20051/1/2002 to 4/31/20054/2005xrnnI@88,"ss@`a@Researchl@DODGEKENNETHDUKE UNIVERSITYDURHAMNCNIDAR01, DA016903"@@!Ij@ @9/20/20038/31/20089/20/2003 to 8/31/20084/2005zkeaYH?88,"rrg@^@Researchl@DJORDJEVICMIRJANAINSTITUTE FOR CANCER PREVENTIONVALHALLANYNCIP20, CA091401Not availableBiology and Cancerl@@Not Given2002? to 20024/2005|xnMD88,"qqg@p@4Research@DJORDJEVICMIRJANAINSTITUTE FOR CANCER PREVENTIONVALHALLANYNCIP01, CA068384V+p.L@ Il@@Not GivenNot GivenUncertain4/2005|xnMD88,"pp8@R@Research`@DINNINGAYAHEALTHCARE PARTNER'S INSTITUTERWJFNot Given@j@IT@@3/1/20029/25/20023/1/2002 to 9/25/20024/2005wlfffFA88,"oo%@@ResearchJ@DIFRANZAJOSEPHUNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOLWORCESTERMANIDAR01, DA014666 @Biology and Cancer Addiction@@9/30/20018/31/20069/30/2001 to 8/31/20064/2005vJB88,"nnp@@ResearchL@DEVESASUSANDIV. OF CANCER EPIDEMIOLOGY AND GENETICSBETHESDAMDNCIZ01, CP010183>]V+p.t@I@h@5/19/20039/30/20035/19/2003 to 9/30/20034/2005{qG@88,"mm@1@ResearchDESCRIPTIVE STUDIESDEVESASUSANDIV. OF CANCER EPIDEMIOLOGY AND GENETICSBETHESDAMDNCIZ01, CP010108z*V+p.t@IT@@200020012000 to 20014/2005\UMM,"ll@p@4Research\@DENTCLYDEUNIVERSITY OF SOUTHERN CALIFORNIACACTRDRP9HT-3201V @T@I@@2000Not Given2000 to ?4/2005~tlhhE>88,"kk@]@Researchr@DEMERATHELLENWRIGHT STATE UNIVERSITYDAYTONOHNIDDKR01, DK0648708V+p.Biology and Cancerl@J@9/20/20037/31/20089/20/2003 to 7/31/20084/2005unjbIB88,"jjg@@Researchx@\DEFFENBACHERJERRYCOLORADO STATE UNIVERSITYFORT COLLINSCONIDAP50, DA007074V+p.T@I@@Not Given2004? to 20044/2005zvhMF88,"ii@@ResearchR@\DE WITHARRIETUNIVERSITY OF CHICAGOCHICAGOILNIDAR01, DA002812V+p.Biology and Cancer Addiction@Xj@1/1/19815/31/20091/1/1981 to 5/31/20094/2005smi`I@88,"LVALV+p.Project V: Some people use drugs and alcohol to cope with emotional distress. Some find that alcohol and drugs exacerbate their emotional problems and/or that an emotional problem, when combined with drugs and alcohol, leads to damaging consequences. Angry people drink more, get drunk more often, and use tobacco and other drugs more frequently. Drugs and anger are dangerous partners; the angry person who is high is more likely to engage in aggression, violence, risky driving, vandalism, and inappropriate sex,, and/or to suffer personally, becoming victims of violence, sexual abuse, and damaged relationships. Anger can be treated successfully by the most empirically validated intervention to date, a combination of cognitive and relaxation coping skills (CRCS) The proposed research will select high trait angry, binge drinking college students. These students have high levels of both alcohol and drug abuse and suffer and cause serious adverse consequence.. The high anger, binge drinking students will be randomly assigned to an experimental treatment (CRCS) or a non treatment control. Anger, anger expression and consequences, drug and alcohol use and consequences, anxiety and depression will be assessed at five points in time (pre-treatment, post- treatment, and one, six, and 24 month follow-ups), using self-report and key informant methodologies. Grades, academic attrition, and university disciplinary actions will be retrieved from archival records. The primary research question is whether treatment of angry, treatment of anger reduce the use of alcohol, tobacco, and other drugs to cope with anger-produced emotional distress? (2) Does treatment reduce the frequency and intensity of anger if alcohol and drugs are abused? (3) Does treatment reduce the violence and victimization that result from combining anger and alcohol/drug abuse? (4) Does treatment have ancillary effects, reducing other emotional issues, improving college grades, or reducing college attrition? (5) Are there either short or long term diNLVAL^fferences in the effects of treatment by gender or ethnicity on these outcomes?LVALXb : d  D L R\4DfbDiscovery 2a Development 1 Evaluation 1aDiscovery 1c Discovery 3 Development 2 Evaluation 1aDiscovery 1c Discovery 2a Discovery 3 Development 3 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1c Discovery 3 Development 1 Development 3 Delivery 1 Delivery 2 Partnerships 2 Evaluation 1aDiscovery 1a Discovery 1b Discovery 1c Discovery 2a Development 2 Delivery 1 Evaluation 1a Evaluation 1bDiscovery 2a Discovery 2b Development 4 Partnerships 1 Partnerships 2 Partnerships 3 Partnerships 4 Evaluation 1aDiscovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1aDiscovery 1a Development 1 Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1b Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1b Discovery 1c Discovery 3 Development 3 Delivery 1 Delivery 2 Partnerships 1 Evaluation 1a Evaluation 1bDiscovery 1c Development 1 Delivery 1 Delivery 2Discovery 1c Development 2 Delivery 1 Evaluation 1aDiscovery 1c Development 1 Delivery 1Discovery 1c Discovery 2a Delivery 1 Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Development 1 Evaluation 1aDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1b Evaluation 1a Evaluation 1bDiscovery 1c Development 2 Development 3 Delivery 1 Evaluation 1aDiscovery 1a Discovery 2a Discovery 3 Evaluation 1bDiscovery 1c Discovery 2a Discovery 3 Development 1 Evaluation 1a Evaluation 1cLVALV+p.The goal of the proposed study is to understand the genetic architecture underlying visceral obesity and its associated physiological components. Accumulation of fat deep within the abdomen (i.e., visceral adipose tissue) is known to play a pivotal role in the development of non-insulin dependent diabetes mellitus and cardiovascular disease (CVD). In our proposed study, we aim to disentangle the genetic and environmental factors that explain human variation in visceral adiposity by viewing it as a component of a phenotypic complex that also includes insulin resistance, vascular inflammation, and hormonal variations (the "visceral obesity complex"). The proposed study is built upon an existing study of 1,000 individuals in five large multi-generational kindreds, in which whole-genome genotyping and disease risk factor phenotyping are already underway. The proposed study has three specific aims. In Specific Aim 1 we will phenotype the study population using MRI and dual energy x-ray absorptiometry to measure the amount and distribution of visceral and subcutaneous adipose tissue, using ELISA to assay concentration of adipocyte-derived hormones, and using a repeated 24-hour dietary recall protocol to characterize current energy and macronutrient intake. In Specific Aim 2 we will use variance components-based quantitative genetic methods for extended pedigrees to estimate the heritability of the independent components of the visceral obesity complex, identify key environmental variables and covariates (i.e., sex, age, diet, physical activity, hormone usage, smoking and alcohol consumption) that influence the visceral obesity complex alone or in interaction with genetic factors, and examine the extent to which common genetic factors underlie this complex of closely related traits. In Specific Aim 3, we will use variance components-based linkage methods to identify quantitative trait loci (QTL) harboring genes that influence variation in constituent components of the visceral obesity complex. We also will e LVAL xamine gene-by-environment, gene-by-sex, and gene-by-age interactions in these traits. Fine mapping procedures will be used further localize QTL that are identified. At the conclusion of the proposed study, we will have identified particular genetic loci that influence the visceral obesity complex, and will better understand how particular genotypes may, when confronted with particular environments, predispose individuals to the accumulation of visceral adipose tissue, thereby putting them at increased future risk for developing diabetes and CVD.LVAL#2< F T , X 8R(nN@MOTIVATIONAL INTERVENTION FOR PREGNANT SMOKERSOUTREACH TO END SMOKING AND REDUCE SECOND-HAND SMOKE EXPOSURENEUROTOXIC EFFECTS OF NICOTINE: ANATOMY, MECHANISMS, EFFECTSCHRONIC PROGRESSIVE KIDNEY DISEASE AND EXPOSURE TO CIGARETTE SMOKE IN THE POST-MENOPAUSAL STATESCHOOL BASED DRUG USE PREVENTION FOR GIRL ATHLETESREDUCING CANCER RISK IN MIGRANT HISPANIC ADOLESCENTSSEX DIFFERENCES IN THE EFFECTS OF NICOTINEDRUG CRAVING: PHARMACOLOGIC AND ASSOCIATIVE INFLUENCESLUNG HEALTH STUDY--LONG TERM FOLLOW-UPSMOKING AND ECHOGENICITY OF THE ARTERIAL INTIMASOCIAL INFLUENCES ON ADOLESCENT ALCOHOL USE DEVELOPMENTBUPROPION TREATMENT FOR YOUTH SMOKING CESSATIONSPANISH/ENGLISH WEB SITE FOR SMOKING CESSATION TRIALSINTERNET HEALTH RESEARCH CENTER: SMOKING, LATINOS, AND THE WEBEXERCISE AND NICOTINE REPLACEMENT FOR FEMALE SMOKERSPSU--WESTERN AND SOUTHERN AFRICAN TOBACCO RESEARCH PROJECTOBESITY PREVENTION AFTER SMOKING CESSATION IN MENOPAUSEINDIVIDUALIZING TREATMENT FOR ADDICTED SMOKERSPILOT--PRENATAL NICOTINE EXPOSURE AND THE DOPAMINERGIC SYSTEMBREAST CANCER AND THE ENVIRONMENT ON LONG ISLANDENVIRONMENTAL EPIDEMIOLOGY OF LUNG CANCER IN NEW HAMPSHIREDNA REPAIR GENE POLYMORPHISMS AND PANCREATIC CANCERMATERNAL LIFESTYLE STUDY--8-11 YEAR FOLLOW-UPBIOBEHAVIORAL MECHANISMS IN GENETIC RISK FOR SMOKINGMATERNAL INTERVENTIONS TO STOP SMOKINGBIOCHEMICAL FEEDBACK AND BENEFITS EXPANSION FOR SMOKING CESSATION: SUSTAINED TREATMENTS OVER THE PRENATAL PERIOD (STOPP)OREGON SMOKE-FREE MOTHERS AND BABIESDEVELOPMENT AND PREVENTION OF SUBSTANCE ABUSE PROBLEMSEXPOSURE TO CARCINOGENS IN TOBACCO SMOKE--ROLE OF RACEDOSIMETRY OF RISK FOR LUNG AND BLADDER CANCER AMONG CIGARETTE SMOKERSHEALTHCARE PARTNER'S PRENATAL TOBACCO INITIATIVETHE TRANSITION OF NICOTINE DEPENDENCEDESCRIPTIVE STUDIES AND RECORD LINKAGENICOTINE REPLACEMENT IN SCHOOL-BASED CESSATIONVISCREAL ADIPOSITY: GENETIC AND ENVIRONMENTAL INFLUENCESLVALCurrently, their exists little research on how to get teenagers to stop using tobacco. The research that does exist does not include looking at the usefulness of nicotine gum as an aid to quitting. This study will provide that evidence. Coordinated through the Humboldt County Office of Education, the study will offer a quit program to all high school students and staff in Humboldt county in their schools. We hope to involve approximately 300 students in the program. Half of the students will be offered nicotine gum, and half will be offered an herbal gum, both of which are sold in stores as an aid to stop smoking. They will use the gum for 6 weeks, in lesser and lesser amounts. We will determine how many in each group have quit using tobacco 8 weeks and 6 months after they start using the gum. School teachers and school nurses will lead classes on how to deal with the gum and quitting. Through their experience working with the study, they will be able to continue the effective parts of the program after the study is over. They may also be encouraged to conduct more studies on their own on ways to get students to quit using the results and experiences they gain in this study.LVALV+p.Evaluation of demographic, temporal, and geographic variation in cancer rates may suggest clues to the roles of environmental or cultural influences; identification of population subgroups or regions at notably high or low risk may indicate areas where more intensive studies might be particularly fruitful. The Atlas of Cancer Mortality in the United States, 1950-94 was published in 1999, and the online version is available at http://www.nci.nih.gov/atlasplus. Users can create customized maps and have flexibility in choice of cancers, age groups, and sex and race aggregation. We have been analyzing changes in the geographic patterns of mortality for those cancers with substantial variation by area, race, and/or gender. The geographic patterns for breast cancer mortality have remained remarkably static, but are more pronounced for women older than age 50 years than for younger women. Race- and age-specific breast cancer mortality rates from 1950 through 1999 were calculated for four census regions and 508 state economic areas of the United States. We found that although rates of breast cancer still tend to be highest in the Northeast, intermediate in the West and Midwest, and lowest in the South, the underlying mortality trends suggest somewhat slower recent dissemination of effective breast cancer treatment in the South. We used a spacial scan statistic to further characterize the elevated prostate cancer mortality rates in certain areas of the country, and we identified five clusters of elevated mortality rates among white men and 3 in black men. The patterns observed could not be attributed to selected demographic or socioeconomic characteristics but should provide leads for further study into the risk factors and the medical or reporting practices that may contribute to geographic variation in prostate cancer mortality. With our collaborators in Beijing, China, we mounted a pilot study, using data from five provinces, to investigate the feasibility of comparing cancer mortality rates from the sampleLVAL survey of 1990-92 with rates from the full survey of 1973-75. Preliminary results suggest that we can proceed, and we recently received data for the full 27 provinces for both time periods. We are editing the data and preparing for our full analysis. In contrast to mortality data, which are limited to specifying the form of cancer, incidence data include information on histologic type of the tumor and in many instances, the subsite of origin. We have used incidence data from the Surveillance, Epidemiology, and End Results (SEER) program to investigate further the demographic patterns to discern subgroups that may be of etiologic significance. We evaluated age-adjusted incidence rates based on data for cases diagnosed in nine SEER registries for oral cavity and pharynx (OCP) cancers by histologic type, anatomical site, race, and sex to identify subgroups that may be etiologically distinct. The data suggest that OCP cancers may be separated into five subgroups: squamous cell carcinoma (SCC) of the lip, SCC of the oral cavity, SCC of the pharynx, adenocarcinoma, and Kaposi?s sarcoma. Squamous cell carcinoma of the esophagus was the main form of esophageal cancer in the past, and rates have been decreasing while remaining higher among blacks than whites. Declines in tobacco use and heavy alcohol ingestion, and increases in consumption of raw fruits and vegetables likely have contributed to decreasing incidence. In contrast, adenocarcinoma of the esophagus has been rising and is more frequent among whites than blacks; obesity, gastroesophageal reflux disease, and possibly reductions in H. pylori prevalence most likely have contributed to the increases. Reductions in smoking, improved diet, and reductions in H. pylori prevalence probably have contributed to the consistent reductions observed for distal gastric cancer. Our analysis of the recent U.S. trends in lung cancer incidence and mortality found convergence of rates among men and women born after 1960, supporting the idea that males and females may beBLVALR equally susceptible to develop lung cancer from a given amount of cigarette smoking, rather than the hypothesis that women are more susceptible. Breast cancer accounts for one-third of cancer diagnoses and 15% of cancer deaths in U.S. women, making it the most common incident cancer (excluding superficial skin cancers) and the second leading cause of cancer death. Internationally, incidence rates vary threefold, with rates low in Asia, intermediate in South America and Eastern Europe, and high in North America and Western Europe; migrant studies suggest that lifestyle factors largely explain these international differences. We examined crude cumulative probabilities of death from breast cancer and other causes subsequent to a diagnosis of breast cancer by race, stage of disease, age, and tumor size using data from the SEER program. We found that the probability of death from breast cancer declines with age within stage and increases with advancing stage regardless of age. We investigated why incidence rates for malignant tumors of the uterine corpus are lower among blacks than among whites, whereas mortality rates are higher among blacks. We found that less favorable outcomes for usual types of endometrial adenocarcinoma and for rare aggressive tumors contribute equally to the relatively high mortality due to corpus cancer among black women. LVALV+p.Descriptive Studies: Evaluation of demographic, temporal, and geographic variation in cancer rates may suggest clues to the roles of environmental or cultural influences; identification of population subgroups or regions at notably high or low risk may indicate areas where more intensive studies might be particularly fruitful. The Atlas of Cancer Mortality in the United States, 1950-94 was published in 1999, and the online version is available at http://www.nci.nih.gov/atlasplus. Users can create customized maps and have flexibility in choice of cancers, age groups, and sex and race aggregation. We have been analyzing changes in the geographic patterns of mortality for those cancers with substantial variation by area, race, and/or gender. The geographic patterns for breast cancer mortality have remained remarkably static, but are more pronounced for women older than age 50 years than for younger women. Race- and age-specific breast cancer mortality rates from 1950 through 1999 were calculated for four census regions and 508 state economic areas of the United States. We found that although rates of breast cancer still tend to be highest in the Northeast, intermediate in the West and Midwest, and lowest in the South, the underlying mortality trends suggest somewhat slower recent dissemination of effective breast cancer treatment in the South. We used a spacial scan statistic to further characterize the elevated prostate cancer mortality rates in certain areas of the country, and we identified five clusters of elevated mortality rates among white men and 3 in black men. The patterns observed could not be attributed to selected demographic or socioeconomic characteristics but should provide leads for further study into the risk factors and the medical or reporting practices that may contribute to geographic variation in prostate cancer mortality. With our collaborators in Beijing, China, we mounted a pilot study, using data from five provinces, to investigate the feasibility of comparing cancer mortality LVALrates from the sample survey of 1990-92 with rates from the full survey of 1973-75. Preliminary results suggest that we can proceed, and we recently received data for the full 27 provinces for both time periods. We are editing the data and preparing for our full analysis. In contrast to mortality data, which are limited to specifying the form of cancer, incidence data include information on histologic type of the tumor and in many instances, the subsite of origin. We have used incidence data from the Surveillance, Epidemiology, and End Results (SEER) program to investigate further the demographic patterns to discern subgroups that may be of etiologic significance. We evaluated age-adjusted incidence rates based on data for cases diagnosed in nine SEER registries for oral cavity and pharynx (OCP) cancers by histologic type, anatomical site, race, and sex to identify subgroups that may be etiologically distinct. The data suggest that OCP cancers may be separated into five subgroups: squamous cell carcinoma (SCC) of the lip, SCC of the oral cavity, SCC of the pharynx, adenocarcinoma, and Kaposi?s sarcoma. Squamous cell carcinoma of the esophagus was the main form of esophageal cancer in the past, and rates have been decreasing while remaining higher among blacks than whites. Declines in tobacco use and heavy alcohol ingestion, and increases in consumption of raw fruits and vegetables likely have contributed to decreasing incidence. In contrast, adenocarcinoma of the esophagus has been rising and is more frequent among whites than blacks; obesity, gastroesophageal reflux disease, and possibly reductions in H. pylori prevalence most likely have contributed to the increases. Reductions in smoking, improved diet, and reductions in H. pylori prevalence probably have contributed to the consistent reductions observed for distal gastric cancer. Our analysis of the recent U.S. trends in lung cancer incidence and mortality found convergence of rates among men and women born after 1960, supporting the idea that malLVALes and females may be equally susceptible to develop lung cancer from a given amount of cigarette smoking, rather than the hypothesis that women are more susceptible. Breast cancer accounts for one-third of cancer diagnoses and 15% of cancer deaths in U.S. women, making it the most common incident cancer (excluding superficial skin cancers) and the second leading cause of cancer death. Internationally, incidence rates vary threefold, with rates low in Asia, intermediate in South America and Eastern Europe, and high in North America and Western Europe; migrant studies suggest that lifestyle factors largely explain these international differences. We examined crude cumulative probabilities of death from breast cancer and other causes subsequent to a diagnosis of breast cancer by race, stage of disease, age, and tumor size using data from the SEER program. We found that the probability of death from breast cancer declines with age within stage and increases with advancing stage regardless of age. We investigated why incidence rates for malignant tumors of the uterine corpus are lower among blacks than among whites, whereas mortality rates are higher among blacks. We found that less favorable outcomes for usual types of endometrial adenocarcinoma and for rare aggressive tumors contribute equally to the relatively high mortality due to corpus cancer among black women. Our analysis of ovarian cancer incidence rates revealed that white women had significantly higher rates compared with black women of all types of epithelial tumors, whereas black women had higher rates of gonadal stromal tumors. The reported rates for some specific histopathologic tumor types have changed over time, in part reflecting more specific pathologic classification. Our investigation of testicular cancer incidence trends revealed that seminoma incidence continues to increase among white males, although the rates of increase have become less pronounced; nonseminoma rates appear to have plateaued. An investigation the incidence of maliLVALgnant thymoma revealed the tumor to be quite rare and to occur more frequently among Asian/Pacific Islanders than other racial groups, suggesting a potential role for genetic factors. The incidence of Kaposi?s sarcoma (KS) and non-Hodgkin?s lymphoma (NHL) increased markedly since the onset of the AIDS epidemic in 1981, but HIV infection rates slowed and effective antiretroviral therapies were introduced during the 1990s. We found that KS incidence declined sharply during the mid-1990s, with the declines most evident in San Francisco; NHL rates also decreased, with the most highly AIDS-associated types of NHL declining the most steeply. However, non-AIDS-associated NHL incidence has continued to increase steadily through 1998. The descriptive epidemiology of a number of cancers has been updated in a series of chapters, including cancers of the breast, corpus uteri, biliary tract, and bladder, and non-Hodgkin lymphoma, multiple myeloma, and the leukemias; and cancer incidence and mortality patterns in the United States have been updated. Cancer incidence and mortality rates may be used to assess consistency with hypotheses regarding cancer etiology suggested by other scientific studies. Colorectal cancer incidence rates have been rising rapidly in Shanghai, China, and dietary factors are suspected to play a role in colorectal cancer risk. Our investigation of incidence trends and dietary patterns found significant positive associations between colon cancer rates and per capita consumption of vegetable oil, poultry, fresh eggs, and pork. Because simian virus 40 (SV40) DNA sequences had been detected in some human pleural mesotheliomas, we examined the relationship between contaminated poliovirus vaccine exposure and subsequent rates of pleural mesothelioma in the United States; we found that age-specific trends in incidence rates were not consistent with an effect of exposure to SV40- contaminated poliovirus vaccine. A fourfold risk of ocular melanoma associated with employment in occupations involving uLVALse of cellular telephones was reported; we found that the dramatic increase in use of cellular telephones was not accompanied by an increase in the incidence of ocular melanoma. Record-Linkage Studies: Census and hospital discharge data from Sweden, Denmark and U.S. Veterans hospitals, linked for follow-up to cancer, mortality, and population registries where available, were used to assess cancer risk among individuals with specific medical and occupational exposures. Swedish and Danish patients with Down's syndrome (DS) had an increased risk of incident cancers at a young age, particularly acute leukemia, both lymphocytic and non-lymphocytic. Risk of solid tumors was somewhat reduced, except for testicular and digestive cancers. Mortality risks were also elevated for cancer, dementia/Alzheimer's disease, heart disease, cerebrovascular disease, infectious diseases and congenital anomalies. Danish patients with hyperparathyroidism had an increased risk of multiple myeloma and cancers of the urinary tract, breast and thyroid gland. In Swedish, Danish and U.S. Veterans hospital data, we investigated the link between inflammatory bowel diseases (ulcerative colitis and Crohn's disease), appendectomy and cancer. We found no evidence of a reduced risk of ulcerative colitis subsequent to appendectomy in either Danish patients or U.S. veterans. In Sweden, children who had undergone appendectomy under age 20 were found to be at no overall increased risk of cancer after an average of 11 years of follow-up; some elevated risks were seen, however, for cancers of the stomach and NHL more than 15 years after appendectomy. Further follow-up of this young cohort is necessary. Swedish celiac patients had an increased risk of lymphoma incidence and cancers of the upper digestive tract. Mortality risks were elevated two-fold overall, but especially increased were lymphoma, auto-immune disorders, and other disorders characterized by immune dysfunction. The Danish Hospital Discharge Register was used to evaluate the potent6LVALFial role of tubal sterilization on subsequent cancer risk; the overall risk of ovarian, endometrial, and cervical cancers was decreased. Swedish men with benign prostatic hyperplasia (BPH) were studied to estimate their risk of subsequent prostate cancer; overall, little, if any, excess risk was apparent. However, differences in prostate cancer incidence and mortality by BPH treatment type suggested that factors related to treatment or health reasons underlying the selection of treatment may influence subsequent prostate cancer risk. A large study was initiated to assess familial aggregation of autoimmune diseases and lymphoproliferative malignancies (LP). We are studying 50,000 Swedish and 10,000 Danish cases of LP, twice that number of non-cancer controls, and all their relatives' computerized medical data (cancers and hospital diagnoses). Swedish women employed in paper packaging, graphic work, dry cleaning, telegraph and telephone work were at increased risk of ovary cancer. Increased risks of melanoma and esophagus, colon, pancreas and brain cancers were observed among Swedish veterinarians. Some of these results may reflect the carcinogenicity of occupational exposures, including physical, chemical, viral, and solar or ionizing radiation. A study of a large cohort of male U.S. veterans hospitalized with a diagnosis of obesity and subsequent cancers revealed elevated risks for several cancers, including lower esophagus, gastric cardia, small intestine, colon, rectum, gallbladder and ampulla of Vater, male breast, prostate, bladder, thyroid, and connective tissue, and for malignant melanoma, multiple myeloma, chronic lymphocytic leukemia, and acute myeloid leukemia, with patterns generally similar for white and black men.LVAL  p4ECONOMICS Socio-Economic Status Medicaid/Medicare Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Other Pharmacological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumCOMMUNITY General Partnerships Health Care Provider LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Quitline RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child Young Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesLOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use Nicotine MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer LOCATION National RESEARCH Human Studies STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Health Care Provider LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child Young Adult DISEASE/BIOLOGY Mechanisms Other Disease/Biology LOCATION National PREVENTION/TREATMENT Interview/Focus Group RESEARCH1 Animal Studies RESEARCH Human Studies Clinical Research TOBACCO NicotineLVALThe goal of this project is to understand the role that conduct disorder plays in the development of substance-abuse problems in young adulthood.This study seeks to test the feasibility and impact of incorporating biochemical assessment of smoking status in a Managed Care Organization within the context of routine prenatal medical care encounters, via the use of urinary cotinine dipsticks.Animal and human studies will be conducted in parallel to determine the threshold dosing for the first symptoms of nicotine dependence in adolescent humans and for the first neurochemical changes brought on by nicotine in the brains of adolescent rats. Separate experiments will evaluate the upregulation of high affinity nicotinic cholinergic receptors in the midbrain reward centers, and the activation of cholinergic reward pathways. These experiments will be conducted to explore the effects of low-dose intermittent exposure to nicotine, simulating the nicotine exposures commonly present at the onset of nicotine dependence in teenagers. A comparison will be made regarding the sensitivity of adolescent and adult rats to the neurochemical effects of nicotine that are thought to be responsible for dependence. Intermittent and continuous dosing will be compared and gender differences will be explored. Adolescents and adults will be compared in the speed with which neurochemical changes occur. In humans, a prospective longitudinal study employing 1200 subjects and individual interviews will be conducted to explore individual differences in the speed with which nicotine dependence develops. The nicotine dosing and pattern of use at the onset of the first symptoms and full dependence will be studied. Investigations will explore why some youths develop symptoms of dependence upon exposure to nicotine while others do not. A new theory-based measure of early dependence for youths will be tested against established measures of dependence.LVALV+p.During the past four decades the cigarette consumption in the U.S.A. gradually changed from high-nicotine, high-"tar" to low-nicotine, low- "tar" brands. Concurrently, there was also a gradual shift observed in the major types of cancer and sites within the lung in cigarette smokers. These changes went from predominance of squamous cell carcinoma, located primarily in the bronchi, to adenocarcinoma in the peripheral lung. It is our working hypothesis that the reduction of the smoke yields of U.S. cigarettes and especially that of the addicting nicotine (sales weighted average changed from 2.7 mg in 1955 to 0.85 mg in 1993) resulted in deeper inhalation of the smoke and thus greater exposure of the peripheral lung to cigarette smoke carcinogens. Increased exposure is also to be considered since more intense smoking of low-nicotine cigarettes leads to higher yields of nicotine and certain carcinogens. Four groups of white and African-American male and female smokers of low- (<0.8 mg), medium- (0.8-1.2), and high- (>1.2) nicotine cigarettes will be studied to assess the relationship between their smoking habits and their actual exposure to nicotine, "airborne", and "bloodborne" carcinogens. Currently, the exposure to nicotine and "tar" is assessed on the basis of FTC data. These are established with standard machine-smoking parameters which were developed in 1936. This method does not reflect the smoking habits of today's cigarette smokers. This project together with the risk estimates established in Project 1 for the major types of lung cancer among smokers of cigarettes with low-, medium-, and high-nicotine content, will result, for the first time, in meaningful estimates of exposure to nicotine and to nicotine-derived carcinogens for each of the three classes of cigarettes. The study will also clarify if the low-nicotine cigarette is indeed less "harmful" than the medium- and high-nicotine cigarette. This study has major public health implications. Lung cancer remains the leading cause of cancer death.LVAL> in the U.S.A, while the overall mortality rate from lung cancer continues to rise. Currently, cigarette smoking contributes to more than 90% of the lung cancer deaths in American men and to more than 75% in American women.LVALXT H j  p$fb>Biology and Cancer Epidemiology and National Surveillance Global IssuesBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National Surveillance Global IssuesInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsAddiction Interventions for Prevention and TreatmentEpidemiology and National Surveillance Interventions for Prevention and TreatmentEpidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and Communications Community and Policy InterventionsBiology and Cancer Addiction Interventions for Prevention and TreatmentEpidemiology and National Surveillance Community and Policy Interventions Global IssuesEpidemiology and National Surveillance Interventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and Treatment LVAL.This is a four-year randomized controlled trial that will assess whether a package of interventions will reduce the rate of smoking in pregnant women and new mothers enrolled in the Medicaid-sponsored Community Health Plan of Washington (CHPW). The objective is to test whether cessation rates, including end-of-pregnancy and 12-month postpartum cessation rates, will improve in women who attend clinics receiving the CHPW-sponsored package of perinatal cessation benefits compared with those who attend control clinics.The intervention is a coordination system of tobacco treatment by case managers, prenatal care providers, and a quitline. The case manager works with the prenatal care provider to share information on their clients, ensure that the "5 A's" are followed at every prenatal and case management visit, and proactively refer clients to the quitline. From each of the participating counties, one maternity case manager is selected to participate on an Implementation Team. This team has quarterly meetings to address smoking cessation counseling, data collection, and office system strategies. The Leadership Team is composed of project staff from the state health department, and they are responsible for technical assistance and training, monitoring the intervention, and conducting the process and outcome evaluation. The Steering Committee is composed of MCH and tobacco control representatives from the Department of Human Services, community-based organizations, non-profits, and advocacy groups.LVALf+p.Mullerian Inhibiting Substance (MIS) causes regression of female reproductive tract structures in the male fetus. To investigate whether MIS can be a therapeutic for ovarian cancer, which originates from the Mullerian duct derived coelomic epithelium, binding of MIS to both ovarian cancer cell lines and primary ascites cells from patients with stage III or IV cystadenocarcinoma was demonstrated. These cells express the MIS type II receptor mRNA and respond to MIS in growth inhibition assays. These experiments paralleled efforts to produce MIS that would be suitable for clinical trial in humans because of concern over mouse immunogens in the immunoaffinity purification of MIS and the preponderance of high molecular weight aggregates and multiple products of the primary and secondary cleavage sites of holo MIS. In order to address those concerns, preliminary studies were done that indicate conditioned serum free media from MIS transfected mammalian cells could be used to advantage to produce a homogeneous preparation of MIS by size exclusion chromatography with an FPLC system. Peptides with high affinity can also be used in purification, and tobacco sources for rhMIS will be compared to mammalian sources. Thus, the first Specific Aim is to purify homogenous MIS using these approaches and to scale up production for use in clinical trials. The second Specific Aim is to crystallize MIS or its derivative in order to begin the process of characterizing the secondary structure of MIS and understand the molecular interactions both between the amino and carboxy terminal MIS domains and between the C terminal domain and its receptor. The third Specific Aim is to determine if the MIS type II receptor is mutated in patients with ovarian cancer by sequence analysis and correlate absence of functional receptor with the occurance of ovarian cancer. The fourth Specific Aim is to study the tissue specific and developmental expression of the MIS type II receptor using antibodies developed during the past grant and other* LVAL: s to be developed during the course of the proposed grant. A homogeneous MIS product whose structure is defined by crystallography, which can be scaled up for human use in clinical trials against human ovarian cancer, can then be used in parallel with MIS type II receptor molecular probes and antibodies to select tumors appropriate for such therapies.i } Z  j; Q@@Researcht@KINGGARYPENNSYLVANIA STATE UNIVERSITY--UNIVERSITY PARKUNIVERSITY PARKPAFICR01, TW005955l@@ @j@9/20/20028/31/20049/20/2002 to 8/31/20044/2005tD>88,"@@`@Researchn@GEISELMANPAULALSU PENNINGTON BIOMEDICAL RES. CENTERBATON ROUGELANIAR01, AG018239u+p.@ @@3/1/20002/28/20053/1/2000 to 2/28/20054/2005~qJC88,"@@Research\@GARVEYARTHURHARVARD UNIVERSITY MEDICAL SCHOOLBOSTONMANIDAR01, DA012165u+p.j@@@1/1/200012/31/20041/1/2000 to 12/31/20044/2005}wskH@88,"g@p@4Researchz@GARCIA-DAVILAMARTHAGEORGETOWN UNIVERSITYWASHINGTON DCNCIP50, CA084718 @Biology and Cancer AddictionT@@Not GivenNot GivenUncertain4/2005|wsfOG88,"~~ @@Research`@GAMMONMARILIEUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL CHAPEL HILL NCNCIU01, CA066572u+p.t@p@@8/8/19957/31/20058/8/1995 to 7/31/20054/2005wI@88,"}}g@p@4Research"RECORD-LINKAGE STUDIES OF CANCERGAILMITCHELL DIV. OF CANCER EPIDEMIOLOGY AND GENETICSBETHESDAMDNCIZ01, CP010105f+p.L@Discovery 1b Evaluation 1b@Not GivenNot GivenUncertain4/2005-%k`ZZ,"||@Y@Researcht@DUELLERICDARTMOUTH COLLEGEHANOVERNHNCRRP20, RR018787:f+p.L@@@9/30/20036/30/20089/30/2003 to 6/30/20084/2005zkeaXE?88,"{{ }@@Researchf@ DUELLERICDARTMOUTH COLLEGEHANOVERNHNCIR01, CA098889f+p.Biology and Cancerl@@9/1/20038/31/20069/1/2003 to 8/31/20064/2005yjeaXE?88,"zz F@@ResearchZ@ DUARASHAHNAZUNIVERSITY OF MIAMI MEDICAL CENTERCORAL GABLESFLNICHDU10, HD021397f+p.t@R@@4/1/19913/31/20064/1/1991 to 3/31/20064/2005~zlH?88,"yy`@C@Researchh@ DROBESDAVIDMEDICAL UNIVERSITY OF SOUTH CAROLINACHARLESTONSCNCIR21, CA081638f+p.Biology and Cancer Addiction@@6/4/19995/31/20026/4/1999 to 5/31/20024/2005 }ymG@88,"xx @G@ResearchKEEP ME SMOKEFREED'ONOFRIOCAROLYNETR ASSOCIATESSANTA CRUZCACTRDRP7RT-0090f+p.@@ 0@7/1/19986/30/20027/1/1998 to 6/30/20024/2005{o_VKK,"ww@@@ResearchL@ DONATELLEREBECCAOREGON STATE UNIVERSITYCORVALLISORRWJF40669f+p.T@f@ @10/1/20003/31/200510/1/2000 to 3/31/20054/2005ztpeLC88,"vv@@Research MULLERIAN INHIBITING SUBSTANCEDONAHOEPATRICIAMASSACHUSETTS GENERAL HOSPITALBOSTONMANCIR01, CA017393f+p.Biology and CancerDiscovery 1b Evaluation 1b4@6/1/19784/30/20056/1/1978 to 4/30/20054/2005@8!! kaXX,"LVALf+p.Tobacco use is widely recognized as the single, most important public health issue today, causing nearly half a million deaths per year, over $50 billion in smoking-related illnesses, and contributing significantly to the total US burden of disease. The economic burden to Oregon from smoking, based on 1996 data, is $1.5 billion. Of that, $800 million is for medical expenditures (direct costs) and $700 million is for loss of productivity due to illness or premature death (indirect costs). Recent (1998) Oregon Health Division data indicate that over 22% of Oregonians smoke and that 82% of these smokers initiate their smoking behavior before the age of 21. For Pregnant Smokers Smoking has remained the single most important modifiable cause of poor pregnancy outcome in the USA. Smoking accounts for 20% of low birth weight deliveries, 8% of preterm births, and 5% of all perinatal deaths, contributes to Sudden Infant Death Syndrome (SIDS) and may cause important changes in fetal brain and nervous system development. In the US quitting smoking can prevent 40,000 low-birthweight (small for age) babies and can prevent 4,600 perinatal deaths (estimated cost of $69,542 for each perinatal death). New economic estimates indicate that the direct medical costs of a complicated birth for a smoker are 66% higher than for nonsmokers which reflects the intensive medical care required. 28% of the high-risk, low-income, Oregon Health Plan pregnant population smoke, as reported by Oregon Health Division (1999 data). Study Design. Four-year, randomized controlled trial of a theory-based, motivational intervention using patient incentives and clinic supports combined with a core  best practice intervention delivered by OB/GYN practitioners. Purpose. To significantly increase smoking cessation behavior among low-income, high risk (Medicaid/Oregon Health Plan eligible) pregnant women who access private practice managed care prenatal clinics in heavily populated areas of Oregon. Expected Outcomes. (1) Establish LLVAL\whether incentives are more effective than Best Practice in motivating smoking cessation/reduction, (2) Examine feasibility of delivering the intervention in managed care prenatal clinics on a national basis.LVALj : X@DISEASE/BIOLOGY Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Young Adult Adult DISEASE/BIOLOGY Mechanisms Other Disease/Biology LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Hormones MISCELLANEOUS Sex/Gender DifferencesAGE Child COMMUNITY Health Care Provider DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments RESEARCH Human Studies TOBACCO Environmental Tobacco Smoke WOMEN Pregnancy Parent/Mother Partner/SpouseCOMMUNITY Health Care Provider ECONOMICS Socio-Economic Status Insurance Coverage Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyLVALf+p.Babies exposed to secondhand smoke have many more ear infections, colds, other illnesses, and hospitalizations than babies who live in smokefree environments. Even though smoking rates in California are going down, about one of every five newborns in the State has a smoking parent. Babies also are exposed to secondhand smoke from other family members, friends, and at day-care centers. Keep Me Smokefree is an exciting new program to help mothers and other household members keep their newborn babies and other children away from cigarette smoke. This research project will make the new program available to 300 ethnically diverse women and their families through the doctor that the baby sees. Before the baby is born, these women will be called on the telephone and told more about how dangerous secondhand smoke is for newborns. They also will be helped to identify sources of secondhand smoke that might affect their babies and to develop personal plans for keeping their babies smokefree. When the doctor sees the baby in the hospital, he or she will remind the mother to keep her baby away from secondhand smoke and give the baby a bib to help the family remember. The doctor will discuss secondhand smoke again when family members bring the baby for check-ups. At the end of some visits, the doctor will give the baby more small gifts (such as a rattle or a ball) with the Keep Me Smokefree message. An office working with the doctor will support these efforts by talking with mothers and other family members on the telephone, by helping mothers in developing plans to establish and maintain a smokefree environment, by mailing them written materials, and by referring them to community resources. To see how well the program works, the 300 babies whose families received the program will be compared with 300 other babies when all babies are 12 months old. We expect that mothers of infants in the first group will report that their babies are exposed to much less secondhand smoke than mothers of babies in the second grD LVALT oup. We also expect mothers of babies in the first group to report that their babies didn't have as many ear infections and other illnesses as babies in the second group. Because mothers might be tempted to tell the researchers what they want to hear, their reports will be checked against tests of urine from some babies and with doctors' medical records. This study will help to identify better ways of preventing children's exposure to secondhand smoke. It also will provide a way for mothers, fathers, other household members and doctors to work together in order to keep babies and other young children healthy. After the study is completed, mothers and families who did not receive the program will be sent program materials. These also will be available for distribution to doctors offices and to others who work to protect children's health. fLVALf+p.vTobacco use is associated with approximately 30 percent of all cancer deaths, and cigarette smoking remains the single most preventable cause of cancer and premature death in our society. Recent epidemiological studies have demonstrated a strong genetic component to smoking. Unfortunately, there has been a relative dearth of studies that have attempted to measure the physiological, hormonal, behavioral, or subjective responses that may objectively define the phenotype for smoking. Since these types of responses may figure importantly as mechanisms that mediate the genetic susceptibility for smoking, there is a pressing need for studies that examine differences among those at varying degrees of risk for smoking. The proposed research seeks to examine biobehavioral mechanisms that may underlie an increased genetic risk for smoking within a laboratory-based experimental paradigm. To accomplish this goal, we will examine men and women smokers' and never-smokers' psychophysiological, hormonal, self-report, and information processing responses to standard IV nicotine doses and how these responses relate to family smoking history. The focus will be on affective and attentional responses within these paradigms, since these are empirically and theoretically related to smoking behavior. We will also examine subjects' affective responses to standardized pictures after nicotine dosing. It is hypothesized that affective and attentional responses obtained after nicotine administration, including responses to affective and smoking- related cues, will be predictive of family smoking history. Research examining biobehavioral response to nicotine within a genetics framework has yet to be conducted and may lead to a better understanding of the mechanisms that mediate susceptibility for smoking. This increased understanding could lead to more effective prevention and treatment efforts for cigarette smoking, and consequently decrease the prevalence of cancer in our society.LVALf+p.Prenatal substance exposure continues to be a major public health problem that affects millions of children and places enormous financial and social burdens on society. The Maternal Lifestyle Study (MLS) is an interagency collaboration involving the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the Administration on Children, Youth and Families, and the Center for Substance Abuse Treatment. MLS is being conducted in four University sites: Miami, Tennessee at Memphis, Wayne State, and Brown; and it is the largest clinical prospective longitudinal study to date of prenatal drug exposure and child outcome. The follow-up cohort includes 658 exposed and 730 comparison children who have been studied through 7 years of age with 71% retention. This proposal is to continue the follow-up through age 11. One aim is to study the effects of prenatal cocaine/opiate exposure on immediate child outcomes that start in infancy (e.g. attention, relationship to parent, neuromotor, physiologic reactivity, arousal/regulation, and medical status) as well as latent effects on domains of function that emerge later and become salient as children reach school age (e.g. cognition, antisocial behavior, substance use onset, psychopathology, neuroendocrine function, and health disorders). This includes determining the effects of heavy cocaine exposure and controlling for exposure to other drugs (alcohol, marijuana, and tobacco), medical (e.g. physical growth) and environmental factors, gender, minority status, and study site. The second aim is to study a broader conceptualization of the consequences of maternal drug use that includes determining how drug effects, and the effects of the postnatal environment combine to affect child outcome, including specific aspects of the environment unique to the drug culture. As a major longitudinal study, MLS is important to the field of developmental science by contributing to our understanding of developmental processes in normal and at-risk cLVAL"hildren. MLS will also contribute to the field by addressing health indicators related to Healthy People 2010. Understanding the consequences of prenatal cocaine exposure and risky environments is crucial for treatment and public policy.LVALf+p.Pancreatic cancer is the fourth leading cause of cancer-related deaths among men or women in the U.S. It has the lowest 5-year survival (4%) of all cancers and has been difficult to study due to its rapidly fatal course and the lack of intermediate endpoints or early markers for the disease. Cigarette smoking is one of the few documented environmental risk factors. This study will use previously collected germ-line DNA and epidemiologic data from one of the largest population-based, case-control studies of pancreatic cancer to investigate associations between risk of adenocarcinoma of the pancreas and polymorphisms in candidate DNA repair, cell-cycle control, and oxidant defense genes. The main study was conducted in the San Francisco Bay Area between 1994 and 2001 and used random digit dialing and Health Care Finance Administration lists to identify controls. Genomic DNA and questionnaire information is available on 309 cases and 964 population-based controls. DNA repair pathways are known to be involved in correcting diverse forms of damage induced by agents such as tobacco smoke. Recent studies indicate that DNA repair pathways cross talk with pathways involved in cell cycle regulation such that cell-cycle delay or arrest allows for optimal DNA repair. DNA repair capacity is known to vary among individuals and is likely to be genetic. Genetic variation in carcinogen metabolism and DNA repair has been shown to play a role in susceptibilities to smoking-related cancers. We will analyze genomic DNA from cases and controls for known polymorphisms in genes involved in pathways for base excision repair, nucleotide excision repair, double-strand break repair, direct repair, cell-cycle control, and oxidant defense. We will estimate genotype and allele frequencies, examine main gene (genotype) effects, and explore potential genotypesmoking and genotype-genotype interactions as they relate to the risk of adenocarcinoma of the pancreas. We anticipate that these data will contribute to our understanding of disLVAL*ease mechanisms, and may ultimately improve the prevention, detection and treatment of pancreatic cancer.LVALf+p.This project integrates spatial analytic techniques and traditional case-control methods in epidemiology to study environmental risk factors for lung cancer in New Hampshire. We will adopt a three-phase approach. First, a geographic information system (GIS), which is the technical environment in which spatial analyses are performed, will be used to reveal spatial patterns and relationships between environmental factors (such as fine particulate air pollution) and lung cancer in New Hampshire. Second, traditional population-based, case-control methods of epidemiology will be used to study individual-level risk factor information (collected from questionnaires, drinking water samples, toenails clippings, sera, and germ-line DNA). This will permit us to model causal relations between environmental factors and risk of incident lung cancer in New Hampshire. As part of this approach, we will explore potential modifications in relative risk due to synergy between exposures (arsenic and smoking), host genetic susceptibility, dietary factors, and gender. We also will employ multilevel modeling (hierarchical regression) of individual lung cancer risk using group-level (ecologic/geographic) exposure information (e.g., fine particulate air pollution) and individual-level exposure information (e.g., smoking status, age, gender, education, occupation, use of wood burning stoves, water arsenic concentration, toenail arsenic concentration, DNA repair genotype, and other variables). Multilevel modeling will allow us to improve estimates of individual lung cancer risk by including group-level data that have no individual-level analogue (e.g., exposure to fine particulate air pollution). Third, using spatial environmental data and risk models built in phase 2, we will create a risk map of lung cancer in New Hampshire. We will test the validity of our environmental models and our risk map of lung cancer using newly collected lung cancer incidence data from New Hampshire. Through this three-phase approach, we expect that  LVAL new etiologic factors for lung cancer will be uncovered and that this information will aid scientists and policy makers regarding risk assessment and disease prevention. This project will also set the stage for a comprehensive regional environmental health information system that will serve as a database and knowledgebase for future environmental health studies of lung diseases and other health outcomes in New Hampshire. LVALf+p.Census and hospital discharge data from Sweden and Denmark and U.S. Veterans hospitals, linked for follow-up to cancer, mortality, and population registries where available, were used to assess cancer risk among individuals with specific medical and occupational exposures. Mortality among diabetics in Sweden was elevated for all major causes of death, particularly circulatory, respiratory, digestive, genito-urinary, and malignancies. The youngest diabetics had the greatest increased mortality from all causes. We saw the greatest improvement in mortality (34%) in this group during the study period (year of entry 1965-1983), however. Obese Swedish patients were at increased risk of cancers of the digestive tract, urinary tract, female reproductive organs and connective tissue. Swedish psoriasis patients were at increased risk of several cancers associated with alcohol and tobacco consumption, but they had no increase in malignant melanoma. Swedish and Danish acromegaly patients were at increased risk of several cancers, including cancers of the small and large intestine, rectum, brain, thyroid, kidney and bone. Several possible mechanisms could be involved, such as elevated levels of IGF-1 in these patients. Swedish and Danish patients with Down's syndrome (DS) had an increased risk of incident cancers at a young age, particularly acute leukemia, both lymphocytic and non-lymphocytic. Risk of solid tumors was somewhat reduced, except for testicular and digestive cancers. Mortality risks were also elevated for cancer, dementia/Alzheimer's disease, heart disease, cerebrovascular disease, infectious diseases and congenital anomalies. Danish women hospitalized with gonorrhea were at increased risk of cervical pre-neoplasia, but not invasive cervical cancer or any other cancers. Danish patients with hyperparathyroidism had an increased risk of multiple myeloma and cancers of the urinary tract, breast and thyroid gland. In Swedish, Danish and U.S. Veterans hospital data, we investigated the link between inflamLVAL,matory bowel diseases (ulcerative colitis and Crohn's disease), appendectomy and cancer. We found no evidence of a reduced risk of ulcerative colitis subsequent to appendectomy in either Danish patients or U.S. veterans. In Sweden, children who had undergone appendectomy under age 20 were found to be at no overall increased risk of cancer after an average of 11 years of follow-up; some elevated risks were seen, however, for cancers of the stomach and NHL more than 15 years after appendectomy. Further follow-up of this young cohort is necessary. Swedish celiac patients had an increased risk of lymphoma incidence and cancers of the upper digestive tract. Mortality risks were elevated two-fold overall, but especially increased were lymphoma, auto-immune disorders, and other disorders characterized by immune dysfunction. A large study was initiated to assess familial aggregation of autoimmune diseases and lymphoproliferative malignancies (LP). We are studying 50,000 Swedish and 10,000 Danish cases of LP, twice that number of non-cancer controls, and all their relatives' computerized medical data (cancers and hospital diagnoses). Swedish men and women employed in the painting trades and paint manufacturing were found to be at increased risk of cancers of the head and neck (women) and cancers of the lung, bladder, pancreas and leukemia (men). Swedish women employed in paper packaging, graphic work, dry cleaning, telegraph and telephone work were at increased risk of ovary cancer. Increased risks of melanoma and esophagus, colon, pancreas and brain cancers were observed among Swedish veterinarians. Prostate cancer incidence, but not mortality, was elevated for Swedish men employed in sedentary occupations in 1960 and 1970. Some of these results may reflect the carcinogenicity of occupational exposures, including physical, chemical, viral, and solar or ionizing radiation.LVALu+p.This continuation proposes to follow-up 1,508 case women newly diagnosed with breast cancer who are participants in an ongoing population-based, case-control study of breast cancer among women on Long Island. The primary aims of the ongoing parent case-control study are to determine whether risk of developing breast cancer is increased among women with higher levels of serum organochlorine compounds, including DDT and PCBs, or higher levels of polycyclic aromatic hydrocarbons, assessed by PAH-DNA levels in blood samples. The proposed continuation will follow-up the case women 3- and 5-years after diagnosis of the primary breast cancer to identity environmental factors that affect the risk of disease-free and overall survival, including (1) serum levels of DDT and PCBs, and PAH-DNA adducts based on blood samples collected at the parent case-control interview; and (2) cigarette smoking, physical activity, hormone replacement therapy, changes in weight as an adult, alcohol diet, and other factors assessed by structured questionnaire during the parent case-control interview. An additional aim is to explore whether the survival risk associated with these potential environmental risk factors is modified by known prognostic indicators in the tumor, including p53 and HER-2/neu. During the 3- and 5-year follow-up periods, medical treatment and outcomes (recurrence, second primary) will be assessed by telephone interview with the subject and by checking with physicians and medical records. Mortality will be determined by cross checking the National Death Index, and by contacting next of kin and physicians. For the parent study, blood samples were successfully obtained for 1,087 case women and assays of DDT/PCBs and PAH-DNA adducts will be completed as planned for 643 and 577 cases, respectively. Blood samples for the remaining 444 and 320 case women, respectively, with sufficient blood volume will be assayed for these environmental compound as part of the proposed study. Assays for HER2/neu overexpressi LVAL( on in case tumor tissue, assessed by immunohistochemisty, will be conducted for the proposed follow-up; funding for the immunohistochemical assays of p53 expression has already been obtained. Standard statistical techniques for the analysis of cohort data will be used to determine the risk of disease-free survival and overall survival, at the 3- and 5-year follow-up periods, associated with higher levels of environmental factors, with adjustments made for breast cancer treatment, breast tumor characteristics, and other clinical predictors of survival. Potential subgroup effects, with cases partitioned on p53 and HER-2/neu expression, the relation between environmental factors on breast cancer survival will be explored, where possible.6LVAL( V \NADDICTION Cessation AGE Young Adult Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary ECONOMICS Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle MISCELLANEOUS Weight Gain/ExerciseAGE Child Young Adult EDUCATION LEVEL High School College and Above LOCATION International POLICY Guidelines/Best Practices Regulatory Intervention Other Policy PSYCHOLOGICAL Cultural Factors RESEARCH Human Studies TOBACCO Non-Specified Tobacco UseAGE Adult LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking WOMEN Menopause MISCELLANEOUS Weight Gain/ExerciseADDICTION Cessation Withdrawal Relapse EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies Clinical Research TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use WOMEN Hormone Replacement Therapy MISCELLANEOUS Weight Gain/Exercise(LVAL8The mesolimbic system has been implicated in the addictive properties of most drugs of abuse and dependence including cocaine, heroin, amphetamines and nicotine from tobacco. Nicotine affects the dopaminergic system in multiple ways including increasing both the firing rate and bursting activity of dopaminergic cells and by enhancing synthesis, metabolism and release of dopamine. In these studies we propose to examine, using an animal model, the acute and chronic effects of nicotine of dopaminergic function (dopamine release and dopamine uptake) at various developmental ages. The relationship between the nicotine-induced change in nicotine acetylcholine receptor (nAChR) numbers following chronic prenatal nicotine and the number of dopamine transports will also be assessed. Finally, the identify of the nAChR involved in the dopaminergic regulation will be determined by labeling the receptors with [125I]epibatidine, a high affinity radioligand for a variety of nAChRs, and immunoprecipitation of the receptors with subunit-specific antibodies. To determine the identify of these nAChRs involved in regulating dopaminergic function may lead us to a better understanding of nicotine's effects in brain and in addictive properties during various developmental stages. This knowledge will also help in the development of specific therapeutics, as well as in assessing the validity of using nicotine as a therapeutic agent in developmental disorders or during pregnancy as an aid to quit smoking.LVALu+p.Nicotine replacement continues to be the most promising treatment to date for tobacco addiction. Many questions remain, however, concerning how to optimize the effectiveness of nicotine replacement therapies. A major issue is how to prevent relapse to smoking after a quit-smoking attempt. Relapse rates are disappointingly high (typically 75 percent-80 percent), even for those receiving nicotine replacement treatment. We have planned a study very different from previous studies of nicotine replacement. Our study will be guided by the basic concept that generally characterizes medical management of any disorder: individualization of treatment based upon physiological characteristics unique to each person. Our plan is to test the efficacy of a procedure for tailoring the degree of nicotine replacement to match the smoker's usual nicotine intake using nicotine patches. We will randomly assign 750 smokers to one of 5 treatment conditions. 300 subjects will be given individualized treatment to replace either 50 percent or 100 percent of their pre-quit cotinine levels (cotinine is a major metabolite of nicotine that provides a stable measure of nicotine intake). A key feature of this treatment procedure involves close monitoring of cotinine levels after cessation and subsequent adjustment of dose if necessary. An additional 300 smokers will be given fixed standard or higher-dose patches rather than tailored nicotine replacement. These smokers will provide a dose-response control condition, which will allow us to compare individualization of treatment with a simpler model involving just standard or higher-dose patches. A final control group of 150 subjects will be given only placebo patches, to allow comparisons with a no-treatment condition. Our central hypothesis is that those who receive tailored 100 percent replacement (i.e., matching their usual smoking nicotine intake with nicotine patches) will be the most likely to succeed in quitting. We will also measure relevant biological, behavioral, and withdraw LVAL al variables. These data will allow us to examine mechanisms by which greater nicotine replacement affects cessation rates, to study effects of greater nicotine replacement for important subgroups of smokers (e.g., women, depressed smokers, older smokers), and to investigate additional factors, besides degree of nicotine replacement, that may be related to abstinence or relapse. Results will provide a clear, definitive test of the hypothesis that matching the degree of nicotine replacement to usual nicotine intake improves cessation rates. If this hypothesis is supported, our findings will have major implications for the treatment of addicted smokers.LVALu+p.The present proposal is an obesity prevention pilot study that addresses the high risk of weight gain associated with smoking cessation in postmenopausal women, especially African Americans. This proposal is innovative and unique in its analysis of at and other macronutrient intake as a target for individually tailored, weight control intervention following smoking cessation in women. This treatment program is designed for the primary prevention of weight gain that can lead to overweight in normal- weight women, that can progress to obesity in women who are already overweight (BMI=25.0-29.9), and for the prevention of additional weight gain in obese women with BMI's greater than or equal to 30.0. Postmenopausal African-American and Caucasian women aged 45-59 years will undergo the same standard two-week smoking cessation program followed by a 20-month, experimental or control follow-up intervention. Specific aim 1; To compare the relative effectiveness of following an empirically validated smoking cessation program with either 1) a group cessation maintenance program with standard exercise advice and food pyramid instructions for healthy eating or 2) a novel, individually tailored dietary-control and exercise, weight-management and cessation program in Caucasian and African-American postmenopausal women as assessed by weight change from baseline to post-cessation months 6, 12, and 20. It is hypothesized that our individually tailored, long-term, experimental intervention will effectively control dietary intake, particularly fat intake, thereby preventing weight gain post-cessation. Specific Aim 3: To assess whether there is differential responsiveness on the above measures in postmenopausal Caucasian versus African-American women. It is hypothesized that African-American women may respond differently from Caucasian women on the above measures. This pilot study is an extension of our research program with the long-term objective of developing individualized, multi-disciplinary, long-term interventions LVALfor the prevention of weight gain following smoking cessation in various subsets of women throughout the American population.LVALThe overall goals of the Pennsylvania State University Western and Southern African Tobacco Research (PSU-WSATR) Program are to: 1) conduct research on tobacco control among youth; 2) establish two Centers of Excellence (COEs) in Dakar, Senegal and Cape Town, South Africa focusing on tobacco control research; 3) develop regional networks of researchers and graduate students; 4) provide training and internships; and 5) promote links and academic exchanges between the COEs to conduct innovative and relevant studies examining the effects of tobacco use by youth in Senegal and South Africa. The investigators aim to conduct research studies focusing on prevalence and risk factors; psychopathology and tobacco use among youth; community influence and protective factors in tobacco use among high school students; qualitative studies of the tobacco use among adolescent girls; smoking cessation among young adults; political economy of tobacco use; pilot intervention studies; and a study of the ethnographic and traditional cultural uses of tobacco among Western and Southern African populations. The PSU-WSATR will establish over the course of five years two COEs consisting of a core of 10-15 researchers, graduate students, and administrative personnel at the University of Chiekh Diop in Dakar, Senegal and the University of Cape Town, South Africa specializing in tobacco research and control studies focusing on youth populations. A regional network consisting of researchers and graduate students will be developed in at least two neighboring countries (i.e., Gambia and Bukino Faso) in Western Africa and (i.e., Namibia and Tanzania) in Southern Africa who will collaborate with the COEs as researchers and in capacity building initiatives intended to build and strengthen training and empirical research focusing on youth populations.LVALu+p.Each year nicotine addiction is responsible for more than 125,000 deaths of American women. In 1987, cigarette smoking related lung cancer surpassed breast cancer as the leading cause of death by cancer among women. The prevalence of smoking has declined more slowly for women than for men, suggesting that quitting smoking is more difficult for women. Factors that may contribute to the gender difference in cessation rates include women's greater tendency to smoke as a means of coping with negative affect, and their greater concern about postcessation weight gain. It seems clear that special interventions are needed to address these unique concerns of female smokers. Nicotine replacement therapy has shown some success in improving smoking cessation rates, reducing the severity of negative affect usually experienced during cessation, and, in the case of nicotine gum, minimizing postcessation weight gain. Aerobic exercise has also been found to improve mood and control weight. In combination, nicotine replacement therapy and aerobic exercise should be a powerful smoking cessation treatment for women. The proposed study will investigate the effects of an aerobic exercise intervention as an adjunct to nicotine polacrilex gum therapy. Three hundred female smokers will receive nicotine gum therapy and will be randomly assigned to an exercise intervention, an equal contact control condition, or a gum alone control condition. The exercise intervention will consist of three 45-minute sessions of aerobic exercise per week from 3 weeks precessation through 16 weeks postcessation. All participants will be followed for one year after cessation. In addition to determining the effectiveness of the adjunct exercise intervention on cessation rates, the mechanisms (e.g., relief of negative moods, suppression of cessation-related weight concerns, relief of premenstrual distress) by which exercise affects cessation will be examined. The proposed study will provide the first large-scale test of a very promisi LVAL ng intervention to aid women in smoking cessation. The combination of an exercise intervention with nicotine replacement, which has not yet been investigated, should provide a particularly effective treatment program for female smokers. Intensive focus on the mechanisms by which exercise affects cessation will provide information essential both for understanding the nature of the relationship between exercise and smoking cessation, and for later refinement and enhancement of the exercise intervention.  _ I  Z@G@Researchz@ ELLISONGAYLORDUNIVERSITY OF CALIFORNIA AT LOS ANGELESLOS ANGELESCACTRDRP8RT-0005P+p.Biology and Cancer AddictionP@@7/1/19996/30/20027/1/1999 to 6/30/20024/2005sJA88,"`@B@Research@ELLIOTSHARONUNIVERSITY OF MIAMI SCHOOL OF MEDICINE VASCULAR BIOLOGY INSTITUTEMIAMIFLFTCPNot Given @Biology and CancerDiscovery 1b Evaluation 1b(@200420072004 to 20074/2005*"H@88,"@@@Researchd@ELLIOTDIANEOREGON HEALTH AND SCIENCE UNIVERSITYPORTLAND ORNIDAR01, DA011748Not availableT@@l@5/10/19994/30/20055/10/1999 to 4/30/20054/2005|xmG@88,"@ @Researchh@ELDERJOHNSAN DIEGO STATE UNIVERSITYSAN DIEGOCANCIR01, CA058858 @@@l@5/1/19952/29/20005/1/1995 to 2/29/20004/2005uplaE?88,"g@@ResearchT@EISSENBERGTHOMASVIRGINIA COMMONWEALTH UNIVERSITYRICHMONDVANIDAP50, DA005274+p.Biology and Cancer Addiction@@Not Given2004? to 20044/2005|xnLD88,"c@@$@Researchn@EISSENBERGTHOMASVIRGINIA COMMONWEALTH UNIVERSITYRICHMONDVANIDAR01, DA011082+p.j@@@@7/1/19974/30/20077/1/1997 to 4/30/20074/2005|xnLD88,"`~@b@ResearchL@EICHENHORNMICHAELHENRY FORD HEALTH SYSTEMDETROITMINHLBIU10, HL059739u+p.@@L@2/1/19981/31/20032/1/1998 to 1/31/20034/2005{tpgMD88,"@1@Research^@DWYERJAMESUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP9IT-0177u+p.Biology and Cancerl@@7/1/200012/31/20017/1/2000 to 12/31/20014/2005zviF?88,"@`a@Researchn@DUNCANSUSANOREGON RESEARCH INSTITUTEEUGENEORNIAAAR01, AA011510>@L@T@@9/8/19988/31/20089/8/1998 to 8/31/20084/2005unjbG@88,"n@@Research^@MURAMOTOMYRAUNIVERSITY OF ARIZONA COLLEGE OF PUBLIC HEALTHTUCSONAZNCIR01, CA077081u+p.j@n@p@9/30/19977/31/20049/30/1997 to 7/31/20044/2005xHB88," @@Researchj@MUNOZRICARDOUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP10RT-0326 @@ @P@7/1/20016/30/20047/1/2001 to 6/30/20044/2005sH?88,"`@p@4Research|@MUNOZRICARDOUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP13RT-0050u+p.@ @@2004 (Cycle XIII)2004 to? (Cycle XIII)4/2005sH?88,"o @@N@Researchh@KINNUNENTARUHARVARD UNIVERSITY MEDICAL SCHOOLBOSTON MANIDAR01, DA012503u+p.@ @@4/15/19993/31/20084/15/1999 to 3/31/20084/2005~xtkHB88,"LVALu+p.Faculty from the School of Medicine of the University of California, San Francisco propose to create the  San Francisco Internet Health Research Center. This proposal is intended to fund the first study under the Center s umbrella. One of the major priorities of the Center will be reaching populations that have little access to health information, especially those with little access to the Internet. Thus, though we fully intend the interventions developed by the Center to be heavily used by individuals from any ethnic group already adept at using the Internet, our specialty will be to pioneer interventions that are accessible by individuals who currently do not have Internet access, including development of interventions in languages other than English, and methods of providing access to populations that currently do not use computers or the Web. The Tobacco-Related Disease Research Program has funded the UCSF/SFGH Latino Mental Health Research Program s  Spanish/English Web Site for Smoking Cessation Trials since 1998. With TRDRP s support, we have already recruited well over 5,500 English speakers, and 3,500 Spanish speakers from 89 countries into our smoking cessation studies. We would now like the TRDRP to be the agency that provides the funds for the first study of the Internet Health Research Center at UCSF. We will use this support to leverage funding for the full-fledged Center from additional public and private sources. This proposal addresses TRDRP s Mission of helping build the infrastructure for research into tobacco control, and the Primary Area of tobacco-related health disparities among California s diverse populations. SPECIFIC AIMS 1. To plant the seed for the  San Francisco Internet Health Research Center by conducting its first study. 2. To ensure that the Center s work from its inception is done in both English and other languages (so that smokers of all ethnicities are able to participate and benefit from the methods being tested), and that it includes a focus on disparRLVALbities. Thus we will recruit a minimum of 480 Spanish speakers and 480 English speakers and specifically recruit a substantial number of Latinos as part of the study. The main study will compare four web-administered methods to stop smoking: 1) A standard smoking cessation guide, the  Guia para Dejar de Fumar (Guia) 2) Guia + email reminders to use the site 3) Guia + email reminders + mood management lessons 4) Guia + email reminders + mood management + a  virtual group We will ensure that each condition has a similar distribution of men and women, and of individuals with histories of clinical depression, so that when we compare the quit rates across the four conditions, these characteristics of the participants are accounted for. We hypothesize that the additional components will increase quit rates over the standard smoking cessation alone. We also propose to study different methods of recruiting Latinos into the study, especially those with low incomes, so that Latinos in California and the U.S. can also benefit from this resource. These methods will include community outreach efforts in San Francisco. Conditions with the best quit rates will be included in future studies and made available to smokers.LVALx ( AGE Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Young Adult ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural National PSYCHOLOGICAL Social Factors RESEARCH Human Studies STUDY POPULATION African American Caucasian TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation Withdrawal AGE Child Young Adult LOCATION National PREVENTION/TREATMENT Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation ECONOMICS Socio-Economic Status LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials RESEARCH Human Studies STUDY POPULATION Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesLVALLThe purpose of this project is to develop, evaluate, and disseminate a community-based cancer risk reduction program for Hispanic migrant youth.This proposal is a continuation of a current research project studying the development of alcohol use among White and African American youth and their familiestion of English- and Spanish-speaking smokers have quit smoking 1 and 6 months after using the Guide to Stop Smoking (Guide) we made available on the web site's first study. 2) To complete a study in which we will compare the Guide versus the Guide plus a Mood Management (MM) course. The 8-week web-based course teaches users how to use their thoughts and activities to improve their mood while quitting, so they will be less likely to start smoking again. 3) To build a more complex web site, which will compare four methods to stop smoking: 1. the Guide when used individually, 2. the Guide plus the Mood Management Course used individually, 3. the Guide when used as part of a web-based group, and 4. The Guide plus the Mood Management Course when used as part of a web-based group. The group format will allow smokers to give each other information and support. For aims 2 and 3, quit rates will be compared at 1, 3, 6, and 12 mos. 4) For each of the above, we will document how best to use the World Wide Web to reach specific populations: ethnic minorities, Spanish speakers, diverse age groups, rural and urban groups, and women. The web is a powerful tool for smoking cessation efforts. It can be used at home, work, or a public library. We need to evaluate carefully which smoking cessation methods have the best success rates for which groups when delivered over the web. Underrepresented groups, such as Spanish-speakers, should have access to these new resources. Groups with limited reading ability will be able to use the web more as we make advances to allow video and audio to reduce the need to read text. LVALu+p.Tobacco use remains the leading preventable cause of premature death in the U.S., and this public health problem will remain so if advances in the treatment of nicotine dependence do not occur. While the approved medications for smoking cessation to date are those that provide nicotine replacement, recent studies evaluating the effects of novel non-nicotine medications suggest that significant improvements in cessation rates may be possible. One of the most promising non-nicotine medications is bupropion (Zyban). Bupropion has been available as an antidepressant that increases dopamine availability and thus elevates mood, and will be FDA approved as a smoking cessation medication. Furthermore, it has been investigated as a medication for the treatment of attention deficit/hyperactivity disorder in youth. Because the efficacy of bupropion for adult smoking cessation is greater than nicotine replacement, and because the safety of bupropion has been shown in youth, it is the clear choice for investigation as a pharmacologic treatment for youth smoking cessation. Since the optimal dose for smoking cessation has not been assessed in youth, a dose ranging study to evaluate the safety and efficacy of bupropion for smoking cessation in youth is proposed. The proposed study is a randomized, double-blind, placebo-controlled clinical trial designed to assess (1) which bupropion dose, if any, increases abstinence rates over placebo, and (2) which factors, such as medication adherence, nicotine dependence, and motivation to quit, affect treatment outcome. There are a number of potential benefits from the proposed study. The results of the proposed study could lead to a better understanding of how to use a pharmacologic treatment for youth smoking cessation. Initiation of tobacco use is largely a sociocultural process, nicotine dependence is a medical condition whose treatment is optimized when the full armamentarium of medical care is provided. The proposed study will follow Agency for Health Care Policy and Resea LVAL$ rch guidelines for smoking cessation, including a medical model approach that combines behavioral and pharmacologic intervention within a health care environment. While many studies have evaluated cessation methods for adults, there remains a dearth of research evaluating methods for enhancing youth smoking cessation. With so little research upon which to expand, the proposed study could lead to important new understandings regarding the process and mechanisms of youth smoking cessation.LVALu+p.The Los Angeles Atherosclerosis Study (LAAS) is a study of the development of the disease known as atherosclerosis in the carotid arteries (the large arteries that feed the brain and head). The cohort of middle aged adults includes an enlarged number of smokers so that the effects of smoking on atherosclerosis can be investigated with greater precision. Atherosclerosis is a disease of the artery wall that leads to most heart attacks and strokes. Change in an indicator of atherosclerosis (thickness of the two inner layers of arteries, the intima-media thickness, or IMT) has been measured noninvasively at 18 month intervals in the carotid arteries with 2-dimensional ultrasound. These repeated observations on the same participants have yielded a new look into the emergence of an effect of smoking and other factors on atherosclerosis in humans. An effect of smoking on thickening of the inner two layers of the artery wall emerges in men, on average, in the age range 40-45 years. Emergence of a smoking effect in women is delayed until, on average, age 55-60 years. This delay in women is presumably due to protective factors associated with pre-menopausal hormones. The factors that delay a smoking effect on thickening of the artery wall in younger ages in men and women remain to be elucidated. Current 2-dimensional ultrasound measurement of the carotid artery focuses on the combined intimal and medial layers. Atherosclerosis only involves thickening of the inner most layer (the intimal layer) of the artery wall. A more desirable measurement of arterial wall thickening, from the perspective of studying the progress of atherosclerosis, would involve the measurement of intimal layer itself. The proposed study involves using a newly developed technique for computer processing of an ultrasound image to measure the thickness of the intima, separate from the media. The project involves re-processing the videotapes of repeated scans on 573 persons to determine the relations between this new measure and smoking.T LVALd This new measurement may reveal new information concerning the causes and time-course of atherosclerosis and subsequent cardiovascular disease in response to smoking. If the new measurement of intimal thickness proves to be superior to the current measurement of arterial wall thickness, then it may be feasible to use this measure for individual diagnosis and tracking. The current measurement is appropriate primarily for measurement of groups of persons.LVAL( v  t@d6<Discovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 2 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 2a Development 4 Delivery 3 Partnerships 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 1c Development 2 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Development 3 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2a Discovery 2b Discovery 3 Development 3 Delivery 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1b Discovery 2a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1b Evaluation 1a Evaluation 1bDiscovery 1c Development 1 Development 3 Evaluation 1aDiscovery 1c Development 1 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Development 1 Delivery 1 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2a Development 1 Delivery 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 1 Development 3 Delivery 2 Evaluation 1aDiscovery 1c Discovery 2a Discovery 2b Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1c Discovery 3 Development 2 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1a Evaluation 1bDiscovery 1b Discovery 1c Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bLVALu+p.The Lung Health Study (LHS), conducted from 1986-1994, demonstrated that smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long-term effects of the LHS smoking intervention program on lung function. The main objectives of the study are: 1) to determine, using an intent- to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15- year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persist through 10 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4)to study the role of other factors [gender, airways reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality; and 5) to determine whether the improvement in lung function and reduction in respiratory symptoms associated with smoking cessation result in improved health-related quality of life (HRQL) and less depression over an extended follow-up period. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential samplLVALe size of 5600.LVAL+p.Cigarette smoking costs an estimated 418,000 American lives annually. Cessation reduces this cost, but is difficult because smoking is maintained by factors such as withdrawal, tobacco's direct effects, and smoking-related stimuli. Current cessation methods address these factors: nicotine replacement treatments (NRTs) suppress withdrawal and/or blunt the effects of cigarettes. Behavioral treatments reduce the influence of smoking-related stimuli. Nonetheless, about 70 percent of smokers who try to quit, fail. Improving smoking cessation rates is a national priority that may be achieved by tailoring treatment to the separate needs of subgroups, such as men and women. Treatment studies demonstrate that current cessation techniques are less effective for women. There is no clear explanation for this difference, but it may involve a differential response NRT and/or smoking-related stimuli. For women, NRT may be less effective at suppressing withdrawal (Hypothesis 1) or blunting the effects of smoking during a quit attempt (Hypothesis 2). Women may also be more sensitive to smoking-related stimuli, such as the taste, sight, and smell of smoke (Hypothesis 3). These hypotheses can be examined efficiently in the clinical laboratory. Strengths of this setting include control over extraneous variables, repeated measure designs that yield dose effect curves, and validated tools for measuring puff topography, tobacco withdrawal, and the direct effects of nicotine and/or cigarettes. Three such studies are proposed. In each study, 64 men and 64 women who smoke will participate in 4 double blind, randomly ordered, 6.5-hour sessions. Objectively verified cigarette abstinence will be required before each session. Studies 1 and 2 will compare, in men and women, the NRT dose response functions for suppression of tobacco and blunting the effects of cigarettes; study 3 will compare the effects of smoking-related stimuli. Thus hypotheses 1, 2, and 3 are each addressed in separate studies. Overall, this project may improve 8LVALHcessation interventions for all smokers, particularly women. Given the costs of smoking and the dramatic reduction in these costs when smokers quit smoking, improving the treatment options for all smokers is essential.8LVAL l VDISEASE/BIOLOGY Cancer LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingCOMMUNITY Health Care Provider LOCATION National PREVENTION/TREATMENT Interview/Focus Group RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN PregnancyAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology RESEARCH1 Animal Studies TOBACCO NicotineDISEASE/BIOLOGY Mechanisms Other Disease/Biology RESEARCH1 Animal Studies TOBACCO Cigarette/Other Smoking WOMEN HormonesAGE Child Young Adult EDUCATION LEVEL Less than High School High School LOCATION National PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Weight Gain/ExerciseAGE Child EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesADDICTION Withdrawal DISEASE/BIOLOGY Other Disease/Biology LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Withdrawal Relapse EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesLVAL+p.Each year, cigarette smoking costs an estimated 418,000 American lives. Smoking cessation reduces this work, but is extremely difficult because smoking is maintained by factors such as nicotine withdrawal, tobacco's direct effects, and smoking-related stimuli that can control smoker's behavior. Current cessation methods address these factors. Nicotine replacement treatment suppresses withdrawal and/or blunts the effects of cigarettes. Behavioral treatments reduce the influence of smoking-related stimuli. Nonetheless, about 70% of smokers who try to quit, fail. Improving smoking subgroups, such as men and women. Treatment studies demonstrate that quitting is more difficult for women. There is no definitive explanation for this sex difference, but it may involve a differential response to nicotine replacement treatment and/or smoking- related stimuli. For women, nicotine replacement may be less effective at suppressing withdrawal symptoms (Hypothesis 1) or at blunting the effects of cigarettes smoked during a quit attempt (Hypothesis 2). Women may also be more sensitive to smoking-related stimuli, such as the taste, sight, and smell of cigarette smoke (Hypothesis 3). These hypotheses can be examined efficiently in the clinical laboratory. Strengths of this setting include control over extraneous variables, repeated measure designs that yield nicotine dose effect curves, and validated tools for measuring puff topography, tobacco withdrawal, and the direct effects of nicotine and/or cigarettes. Three such studies are proposed. In each study, 45 men and 45 women non-treatment seeking smokers will participate in 4 double blind, randomly ordered, 6.5-hour sessions. Objectively verified cigarette abstinence will be required before each session. Studies 1 and 2 will compare, in men and women, the nicotine dose response functions for suppression for tobacco withdrawal and for blunting the effects of cigarettes. Study 3 will compare, in men and women, the effects of smoking-related stimuli (denicotinized cigaret LVAL tes). Thus hypotheses 1, 2, and 3 will be addressed in separate studies in this 5-year project. The project will help to elucidate the mechanism underlying oft-reported sex differences in smoking cessation and may help tailor combined pharmacological and behavioral treatments that maximize the likelihood of cessation for men and women smokers. Given the overwhelming costs of cigarette smoking and the dramatic reduction in those costs when smokers quit smoking, improving the treatment options for all American smokers is essential.LVALhA novel community-based program to motivate pregnant women to stop smoking was evaluation in this study. The intervention consisted of measuring a participant's health status, the secondhand smoke levels in her home, and her use of health care services, and then making her aware of the measurements.There is clear evidence that cigarette smoking is associated with an increased risk for progressive kidney disease in both men and women. Unfortunately, there have been few studies of the mechanisms involved in this important problem. Interestingly, the renal diseases involved have been found to be very diverse and include primary vascular diseases such as hypertension, metabolic diseases affecting glomeruli such as diabetic nephropathy, and genetic diseases affecting tubules such as polycentric kidney disease. In addition, data from the United States Renal Data System reveals that certain risk factors aggravate renal injury, and that estrogen deficiency compounds the effect of these risk factors on renal disease. Since the number of aging women in the population is increasing, and the number of women who are smokers is also increasing, the relationship between estrogen deficiency and smoking can now be considered to be a significant health care issue. The specific aims are as follows: Aim 1. Determine whether exposure to cigarette smoke induces glomerular changes in young B6 mice that are characteristic of the aging kidney and whether estrogen deficiency contributes to induction or aggravation of these vascular pole lesions. Aim 2. Determine whether estrogen replacement ameliorates the vascular pole lesions in aging B6 mice. Aim 3. Determine whether mesangial cells isolated from the mice in aims #1 and #2 demonstrate stable phenotypic changes in vitro and whether they are associated with changes in estrogen responses, and whether estrogen replacement prevents these changes.LVAL+p.We propose to study the patterns of neural degeneration in brain induced by nicotine (i.e., cell death, or death of parts of brain cells). This includes: what are the primary brain structures involved, what are the doses necessary to induce the degeneration, and what are the drug regimens of nicotine which are most potent in inducing degeneration. We seek to determine not how much neurotoxicity we can achieve with massive doses, but rather what are the parts of brain which first demonstrate vulnerability at the lowest doses possible. This makes it likely that these would be the "weak link" structures which would show alterations in humans. Degeneration has already been shown in our previous animal studies utilizing continuous nicotine administration. Once the critical brain regions are determined, and the lowest doses which produce this degeneration, we will attempt to determine the mechanisms involved in this neurotoxicity. Not only why does this particular part of brain degenerate, but also what happens chemically to produce the damage? Studying how various types of brain receptors respond to the lowest effective (neurotoxic) dose, and whether prolonged and highly repeated exposure to nicotine is especially damaging, will provide clues as to why these parts of brain degenerate first. We will also determine whether rats exposed to nicotine prenatally show degeneration in the critical anatomical structures found in adults, or if other structures are involved in the fetal damage. Other studies will investigate how the neurotoxicity is altered by prior exposure to the drug. We will also study other novel psychopharmacological agents related to nicotine, both to determine if they are as neurotoxic as nicotine and if they produce the cognitive enhancement produced by nicotine. A most promising outcome would be if it could be determined that some more selective nicotinic agonists do not induce the toxicity, yet still have the apparent beneficial effects of nicotine in stimulating cognitive function andLVAL delaying the onset of various age-related diseases.  \ I $ 1@@@Research@ FLEISCHAUERAARONUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILLCHAPEL HILL NCCDMRPBC000437@@R@@200020032000 to 20034/2005yLE88,"@@u@Researchr@ FISHERSUSANUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP9RT-0112+p.Biology and CancerDiscovery 1b Evaluation 1b@7/1/20006/30/20037/1/2000 to 6/30/20034/2005,$  rG@88,"J@@Research^@FILLMORECAPRIMARAMEDICAL COLLEGE OF WISCONSINMILWAUKEEWINCIK22, CA095555+p.t@p@d@7/26/20026/30/20057/26/2002 to 6/30/20054/2005zvkMB88,"Q@b@Research@FEINGEORGENEUROBEHAVIORAL RESEARCH, INC.CORTE MADERACANIDAR01, DA009453+p.Biology and Cancer Addictionl@@2/10/19971/31/20032/10/1997 to 1/31/20034/2005 ~xtfF>88,"@`%@ResearchX@FARRERLINDSAYBOSTON UNIVERSITY MEDICAL CAMPUSBOSTONMAFICR03, TW000886 @t@n@@9/30/19989/29/20019/30/1998 to 9/29/20014/2005|wskI@88,"`@ y@Researchf@FANGCAROLYNFOX CHASE CANCER CENTERPHILADELPHIAPANCIR21, CA088307^+p.t@T@ @8/1/20007/31/20038/1/2000 to 7/31/20034/2005wrn`G>88,"z@1@Researchp@EYFJORDJORUNNICELANDIC CANCER SOCIETYNot GivenICELANDCDMRPBC980890z@@Discovery 1b Evaluation 1b@199820011998 to 20014/2005~wncIA88,"g@p@4Research`@ERSHOFFDANIELKAISER FOUNDATION RESEARCH INSTITUTEOAKLANDCASFFNot Given@T@r@ @Not GivenNot GivenUncertain4/2005|xoIA88," @@@Researchf@ERSHOFFDANIELKAISER FOUNDATION RESEARCH INSTITUTEOAKLANDCANICHDR01, HD0367194+p.T@l@ t@5/1/19994/30/20025/1/1999 to 4/30/20024/2005|xoIA88,"Q@+@Researchb@ERBLICHJOELMOUNT SINAI SCHOOL OF MEDICINE--NEW YORK UNIVERSITYNEW YORKNYNCIK07, CA093387+p.t@@ @9/19/20026/30/20079/19/2002 to 6/30/20074/2005|GA88,"@@Researchp@EPSTEINALYSSAILLINOIS INSTITUTE OF TECHNOLOGYCHICAGOILNIAAAF31, AA015017 @ Addictionn@ @3/15/20043/14/20063/15/2004 to 3/14/20064/2005xtkIA88,"?@@Research\@"EMMONSKARENDANA-FARBER CANCER INSTITUTEBOSTONMANCIR01, CA0732424 @@@@9/16/19966/30/20019/16/1996 to 6/30/20014/2005vqmeG@88,"g@p@4Researchz@!EMMONSKARENDANA-FARBER CANCER INSTITUTEBOSTONMANCINot GivenZ@@@@Not GivenNot GivenUncertain4/2005vqmeG@88,":LVAL ^ .LTDISEASE/BIOLOGY Cancer Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Menstral Cycle Menopause Hormones Hormone Replacement Therapy MISCELLANEOUS Weight Gain/ExerciseECONOMICS Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Cessation Relapse COMMUNITY Health Care Provider ECONOMICS Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesLOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Postpartum Parent/Mother Partner/Spouse MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionLVALSmoking cessation during pregnancy remains an elusive public health goal. For poor and undereducated women, smoking may not be a priority in light of other pressing life issues. The proposed research evaluates the role of outreach health nurses in delivering a novel smoking intervention to poor, high-risk pregnant women. The smoking intervention will be conducted in the context of the Healthy Baby Program (HBP), an innovative community based outreach program that addresses basic life needs and medical care issues for pregnant women. A quasi-experimental design will evaluate the impact of a motivational intervention delivered via a well-established resource to reach women who would not typically present themselves for smoking interventions. A home visitation model will be used to deliver motivational and skills- based intervention components designed to increase women's awareness of smoking's impact on the fetus, their own health, and their household environment. The motivational intervention includes measurement and personalized feedback about the woman's pulmonary function and carbon monoxide, her household nicotine concentration, and linkages to the health care system. The control group receives usual care, as currently delivered by the HBP staff. Both groups will be followed for 12 months post- partum. The primary outcome is reduction in 7-day point prevalence smoking status. Secondary and intermediate outcomes include reduction in household nicotine concentrations, movement in stages of change, and smoking cessation attempts. Results will test the outcome and cost- effectiveness of a motivational intervention delivered via an existing social service program..LVALZBTwo hypotheses will be tested: (1) The penetrance of BRCA germline mutations is affected by hormonal and environmental risk factors and genetic polymorphisms in metabolic enzymes, and these effects may interact. (2) Hormonal and environmental risk factors interact with polymorphisms in metabolic enzymes, affect the breast cancer risk in the general population, and thus influence risk in the >90% of patients who do not carry a BRCA mutation. This study tested the effectiveness and cost-effectiveness of three different smoking interventions for pregnant women, each targeted to the woman's initial stage of readiness to change her smoking behavior.The purpose of the proposed studies is to investigate the relationships between nicotine and alcohol consumption. Several studies have established a strong positive association between cigarette smoking and alcohol use, but the exact mechanisms underlying this association are unknown. Also, few studies have stratified their samples to examine gender differences in the link between alcohol and tobacco. The first goal is to examine whether acute alcohol consumption increases cigarette craving in a dose and BAC-limb dependent manner, and to examine if men show more sensitivity to alcohol-induced cigarette craving compared to women. Although studies have examined the effects of alcohol consumption on concomitant cigarette smoking or craving, there is a paucity of research examining the reverse pathway (i.e., effects of nicotine on alcohol consumption). Therefore, the second goal is to determine whether nicotine exposure increases alcohol craving and consumption, and to examine gender differences in such responses. Understanding the potential unique biobehavioral mechanisms underlying alcohol and nicotine interactions for men and women may help to tailor early prevention and treatment programs specifically for the sexes.LVAL .h : R  f PVTSMOKING AND LIFESTYLE RISK FACTORS FOR PREMENSTRUAL CHANGESDRUG ABUSE PREVENTION AMONG ADOLESCENT WOMENHPV METHYLATION: A BIOMARKER OF CERVICAL LESION PROGRESSGENDER, NICOTINE, AND STRESS-INDUCED ANALGESIASMOKING, ESTROGEN, AND CARDIOVASCULAR HEALTH IN WOMENSMOKING, ESTROGEN, AND CARDIOVASCULAR HEALTH IN WOMENTHE BEHAVIORAL DYNAMICS OF SMOKINGANALYZING STATE POLICIES RELATED TO THE TREATMENT OF PRENATALLY DRUG-EXPOSED NEWBORNS AND THEIR MOTHERSNICOTINE: COGNITION-AFFECT INTERACTIONSATTENTIONAL BIAS AND AFFECT IN STRESS-VULNERABLE SMOKERSROLE OF CYTOKINES IN THE DEVELOPING IMMUNE SYSTEMPILOT STUDY--SELEGILINE FOR SMOKING CESSATIONPERIODONTAL INFECTION AND RISK FOR MYOCARDIAL INFARCTIONA MALE PARTNER'S INFLUENCE ON SMOKING CESSATION OF WOMEN DURING PREGANCYSMOKE-FREE CONNECTIONS: HELPING PREGNANT WOMEN BUILD SUPPORT FOR NOT SMOKINGDEVELOPING AN INTERACTIVE MULTIMEDIA PROGRAM TO HELP PREGNANT PATIENTS STOP SMOKINGPROSPECTIVE STUDY OF PANCREATIC CANCER PATHOGENESISCANCER PREVENTION BEHAVIORS IN ADOLESCENCEPERFUSION FMRI OF CUE-INDUCED NICOTINE CRAVINGYOUTH-FOCUSED MEDIA TO PREVENT SUBSTANCE ABUSEREDUCING YOUTH SMOKING USING MASS MEDIAAN INVESTIGATION OF ANTIOXIDANT SUPPLEMENTS AND MEDICINAL HERBS IN BREAST CANCER RECURRENCE AND SURVIVALEFFECT OF MATERNAL SMOKING ON HUMAN PLACENTAL DEVELOPMENTFOLATE, SMOKING, RACE, AND CERVICAL CANCER RISKCHRONIC COCAINE ABUSE EFFECTS ON P50 AND P3A EVENT-RELATED POTENTIALSGENETIC FACTORS UNDERLYING ALZHEIMER DISEASEPSYCHOLOGICAL INFLUENCES ON IMMUNE RESPONSES TO HPVTHE IMPACT OF RISK FACTORS AND GENETIC POLYMORPHISM IN METABOLIC ENZYMES ON BREAST CANCER RISK IN BRCA1 AND BRCA2 MUTATION CARRIERS AND NON-MUTATION CARRIERS. A POPULATION BASED STUDYTESTING SMOKING INTERVENTIONS FOR PREGNANT WOMENPRENATAL SMOKING CESSATION RELAPSE PREVENTION TRIALDOPAMINE POLYMORPHISMS AND SMOKING CUE-REACTIVITYACUTE ALCOHOL AND NICOTINE INTERACTIONS IN MEN AND WOMENLVAL+p.This 5-year K07 award application is designed to provide the applicant, whose formal training has been in clinical psychology, with the mentoring and "protected" time to pursue multidisciplinary research training spanning basic biology, genetics, behavioral sciences, epidemiology, and biostatistics. At the end of this training, the applicant will have developed sufficient expertise to be a fully established, independent investigator at the forefront of research exploring the biobehavioral links between genetic factors and smoking behavior. The proposed training includes both formal and informal didactics, as well as a complementary program of innovative research. Didactics will include completion of an MPH degree, other selected graduate course work in biology, and informal colloquia. The research project, which explores genetic factors in persistent smoking, will serve as a hands-on model of biobehavioral investigations of clinically relevant hypotheses grounded in the basic sciences. Most smokers express a strong interest in quitting, but only a small minority are successful. Accumulating evidence suggests that genetic factors play a role in this persistent smoking. In particular, research has demonstrated that smokers who carry specific polymorphisms that confer increased sensitivity to dopamine have higher levels of persistent smoking behavior. The underlying biobehavioral mechanisms linking these polymorphisms to persistent smoking are not yet known. Based on several independent lines of research, we propose to test the possibility that smokers with these polymorphisms display greater craving reactions to specific smoking cues, and perhaps appetitive cues generally, than smokers without, which may account for their higher levels of persistent smoking. To that end, a 4 year, laboratory-based study with 448 smokers (50 percent male, 50 percent female), is proposed. These healthy participants will be tested for specific polymorphisms, and their reactions to smoking cues, chocolate cues, and neutral 6 LVALF cues will be assessed by self report and cardiovascular monitoring. In addition, they will complete questionnaires about their smoking patterns. Statistical analyses will examine relations between genetype, cue reactivity, and persistent smoking, behavior. Based on the results et that study, the applicant will begin developing and pilot testing interventions to reduce heightened reactivity among smokers with genetic vulnerability. The award is viewed as instrumental to the applicant in achieving his short-term goal of becoming an independent biobehavioral cancer control researcher, as well as his longer-term objective- to "bridge the gap" between the basic sciences and clinical applications by becoming competent in developing and testing clinically relevant "multidisciplinary" hypotheses informed by the basic biological and biobehavioral sciences.LVAL+p.Smoking during pregnancy exerts an independent, adverse effect upon numerous reproductive outcomes, and thus the reduction in the prevalence of prenatal smoking has been a national priority for the past decade. Approximately a quarter of US women smoke prior to becoming pregnant, with a third of these smokers quitting prior to the start of prenatal care - and are referred to as Spontaneous Quitters (SQs). Several studies have documented that at least 25 percent of SQs relapse prior to delivery, and therefore the health of the mother and fetus is once again jeopardized due to tobacco exposure during pregnancy. To date, randomized trials testing various interventions have failed to reduce prenatal relapse with this group. This study proposes to develop a telephone counseling relapse prevention program based on the principles of motivational interviewing to address the needs of this unique group of recent quitters. The theoretically-grounded program will be developed during a formative assessment period consisting of in-depth interviews and focus groups with a representative sample of SQs. The effectiveness of the intervention will be tested under conditions of typical clinical practice among a diverse population of prenatal patients who are members of a large HMO (Southern California Kaiser- Permanente). A total of 480 SQs will be randomly assigned to either a) usual care -- consisting of provider advice which may be offered during prenatal visits and a self-help smoking cessation/maintenance booklet; or b) usual care + the experimental telephone-based counseling intervention. The principal dependent variable will be biochemically confirmed maintenance of cessation for the duration of pregnancy. If effective, the proposed intervention offers the opportunity to decrease the prevalence of prenatal smoking among the approximate 1 million US women who annually initiate prenatal care as prepregnancy smokers. Finally, as more than 75 percent of the women who stop smoking during pregnancy are SQs and given theLVAL high rate of postpartum relapse, learning about successful maintenance during pregnancy may aid intervention efforts to prevent the return to smoking after delivery.LVAL+p.The role of certain types of human papillomavirus (HPV) in the etiology of cervical cancer is well-established. However, the influence of psychosocial, behavioral and immunologic factors on cancer risk and development needs further exploration. The proposed project aims to elucidate the potential links between psychological (e.g., distress, coping processes) and behavioral (e.g., cigarette smoking) risk factors and novel immunologic measures (e.g., T-cell proliferative responses to HPV proteins) in women with mild dysplastic lesions of the cervix due to infection with highly oncogenic subtypes of HPV. Specifically, the proposed project is designed to identify potential behavioral and immunologic correlates of psychological distress and coping, with a particular emphasis on the effects of avoidant coping strategies on cancer risk and development. Sixty-two women referred for a follow-up colposcopy will complete baseline psychosocial assessments and provide a blood sample (for immune assays) prior to their colposcopy. In addition, HPV typing of cervicovaginal cells will be conducted at baseline. Follow-up assessments will be conducted at 6-months and 12-months post-baseline. Psychosocial assessments include measures of psychological distress, cancer-specific intrusive and avoidant ideation, and a variety of coping strategies. Relevant immune measures include numbers and percentages of circulating lymphocytes, as well as T-cell proliferative responses to synthetic peptides derived from HPV 16, a specific marker of immunocompetence and one that has been shown to be associated with viral clearance and cervical disease regression. In addition, medical outcome (regression, persistence, or progression of cervical lesions), demographic variables, and behavioral risk factors (e.g., smoking) will be assessed. The identification of potential interrelations among psychosocial, behavioral, and immunologic variables has important implications for cancer prevention and control, as this information can be usedvLVAL to guide the development of psychological and behavioral interventions aimed at reducing distress and avoidance, which may lead to improved behavioral, immunologic, and health outcomes. LVALv f dAGE Adult Older Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Young Adult ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Other Psychological RESEARCH Human Studies STUDY POPULATION African American Caucasian Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN MenopauseAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use Environmental Tobacco SmokeDISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Mechanisms Other Disease/Biology LOCATION International RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesLVAL(The parent project for this FIRCA application is a large, ongoing multicenter project that has as its goal the assembly of 2,000 patients with probable or definite Alzheimer Disease (AD) in order to study family history, medical history, epidemiologic data, and genotype patients for apolipoprotein E (ApoE)and other genetic markers. The aims of the parent project are to assess gene-gene interaction on risk of AD, specifically by estimating the proportion of genetic variability in AD susceptibility accounted for by APOE and ascertain likely genetic models for other common AD susceptibility genes; and to assess gene- environment interaction on risk of AD, by evaluating the joint effects of APOE, MGAD (major gene for AD) probability, gender, age, and factors such as smoking, education, and anti-inflammatory drugs) on AD risk. They also plan to identify factors which enable an individual to survive to age 90 without succumbing to AD. The goals of the FIRCA grant are to develop additional genetic markers/polymorphisms in candidate genes, including PSEN1, PSEN2, APP, mitochondrial cytochrome oxidase, and APOE, to evaluate them in familial and non-familial AD subjects, to identify novel genes and search for polymorphisms or mutations which may promote an AD pathway, and to evaluate their interaction with other factors on AD risk and phenotypic variation. The ethnically diverse Russian population of AD patients will be sampled from the AD Center in the Mental Health Research Center in Moscow, Russia.LVAL+p.The research goals are to use P50 and P3A event-related potentials (ERPs) to (1) study chronic cocaine abuse effects on CNS information processing, (2) to compare these effects with the effects of chronic alcohol abuse and cocaine-- alcohol co-abuse, (3) to determine the permanence of these effects during abstinence, (4) to determine whether these effects differ by gender and (S) to determine how these effects are effected both chronically and acutely by cigarette smoking. Amplitude and gating of the auditory middle-latency P50 response to repeated stimuli will be studied to assess neural systems affected by cholinergic, dopaminergic and non-adrenergic disturbances. Preliminary results show very large P50 amplitude and gating reductions in two week abstinent cocaine dependent individuals, but not in alcohol abusers. If these P50 disturbances reflect damage to neuronal system or pathways, they should be relatively permanent. If they reflect neurotransmitter system disturbance, they may resolve during persistent abstinence and may be used to evaluate pharmacological treatments designed to impact these specific neurotransmitters systems in cocaine addiction. Cigarette smoking temporarily normalizes P50 gating in schizophrenics, and it has been suggested that nicotine may transiently treat part of the information processing abnormality in schizophrenia We will test the hypothesis that cigarette smoking in cocaine abusers also transiently normalizes cocaine-abuse associated P50 abnormalities. Increased latency of the P3A ERP component is potential objective and sensitive early measure of information processing abnormalities secondary to chronic cocaine abuse and does not suffer from many of the problems inherent in neuropsychological testing. Preliminary results demonstrate increased P3A latency is a sensitive indicator of CNS disturbance in a variety of diseases (e.g., HIV disease, Alzheimer's disease) and as a result of drug use. We will study recently abstinent male and female samples of cocaine depende< LVALL nt, alcohol dependent, cocaine/alcohol co-dependent and control subjects who were never substance dependent. We will study these samples supplemented by samples to control for nicotine co-dependence. We will study all cocaine and/or alcohol dependent subjects at two weeks abstinence, six weeks abstinence and six mon abstinence. All subjects who are cigarette smokers will be tested on two days at each testing period, on one day they will be studied twelve hours after their last cigarette; on the other day immediately after a cigarette. Finally, samples of active cocaine abusers will be studied.LVAL+p.Nutrition, environment, and race are implicated in the etiology of several cancers. This study will assess the interrelationships of these three factors in cervical cancer, by examining the interaction of folate, smoking, and race. Smoking is an established risk factor for cervical cancer, but poor study designs, small sample sizes, and inadequate folate measurements have interfered with assessment of folate as a cervical cancer risk factor. Smoking has been associated with lower blood levels of folate, but we know of no study designed to test if the interaction between smoking and folate is associated with cancer. Many smoking-related cancers have disproportionately high mortality and incidence rates for black Americans. However, the interaction of nutrition with smoking has been relatively unexplored as a contributor to this racial disparity. By improving study design, increasing sample size, utilizing dietary folate equivalents (DFEs) and homocysteine levels (a functional marker of folate sufficiency) in assessing these inter-relationships, and sub-group analysis by race, our study will make a significant addition to the current body of knowledge. At three colposcopy clinics, 1500 women (50 percent black and 50 percent white race) will fill out a questionnaire on frequency of foods eaten, smoke exposure and other factors affecting folate levels and cervical cancer. Each woman will have blood drawn and cervical testing for 13 oncogenic human papillomavirus (HPV) types. Only women testing positive for these HPV types will be kept in the study. Women with cancer or cervical intraepithelial neoplasms 2 or 3 (CIN 2 or 3) on biopsies will be classified as "high risk". All other oncogenic HPV positive women (with normal or CIN I biopsies) will be classified as "low risk". Plasma will be tested for homocysteine. The interaction between folate (dietary intake or plasma homocysteine) and smoking associated with increased cervical cancer risk will be analyzed using ordinal logistic or logistic regression, incLVALluding analysis by race. Cervical cancer has a step-wise histologic progression (which allows ordinal analysis or increase in the number of "cases" collected in a short time period). It is one of the few cancers with a known necessary, though not sufficient, cause - HPV. By limiting analyses to women with HPV exposure, this study insures that all women have an equal chance of their smoking and folate exposure affecting whether they acquire the disease. This study may be the first cancer study to utilize DFEs, which reflect dietary folate bioavailability and are more likely to be associated with cancer risk than crude folate intake. Our study will be among the first to analyze the interaction of DFEs (or homocysteine) and cigarette associated with cancer. This study will have implications for smoking cessation, cancer prevention, folate supplementation and duration between Papanicolaou (Pap) smears. It may also explain some of the racial disparity in cervical cancer and possibly other smoking-related cancers.LVAL+p.Maternal cigarette smoking significantly increases the risk of serious pregnancy complications. Estimates suggest that each year tobacco use is responsible for 19,000 to 141,000 abortions, 32,000 to 61,000 low birth weight infants, 14,000 to 26,000 infants who require admission to neonatal intensive care units, and 1,900 to 4,800 infant deaths. Thus, it is not surprising that maternal cigarette smoking is unequivocally the largest and most important known, modifiable risk factor for low birth weight and infant death. In spite of the severe negative consequences of maternal smoking on pregnancy outcome, studies suggest that approximately 20-30% of pregnant women in this country smoke. Results of a recent population-based epidemiological study conducted in California highlight the problem locally. Prevalence of prenatal tobacco use was 9% in the general population, and 29% among mothers who did not receive prenatal care. It is important to note that in this study cigarette smoking was self-reported, i.e. not verified by biochemical testing. Thus, the actual rates of prenatal smoking are likely to be far greater. Currently, little is known about how maternal tobacco use is linked to a dramatic increase in serious pregnancy complications. We are testing the theory that smoking harms the placenta. The placenta is a transient organ that exists only during pregnancy. Its short life span belies its unique functions which are vital to human development before birth. For example, pregnancy begins when placental cells attach the embryo to the mother's uterus. Once pregnancy is established, a child must develop in the uterus for many months before its organ systems can function on their own. During this time the placenta carries out, for the child, the roles played by many important organs including the heart, lungs, digestive system and kidneys. Thus, throughout this critical period toxic substances that harm the placenta likewise harm the developing child. Results of experiments we published duriLVALng the previous grant period showed that the placenta is vulnerable to the toxic effects of maternal tobacco use. Smoking interferes with the way placental cells attach to the uterus, and subsequently, the way they function. Our findings suggest that the problems are primarily due to the negative effects of maternal smoking on placental growth, the focus of our current application. We envision that the results of our study could be used in cessation studies to help women quit smoking during pregnancy. Research suggests that pregnancy is an ideal time to intervene, since many women reduce or stop cigarette consumption on learning they are pregnant. However, the effectiveness of cessation programs in this population is greatly enhanced when they use materials that are specific to pregnant women. A simple explanation of how smoking harms a child before birth, one possible outcome of our work, could be an important part of these specially designed materials. It is likely that a subset of mothers who smoke during pregnancy will be more likely to quit if they better understand the added risk their infants incur as a result of their cigarette use. In addition, if the mother is able to stop smoking permanently, her own health will greatly benefit. LVAL Objective/Hypothesis: Our central study hypothesis, based on prior clinical trials and laboratory investigation, is that antioxidant supplements may be positively related to breast cancer recurrence and disease-related mortality, and the effect of antioxidants may be modified by herbal medicines and nutritional supplement usage. The primary research question we intend to address is: are women who maximize their dietary antioxidant intakes through supplementation at greater risk of breast cancer recurrence and cancer-related death than nonsupplement users, and does effect modification by medicinal herb use, soy consumption, and/ or smoking exist?LVALP < ^ ` x x  D|0b>VBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsAddiction Epidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National Surveillance Global IssuesBiology and Cancer Epidemiology and National SurveillanceAddiction Epidemiology and National Surveillance Awareness Risk Perception and CommunicationsBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National Surveillance Interventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National Surveillance Community and Policy InterventionsAddiction Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National Surveillance Awareness Risk Perception and Communications Community and Policy InterventionsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsLVAL&This project will assess the impact of a focused program of mass media messages on cigarette smoking behaviors of young people in grades 4-12. Theory-based educational messages addressing both prevention and cessation of cigarette smoking will be tailored to the needs of three audience segments defined by age, with further tailoring by gender, racial/ethnic identity, and risk of cigarette smoking as indicated by research conducted in Project 1. Messages 2will be delivered over television and radio media preferred by young people during Years 2-5. The study will be conducted in four states; in each state a matched pair of mass media markets will be selected, with one member of each randomly allocated to receive the intervention, while the other market serves as a comparison area. Lower-income areas selected within these metropolitan areas will include substantial proportions of African American, Hispanic, and non-Hispanic white populations. Summative surveys will be conducted with young people in grades 7-12 in these areas during Year 1, before interventions are initiated, and during Year 5, after completion of the interventions (n=24000). These surveys will assess cigarette smoking status and history, hypothesized mediators of cigarette behavior, exposure to interventions and exposure to other tobacco education efforts. Campaign monitoring surveys will be conducted with students in grades 4-12 in Years 2-4 (n=3840); other process evaluation activities will document school and community levels of prevention programming and concurrent tobacco control mediator efforts. This project will provide new information about the impact of a highly focused theory-based mass media program on tobacco use behaviors among important populations of young people.  i F - 2 9j@@ResearchP@GILBERTDAVIDSOUTHERN ILLINOIS UNIVERSITY AT CARBONDALECARBONDALEILNIDAR01, DA014104+p.Biology and Cancer Addictionn@z@4/1/20033/31/20064/1/2003 to 3/31/20064/2005tHA88,"`@U@Researchp@GILBERTDAVIDSOUTHERN ILLINOIS UNIVERSITY AT CARBONDALECARBONDALEILNIDAR01, DA017837+p.Biology and Cancer Addictionn@@6/1/20045/31/20086/1/2004 to 5/31/20084/2005tHA88,"g@p@4Researchb@GERMOLECDORINot GivenNIEHSZ01, ES030108\+p.Biology and CancerDiscovery 1b Evaluation 1b@Not GivenNot GivenUncertain4/2005uiZSSSHB88,"!@}@ResearchZ@GEORGETONYYALE UNIVERSITYNEW HAVENCTNIDAP50, DA013334P+p.j@@j@9/1/20018/31/20039/1/2001 to 8/31/20034/2005{lfbWF@88,"@T@f@Researchp@GENCOROBERTSTATE UNIV. OF NEW YORK AT BUFFALOBUFFALONYNIDCRR01, DE012085"+p.t@@n@3/1/19972/28/20033/1/1997 to 2/28/20034/2005xtkG?88,"`@@Research@GAGEJEFFREYUNIVERSITY OF MISSOURI, SINCLAIR SCHOOL OF NURSINGCOLUMBIAMORWJFNot Given@ AddictionDiscovery 2a~@6/1/200411/30/20056/1/2004 to 11/30/20054/2005{G>88," 1@@Research@GAFFNEYCECELIANORRIS COTTON CANCER CENTER, DARTMOUTH MECIAL SCHOOLLEBANONNHRWJF40666@j@@~@200220042002 to 20044/2005JA88,"`@@Research@GAFFNEYCECELIADARTMOUTH MEDICAL SCHOOLHANOVERNHRWJF37958Not available2/1/20011/31/20052/1/2001 to 1/31/20054/2005~wqmdJA88,"?~@@`@Researchf@FUCHSCHARLESBRIGHAM AND WOMEN'S HOSPITALBOSTON MANCIR01, CA086102+p.t@@@9/1/20008/31/20059/1/2000 to 8/31/20054/2005xsofH?88,"`@B@ResearchT@FRAZIERLINDSAYBRIGHAM AND WOMEN'S HOSPITALBOSTONMAACSRSGPB-04-009-01-CPPB @@@@1/1/200412/31/20071/1/2004 to 12/31/20074/2005ytphJA88,"@~@@Research\@ FRANKLINTERESAUNIVERSITY OF PENNSYLVANIAPHILADELPHIAPANIDAK01, DA015426+p.Biology and Cancer Addiction@@9/10/20034/30/20069/10/2003 to 4/30/20064/2005 ~xtfJB88,"@`@Research\@ FLYNNBRIANUNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGEBURLINGTONVTNIDAR01, DA011958`+p.@@.@9/10/19998/31/20059/10/1999 to 8/31/20054/2005|F?88,"g@^@ResearchN@ FLYNNBRIANUNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGEBURLINGTONVTNCIP01, CA082708 @@@d@Not Given2002? to 20024/2005|F?88,"LVAL+p.The overall goal of "Youth-Focused Media to Prevent Substance Use" is to develop mass media messages that support young people in maintaining a substance-free lifestyle as they move from late childhood into adolescence. Marijuana and cigarette use have risen substantially in recent years, particularly among eighth graders, despite prevention efforts in schools and communities. The media are major sources of information and modeling for young people during adolescence. Previous research has shown that targeted media messages can reduce the prevalence of substance use during early adolescence and that these reductions are sustained through the end of high school. This project will build on and extend this previous research. The major aims are to reduce cigarette and marijuana use among adolescents using targeted media messages broadcast over their preferred media as they mature from grades 4-5 to grades 7-8. Targeted populations include urban samples of African American and white children and non- urban samples of primarily white children. Educational objectives for message development were defined based on social cognitive theory and prior research on psychosocial factors influence adolescence substance use. Messages based on these objectives and on diagnostic research with youngsters in the targeted populations will be pretested before delivery over television and radio to audience segments defined by grade and gender. Pretests will provide information on perceived effectiveness of messages across urban and non-urban samples. Message development cycles will be repeated annually to provide fresh messages as the target group matures over four years. Impact of the messages on targeted and matched comparison areas in one state. Surveys of grade 7-8 students will be conducted in 20 urban and non-urban schools from these areas at baseline and after four years of media exposure in one area to assess impact and outcome expectancies, social-normative perceptions, self- efficacy, and substance use behaviors. IntLVALdicators of social climate for substance user use and exposure to school and community programs and mass media campaigns with similar objectives will be assessed in the process evaluation.LVAL 448LOCATION National PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Partner/SpouseADDICTION Maintenance Cessation COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status Medicaid/Medicare LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Partner/SpouseDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Child COMMUNITY Health Care Provider Other Community DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN Parent/Mother MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology LOCATION National PREVENTION/TREATMENT Other Pharmacological RESEARCH Human Studies Clinical Research TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Child Young Adult EDUCATION LEVEL Less than High School High School LOCATION Urban Rural National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesLVAL+p.This five year training program is the path that Teresa R. Franklin, Ph.D., a Post-doctoral Fellow at the TRC, University of Pennsylvania, will travel to become an independent investigator with expertise in brain imaging and substance abuse research. The foundation underlying this proposal is her behavioral neuroscience background in which she studied conditioned responses to drug-related environmental cues. The proposal outlines the training and research experience necessary for her to develop and launch a fully independent career using a novel imaging technique, perfusion fMRI, to characterize the CNS structures underlying cue-induced nicotine craving. An extensive training program is required to prepare Dr. Franklin to fill the role of an independent investigator, as several research areas new to her are involved. Dr. Franklin will participate in ongoing structured didactics in human ethics, biostatistics and fMRI. She will attend and present at international- national- university- and center-wide seminars, forums and meetings; and will receive hands-on mentored training in collection and analysis of perfusion fMRI data. The candidate will be supported by a Mentoring team and Advisory board with expertise in areas critical to her proposal; clinical substance abuse research (Childress, O'Brien), neurobiology of nicotine dependence (Lerman), cue-induced drug craving (Childress, O'Brien), biostatistics, fMRI imaging and analysis techniques (Listerud) and perfusion fMRI (Listerud). Dr. Franklin will focus on the phenomenon of cue-induced nicotine craving during her training using arterial spin labeled (ASL) perfusion fMRI. This technique will be used to determine regional brain activation (Study 1, Aim 1) and possible sex differences (Study 1, Aim 2) in response to smoking cues. ASL perfusion fMRI is ideally suited for imaging low frequency changes observed in behavioral states, such as craving, that recruit over time. ASL perfusion fMRI will diminish susceptibility artifact in brain regions that are i LVAL mportant in drug dependence but difficult to elucidate with BOLD fMRI (e.g., ventromedial prefrontal cortex). In Study 2, Dr. Franklin will assess the impact of a promising anticraving medication, the GABA B agonist, baclofen, on subjective and brain responses to nicotine cues. Tobacco use is a monumental health concern as it is the number one cause of preventable death in our nation. Despite current interventions, smoking relapse rates remain high: 80-95% at one year post cessation. Thus, research into its neurological underpinnings is critical in guiding the development of behavioral and pharmacological therapies to battle nicotine addiction.$LVAL6Determine whether home-based solution-focused smoking cessation counseling when combined with clinic-based best practice will increase the number of women who quit or significantly reduce cigarette smoking during pregnancy. Over 45% of adult malignancies can be attributed to behaviors established and exposures that have occurred in adolescence. Lung cancer and other tobacco-related malignancies are due to tobacco use, over 90% of which is initiated in adolescence. Melanoma as well as basal and squamous cell skin cancers are due in large part to inadequate sun protection, especially during childhood and adolescence. Risky sexual behaviors during adolescence lead to human papilloma virus which causes cervical cancer. Lack of Pap screening allows progression of the infection from dysplasia to invasive malignancy. We have developed a model of adolescent behavior to examine the predictors of cancer-preventing behaviors (tobacco abstinence or cessation, sun protection, Pap smear screening) during adolescence. We will test the model's predictions about the importance of maternal and provider influences on adolescent knowledge, attitudes and behaviors using data collected from a cohort of 16,700 adolescents who fill out an annual survey on these issues. The insights gained will form the basis of new interventions to promote cancer-preventing behaviors in adolescence.LVAL+p.Pancreatic cancer is the fourth most common cause of cancer-related mortality for both men and women in the United States. Relatively little is known about the pathogenesis and epidemiology of this malignancy. Our general goals are: first, to examine prospectively hypotheses regarding the etiology of pancreatic cancer, and, second, to establish a unique database consisting of repeated dietary and lifestyle assessments over several decades, archived blood specimens, and archived tumor tissue. This resource will allow for the rapid examination of future hypotheses as they emerge. We will use the resources of three large cohort studies with prospectively collected blood specimens: the Nurses' Health Study (NHS), Health Professionals' Follow-up Study (HPFS), and Physicians' Health Study (PHS). Blood specimens will be analyzed using a matched, nested case-control design of projected cases through 2002 to evaluate hypotheses focusing on mechanisms of pancreatic cancer pathogenesis. First, we will examine whether an association between energy intake, obesity, greater adult height, sedentary lifestyle, or diabetes mellitus and pancreatic cancer is mediated through insulin-like growth factors and binding proteins. Second, we will examine whether biochemical indicators of methyl-group availability are associated with pancreatic cancer risk and whether the influence of folate is modified by methylene tetrahydrofolate reductase polymorphisms. Third, we will examine whether polymorphisms of genes responsible for detoxification and activation of aromatic/heterocyclic amines influence the risk of pancreatic cancer, and whether the associations of smoking and red meat intake with pancreatic cancer are influenced by these polymorphisms. Finally, we will examine the prevalence and spectrum of K-ras mutations, the prevalence of pl6 loss of heterozygosity and the level of p53, p21 and p27 expression among pancreatic cancers, and assess the influence of dietary and other factors on the prevalence of these molecular changeLVAL&s. These studies will enhance our understanding of pancreatic carcinogenesis and provide a scientific foundation for future preventive efforts. This is the first R01 submitted by the principal investigator following a K award from NCI.LVAL+p.We propose a comprehensive evaluation of the reported association between periodontal infections and myocardial infarction. Periodontal diseases, which are caused by bacteria and associated with increased prevalence and severity of bacteremia, may represent significant, previously unrecognized risk for coronary artery disease. The bacteremias associated with periodontal infections often involve bacteria with the ability to aggregate platelets and stimulate cells involved in atheromatous plaque formation. Hence, frequent bacteremia with subgingival plaque bacteria may increase the chances of thromboembolic events leading to myocardial infarction. Our specific aims include: 1) To evaluate the association between myocardial infarction and infectious periodontal disease in a population based case-control study, and 2) To evaluate the association between myocardial infarction and the subgingival microflora associated with infectious periodontitis including organisms such as S. sanguis and P. gingivalis which express platelet associated aggregation protein. The dependent variable, or outcome of interest, will be documented non-fatal myocardial infarction in approximately 960 cases, 35 to 69 years of age, compared to 2200 age-matched controls. Cases and controls will include blacks and whites of both genders who are being assembled at the University at Buffalo for a study of myocardial infarction and alcohol consumption. We propose adding an oral health component to this funded study, clarifying the relationship between the exposures of interest, destructive periodontitis and the subgingival microflora, and coronary artery disease, specifically myocardial infarction. We will systematically evaluate the role of multiple confounders and co-risk factors such as smoking, age, diet, and alcohol use. The proposed study will help clarify the relationship between periodontal disease and myocardial infarction. Detailed evaluation of the potential of chronic infections such as periodontal disease to contribute to the  LVAL risk of myocardial infarction is important, since cardiovascular disease remains a leading cause of death in most developed countries. Furthermore, periodontal disease is one of the most common infections of man. Therefore, understanding the association between these two diseases is of significant importance, both to individuals and for public health measures directed to reducing their morbidity and mortality.LVAL+p.We are proposing a placebo-controlled pilot study of selegiline versus placebo for nicotine dependent smokers (N=30) with depressive symptoms. There is evidence that catecholamines have an important role in the rewarding and withdrawal effects of tobacco smoking, and monoamine oxidase inhibitors (MAOIs) which augment catecholamine (i.e. dopamine, norepinephrine) function may be helpful in attenuating nicotine craving and withdrawal symptoms in nicotine dependent smokers. Thus, the selective MAO-B inhibitor selegiline may be helpful as a pharmacologic adjunct for smoking cessation. The proposed study would be a 6 week trial in nicotine-dependent smokers which will compare selegiline (10 mg daily; n=15) versus placebo (n=15) treatments on smoking cessation outcomes. Subjects would be inducted onto 10 mg/day of selegiline (5 mg po bid) or matching placebo (twice daily) over a two week period prior to the "quit date" at the beginning of Week 1. All subjects would receive brief weekly sessions of smoking cessation counseling consistent with AHCPR smoking cessation guidelines. The primary outcome measures include 1 week post-quit (Week 2) and endpoint (Week 6) smoking abstinence rates, and continuous smoking abstinence during the last four weeks of the trial. Secondary outcomes measures include treatment retention, depressive symptoms, nicotine withdrawal symptoms, weight change, plasma cotinine levels, expired breath carbon monoxide (CO) levels and urinary catecholamine excretion. Data analyses to compare groups will focus of an intention-to-treat sample and will utilize Chi square 2x2 contingency tables for smoking abstinence rates, repeated measures analysis of variance (ANOVA) models for continuous outcome measures (i.e. depression and nicotine withdrawal ratings, CC, plasma cotinine and urinary catecholamines) and Kaplan-Meir survival analysis for treatment retention. Results from this pilot study would be used to calculate an effect size for planning a larger controlled trial if results from this piloLVALt study appear promising. We predict that selegiline will be superior to placebo for smoking cessation in nicotine dependent smokers on both primary and secondary outcome measures.LVAL ~ b^DISEASE/BIOLOGY Cardiovascular/Pulmonary ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PSYCHOLOGICAL Social Factors Cultural Factors TOBACCO Cigarette/Other Smoking WOMEN Menopause Hormones Hormone Replacement TherapyDISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN HormonesAGE Child Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National International POLICY Excise Tax Regulatory Intervention PSYCHOLOGICAL Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesPSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesLOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology RESEARCH1 Animal Studies TOBACCO Environmental Tobacco SmokeADDICTION Cessation Withdrawal Relapse EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Other Pharmacological PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesLVAL+p.It has been suggested that SIDS may be a patho-physiological response elicited by combinations of microbial products and/or other environmental factors such as environmental tobacco smoke (ETS) at a time when the developing immune system is more vulnerable to the effects of inflammatory mediators. We have developed an animal model to mimic dual infection, using a non-lethal strain of Influenza A virus and a sub-lethal dose of endotoxin. In this model inoculation with influenza at 10 days of age followed by endotoxin 0.2 mg/kg 2 days post influenza caused mortality with the lowest morbidity. These elements became the defining parameters of the model. Mortality only occurred when specific criteria such as timing between infectious insults and developmental age of the pup were met and age was a key risk factor in the model. We have defined similarities of SIDS pathology in human infants and that seen in this model and examined basic immune factors associated with dual challenge. These studies suggest that the developing immune system can be primed to respond in an exaggerated way to a second immune challenge resulting in unexpected death. To examine the mechanisms underlying this mortality, a series of experiments were conducted to evaluate immune parameters 2-8 hours following endotoxin administration. As the pathologic findings a suggested modulation of systemic immunity rather than lung-specific damage, we evaluated cytokine responses related to systemic shock and oxidative stress. Significant alterations in serum and spleen IFN gamma levels were observed in dually challenged pups, as well as changes in specific immune cell populations in the spleen and lung. Inflammatory cytokine gene expression peaked earlier in dually challenged animals in both the lung and liver. As nitric oxide is an important aspect of the immune response to both bacterial and viral infection, nitric oxide synthase mRNA expression was examined in the target tissues. Increased gene expression was observed in the liver (iNOS, eNOSxLVAL and nNOS) and the lung (iNOS, eNOS) in dually challenged animals as compared to animal receiving only endotoxin. We also investigated whether intranasal administration of endotoxin, which would more closely mimic potential human exposure, would show similar patterns of immunologic changes. No mortality was observed in animals challenged in this fashion. No further studies will be conducted at NIEHS; however, Dr. Blood-Siegfried will continue this work at Duke University investigating the role of environmental tobacco smoke in SIDS using this model. Neonatal exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to alter thymocyte maturation and significantly impair immune function in adult animals. We hypothesized that prenatal exposure to TCDD may increase or exacerbate post-natal development of autoimmune disease in genetically-prone MRL/lpr mice. We have observed significant, dose-dependent increases in anti-ssDNA, urinary protein, and renal abnormalities in TCDD-exposed female MRL/lpr mice as compared to controls at six, ten, and 12 weeks of age, respectively. Similar results were noted in TCDD-exposed males at eight, ten and 12 weeks of age.LVAL+p.The primary objective of this proposal is to characterize more fully when and why stress-prone individuals, compared to others, are more likely to experience larger increases in stress-related forms of negative affect when they quit smoking. Evidence suggests that stress-prone individuals focus their attention on cues associated with potential stressors and that nicotine may alter attentional processes in such a manner as to reduce subjective stress (negative affect). Thus, it is hypothesized that nicotine acts as a form of serf-medication for stress-prone individuals because it attenuates attentional bias to stressors (cue predicting aversive events and negative emotional stimuli), thereby decreasing negative emotional states (subjective stress). This attenuation of negative attentional bias and associative processing by nicotine is hypothesized to result from nicotine's enhancing attentional and associative bias to positive and neutral stimuli that in turn compete with and inhibit negative affect-related processing. That is, nicotine is predicted to enhance the salience of neutral and positive stimuli and to reduce the salience of negative stimuli. Nicotine-induced attentional and associative biasing is hypothesized to occur most strongly in situations where the subject has a significant degree of freedom of attentional choice. Thus, the effects of attentional choice (two-picture/movie viewing with one stressful and one neutral or positive alternative) versus no-choice (one stressful picture/movie viewing with no alternative) conditions on nicotine's ability to reduce negative affect will be assessed by presenting blocks with a series of single or dual pictures/mini-movies on a computer monitor. Mood will be assessed before and after each picture/mini-movie series block. In the no-choice task, single pictures will be presented centrally on the computer screen. In the choice task, dual picture images or mini-movies will be presented simultaneously in the left and right visual field. In the choice conLVAL$dition, subjects will be instructed to allocate as much or little of their gaze time to a given picture/mini-movie, but to always be gazing at one of two pictures/movies, in the no-choice condition, subjects will be required to gaze at each picture for the duration of its presentation. Neutral or positive pictures/movies will be interspersed in both the choice and no-choice tasks. Eye-gaze patterns during the choice task and no-choice task will be obtained with an infrared, computerized tracking system. In the choice task, maximal stress-reducing effects of nicotine are predicted to occur during blocks with a high frequency of negative pictures. Nicotine is predicted to reduce gaze directed toward negative pictures and to enhance attention to positive pictures. In the no-choice task, nicotine is expected to have maximal dysphoria-reducing effects when a low frequency of negative pictures is combined with intervening positive pictures. Potential moderating influences of gender, history of traumatic and chronic stress, and individual differences in trait anxiety, depression, and anhedonia will be assessed with regression analyses. This work will use new experimental procedures and technologies, including the precise assessment of individual differences in continuously monitored eye-gaze patterns with an infrared, computerized tracking system. The new knowledge derived from these studies will be useful in developing empirical model-based treatment strategies aimed at increasing smoking abstinence. An EEG stress response index (alpha asymmetry) will be used in a subgroup of subjects during each of the 3 proposed studies.LVAL$f B J R  x H*PXDiscovery 1a Discovery 2a Discovery 2b Evaluation 1a Evaluation 1cDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Delivery 1 Delivery 2 Partnerships 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDelivery 3 Evaluation 1a Evaluation 1cDiscovery 2a Discovery 2b Development 4 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 1c Discovery 2b Discovery 3 Development 2 Evaluation 1b Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 2b Discovery 3 Development 1 Development 3 Delivery 2 Delivery 4 Evaluation 1a Evaluation 1cDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 3 Development 1 Evaluation 1bDiscovery 1a Discovery 3 Development 1 Evaluation 1bLVAL+p.The primary objective of this revised proposal is to characterize more fully when, how, and in whom nicotine modulates affect and attention to emotional stimuli. It is hypothesized that nicotine attenuates attentional bias to negative emotional stimuli and associative processing of such stimuli, thereby decreasing negative emotional states. This attenuation of negative attentional bias and associative processing by nicotine is hypothesized to result from nicotine's enhancing attentional and associative bias to positive and neutral stimuli that in turn compete with and inhibit negative affect-related processing. Nicotine-induced attentional and associative biasing is hypothesized to occur most strongly in situations where the frequency of negative stimuli is moderate or low and the subject has a significant degree of freedom of attentional choice. Thus, the effects of attentional choice (two-picture viewing) versus no-choice (one picture viewing) conditions on nicotine's ability to reduce negative affect will be assessed by presenting blocks with a series of 64 single or dual pictures on a computer. Mood will be assessed before and after each picture series block. The frequency of negative pictures in these series will be manipulated (either 16 [low frequency] or 48 [high frequency]). In the no-choice task, single pictures will be presented centrally on the computer screen. In the two-choice task, dual picture images will be presented simultaneously in the left and right visual field. Picture series blocks (64 single or dual pictures) will consist of the following 4.5 sec. sequence: the word "blink", a fixation cross, and a picture (or dual picture). In the two-choice condition, subjects will be instructed to allocate as much or little of their gaze time to a given picture, but to always be gazing at one of two pictures. In the no-choice condition, subjects will be required to maintain a 3 sec. gaze at each picture. Neutral or positive pictures will be interspersed in both the two-choice and no-choice  LVALtasks. Eye-gaze patterns during the two-choice task and no-choice task will be obtained with an infrared, computerized tracking system. In the two-choice task, maximal dysphoria-reducing effects of nicotine are predicted to occur during blocks with a high frequency of negative pictures. Nicotine is predicted to reduce gaze directed toward negative pictures and to enhance attention to positive pictures. In the no-choice task, nicotine is expected to have maximal dysphoria-reducing effects when a low frequency of negative pictures is combined with intervening positive pictures. Potential moderating influences of gender, smoker-nonsmoker status, and individual differences in trait anxiety, depression, and anhedonia will be assessed with regression analyses. This work will use new experimental procedures and technologies, including the precise assessment to individual differences in continuously monitored eye-gaze patterns with an infrared, computerized tracking system. The new knowledge derived from these studies will be useful in developing empirical model-based treatment strategies aimed at increasing smoking abstinence.  r . vX:`@@Researchv@GOODALLAMYOREGON STATE UNIVERSITY COLLEGE OF HEALTH AND HUMAN SERVICESCORVALLISORRWJF51414Not available6/1/20045/31/20066/1/2004 to 5/31/20064/2005FA88,"?~@@Research@GOLDENBERGROBERTUNIVERSITY OF ALABAMA AT BIRMINGHAM SCHOOL OF MEDICINEBIRMINGHAMALRWJF48079Not available5/1/20044/30/20055/1/2004 to 4/30/20054/2005LD88,"?~m@@Research@GOLDENBERGROBERTUNIVERSITY OF ALABAMA AT BIRMINGHAM SCHOOL OF MEDICINEBIRMINGHAMALRWJF45729Not available5/1/20037/31/20045/1/2003 to 7/31/20044/2005LD88,"?~`<@`@Research@GOLDENBERGROBERTUNIVERSITY OF ALABAMA AT BIRMINGHAM SCHOOL OF MEDICINEBIRMINGHAMALRWJF41430Not available4/1/20024/30/20044/1/2002 to 4/30/20044/2005LD88,"?~m@3@ResearchX@GOLDBERGLEWISOREGON RESEARCH INSTITUTEEUGENEORNIAR01, AG020048+p.L@ @@9/20/19978/31/20079/20/1997 to 8/31/20074/2005upldIB88," @1@Researchv@GOLDELLENUNIVERSITY OF CALIFORNIA AT DAVISDAVISCACTRDRP7RT-0105+p.t@ @*@7/1/199812/31/20017/1/1998 to 12/31/20014/2005{sohE>88,"@@ResearchX@GLASSMANJILLINTERSYSTEMS, INC.NEW YORKNYNIDAR43, DA013305+p.@ .@@9/30/20003/31/20019/30/2000 to 3/31/20014/2005pjf\HB88,"`M@@Researchr@GIULIANOANNAUNIVERSITY OF ARIZONATUCSONAZNCIR03, CA097752+p.t@ P@@8/15/20026/30/20048/15/2002 to 6/30/20044/2005pkg_HB88,"@@Research\@GIRDLERSUSANUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL CHAPEL HILL NCNIDAR01, DA013705R+p.Biology and Cancerl@@8/1/20014/30/20058/1/2001 to 4/30/20054/2005 vHA88,"P@4@Researchj@GIRDLERSUSANUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL CHAPEL HILL NCNHLBIR01, HL056144 +p.Biology and CancerR@@2/1/19971/31/20022/1/1997 to 1/31/20024/2005vHA88,"g@p@4Researchj@GIRDLERSUSANUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL CHAPEL HILL NCNCRRM01, RR000046@ t@Discovery 1b Evaluation 1bh@Not GivenNot GivenUncertain4/2005 vHA88,"G@@ResearchD@GILLESKIEDONNANATIONAL BUREAU OF ECONOMIC RESEARCHCAMBRIDGE MANICHDR01, HD042256F +p.@Development 4 Evaluation 1a@7/1/20026/30/20057/1/2002 to 6/30/20054/2005|pJC88,"@`@Research@GILBERTNEILUNIVERSITY OF CALIFORNIA AT BERKELEYBERKELEYCARWJF51604Not available7/15/20047/14/20057/15/2004 to 7/14/20054/2005{wmGA88,"?~LVAL+p. Despite its well known effects on health, smoking remains quite common in the United States. In order to devise anti-smoking measures it is essential to understand the long-term impact of current policies such as taxes. The goal of this research proposal is to evaluate possible explanations for the persistence over time of individual smoking behavior and to explore the resulting implications for policy analysis. One theory is that smoking is addictive and that persistence reflects behavioral or physical modification. Alternatively, persistence could be the result of individual-specific propensities to smoke: some people have characteristics which lead them to smoke while others have preferences to never smoke. Only if addiction is important will tax increases have significant effects on long-run smoking rates. We propose to develop a dynamic empirical model of smoking decisions which explicitly accounts for the impact of previous smoking behavior. After controlling for individual smoking differences in a very general manner, allowing both observed and unobserved individual differences, we will be able to estimate the empirical importance of smoking addiction. The framework will applied to two groups, teens and adults. Teens are important to study because this is the typical age of smoking initiation while adults may evidence strong addiction due to longer smoking histories. We will utilize the restricted use versions of the National Education Longitudinal Study of 1988 (NELS:88) and the Russia Longitudinal Monitoring Survey (RLMS) which contain data on the two groups. These are appropriate data-sets because they follow the same individuals over time, contain detailed smoking questions, and have a wealth of information about individual, family and community characteristics. The resulting parameter estimates will be used to simulate individual behavior following policy changes such as tax increases of various sizes and durations. To understand the importance of addiction, the estimates will also be used LVAL to simulate long-run behavior when all individuals are initially forced to smoke. Finally, this methodology will be extended to study the importance of alcohol addiction in the two data-sets. These results will be relevant for understanding the salience of public policy in reducing excessive drinking.LVALThe purpose of this research project is to continue to collect comprehensive data in 2002 and 2003 on state Medicaid for tobacco dependence treatments with special focus on coverage of treatments appropriate for pregnant smokers and on state activities to stimulate consumer demand for these treatments. The project will be considered successful if it generates results and articles that document trends in coverage and identifies potentially successful strategies for boosting consumer use of and demand for covered services.The aim of this research is to determine the importance of selected factors that affect smoking decision-making in women who remain abstinent or continue to smoke in the postpartum period. Negative body image and fear of weight gain will be considered as barriers to remaining abstinent while breastfeeding will be examined as a protective factor against relapse.The purpose of this research study is to compare smokers with non-smokers in cardiovascular (i.e. blood pressure and heart activities) responses to stressors. An additional purpose is to compare, in women who are already taking oral contraceptives (i.e. birth control pills), two different types of commonly prescribed oral contraceptives: those containing the progesterone levengestrel or norethisterone versus those containing the progesterone desogestrel, gestodene or norgestimate, and how the combination of smoking and oral contraceptives use affects the cardiovascular system in women. The purpose is also to examine two different ways of administering Hormone Replacement Therapy (HRT) in postmenopausal women smokers. HRT is the administration of the female sex hormones, estrogen and progesterone, after women have reached menopause. This study will compare oral administration (by mouth) with transdermal administration (through the skin by wearing a skin patch) for effects on blood pressure and other cardiovascular measures.\LVAL+p.lAlthough epidemiological data indicate that the postmenopausal use of estrogen is associated with significant reductions in risk for coronary mortality, analyses of these data separately by smoking status reveal that the protective effects of hormone replacement therapy (HRT) may be eliminated in women smokers. Alterations in the hepatic metabolism of estrogen have been demonstrated in female smokers and this may be the mechanism rendering oral estrogen ineffective is postmenopausal smokers. Thus, the primary purpose of this study is to examine the differential effectiveness of transdermally administered estrogen (plus progesterone) versus orally administered estrogen (plus progesterone) in 108 postmenopausal women smokers. A secondary goal of this study is to insure the inclusion of an undeserved population of women, thus one half of the investigators~ sample will represent postmenopausal women smokers residing in rural North Carolina, yielding a more diverse study population in areas of socioeconomics as well as cultural and social factors. Using a randomized, placebo controlled trial, each will be initially tested for cardiovascular stress reactivity, including cardiac output and total peripheral resistance, for beta-adrenergic receptor responsivity and for measures of blood flow and vascular hypertrophy and resistance. Then, women will be randomly assigned to either 4 months of transdermal estrogen plus progesterone (n=36), or 4 months of transdermal or oral placebo (n=36). Each will be retested at the end of this intervention period. Since transdermal estrogen delivery avoids the hepatic "first-pass" effect, the investigators hypothesize that transdermal estrogen will be significantly more effective for smokers in reducing vascular tone, increasing beta-adrenergic receptor responsivity and reducing blood pressure than oral administration. Thus, this study is expected to have clinical implications for effective hormone treatment in women smokers.LVAL+p.Epidemiologic as well as laboratory-based studies all document that women are more sensitive to pain than men. Involvement of the female sex hormones is indicated by animal studies that show estrogen increases sensitivity to pain, while progesterone and its metabolites (allopregnanolone and THDOC) decrease sensitivity to pain. Animal studies also indicate that the modulation of pain sensitivity by the female sex hormones involves the endogenous opioids, particularly beta-endorphins. However, whether sex hormones and other neuroendocrine factors can account for gender differences in the human pain experience has not been directly investigated. Another potential factor which may modulate pain sensitivity differently in men and women, and which may itself involve female sex hormones, involves smoking-related analgesia. Thus, the purpose of Study 1 to examine gender differences in sensitivity to a variety of experimental pain procedures as a function of female menstrual cycle phase. Also, since animal studies show that stress-induced analgesia (SIA) is modulated by the estrous cycle, Study 1 will also examine whether the female menstrual cycle influences gender differences in SIA. Using a within-subjects, randomized design, 96 healthy, non-smokers will be tested for sensitivity to tourniquet-induced ischemic pain, cold pressor pain, and thermal pain during three separate test sessions. For women, one session will occur during the early follicular phase (days 2-5; low hormones), one session during the late follicular phase (days 9- 12; high estrogen) and one session during their luteal phase (5- 10 days after ovulation; high estrogen and progestins). Men will also be tested three times. In order to examine SIA, sensitivity to experimental pain will be compared after 20 minutes of mental stress (speech and math) versus after a 20-minute rest control period, counterbalancing order of stress and rest. Relationships between pain sensitivity (i.e., threshold and tolerance levels) and cardiovascular (blood pressLVALure and vascular resistance) and neuroendocrine factors (estradiol, progesterone, allopregnanolone, THDOC, beta-endorphins, cortisol, ACTH and catecholamines) will be examined. It is predicted that gender differences in pain sensitivity will be greatest in the late follicular, followed by the luteal phase, while gender differences will be least in the early follicular phase. Study 2 will examine gender differences in smoking-related analgesia by testing 60 healthy subjects (30 men, 30 women), with half of each group comprised of habitual smokers. Identical test procedures and dependent measures described for Study 1 will be employed. Each subject will be tested only once, however, during the high estrogen phase of the female cycle since it is hypothesized that one mechanism by which smoking reduces pain sensitivity in women is via reductions in estrogen. It is anticipated that men will show greater evidence for smoking-related analgesia since smoking will activate two pain inhibitory mechanisms in men (i.e., blood pressure-related hypoalgesia and beta-endorphin mechanisms) while, for women, smoking will activate primarily beta-endorphin mechanisms (directly and indirectly via estrogen). The results of these studies, combined, are expected to provide insight into endogenous (sex hormones, beta-endorphins, blood pressure) and exogenous (smoking) pain modulatory mechanisms that may contribute to gender differences in the experience of pain.LVAL AGE Adult DISEASE/BIOLOGY Other Disease/Biology ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Cultural Factors RESEARCH Human Studies STUDY POPULATION Asian Pacific Islander TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Young Adult Adult DISEASE/BIOLOGY Other Disease/Biology LOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Menstral CycleAGE Child ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION African American Caucasian Hispanic TOBACCO Non-Specified Tobacco UseAGE Child Young Adult Adult DISEASE/BIOLOGY Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural National International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN HormonesDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle Hormones MISCELLANEOUS Sex/Gender DifferencesLVAL+p.Epidemiologic research has shown that infection with the human papillomavirus (HPV) is a cause of most cases of cervical cancer and that specific HPV types (e.g., 16 and 18) are associated with high risk of progression to cervical cancer. However, HPV infection is an insufficient cause of cervical cancer and appears to require the presence of other factors for the infection to progress to a significant cervical lesion. One factor that may modify progression of HPV to cervical neoplasia is DNA methylation. In support of this hypothesis, in vitro work from zur Hausen's laboratory indicated that methylation in the Upstream Regulatory Region (URR) of oncogenic HPV exerts a powerful effect on transcriptional activity and hence carcinogenicity of the virus. HPV DNA methylation patterns may modify the virulence resulting in increased risk for progression of HPV infection to high grade SIL. However, the association between HPV methylation patterns specifically has only been tested in vitro. In this application, we propose to conduct the first epidemiological study of the association between HPV methylation status and cervical cancer risk. The overall goal of this application is to examine in vivo methylation patterns of oncogenic HPV and determine if these patterns are associated with SIL. The primary aims of this study are to determine: 1) the overall methylation status and site-specific methylation in the URR of oncogenic HPV among women previously identified with normal, ASCUS, LgSIL, and HgSIL cytology; 2) whether methylation patterns of HPV are related to viral load; 3) the factors (such as smoking, oral contraceptives, and co-infections) associated with HPV methylation status; 4) whether HPV DNA methylation status is independently associated with risk of SIL Study Design: Data and biological samples collected from the USA-Mexico Border HPV, Cervical Dysplasia and Chlamydia trachomatis study (1997-1998) will be used for this proposed study. A population of 2,246 women, 246 of whom are HPV positive for on LVAL e of eight oncogenic HPV types, 15 years and older were recruited from family planning clinics in 3 pairs of contiguous communities at the Arizona (US) - Sonora (Mexico) border, and in Tucson, AZ and Hermosillo, Sonora, Mexico. HPV DNA methylation status will be assessed among 246 women positive for one of eight HPV types (HPV types 16, 18, 31, 39, 45, 51, 52, and 58) utilizing the Bisulfite Genomic Sequencing technique. Data available from the completed study include laboratory measures (HPV typing, HPV viral load, C. trachomatis status, and cytology), and risk factor data (reproductive, sexual and medical histories, and demographic data). Results from this study may provide a novel biomarker for women at risk of progression of HPV infection to SIL.LVAL+p.This revised Phase I feasibility study will examine psychosocial factors associated with drug use among adolescent women. Data on those factors will inform the development of an interactive computer-based intervention. Over the course of its 6 months, Phase I will accomplish three aims. First, we will assess the behavioral epidemiology of drug abuse and its prevention among a total sample of 84 Black, Latina, and white adolescent women, aged 10 to 14 years, from six community sites in New York City. Second, Phase I will develop a prototype version of interactive software to reduce the risks of drug and other substance use among those young women. Third, the study will pilot test the prototype interactive software with a sample of 270 Black, Latina, and white young women through the auspices of collaborating New York City community sites. In a randomized design, the pilot test involves a modest clinical trial with two arms. Young women in sites assigned to the computer intervention arm will interact with prototypic software developed in Aim 2. Young women in control sites will receive conventional drug awareness intervention. Before and after intervention, subjects will complete a battery of outcome measures. By meeting its aims, Phase I will lay a foundation for Phase II. That research will fully develop an interactive multimedia product to help young women reduce their risks for drug use. Phase II will include a randomized clinical trial to test the developed software with young women from various community settings in greater New York City. If Phase II software proves successful, Phase III will commercialize and disseminate the interactive program to schools and health care facilities and such community agencies as engaged in this R&D project. PROPOSED COMMERCIAL APPLICATION: Data from this study will shed empirical light on why young women use drugs and other substances and on how computer-mediated interventions can help them prevent that use. Intervening with young women via expressly designed andLVAL interactive content holds promise for reaching and impacting an at-risk population heretofore neglected in drug abuse prevention research. LVAL+p.Premenstrual symptoms are an important health problem among women of reproductive age. Approximately 50% of women experience premenstrual symptoms at some time in their lives. In this proposed project, we plan to investigate the relationship between smoking and premenstrual symptoms. Active and passive smoking pose unique but preventable health risks to women. Exposure to tobacco smoke is known to affect reproductive hormones in women. Since these hormones are likely to play a role in causing premenstrual symptoms, it is plausible that smoking may increase the frequency and severity of symptoms. Some previous studies suggest that smoking may worsen premenstrual symptoms, however, results from other studies do not confirm these findings. Passive smoking has not been investigated as a risk factor for premenstrual symptoms, but may also increase the frequency and severity of symptoms. We plan to conduct a study that will examine the effects of active smoking and passive smoke exposure to premenstrual symptoms. Two groups of' women, between the ages of 20 and 39 will be studied to investigate the role of active and passive exposure to smoke and premenstrual symptoms. The first group of women will be recruited from Kaiser Permanente Medical Care Program in the Sacramento area. These women will be asked to participate in recording their symptoms and other habits and activities in a daily diary. Daily records over several menstrual cycles are important for accurate diagnosis of premenstrual symptoms. We will also conduct a secondary analysis of data previously collected in a study of reproductive health among women in the Semiconductor Health Study (SHS), including six premenstrual symptoms, daily smoking, passive smoke exposure and cotinine levels collected prospectively over a mean of 5 menstrual cycles. A well-designed epidemiologic study of the effects of active and passive smoking on PMC will add much to our knowledge of the health consequences of active and passive exposure to smoke in reLVALproductive age women. Additionally, the results will inform current prevention and treatment strategies for premenstrual symptoms.LVAL+p.The broad objectives of this project are to test the models and mechanisms by which childhood personality traits predict adult health-related behaviors, health status and, eventually, mortality. The specific aims are to test three increasingly complex versions of a health-behavior model in which personality traits influence health status through health behaviors, and to evaluate any cultural influences on these models. The participants comprise a cohort of middle-aged adults for whom unique and irreplaceable teacher personality assessments were obtained about 40 years ago. Specifically, 1,770 members of the original population of Hawaiian schoolchildren have been located and 1,055 have been recruited to participate in this longitudinal study of personality and health. The recruited sample is representative of the original population in terms of personality attributes and gender. Over the next five years, information about the participants' personality traits, health behaviors, and health outcomes will be obtained. The personality measures will be based on several different theoretical perspectives including the five-factor framework. Health behaviors will include dietary practices, physical activity levels, and tobacco and alcohol usage. Health outcomes will include objectively assessed physical fitness and flexibility, obesity, and cholesterol level. Assessment methods will include self-reports, reports from knowledgeable others, observer ratings, physical/medical examinations, and laboratory tests. Frequency and appraisals of stressful life events, coping strategies, and constructs from the Theory of Planned Behavior will also be assessed to evaluate the more complex versions of the proposed health-behavior model. The effects on these models of cultural variables, socioeconomic status, and gender will be examined. The cross-sectional and longitudinal influences of personality traits will be evaluated by bivariate and multivariate linear models and structural equation modeling. This project will creaLVAL$te a longitudinal data archive that will be a treasure chest for the scientific community for years to come.LVAL z x  | 0 PpNn$JzVPHARMACOGENETIC DETERMINANTS OF FETAL SOMATIC MUTATIONHIGH-RISK HEALTH BEHAVIORS, HEALTH SERVICES USE AND AGINGA MOLECULAR MODEL FOR REPRESSION OF BRCA-1 TRANSCRIPTION BY THE ARYL HYDROCARBON RECEPTORNEURORECOGNITION, NICOTINE AND POLYSUBSTANCE ABUSETRANSITIONS IN SMOKING AMONG ADOLESCENT MINORITY GIRLSPRENATAL NEUROENDOCRINE MEDIATORS OF YOUNG ADULT SMOKINGPARKINSON'S DISEASE: A PROTECTIVE EFFECT OF SMOKING?EPIDEMIOLOGY OF GENETIC SUSCEPTIBILITY TO ORAL CANCERCOMMUNITY SURVEILLANCE OF CARDIOVASCULAR DISEASE-RISK FACTORSSTUDIES OF ENVIRONMENTAL AND OCCUPATIONAL EXPOSURESSAFE BABIES: THE DETERMINANTS OF POSTPARTUM SMOKE-FREE STATES AND RELAPSETRIAL OF ACTIVITY FOR ADOLESCENT GIRLSDEVELOPMENT OF SUBSTANCE USE IN GIRLSHEALTH CARE USE/COSTS OF DEMENTIA IN MEDICARE ELDERLYCOHORT STUDY OF GENETIC SUSCEPTIBILITY TO BREAST CANCERBREAST AND PROSTATE CANCER AND HORMONE-RELATED GENE VARIANTSCIGARETTE SMOKING AND POST-PARTUM BREAST CANCER RISKPILOT--REDUCING CARDIOVASCULAR RISK AMONG MINORITY WOMENPREVENTING CHANGE TO REGULAR SMOKING IN COLLEGE STUDENTSMOLECULAR EPIDEMIOLOGY OF HUMAN CANCERBIOCHEMICAL MARKERS IN THE NURSES' HEALTH STUDY COHORTANNUAL MEDICAID SURVEYS TO MEDICAID AND ESPDT TOBACCO DEPENDENCE TREATMENT COVERAGEPROSPECTIVE RELATIONSHIP BETWEEN RISK PERCEPTION AND TEEN TOBACCO USESMOKING CESSATION TO REDUCE CERVICAL CANCER RISKDIET AND DURATION OF CERVICAL HPV INFECTIONTHE ROLE OF BREASTFEEDING AND BODY IMAGE ON SMOKING RELAPSE: A MISS PROJECT SUB-STUDYSTUDYING FACTORS ASSOCIATED WITH POSTPARTUM SMOKING RELAPSETECHNICAL ASSISTANCE AND DIRECTION FOR SMOKE-FREE FAMILIES: INNOVATIONS TO STOP SMOKING DURING AND BEYOND PREGNANCYTECHNICAL ASSISTANCE AND DIRECTION FOR SMOKE-FREE FAMILIES: INNOVATIONS TO STOP SMOKING DURING AND BEYOND PREGNANCYTECHNICAL ASSISTANCE AND DIRECTION FOR SMOKE-FREE FAMILIES: INNOVATIONS TO STOP SMOKING DURING AND BEYOND PREGNANCYPERSONALITY AND HEALTH--A LONGITUDINAL STUDYLVAL AGE Adult Older Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingECONOMICS Medicaid/Medicare Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) TOBACCO Non-Specified Tobacco Use WOMEN PregnancyAGE Child EDUCATION LEVEL High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionAGE Young Adult Adult DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION Asian Pacific Islander Caucasian TOBACCO Non-Specified Tobacco UseADDICTION Cessation DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Postpartum MISCELLANEOUS Weight Gain/Exercise n Z , vY@`@@ResearchJ@LOEBERROLFUNIVERSITY OF PITTSBURGHPITTSBURGHPANIDAR01, DA012237@2b@p@n@12/15/20001/31/20052/15/2000 to 1/31/20054/2005vpl`F@88,"^@@@Researchj@HUSAINIBAQARTENNESSEE STATE UNIVERSITYNASHVILLETNNIGMSS06, GM0080920/+p.L@p@@11/1/200312/31/20061/1/2003 to 12/31/20064/2005zsodHA88,"@7@@$@Researchn@HUNTERDAVIDBRIGHAM AND WOMEN'S HOSPITALBOSTON MANCIR01, CA065725N @.t@p@@&7/12/19964/30/20077/12/1996 to 4/30/20074/2005wrneG@88,"q@ (@Researchx@HUNTERDAVIDBRIGHAM AND WOMEN'S HOSPITALBOSTONMANCIU01, CA098233f,+p.t@@@&6/3/20035/31/20076/3/2003 to 5/31/20074/2005vqmeG@88,"`#@ y@Researchh@HSIEHCHUNG-CHENGUNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOLWORCESTERMANCIR01, CA088891"++p.@R@@&9/13/20017/31/20039/13/2001 to 7/31/20034/2005xL?88," S@3@Researchp@ HOWELLELIZABETHMOUNT SINAI SCHOOL OF MEDICINE--NEW YORK UNIVERSITYNEW YORKNYNCMHDP60, MD000270)+p.t@p@N@&9/30/20028/31/20079/30/2002 to 8/31/20074/2005 K@88,"@@`@Researchp@ HARRISKARIUNIVERSITY OF MONTANAMISSOULAMTNCIK07, CA087714'+p.@@@&9/1/20008/31/20059/1/2000 to 8/31/20054/2005pkg]F@88,"g@p@4ResearchL@ HARRISCURTISCENTER FOR CANCER RESEARCHBETHESDAMDNCIZ01, BC005480$+p.t@l@@&Not GivenNot GivenUncertain4/2005wrndH@88,"@@Researchl@ HANKINSONSUSANBRIGHAM AND WOMEN'S HOSPITALBOSTONMANCIR01, CA049449"+p.Biology and Cancer@ @6/1/19893/31/20046/1/1989 to 3/31/20044/2005ytphJC88,"g@p@4Research@ HALPRINHELENUNIVERSITY OF CALIFORNIA AT BERKELEYBERKELEYCARWJFNot Given@ L@P@ b@Not GivenNot GivenUncertain4/2005|xnHA88,"@@u@Research@HALPERN-FELSHERBONNIEUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP9KT-0072 +p.L@@ @7/1/20006/30/20037/1/2000 to 6/30/20034/2005|QI88,"n@@u@Research`@GREENEPAULUNIVERSITY OF ALABAMA AT BIRMINGHAMBIRMINGHAMALNCIR01, CA075455+p.|@@ @9/30/19976/30/20039/30/1997 to 6/30/20034/2005{wkF@88,"@`@ResearchV@GOODMANMARCUNIVERSITY OF HAWAII AT MANOAHONOLULUHINCIR01, CA077318+p.t@ @ T@9/1/199810/31/20049/1/1998 to 10/31/20044/2005ytpfGA88,"`@`@Research@GOODALLOREGON STATE UNIVERSITYORRWJFNot Given@ Biology and Cancer AddictionR@@6/1/20045/30/20066/1/2004 to 5/30/20064/2005{od^ZZAA88,"]LVAL+p.This project will establish a multiethnic cohort of women for long-term follow-up to identify factors that influence the persistence or resolution of human papillomavirus (HPV) infection of the uterine cervix. The specific aims are to 1) study the association of the dietary intake of fruits and vegetables, and the plasma levels of carotenoids, alpha-tocopherol, and vitamin C with HPV persistence; 2) examine the role of HPV type, quantity (viral load), and multiple (synchronous) HPV infections in HPV persistence; and 3) examine the interaction between nutritional (e.g., beta-carotene) and viral (e.g., HPV 16) factors on the risk of persistent HPV infection. A multiethnic cohort of 1,152 HPV-positive women, aged 18 and older, will be established among patients attending the obstetrics and gynecology clinics of three large medical centers in Honolulu. The cohort will include appreciable numbers of Asian (Japanese, Filipino, Chinese, Korean) Polynesian (Hawaiian, Samoan) and Caucasian women. The cohort will be followed longitudinally with the following data collected at baseline, month 4, month 8, month 12, month 24 and month 36 (6 visits): (a) a cervical cytological (Pap) smear for pathological review; (b) colposcopic visualization of the cervix for confirmation of cytology; (c) a cervical sample for HPV DNA analysis; and (d) a blood sample to measure micronutrient levels. An abbreviated questionnaire will be administered at baseline and an expanded interview will be conducted at month 4 including information on diet, tobacco and alcohol use, and sexual and reproductive history. A diet history and follow-up interview will be conducted at each annual visit. Cervical biopsy specimens obtained from cohort members will be reviewed by the study pathologist and sections will be archived at no cost to the present study. Analysis of the data will focus on the evaluation of dietary and plasma micronutrient levels and viral characteristics that influence the persistence of HPV infection using a generalized estimat LVAL ing equation (GEE) approach that corrects for the correlation between the repeated measures. The identification of these factors may provide insight into the natural history of HPV infection, and may improve our ability to characterize women who are at greatest risk for developing HPV-associated neoplasia. Such knowledge may also assist in the development of appropriate screening strategies involving HPV DNA detection that could be targeted at women who would benefit most from intensive follow-up.LVAL+p.Cervical cancer is a major source of morbidity and mortality among women, with a particularly high burden evidenced among women in Alabama. Although HPV has been identified as the major causative agent for cervical cancer, most women with HPV do not develop cervical neoplasia, suggesting that progression to cervical cancer may be influenced by other factors. Smoking has consistently been associated with increased risk for cervical cancer, even among women already at elevated risk due to cervical dysplasia and HPV infection. Further, available data suggest that smoking cessation may decrease cervical cancer risk. These data justify a prospective, controlled study, examining the efficacy of smoking cessation in halting the progression of cervical dysplasia. The proposed 5-year clinical trial will evaluate the effect of a theory-based smoking cessation intervention on progression from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) in female smokers with HPV. The plan is to recruit 220 current smokers ((10 cigarettes/day) with oncogenic HPV from the University of Alabama at Birmingham Colposcopy Clinic and randomly assign them to one of two treatment conditions: 1)usual care (UC); or 2) smoking cessation intervention (SCI). Patients in both groups will receive standard conservative management for LSIL, biannual pap smears and more aggressive treatment, as needed. Additionally, patients in the SCI group will also participate in an intensive smoking cessation intervention which will include: 1) cognitive-behavioral strategies to facilitate changes in smoking behavior; 2) short-term nicotine replacement therapy to minimize discomfort associated with nicotine withdrawal; and 3) a motivational intervention to promote the optimal use of cognitive-behavioral strategies and nicotine replacement therapy. The primary outcome will be rate of biopsy-confirmed progression to HSIL over 18-month follow-up. The investigators also propose to collect self-rep LVALort and biochemical measures of smoking status and dysplasia progression. Finally, perceptions about cancer risk and cancer control practices will be assessed to examine relationships with smoking cessation program participation and changes in smoking.LVAL+p.!Approximately 3,000 children and adolescents become regular smokers each day, with about six million youth reporting current tobacco use. At least two thirds of adolescents have tried cigarettes, more than one third are currently smoking, and as many as a quarter of these adolescents smoke every day. While adolescent cigarette use has declined since the 1970's, recent research suggests cigarette smoking among teenagers is now on the rise. Given these current rates of tobacco use, at least 5 million children under age 18 will eventually die from smoking-related diseases. Tobacco use accounts for over 450,000 total deaths and 170,000 cancer deaths every year in the United States, and over 30 percent of all cancer deaths are caused by tobacco. Initiation of smoking during adolescence is particularly important to study, especially since approximately 90% of all adult smokers began smoking at or prior to age 18. Many researchers, health practitioners and policy-makers have argued that the reason for adolescents' engagement in risk behaviors, including tobacco use, is that they perceive themselves as invulnerable to harm. Unfortunately, few studies have followed non-smoking adolescents over time. Such a study would allow for the examination of changes in risk perceptions and perceptions of vulnerability once onset of tobacco use occurs. This research is critical in understanding whether risk judgments motivate behavior or are instead reflective of adolescents' past behavioral experiences. The ultimate goal of this research is to inform and improve programs that attempt to reduce or prevent adolescent tobacco use. Following a group of 9th graders, we propose to examine whether: 1) risk judgments influence the onset of tobacco use; 2) the onset of tobacco use plays a role in shaping subsequent risk judgments; 3) risk judgments change once an adolescent has experienced tobacco-related negative outcomes; 4) knowledge of friends' or family members' use of tobacco influence risk judgments and tobacco use; and 5LVAL) the relationship between risk perceptions and tobacco use varies by gender and race/ethnicity. Studies have indicated that following adolescents from age 14 on appears to be the period from which the majority of changes in smoking behavior will be observed. Therefore, the study population will be approximately 600 9th graders from the Bay Area. These participants will vary by ethnicity. Study participants will be recruited from their 9th grade classes and then surveyed, by mail, every 6 months, for a total of three years. Adolescents will answer questions about their perceptions of risk to tobacco-related negative outcomes, their current and past use of tobacco, experiences with any tobacco-related negative or positive outcomes, vicarious exposure to peers and family members who smoke, and vicarious exposure to tobacco-related negative and positive outcomes. Results from this study will be useful for researchers, health practitioners, and policy makers who are interested in understanding why adolescents onset to tobacco use. Results will also be useful to further the development of effective, theory-based interventions to reduce adolescent tobacco use. LVAL+p.#We propose to analyze blood samples in a nested case-control manner from the 32,826 participants in the Nurses' Health Study (NHS) who provided samples in 1989-90 and were 43 to 69 years of age at that time. The samples have been stored at greater than or equal to 130 C in liquid nitrogen freezers since collection. We will assay samples from women who were diagnosed after blood collection and matched controls who remained disease-free, thus efficiently utilizing these prospectively collected samples. We propose to build upon our recent positive findings for several plasma hormones and nutrients in relation to breast and colon cancer risk, and to address new hormonal hypotheses in relation to risk of breast, ovarian and colon cancers and myocardial infarction. Specifically, we will examine (1) plasma estrogens, androgens and prolactin levels in relation to breast cancer risk in postmenopausal women, (2) a polymorphism in the catechol-O- methyl transferase (COMT) gene and risk of breast cancer, (3) DHEA, DHEAS and 5-androstene-3beta,17beta-diol and risk of breast and ovarian cancers and myocardial infarction, (4) insulin-like growth factor I and its binding proteins 1 and 3, plasma vitamin D and polymorphisms in the vitamin D receptor, and plasma antioxidant levels - all in relation to risk of breast and colon cancers. The ongoing NHS (CA40356 and HL34594) will provide follow-up and documentation of disease outcomes in addition to providing information on important covariates (such as exogenous hormone use, diet, smoking status, among others) for the proposed study. Participation in the NHS has been high: among the 32,826 women who provided a blood sample, 98 percent continue to complete questionnaires, and vital status has been documented for 99 percent. Overall, the large size of the cohort, the prospective design, the high follow-up rate, the detailed exposure data, and the availability of archived blood specimens provide a unique opportunity to test several hypotheses of public health importa0 LVAL@ nce. We also propose to collect a second blood sample from about 18,000 of the women who provided a first blood sample in 1989-90. This will increase our statistical power in future analyses, and allow us to assess in detail the temporal relationships between biomarkers and disease risk and to reduce the attenuating effects of measurement error. LVAL+p.%Gene-environment interactions and tobacco-related human cancers are both longstanding areas of research in our molecular epidemiology project and extraordinary opportunities in the NCI Bypass budget. The challenging goal of molecular epidemiology is to identify individuals at a high cancer risk by quantitative assessment of carcinogen exposure and genetic analysis of host susceptibility factors. The molecular archaeology of the mutation spectra of tumor suppressor genes generates hypotheses concerning the etiology and molecular pathogenesis of human cancer. The spectrum of somatic mutations in the p53 gene implicates (a) environmental carcinogens, e.g., sunlight, aflatoxin B1, and tobacco smoke, and (b) endogenous agents, e.g., oxyradicals, and processes, e.g., errors occurring during DNA repair and replication, in the etiology of human cancer. To further investigate the role of codon 249 p53 mutations in hepatocellular carcinogenesis, we have both continued our longstanding collaboration with Professor Sun and assessed the separate and combined effects of hepatitis B virus (HBV), hepatitis C virus (HCV), and aflatoxin B1 in causing hepatocellular carcinoma (HCC) in Qidong, China. A consecutive series of 181 pathologic-diagnosed HCC cases were studied for hepatitis B surface antigen (HbsAg), anti-HBc, HBV X gene sequence, anti-HCV, the 249ser-p53 mutation, and chronic hepatitis pathology. The 249ser-p53 mutation was found in 54% of HCC cases and in all seven cases with tissue for analysis from the hepatitis cohort but in none of 42 matched cases from Beijing. The estimated cumulative dose of aflatoxin B1 in these seven cases ranged from 0.13 to 0.49 mg/kg. Follow-up data through 13.3 years on a cohort of 145 men with chronic HBV hepatitis showed that the relative risk from aflatoxin B1 exposure was 3.5 (1.5-8.1). A similar relative risk was found using 249ser-p53 mutation as a marker for aflatoxin B1 exposure. In conclusion, HBV hepatitis is ubiquitous in Qidong HCC cases, whereas HCV contributes li>LVALNttle to its risk. The 249ser-p53 mutation appears to result from coexposure to aflatoxin B1 and HBV infection. Even modest levels of aflatoxin B1 exposure tripled the risk of HCC in HBV-infected men. We have continued our studies of the molecular epidemiology of human lung cancer risk. We are investigating the gene-environment interactions in tobacco-related lung cancer using case-control and case-case strategies to examine potential gender and racial differences and lung cancer risk. A unique aspect of our study is the matching of lung cancer cases to both hospital and population controls. Examples of recent results include (a) confirmation and extension of the studies indicating that the mutagen sensitivity assays predict individuals at an increased risk of lung cancers; (b) Codon 312 XPD polymorphism significantly correlates with a lung cancer risk, and modulates apoptosis and is the first known functional polymorphism in an apoptotic gene; (c) p53 mutations are a common and early event in lung cancers from ex-smokers; (d) women may be more sensitive than men to tobacco smoke-induced lung cancer, based on the p53 mutation spectra of their lung cancers and our previous results indicating that never-smoking women who are exposed to environmental tobacco smoke and develop lung cancer, are a genetically susceptible population, e.g., GSTM1 deficient; and (e) when compared with Caucasians, African-Americans with lung cancer have an attenuated G2/M cell cycle checkpoint. LVAL,d  JADDICTION Initiation DISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies STUDY POPULATION African American Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology LOCATION Urban National RESEARCH Human Studies Clinical Research STUDY POPULATION African American TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionAGE Young Adult EDUCATION LEVEL College and Above EPIDEMIOLOGY/SURVEILLANCE Large (>=100) PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms LOCATION National RESEARCH Human Studies STUDY POPULATION African American Caucasian TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesLVAL+p.(Tobacco use is responsible for 30 percent of all cancer deaths. Although the overall prevalence of adult cigarette smoking is declining in the US, the prevalence among young adults is increasing, especially among college students where an estimated 28 percent smoke. Career development: Activities include training in cancer prevention and control, advanced biostatistics, advanced epidemiology, nicotine addiction, and medical ethics. Research Program: The goals of the research program are to better understand the smoking behaviors of college students and to identify and test the feasibility of an intervention. The plan involves three studies that address six research questions. Studies will be conducted in collaboration with the Student Health Center and Wellness Center at University of Missouri- Columbia (MU). Study 1 details the natural history of smoking in college students. Measures adapted from existing assessments will be administered to 3,500 students in introductory classes at MU. Students will construct identifiers, which will be used to maintain confidentiality and to match students' responses to a follow-up survey administered in study year 4, when the cohort will be in their senior year. Study 1 will provide information on the progression and correlates of smoking in college students, many of whom may smoke occasionally as freshman but progress to daily smoking while in college. Study 2 consists of conducting three single-gender focus groups and follow-up interviews among each of two distinct groups, occasional (less than 5 cigarettes per day) and regular to heavy (at least 10 cigarettes per day) smokers. The goals of these twelve groups are to identify: a) interest in quitting and/or managing smoking, b) barriers to behavior change, c) strategies used to quit and/or manage smoking, and, d) intervention preferences across levels of smoking. Study 3 is a pilot study examining the feasibility and efficacy of a counseling intervention based on Motivational Interviewing and booster e-mail messag> LVALN es. Students will be randomized to either a tailored (n=40) or standard control (n=40) arm. Trained counselors will tailor two 15-minute sessions and three electronic mail messages based on students' interest in reducing or quitting. Primary outcomes include progression to regular smoking, cigarette consumption, and quit rates over two years. The research plan uses exploratory, descriptive, and intervention research to address tobacco use an understudied population, college students. Each study stands on its own, but is designed to build on the findings of the prior study. The proposed experiences will provide Dr. Harris with the skills to develop and launch a fully independent career in cancer prevention and control.LVAL+p.*Cardiovascular disease (CVD) is the number one cause of death for women in the United States and disproportionately kills minority women, particularly African Americans. Hypertension, diabetes, elevated cholesterol and tobacco use are well-known risk factors for CVD. The increased risk of death from CVD among minority women is linked to a higher incidence of these risk factors. Underuse of prevention/screening services and treatment of cardiovascular risk factors by primary care physicians is well documented. Limited data suggest that the extent of underuse of prevention/screening services for CVD risk factors in the obstetrics and gynecology setting is even more prevalent. Many women use obstetriciangynecologists for primary care and receive preventive health care services by obstetrician-gynecologists. The extent to which women from East and Central Harlem use obstetrician-gynecologists as primary care providers is unknown. Similarly, the extent to which CVD risk factor prevention/screening services are underused in the obstetrics and gynecology setting serving women from East and Central Harlem is also unknown. We propose a pilot study that will develop instruments to assess the extent to which CVD risk factor prevention/screening services are underused in an obstetrics and gynecology setting serving women from East and Central Harlem. The specific aims of this pilot study are: 1. To develop and pilot test an instrument that will determine the usual source of care and usual provider type for non-pregnant women attending a general obstetrics and gynecology (ob/gyn) clinic serving women from East and Central Harlem. 2. To develop and pilot instruments that will measure the extent of underuse of CVD risk factor screening/prevention services (blood pressure screening, cholesterol screening, targeted glucose screening, and tobacco use) in a general ob/gyn clinic serving non-pregnant women from East and Central Harlem. 3. To explore patient factors (knowledge, attitudes, beliefs, health behaviors, and li LVAL teracy levels) associated with underuse of CVD risk factor screening/prevention services. Based on the results of this pilot study we will develop a proposal to design an intervention to decrease rates of underuse of CVD risk factor prevention/screening measures.LVAL+p.Cigarette smoking has been hypothesized to have both carcinogenic and anti-estrogenic effects that may offset each other to produce no overall effect on breast cancer risk. A full-term pregnancy also appears to have opposing effects on breast cancer risk: 1) an adverse effect shortly after delivery and 2) a beneficial effect over time. If the transient increase risk of breast cancer is due to the growth-enhancing consequences of elevated pregnancy hormones on already initiated cells, then cigarette smoking during pregnancy, through its anti-estrogenic effect, can be expected to dampen this risk. Conversely, with its carcinogenic effect, cigarette smoking during pregnancy might also reduce the long-term protection against breast cancer afforded by a full-term pregnancy. We propose to examine the effects of cigarette smoking on the risk of postpartum breast cancer occurring at different intervals following delivery. We will use a database that links together the Swedish Medical Birth Register, National Cancer Register, and Register of Causes of Death. Members of the study population are all mothers who delivered a liveborn or stillborn baby after a gestation period of at least 28 weeks in Sweden between 1973 and 1998. We have adopted a nested case-control sampling design to allow more efficient analyses. Cases are approximately 3,500 women who had one or more childbirths between 1973 and 1998 and who had a breast cancer diagnosis during the same period. For each case subject, five controls who were born in the same year as the index case, were alive at the date of the diagnosis for the index case, and had not been diagnosed with breast cancer by that date, will be randomly selected from the source population. Logistic regression analysis will be applied to examine cigarette smoking as a risk determinant for postpartum breast cancer adjusting for age, parity, and age at first full-term pregnancy.LVAL+p.-This application is one of four submitted concurrently to allow large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism. These proposals combine the resources of six large prospective cohorts from the American Cancer Society (CPS-II study), Harvard University (Harvard Cohort Studies), the IARC (EPIC study), and the Universities of Hawaii and Southern California (Multiethnic cohort); in addition, two NCI intramural cohorts (PLCO and ATBC studies) will participate. The proposed study is unique in having prospective plasma samples, genetic material, anthropometric measurements, and extensive questionnaire data on diet, physical activity, exogenous hormone use, smoking, and other lifestyle factors from over 790,000 men and women. Because of the scope and collaborative nature of this consortium, simultaneous investigation of genetic predisposition and lifestyle factors is possible, to clarify the inter-relationships between, and the relative importance of, genetic and hormonal risk factors. Specifically, this study will define SNPs and haplotypes in steroid hormone metabolizing genes, genes in the IGF pathway, and related receptor proteins. These candidate genes will be resequenced in 96 cases of advanced breast cancer, and 96 cases of advanced prostate cancer, chosen from the European, African, Latino, Japanese, and Hawaiian-origin ethnic groups. Haplotype tag SNPs will be selected after genotyping of a larger number of SNPs from a collection of 768 samples from the multigenerational CEPH (Centre d'Etude du Polymorphisme Humain) pedigrees and human diversity collection, by the Whitehead Institute for Genome Research and CEPH, and will rapidly be made publicly available. The interaction of genetic variants with hormonal, lifestyle and anthropometric factors known to be associated with breast and prostate cancer will be examined. In a subset of studies, the association of these variants with markers of brean LVAL~ st and prostate cancer risk (i.e. plasma steroid hormone levels and IGF-1 levels) will be investigated. Projects developed within the Cohort Consortium will foster continuing interactions between the genomic and epidemiologic research communities and help integrate the rapid advances in genomic research into large-scale epidemiologic studies. The ultimate goal is to provide the foundation for reducing the public health burden of these cancers.LVALWe propose to study the relations between common potentially low-penetrance polymorphisms in candidate genes for breast cancer in three prospective cohorts; the Nurses' Health Studies I and II, and the Women's Health Study. Specific hypotheses relate variants in genes important to steroid hormone metabolism (sex-hormone binding globulin, CYP 19 and the progesterone receptor) with risk of breast cancer, and effect modification of the relation of postmenopausal hormone use with breast cancer by genotype. We will also examine polymorphisms in two genes involved in cell cycle control (the HER2 proto-oncogene, the TGFbeta receptor type I) that have been associated with breast cancer risk in other studies. Finally, we will seek to replicate interactions we observed in the current grant cycle between initiation of smoking at a young age and variants in the CYP1A1 gene, and first degree family history of breast cancer and longer (CAG)n repeats in the androgen receptor. We estimate we will accrue 1540 cases of breast cancer in the Nurses' Health Study I, 261 cases in the Nurses' Health Study II, and 1050 cases in the Women's Health Study. With this total of 2851 incident cases, we will have >90 percent power to detect relative risks of 1.5 or greater for the main effects of most of the genotypes of interest. We will also have substantial power to detect interactions between these genotypes and established breast cancer risk factors.LVAL+p.0This study will examine four key issues: (1) race and gender differences in the correlates of dementia, particularly focusing on morbidity processes that are associated with dementia in its varied forms; (2) race and gender differences in health care service utilization and health care costs among those suffering from forms of dementia; (3) the influence of socioeconomic contexts and the availability of health services on morbidity processes leading to dementia, and health care costs; (4) the impact of contexts of consumption of alcohol and tobacco on morbidity processes leading to dementia and on health care costs. Data: The study will examine a 2.5% random sample of HCFA beneficiaries from 1996-2000 in the states that make up the census designation of the South (N=275,000). Our contextual level analyses on 1425 counties in the South will examine the impact of socioeconomic conditions, the availability of medical services in the area, and alcohol and tobacco consumption. We will estimate a variety of multi-level hierarchical models for logistic regression models, multinomial logistic regression models, and linear models that incorporate the influence of socioeconomic contexts and other factors into predictions of morbidity, service utilization and health care cost of individual beneficiaries. Significance: The proposed work will generate several important contributions: (1) It will help identify how race and gender differences in heart disease and stroke influence the onset of dementia, and how these processes may differ between vascular/multi-infarct dementia and Alzheimer's disease; (2) It will elucidate how race and gender variations in morbidity processes leading to dementia impact health care service utilization and health care costs. (3) It will allow us to discern if contextual factors such as socioeconomic inequality and health care availability influence the development of dementia and its effect on healthcare outcomes (service utilization and costs); and (4) It will allow a systematic assesLVALsment of the influence of contexts of alcohol and tobacco consumption on the development of dementia and its influence on health care service utilization and costs.LVALh DISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse LOCATION National PREVENTION/TREATMENT Interview/Focus Group RESEARCH Human Studies STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Initiation AGE Child COMMUNITY General Partnerships EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PREVENTION/TREATMENT Support Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseADDICTION Initiation AGE Child LOCATION Urban National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION African American Caucasian TOBACCO Non-Specified Tobacco UseAGE Older Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology ECONOMICS Socio-Economic Status Medicaid/Medicare Insurance Coverage Cost of Smoking EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesLVALThe long-term development of substance use and abuse in girls and women are poorly understood. In at least two ways, females compared to males appear more vulnerable to substance abuse and dependence: a speedier development from onset of use to abuse, and a higher propensity to develop comorbid conditions. In addition, females and males with an early onset of substance use are more likely to become substance abusers. The main goal of the proposed research is to investigate the early phases in this development process. Specifically, we propose to study precursors to the onset of early substance use (i.e., mainly alcohol and tobacco use), the transition to onset of use, and the transition to regular use in an inner-city community sample of 2,484 preadolescent girls. The girls, together with their parent and school teacher, will be assessed yearly and will be followed up over a period of five years. The sample will be made up of approximately 50 percent African-American and 50 percent Caucasian girls. The proposed study will be a substudy linked to and benefitting from the NIMH-funded study on the same girls, which has as its main object the study of the development of antisocial and delinquent behavior. The present proposal has three foci: 1). To identify the developmental precursors to the onset and regular use of substances; 2). To examine behavior problems which interact with early substance use; and 3) To elucidate the risk and protective factors predictive of the precursors of early substance use and predictive of the early use. The proposed study will be the foundation upon which follow-ups beyond the current five-year period can be built in order to better understand the long-term antecedents, risk and protective factors for substance abuse and dependence in females.LVAL+p.4This cooperative agreement (RFA HL-00-011) application is for a field center for the collaborative, multi-center "Trial of Activity for Adolescent Girls" (TAAG) study. The primary aim of the six-year study is to prevent the decrease in physical activity (PA) and fitness in adolescent girls through a school-based, community-agency-linked intervention aimed at encouraging PA in school and after school during the 7th and 8th grades. Six vanguard middle schools with a large minority population and a diverse group of agencies (Tucson City Parks and Recreation, YMCA, Boys and Girls Club, PLAY, Amphitheater Extension program) have agreed to participate. Herein we outline strategies for designing a culturally sensitive intervention, based on formative assessment, and guided by the social-ecology framework of Well's "Youth Physical Activity Promotion Model." In-school PA will be increased through enhanced physical education, using the ACTIVITYGRAM and FITNESSGRAM, for motivation and evaluation. Issues of perceived self- worth, body-image, self-efficacy, overcoming PA barriers and other psychosocial mediators of PA will be addressed in health and PE lasses and after-school through an innovative Wellness Theater and Dance approach. Other appealing activities for adolescent girls will be offered after school through agency involvement, e.g., dance and creative movement, martial arts, individual and some team sports. Special events will promote family and community involvement. Physical activity will be assessed by the ACTIVITYGRAM and accelerometers, and fitness by the PWC 170 test. Innovative secondary aims focus on relationships and intervention effects on body image and self-esteem and programs, physical activity patterns, tobacco and drug use, sexual activity, weight concerns, school attendance and academic achievement., Formative assessment and pilot testing of intervention components and assessment instruments will be done during a two-year feasibility phase. Findings from focus groups, interviews and obser LVAL vations with adolescents, parents, and school and agency personnel will guide intervention design. Early and on-going community and agency involvement will foster partnerships and promote sustainability. Our multi-disciplinary team of exercise scientists, nutritionists, epidemiologists, and physical educators has over 15 years of experience in multi-center, collaborative trials (coordinating center and field center) in children and adults. The team brings expertise in PA program design, PA and fitness assessment, formative assessment, behavior theory and curriculum development, intervention delivery, process evaluation, and data management.  ` @ 1 {,@ @Research@URORKEELLENCASE WESTERN RESERVE UNIVERSITYCLEVELANDOHNIEHSR01, ES009126S+p.Biology and CancerDiscovery 1b Evaluation 1b@2/1/20001/31/20042/1/2000 to 1/31/20044/2005!}vrgF?88," @@@Researchl@ROMKESMARJORIEUNIVERSITY OF PITTSBURGHPITTSBURGHPANICHDR01, HD036880Q+p.t@Fl@L@K1/1/199912/31/20031/1/1999 to 12/31/20034/2005{tpdJ@88,"%@`@Researchr@ROMEISJAMESST. LOUIS UNIVERSITYST. LOUISMONIAK01, AG019194ZO+p.j@F@L@K9/30/20018/31/20059/30/2001 to 8/31/20054/2005qlh]G@88," @^@Research@ROMAGNOLODONATOUNIVERSITY OF ARIZONATUCSONAZCDMRPBC990882M+p.Biology and CancerDiscovery 1b Evaluation 1b@199920021999 to 20024/2005unjbKC88," S@ (@Researchd@NIXONSARA JOUNIVERSITY OF KENTUCKYLEXINGTONKYNIDAR01, DA013677I+p.@F@LZ@K9/30/20025/31/20079/30/2002 to 5/31/20074/2005uok`H?88,"@@Researchl@NICHOLSTRACYWEILL MEDICAL COLLEGE OF CORNELL UNIV.NEW YORK NY NCIR03, CA1059984G+p.b@F@@?12/1/200311/30/200512/1/2003 to 11/30/20054/2005{pHA88,"q@@Researchp@NIAURARAYMONDMIRIAM HOSPITALPROVIDENCERINICHDR01, HD043844D+p.@Fn@@?6/1/20035/31/20056/1/2003 to 5/31/20054/2005qjfZI@88,"@@u@Researchj@NELSONLORENESTANFORD UNIVERSITYSTANFORDCACTRDRP8RT-0131B+p.t@@L@?7/1/19996/30/20037/1/1999 to 6/30/20034/2005}skg]H@88,"@@Researchj@NAZAR-STEWARTVALLEUNIVERSITY OF PITTSBURGHPITTSBURGHPANIDCRP60, DE013059@+p.t@P@@?8/1/19997/31/20048/1/1999 to 7/31/20044/2005xthNG88,"D@`@Researchz@LUEPKERRUSSELLUNIVERSITY OF MINNESOTA TWIN CITIESMINNEAPOLISMNNHLBIR01, HL023727B=+p.t@@@?4/1/19792/28/20054/1/1979 to 2/28/20054/2005|oJA88,"g@p@4Researchf@LUBINJAYNot GivenNot GivenNot GivenNCIZ01, CP010113^7+p.t@@@1Not GivenNot GivenUncertain4/2005yjeZOD?88,"@@Research@LOHRJACOBGOVERNOR'S INSTITUTE ON ALCOHOL AND SUBSTANCE ABUSE INCRESEARCH TRIANGLE PARKNCRWJF40668 @6 AddictionDiscovery 1c Discovery 2a@110/1/20006/30/200410/1/2000 to 6/30/20044/20054, ~E>88,"@@ResearchL@LOHMANTIMOTHYUNIVERSITY OF ARIZONATUCSONAZNHLBIU01, HL0668583+p.@@z@19/30/20008/31/20069/30/2000 to 8/31/20064/2005slh`I@88,",LVALT>Specific Aims: The specific aim of this project is to assess the relation of risk of arm lymphedema among women with breast cancer with modifiable exposures, including body weight, physical activity, smoking, and breast reconstruction. We will conduct a prospective study among a population-based cohort of women who have received axillary dissection as part of their treatment for breast cancerTo examine the determinants of relapse and relapse prevention among women who quit smoking during their pregnancy. Research Design: We will enroll a cohort of pregnant women who have successfully quit smoking during pregnancy and follow this cohort for four months postpartum. All women will participate in individual interviews to verify smoking status, and to complete screening and assessment forms. We will conduct focus groups with new mothers who do not resume smoking and focus groups with mothers who relapse. Focus groups will examine determinants of relapse prevention and successful cessation such as social support, clinical support and education, internal and external factors, incentives, addiction, and employment. Study Population: The target population will be white and African American women whose prenatal charts indicate that they were smokers at the start of their current pregnancy and who quit smoking by the end of the second trimester. Outcome Measures (If cessation or reduction, how defined): Expected outcomes include an understanding of (1) interventions that may improve successful maintenance of smoking cessation and (2) a theoretical model for postpartum relapse and maintenance. This model will describe the relapse process, identifying stages of relapse and factors that contribute to postpartum relapse and maintenance.LVAL+p.8A population-based case-control study was carried out in three geographic areas of the U.S. to examine reasons for differences in incidence between Blacks and Whites for a variety of cancers. Analyses are underway using attributable risk modeling to look at social class in four cancer sites, esophagus, multiple myeloma, pancreas, and prostate. The analyses will attempt to determine how much of the risk from social class is due to tobacco use and how much is due to other factors. Results were reported showing no association between multiple myeloma and total number of reported diagnostic X-rays of any type. Investigators examined the relationships between folate and methionine intake, serum homocysteine levels (as a biomarker for folate metabolism), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype and risk of oral cancer in a population-based, case-control study in Puerto Rico. Although increased folate intake was associated with decreased oral cancer risk, the finding was due almost entirely to folate intake from fruit, whereas other dietary folate sources showed no clear association. Methionine intake and serum homocysteine levels were not associated with oral cancer risk. Subjects with the MTHFR C677T homozygous variant genotype had a non-significantly lower risk, and risk patterns tended to differ by level of folate, methionine, alcohol intake and smoking. After controlling for alcohol and tobacco use, there was an increased risk of oral and pharyngeal cancer for subjects reporting a first-degree relative with the same disease. This suggests a heritable component to oral and pharyngeal cancer or shared environmental factors other than alcohol and tobacco. In a case-control study of prostate cancer in Shanghai, China, investigators reported lower risk of disease among men with greater intake of allium vegetables, in particular with greater intake of garlic and scallions. These associations were independent of the intake of other foods and of total calories. An analysis exaLVAL9mined the effects of the timing of occupational asbestos exposure to lung cancer using pooled data from two large case-control studies conducted in Germany. Odds ratios (OR) and 95% confidence intervals (CI) showed an increased risk with duration of asbestos exposure (OR=1.8, 95% CI=1.2-2.7 and OR=2.4, 95% CI=1.7-3.4 for subjects working 3 to 7 years and 8 or more, respectively, in jobs with potential asbestos exposure compared to never-exposed). The OR decreased significantly with time since last exposure to about one-half after more than 20 years since exposure ceased. A spline weight function model revealed that the risk effect reached a maximum 10 to 15 years prior to interview, then declined. The relationship between mortality and protracted low-dose radiation exposure was evaluated in a large cohort of U.S. radiation technologists. Work history variables were analyzed using external and internal comparisons to account for secular trends. Results suggest increased risk for breast cancer, leukemia, and circulatory disease, especially stroke, for subjects working in early years when radiation exposure was likely to be high. No consistent increase of risk was found for multiple myeloma or lymphoma. In a hospital-based case-control study of 159 cases of cancer of the testis and 136 controls, investigators found no association between dietary phytoestrogens and testicular cancer risk in young men. An extended mortality follow-up of a cohort of formaldehyde workers was provided information on the potential effect of formaldehyde on lung cancer risk. Multivariate analyses including exposure to formaldehyde and several other agents revealed no relationship with lung cancer risk, but did reveal an excess risk with malignancies of the hematopoietic system. Investigators conducted a hospital-based case-control study of invasive cutaneous melanoma. There were 718 cases and 945 controls matched by gender, race, age, and geographic area. Results showed that a 10% increase in annual UVB flux was associated withLVAL: a 19% increase in individual odds of melanoma for men and 16% for women. The effect of UVB intensity during the ages 0-19 is as important as UVB intensity during the adult ages. Total time outdoors has an important effect on the risk of melanoma. Another melanoma investigation evaluated objective measurements of constitutive skin color and ultraviolet light sensitivity in relation to risk of invasive cutaneous melanoma in a study in Italy of 183 cases and 179 controls. Constitutive skin color and skin ultraviolet light sensitivity were assessed by colorimetry and minimal erythema dose (MED), respectively. ORs of melanoma increased by a factor of 1.20 (95% CI=1.12-1.30) for each unit of skin brightness and by a factor of 1.24 (95% CI=1.07-1.43) per 10 mJ/cm2 of MED. These associations were largely independent of phenotypic or sun-related characteristics, but were modified by sun exposure. Increased risk of melanoma was observed only among subjects with the highest levels of sun exposure. Another analysis of these data resulted in a chart which linked melanoma risk associated with combinations of factors and could be used to identify subjects from a Mediterranean population who would most benefit from preventive measures. Finally, in these same data, it was also found that glucocorticoid-based therapy appeared to be protective against melanoma incidence, with the degree of protection increased with treatment duration, but not the reason for treatment. Controls from a population-based case-control study of breast cancer in Asian women living in California and Hawaii, in which migration history was associated with a 6-fold risk gradient that paralleled historical differences in incidence rates, were used to evaluate migration history and levels of endogenous hormones. Plasma was measured for estrone, estradiol, estrone sulfate, androstenedione, testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone and sex hormone-binding globulin. Levels of estrogens and sex hormone-binding gLVAL;lobulin did not differ significantly between Asian-born women and western-born women of Asian decent in either pre- or postmenopausal women. Among postmenopausal women, androgens tended to be highest among the least westernized women, and declined as the degree of westernization increased. The relationship between 45 common agricultural pesticides and prostate cancer incidence was evaluated in the Agricultural Heath Study, a large prospective cohort study of private (farmers) and commercial pesticide applicators. The standardized incidence ratio (SIR) for prostate cancer (SIR=1.14, 95% CI=1.05-1.24) was significantly elevated compared to the male populations of Iowa and North Carolina. Factor analysis identified a pesticide use pattern characterized by use of chlorinated pesticides among applicators over 50 years of age, that was significantly associated with prostate cancer risk. Methyl bromide, a widely used halogenated fumigant, was also associated with an excess risk. Several other pesticides showed a significantly increased risk of prostate cancer among study subjects with a family history of prostate cancer but not among those with no family history. Investigators developed two quantitative exposure measures to estimate long-term chemical-specific pesticide exposures, based on data from an enrollment questionnaire and a take-home questionnaire. A `general' algorithm was based on the enrollment questionnaire and used four basic variables (i.e. mixing status, application method, equipment repair status and use of personal protective equipment), as well as measurement data from the published pesticide exposure literature. A second algorithm was based on variables in the general algorithm plus additional information from the take-home questionnaire, including types of mixing system used (i.e., enclosed or open), having a tractor with enclosed cab and/or charcoal filter, frequency of washing equipment after application, frequency of replacing old gloves, personal hygiene and changing clothes after a LVAL<spill. Weighting factors were applied in both algorithms based on measurement data from the published pesticide exposure literature and professional judgment. Investigators conducted a 40-year mortality follow-up study of Korean war navy technicians with potential exposure to high-intensity radar. Compared to US White men, deaths from all causes and from all cancers were below expected values. There was no evidence of increased brain cancer in all subjects or in those technicians in high-exposure occupations. The analysis indicated that radar exposure had little effect on mortality in this cohort of navy technicians. Investigators have examined the pattern of multiple occurrences of four radiation-related neoplasms in a radiation-exposed cohort of 2795 patients receiving conventional radiation treatments for benign conditions in the head and neck area when they were children. There were 350 thyroid cancers, 108 benign and malignant salivary tumors, 87 neural tumors, and 70 cases of hyperparathyroidism. There were 492 individuals (17.6%) with single tumors, and 60 individuals (2.1%) with multiple tumors. An analysis showed that the excess concordance of neoplasms could be explained by known risk factors, such as sex, age and dose, thereby suggesting that susceptibility factors did not play a role in the development of multiple tumors. Analyses of hormone replacement therapy for menopausal symptoms were conducted in a cohort of women from the Breast Cancer Detection Demonstration Project who developed ovarian cancer between 1980 and 1998. Based on 329 cases of ovarian cancer, ever-use of estrogen-only was significantly associated with increased risk. Neither estrogen-progestin-only use nor estrogen-progestin use following estrogen-only use was associated with ovarian cancer. Increasing duration of estrogen-only use was associated with a 7% (95% CI= 2%-13%) increase in relative risk per year of estrogen-only use. There was no association between duration of estrogen-progestin use and ovarian cancer. InveLVALstigators reported results from a case-control study of incident lung cancer in a rural area of China, including 886 cases and 1,659 frequency matched controls, for residential radon exposure, exposure to environmental tobacco smoke, previous diagnosis of lung disease, air pollution, and exposure to cooking oil fumes. Time-weighted average radon concentrations were 230.4 Bq/m3 for cases and 222.2 Bq/m3 for controls. Risk increased with increasing radon level. The excess odds ratio at 100 Bq/m3 was 0.19 (95% CI= 0.05-0.47) for all subjects, and 0.31 (95% CI=0.10-0.81) for subjects with 100% coverage of the exposure interval. Adjusting for exposure uncertainties increased estimates 50 percent. Lung cancer risk was also associated with previous diagnosis of pulmonary tuberculosis (OR=2.1, 95% CI=1.4-3.1) and chronic bronchitis/emphysema (OR=1.4, 95% CI=1.1-1.8). Non-significant associations were observed for a previous diagnosis of asthma (OR=1.4, 95% CI=0.9-2.1) and pneumonia (OR=1.5, 95% CI=1.0-2.3). The OR for lung cancer associated with burning coal compared to biomass was 1.29 (95% CI=1.0-1.6) and increased with percent of time coal was used over the past 30 years (p=0.02). Among 200 female and 33 male lung cancer cases and 407 female and 114 male controls who never smoked. The OR for ever-exposed to environmental tobacco smoke was 1.19 (95% CI=0.7-2.0), with a significant trend (p<0.05) with increasing exposure. Among 233 incident, female lung cancer cases and 459 controls the OR associated with ever-use of rapeseed oil, alone or in combination with linseed oil, was 1.67 (95% CI=1.0-2.5), compared to use of linseed oil alone. ORs for stir-frying with either linseed or rapeseed oil 15-29, 30, and >31 times per month were 1.96, 1.73, and 2.24, respectively (trend, p=0.03), relative to a lower frequency of stir-frying. Lung cancer risks also increased with total number of years cooking (trend, p<0.09).LVAL+p.>Data from the most recent survey (1995-97) of the Minnesota Heart Survey (MHS) indicate that previously favorable trends in cardiovascular risk factor levels are attenuating. While cigarette smoking and self-reported dietary fat intake continued to decline, mean body weight rose substantially and rapidly, physical activity decreased, and the previous decline in serum total cholesterol was no longer apparent. These trends may or may not continue in the future. As part of the Minnesota Heart Survey, we propose to conduct another population survey of 4,000 adults, ages 25-84 years in 2000-02, to detect current trends in cardiovascular disease risk factors, including serum lipids, blood pressure, cigarette smoking prevalence, dietary fat intake, obesity, diabetes, physical inactivity, fibrinogen, and serum vitamin E. The proposed survey will build upon four previous, independent cross-sectional surveys conducted in 1980-82, 1985-87, 1990-92, and 1995-97, which collectively examined 23,000 adults in the metropolitan Minneapolis-St. Paul (2.3 million residents in 1990). Using a sampling strategy identical to that of prior surveys, households will be randomly selected by a two-stage cluster design. A wide range of risk factors for cardiovascular disease will be measured using previously employed methods. Cohort and ecological analyses will link secular trends in risk factors to morbidity and mortality from coronary heart disease, congestive heart failure, and stroke within the same population. To estimate risk factor levels in children and adolescents, 1,000 youth ages 8-17, offspring of selected adults, will also be recruited and examined using youth-specific measurement instruments where appropriate (e.g., physical activity and smoking). New methodological studies are proposed to understand trends in reported dietary intake which are irreconcilable with trends in body weight and serum cholesterol. New information will be collected on measures of leisure time physical inactivity and diet validation. Serial  LVAL ascertainment of risk factor levels in populations is crucial to understanding, predicting, and controlling population trends in cardiovascular disease. The Minnesota Heart Survey has been, and continues to offer, a powerful resource to examine long-term trends in cardiovascular disease risk factors.LVAL| N&ADDICTION Initiation Maintenance AGE Child ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral CycleAGE Child Young Adult Adult Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Pregnancy Hormones MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesAGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Adult Older Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesLVAL+p.AAlthough tobacco smoke and alcohol account for most cases of oral cancer, few smokers and drinkers eventually acquire this disease. The main goal of this study is to determine whether differences in constitutive function of certain biotransformation enzymes (which metabolize tobacco smoke and alcohol) modify risk for oral cancer among smokers and drinkers, and thereby account for some of the observed differences in susceptibility. To meet this goal, we will conduct a case-control study of oral cancer in the Pittsburgh area. Cases (N=244) will be men and women identified through the Ear, Nose, and Throat, and Oncology Offices at UPMC with squamous cell carcinoma of the oral cavity newly diagnosed between 01/01/99 and 12/31/02, who are 18-74 years of age, and reside in one of 16 counties in the Tri-State area (including western Pennsylvania, eastern Ohio and northeastern Western Virginia). Neighborhood controls (N=488) will be men and women identified through Voters' Registration lists (for Allegheny County in Pennsylvania) or Motor Vehicle Drivers' License lists (for all other counties) who are without oral cancer and match the cases on age, gender, race and zip code. Two controls will be matched to each case. Eligible cases and controls will have a history of cigarette use (at least 10 pack-years) or alcohol use (at least 1 alcoholic beverage per week). In person interviews will cover demographic variables, detailed history of tobacco and alcohol use, diet, ethnic background and family history of cancer. Blood will be drawn, and DNA extracted and analyzed for genetic variants of the following polymorphic biotransformation enzymes: CYP1A1, CYP2E1, GSTM1, GSTT1, GSTP1, mEH, MPO, NAT2, ALDH2, ADH2 and ADH3. Each of these enzymes is important in the metabolism of either alcohol or tobacco smoke, or both. We will measure relationships between each genetic enzyme variant and risk for oral cancer, as well as the joint effects of these polymorphisms on risk. We will also examine exposures, e.g. diet, that may0LVAL@ modify or confound these relationships. Identification of genetic biomarkers for susceptibility to oral cancer could be used to focus screening and intervention efforts on individuals who at highest risk for this disease.LVAL+p.CParkinson's disease (PD) is one of a few conditions in which cigarette smoking appears to decrease the risk of developing the disease, with a reduced risk of 50% among ever smokers compared to never smokers. Despite the fact that this reduced risk among cigarette smokers has been consistently observed in studies conducted over the past several decades, there has been very little epidemiologic research to investigate the possible explanations for this apparent protective effect. Although it is possible that a chemical or biological effect of cigarette smoke provides protection against the development of PD, alternative explanations are also plausible. One theory suggests that the effect of smoking is due to another factor, such as personality type or the genetic tendency to take up addictive behaviors, which explain both the decreased likelihood of taking up the smoking habit and the risk of developing PD in later life. We propose to conduct a study of PD patients and normal controls (also called a case-control study) to evaluate genetic, environmental and behavioral factors that may explain this apparent protective effect of smoking in PD. We hypothesize that genetic variants associated with the propensity to engage in addictive behaviors may be less frequent among PD cases than controls, especially since some of these genetic variants alter dopaminergic transmission in the brain (dopamine is the brain chemical that is depleted in PD). We will also assess whether nonsmokers who are exposed to environmental tobacco smoke from the smoking habits of others may be at reduced risk of developing PD. If environmental (or passive) smoke exposure is also more frequent among PD patients than controls, this would suggest that a chemical effect of both mainstream and sidestream tobacco smoke has a direct biological effect that reduces the risk of developing PD. We also plan to gather data from cigarette smokers regarding the perceived strength of their addiction, and more detailed information regarding their liLVALfetime history of alcohol consumption, another factor that has been associated in recent studies with a reduced risk of developing PD. This study will use blood samples and risk factor data obtained from PD cases and controls in a recently completed case-control study conducted within the Northern California Kaiser Permanente Medical Care Program. A lifetime history of cigarette smoking has already been obtained for the study subjects, which include 509 newly diagnosed PD cases and 541 age- and gender-matched controls. Additional information will be sought from all study subjects using a telephone-administered structured interview and will include questions regarding: exposure to passive smoke, an assessment of the addictive potential of cigarette smoke among former and current smokers, a measure of premorbid personality, and a lifetime history of alcohol consumption. By combining laboratory-based investigation of these addiction susceptibility genes with detailed information regarding cigarette smoking and other addictive behaviors, we hope to gain insight regarding the nature of the inverse associations of cigarette smoking and other addictive behaviors with Parkinson's disease that can provide information for future research on the causes of Parkinson's disease.LVAL+p.EMaternal smoking during pregnancy (MSDP) has been linked to significantly increased risk for offspring smoking uptake. Given high societal costs of smoking, and risk for transgenerational transmission of offspring smoking, elucidating mechanisms underlying the MSDP-offspring smoking link is critical for intervention and prevention efforts. Acknowledging the possibility that confounding factors (e.g., genetic influences, maternal psychiatric comorbidities) may also underlie the MSDP-offspring smoking link, we follow up on one potential mechanism shown previously by Kandel and Udry l to influence smoking uptake in offspring of smoking mothers. In the only study to examine mechanisms underlying the MSDP-offspring smoking link, Kandel and Udry found that increased maternal testosterone levels during pregnancy were associated with increased risk for smoking uptake in female offspring. In the proposed study, we have an unprecedented opportunity to expand on Kandel and Udry's findings by examining two maternal hormones (testosterone and cortisol) during pregnancy as mediators of links between MSDP and offspring symptoms of nicotine dependence in both males and females using offspring from the Providence Cohort of the National Collaborative Perinatal Project (NCPP). Six hundred ninety-three adult offspring from the Providence cohort of the NCPP will be included in the study. Maternal smoking was previously assessed prospectively as part of the original NCPP battery. Symptoms of nicotine dependence in offspring were also assessed through a follow-up study of the original NCPP cohort. Maternal sera from three trimesters of pregnancy are accessible through collaboration with NIH personnel. Funding for this proposal will allow us to assay maternal sera for testosterone (and its binding protein) and cortisol (and its binding protein) as well as cotinine (a nicotine metabolite). A series of regression analyses will then be utilized to test our hypotheses regarding maternal levels of free testosterone and free corti LVAL& sol as mediators of links between MSDP and offspring symptoms of nicotine dependence (measured by self-report and maternal cotinine levels) in both males and females. Identification of mechanisms underlying the MSDP-offspring smoking link may lead to targeted intervention and prevention efforts in pregnant smokers and high-risk offspring. Further, elucidating mechanisms underlying the MSDPoffspring smoking link will also represent a first step toward preventing the transmission of MSDP.LVALv  8 & ^ .F~*V:Biology and Cancer Addiction Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National Surveillance Global IssuesInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentAwareness Risk Perception and CommunicationsBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National Surveillance Interventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and Communications Community and Policy InterventionsEpidemiology and National Surveillance Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentInterventions for Prevention and TreatmentEpidemiology and National Surveillance Interventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National Surveillance Global IssuesBiology and Cancer Addiction Epidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceBiology and Cancer Addiction Epidemiology and National SurveillanceLVAL+p.HAlthough adolescent smoking has been a major national concern for many years, there is still relatively little known about its etiology among girls, particularly among young minority girls. While historically smoking rates were greater among males, gender differences in smoking are now virtually non-existent. Studies have demonstrated that at the same level of use, females are more likely to become dependent upon tobacco and are more likely to suffer from a variety of cancers than males, including a greater susceptibility to higher fatality forms of lung cancer. Minority women in particular appear to be at increased risk of developing smoking-related diseases. Therefore, although minority girls demonstrate the lowest rates of smoking during adolescence they may in fact be at highest risk for future smoking and for smoking-related problems. The current project would address existing gaps in the literature in a cost-effective manner through secondary analysis of largely minority, inner-city girls who participated in one of two school-based drug and violence prevention trial (N = 1,138 and N = 1,337). The primary goals of the proposed research are to improve our understanding of how smoking develops among urban minority girls and to examine transitional patterns of smoking behaviors among this population from middle school through high school. Secondary aims of the study are to investigate individual characteristics (i.e., household structure, religiosity, SES, pubertal timing) as potential moderators of the relationship between hypothesized risk factors and smoking as well as to examine relationships between smoking trajectories and indicators of health and well-being among this population. Finally, this study will compare and contrast smoking trajectories by racial/ethnic subgroups as well as examine potential cohort effects. The proposed study represents an important next step in the field of smoking etiology since it examines developmental transitions in smoking behaviors among a severely under-repre LVAL sented population (urban, minority adolescent girls) using state-of-the-art data analytic techniques. Findings from the proposed study will not only advance our understanding of smoking behaviors and transitions among minority girls, but will ultimately help develop and refine prevention efforts for this population and thereby decrease existing gender and racial/ethnic health disparities in the consequences of smoking.LVAL+p.JCurrent research is providing much needed data regarding the effects of chronic drug use on brain-behavior relations. This literature addressing the neurobehavioral concomitants of long-term substance use disorders (SUDs), however, is marked by considerable heterogeneity There are a number of factors which may contribute to this outcome. One likely contributor is the failure to account for the influence of the frequent use/abuse of the stimulant, nicotine. This second revision seeks five years of funding to address the role of nicotine in functionally compensating for the long-term neurocognitive effects of chronic substance abusers (SA s). Specifically, we propose to test the hypothesis that nicotine's cognitive enhancing properties, particularly as evidenced in working memory and attentional processes may serve to counterbalance or functionally overcome the negative effects observed in chronic SAs. The design entails the direct comparison of male and female abstinent, detoxified SA s (n=216) assigned to subgroups on the basis of their primary drug of abuse and current clinical diagnostic information with community controls (smoking and non-smoking; n=144) equated on geographic and demographic variables. In addition to responding to this question, the current design will also extend the on-going work regarding differences among drug using subgroups regarding cognitive compromise. Using a double-blind placebo controlled study, we propose to study the effect of three levels of nicotine via transdermal administration (0, 7 and 21 mg patches) in treatment-seeking SA and community controls (equal numbers of males and females). If the hypotheses are supported, existing research may underestimate the effects of chronic drug use on specific cognitive processes. These findings would have considerable clinical and scientific import. As a secondary aim, we plan to investigate associations among relevant, and understudied, demographic variables, including depressive symptoms, childhood behavioral disorders and a LVAL nxiety symptomatology. Furthermore, we intend to examine the role of race/ethnicity, gender and family history of SUDs. To facilitate this secondary aim, we have instituted plans to over-sample American Indians (Al), African American (AA) and female participants.LVAL tEDUCATION LEVEL Less than High School LOCATION Urban Rural National PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION African American Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Health Care Provider PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN PregnancyAGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other SmokingAGE Child Fetus/Prenatal DISEASE/BIOLOGY Mechanisms ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN PregnancyAGE Adult Older Adult LOCATION International PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research STUDY POPULATION African American American Indian/Alaskan Native TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesLVALv X  Zb4Xzh6"Discovery 1c Discovery 2a Development 1 Development 3 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1c Development 3 Evaluation 1cDiscovery 1a Evaluation 1a Evaluation 1bDiscovery 1c Development 3 Evaluation 1aDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1c Development 2 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Partnerships 2 Evaluation 1bDiscovery 1c Discovery 2a Development 1Development 3 Delivery 2 Partnerships 1Discovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1c Discovery 2a Development 1 Evaluation 1aDiscovery 1a Discovery 1b Discovery 1c Discovery 2a Discovery 3 Development 2 Delivery 2 Evaluation 1a Evaluation 1bDiscovery 1c Development 3 Delivery 3 Partnerships 2Discovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Development 1 Evaluation 1bDiscovery 1c Discovery 2a Discovery 2b Discovery 3 Development 2 Delivery 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Evaluation 1aDiscovery 1c Development 1 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1c Development 1 Development 2 Delivery 1Discovery 1c Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1c Discovery 2a Development 1 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2a Discovery 2b Development 1 Development 3 Delivery 2 Partnerships 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bLVAL+p.NWe propose to investigate whether repression of the tumor suppressor BRCA-1 gene in breast epithelial cells exposed to polycyclic aromatic hydrocarbons (PAHs) is mediated by the aryl hydrocarbon receptor (AhR). PAHs are environmental xenobiotics found in tobacco smoke, coal tar, and auto exhaust. The central hypothesis is that the AhR, upon activation by PAHs, acts as a negative transcription factor. We postulate that the AhR, complexed with the aromatic receptor nuclear transporter (ARNT) protein, binds to several xenobiotic responsive elements (XRE) strategically located in the proximal promoter regions flanking exon-1a and exon-1b in the BRCA-1 gene. This hypothesis hinges upon the supporting rationale that (1) exposure to benzo[a]pyrene (B[a]P), a PAH and AhR agonist, lowers the cellular content of BRCA-1 mRNA and protein in breast (MCF-7) and ovarian (BG-1) cancer cells. Actinomycin-D experiments indicated that loss of BRCA-1 was not due to adverse effects of B[a]P on BRCA-1 mRNA stability; (2) disruption of BRCA-1 expression was overcome by cotreatment with antagonists of the AhR; (3) B[a]P repressed the promoter activity of a 2.3-kb BRCA-1-luciferase reporter construct; (4) computer searches of the region upstream exon-1A have mapped a CYP1A1-like XRE (CCGTGAGAA) at -539 bp, and a (XRE-1) consensus (GCGTG) sequence localized in close proximity (+20 bp) to the transcription start site on exon-1A. In addition, two additional elements, termed XRE-2 and XRE-3, have been localized, respectively, at -107 bp in the intervening sequence upstream, and +218 bp into, exon-1B. Specific Aim 1 of this study will examine whether, upon binding by the AhR-heterocomplex, the XRE function as negative cis-acting elements. We will perform analysis of internal deletion constructs of the BRCA-1 promoter to identify the XRE responsible for negative regulation. Next, specific mutations will be introduced in the XRE sites to study their role in the context of the intact BRCA-1 promoter. Specific Aim 2 will focus on the LVAL role of XRE and ARNT proteins in the negative regulation of BRCA-1. Nuclear extracts prepared from breast epithelial cells treated with AhR ligands will be reacted with BRCA-1 promoter fragments containing the XRE. Nuclear protein:DNA complexes will be subjected to competition with cold oligonucleotides corresponding to consensus XRE. We will use antibodies against the AhR and ARNT for supershift and mutational electrophoretic mobility shift assays to discern binding by AhR-heterocomplex proteins to XRE. The relevance of the proposed work to breast cancer research is paramount in that this experimental plan will provide significant insight into how PAHs repress transcription of BRCA-1. This is a novel proposal because it fills a gap in an area of research directed to understanding how environment-gene interactions contribute to the etiology of sporadic breast cancer. In fact, while there exists compelling evidence that PAHs are involved in breast cancer development, until the regulatory mechanisms are defined, they cannot be targeted for preventive and therapeutic purposes. We believe that this application falls well into the programmatic mission of the Department of Defense Breast Cancer Research Program. An important outcome from this research is new information that may be used for the development of chemopreventive drugs to counteract the negative effects of PAHs.LVAL+p.PThis MRSDA K01 requests 3 years support for advanced research training in genetic gerontology and research support to study genetic and environmental influences on psychosocial geriatrics, health behavior, health services use, and aging. The long-term overall goal of the proposed study is to establish the Vietnam Era Twin [VET] Registry s promise for longitudinal health behavior and aging research. The intermediate goal is to conduct a study that points to research directions for health behavior and aging using the VET Registry. Aims 1 and 2 use data from the Swedish Adoption and Twin Survey and Aging (SATSA) and VET studies to evaluate genetic and environmental influences on stability versus change in (a) self-reported health, (b) health services utilization in Sweden and (c) high-risk health behaviors (obesity, smoking, low physical activity, excess alcohol consumption) in aging male and female like-sex twin pairs. Effects of cohort, gender, and medical condition will be controlled. Aim 3 evaluates the influence of psychiatric Hx and history of substance abuse on self-reported health and high-risk health behaviors among VETs. Aim 4 uses prospective data on obesity, smoking and alcohol use to evaluate genetic and environmental influences on persistence and change in health behaviors and the extent to which these are mediated through psychiatric risk factors. Both Registries have four assessments spanning periods 1984-1996 [total N ~ 3,100 like-sex twin pairs] aged 40-80+ [SATSA] and 40-55 [VET]. For Aims 1-2, bi-variate and developmental genetic modeling will evaluate stability and change in self- reported health, health services use and high-risk health behaviors, controlling for gender, cohort and medical conditions. Replicability of SATSA modeling for VETs will be assessed. Aims 3-4, use developmental genetic modeling and include nine year risk factor Hx and psychiatric Hx to evaluate genetic and environmental influences on persistence and change in high-risk health behaviors, mediated through psyz LVAL chiatric risk factors. The training is designed to provide analytical skills in genetic gerontology to be competitive as an independent investigator. The research project will add significantly to the literature on the role of genetics in understanding persistence of high- risk behaviors in the context of aging.LVAL+p.RMaternal lifestyle factors such as cigarette smoking and alcohol consumption are known to be the most prevalent sources of in utero exposure to toxic substances and clearly impact the health of newborn children. Our goal is to address the fundamental question concerning the extent to which genetic background modulates the impact of environmental exposures on levels of DNA damage. Interindividual and interethnic differences in xenobiotic metabolism are considered to be major contributors to variations observed in disease susceptibility. This proposal will evaluate the hypothesis that environmental and genetic determinants of enzyme activities which bioactivate and detoxify xenobiotics are important factors in modulating transplacental DNA damage. This proposal is directly linked to the ongoing NICHD funded grant 5 R01 HD33016 entitled "Lifestyle Factors Affecting Fetal Somatic Mutation", P.I. W. L. Bigbee. This parent study is investing substantial resources in the acquisition of clinical and epidemiological characterization of 1,500 women and newborns across a wide sociodemographic spectrum and is applying several molecular biomarkers of exposure and effect. These biomarkers include determination of 4- aminobiphenyl hemoglobin adducts levels and mutation frequency levels at two independent loci (glycophorin A and hypoxanthine phosphoribosyl transferase). For these same subjects, we propose to apply genotyping assays to both maternal and newborn blood samples focusing on the polymorphic enzymes involved in the metabolism of chemicals found in cigarette smoke, specifically CYP1A1, CYP2E1, GSTM1, GSTT1, NAT1*, and NAT2*. Screening by RT-PCR for the level of mRNA expression of CYP1A1, CYP1B1 and CYP2E1 in peripheral blood mononuclear cells will also be performed as biomarkers of enzyme phenotypic activity and exposure to tobacco smoke. The integration of pharmacogenetic information from this genotype and phenotype data with sociodemographic information for individually measured environmental risk factors L LVAL\ and the measured exposure/effect biomarkers, will enable the study of the specific associations between the expression of the metabolizing enzyme genes and the presence of specific allelic variants, to the induction of genetic damage in newborns. Preliminary data from maternal samples acquired to date support this hypothesis and blood samples continue to be banked to ensure the availability of complete information for each subject. This proposed investigation, in the context of the ongoing funded study, therefore represents a very powerful and cost-effective strategy to investigate the relative contributions of genetic risk factors and maternal environmental interactions to newborn susceptibility to DNA damage.LVAL+p.THuman cervical cancer development begins with infection by the DNA tumor virus, human papillomavirus (HPV). The HPV genome encodes two oncoproteins, E6 and E7, that are required for cell immortalization, E6 causes degradation of the cell cycle checkpoint/tumor suppressor protein, p53. However, development of invasive diseases requires additional events including the activation of secondary oncogenes. In this regard, environmental carcinogens play a major role. Cigarette smoking is correlated with an enhanced risk for cervical cancer development. An active agent in cigarette smoke is the ubiquitous environmental carcinogen, benzo[a]pyrene. Metabolites of B[a]P are potent DNA mutagens. B[a]P is mutagenic in cervical cells in vitro, accumulates in cervical mucus in vivo, and ras oncogene, a known target of B[a]P, is mutated at a high frequency in cervical tumors. p53 is an important cell cycle control protein. Following DNA damage, p53 pauses cell cycle progression until DNA repair is complete. Our previous in vitro studies show that treatment with B[a]P strongly inhibits the proliferation of cultured normal cervical epithelial cells This inhibition is correlated with a large increase in p53 level. In contrast, in HPV-immortalized cells, which have low p53-immortalized cells do not significantly pause in the cell cycle. Based on these studies, we hypothesize that B[a]P should be a more potent mutagen in HPV-immortalized cells, because these cells do not pause in proliferation long enough to adequately repair DNA following B[a]P exposure. Although our in vitro results are consistent with this hypothesis, our goal is to test this hypothesis in vivo. However, work in this field has been stymied by the lack of a suitable animal model of HPV-dependent neoplasia. During the past two years, we have developed an innovative transgenic mouse model of cervical cancer, in which the mice express the HPV16 E6 and E7 oncoproteins in the cervical epithelial, and we are now ready to test our hypotheses in vivo. In SpecifLVALic Aim 1 we test the hypothesis that B[a]P treatment should increase tumor formation in HPV-immortalized cervix compared to normal cervix, and examine the tumorigenic phenotype of the cells in nude mice, in soft agar, and in microinvasion assays. In Specific Aim 2 we hypothesize that B[a]P treatment should increase tumor formation in HPV-immortalized cervix compared to normal cervix, and examine the tumorigenic phenotype of the cells in nude mice, in soft agar, and in microinvasion assays. In Specific Aim 3 we examine the hypothesis that in vivo B[a]P treatment should differentially increase DNA mutations in HPV-immortalized cells, and that the increased mutation rate should be correlated with reduced p53 levels. We examine the effects of B[a]P treatment on p53 level, DNA adduct formation, and mutation at the H-ras and K-ras loci. The ultimate aim of these studies is use our HPV16 E6/7 cervical neoplasia mice to provide new understanding regarding the role of environmental carcinogens (polycyclic aromatic hydrocarbons) in the genesis of cervical cancer. Use of our novel transgenic model provides an innovative approach for addressing these questions.LVAL* l X  T fpRVr<PREVENTING INITIATION OF SMOKING BY CHILDRENINTERVENTION TO PREVENT ONSET OF SMOKING IN CHILDHOODIMAGING OF SEROTONERGIC AND CHOLINERGIC MARKERS IN SMOKERSCIGARETTE SMOKING AND COLORECTAL CANCER RISKEXPOSURE OF INFANTS IN THE WIC PROGRAM TO THEIR MOTHER'S TOBACCO SMOKEREPRODUCTIVE AND HORMONAL RISK FACTORS FOR ADENOMYOSISCOTININE MEASURES AS A TOOL IN COUNSELING PREGNANT WOMEN TO STOP SMOKINGENVIRONMENTAL FACTORS AND INFLAMMATORY BOWEL DISEASEVOUCHER-BASED INCENTIVES TO TREAT PREGNANT SMOKERSDES ASSOC CCA OF VAGINAL/CERVIX--COLLABORATIVE STUDIESTHE INFLUENCE OF HEALTH CONFIDANTES ON SMOKING AND ENVIRONMENTAL TOBACCO SMOKE EXPOSURE IN PREGNANCY AND POSTPARTUMVIRTUAL PRACTICUM FOR COUNSELING TOBACCO CESSATION IN PREGNANCYBREAST AND PROSTATE CANCER AND HORMONE-RELATED GENE VARIANTSPHARMACOGENETICS OF DRUG AND CARCINOGEN METABOLISMCHARACTERIZING NICOTINE WITHDRAWAL AND CRAVING AND EXAMING THEIR UTILITY AS PREDICTORS OF RELAPSE IN PREGNANT AND RECENTLY POSTPARTUM CEGARETTE SMOKERSOXIDATIVE STRESS, HORMONES, AND WOMEN'S HEALTHSMOKING CESSATION FOR PREGNANT SUBSTANCE-DEPENDENT WOMENPARTNERSHIP FOR SMOKE-FREE FAMILIES PROGRAMEFFECTS OF TOBACCO-INDUCED MEDIATORS IN DEVELOPING LUNGA CHEMOPREVENTION TRIAL TO STUDY THE EFFECTS OF HIGH TEA CONSUMPTION ON SMOKING-RELATED OXIDATIVE STRESSINSULIN RESISTANCE AND ADENOMAS OF THE COLORECTUMINNOVATION TO PREVENT POST-PARTUM RELAPSEBPDE SENSITIVITY AT 9P21 AND BLADDER CANCER RISKA ROLE FOR VISITING NURSES IN PREVENTING POSTPARTUM RELAPSESTAYING SMOKE-FREE: A ROLE FOR VISITING NURSES IN PREVENTIING POSTPARTUM RELAPSEEFFICACY OF MOTIVATIONAL ENHANCEMENT AND PHYSIOLOGIC FOR PRENATAL SMOKING CESSATIONCOMPETENCE SKILLS AND SMOKING AMONG SUBGROUPS OF YOUTHNEW RISK ASSESSMENT/ INTERVENTION FOR PREGNANT WOMENMODIFIABLE RISK FACTORS FOR LYMPHEDEMA IN BREAST CANCER SURVIVORSEFFECTS OF BENZO[A]PYRENE IN TRANSGENIC MODEL OF CERVICAL CANCER   `6x= @`@ResearchTOBACCO EXPOSURE REDUCTIONHATSUKAMIDOROTHYUNIVERSITY OF MINNESOTAMINNEAPOLISMNNIDAP50, DA013333g+p.@F@L@c9/30/19999/29/20049/30/1999 to 9/29/20044/2005 h_TT,"@p@4ResearchV@ UHARTIGANPHYLLISCHILDREN'S HOSPITAL AND HEALTH CENTERSAN DIEGOCASFFNot Given@f@ Fn@ L@c10/1/1998Not Given10/1/1998 to?4/2005}rKB88,"!@@Researchn@ UHALEYKATHLEENBRIGHAM AND WOMEN'S HOSPITALBOSTONMANHLBIK08, HL067910 @eBiology and CancerR@ L@c9/1/20018/31/20069/1/2001 to 8/31/20064/2005zsogI?88," 1@@Research@ UHAKIMIMANUNIVERSITY OF ARIZONAAZCDMRPPR023104@dBiology and Cancer@ L&@c200220052002 to 20054/2005}qg`\\E?88,"` @@Researchb@ UHAFFNERSTEVENUNIVERSITY OF TEXAS HEALTH SCIENCES CENTER AT SAN ANTONIOSAN ANTONIOTXNCIR01, CA087823a+p.Biology and CancerDiscovery 1b Evaluation 1bz@Z8/20/20017/31/20058/20/2001 to 7/31/20054/2005@8   IA88,"@G@ResearchR@UHAASJENNIFERUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP9IT-0192_+p.@ F@ L@Z7/1/20006/30/20027/1/2000 to 6/30/20024/2005sH>88,"@@Research`@UGUJIANUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNCIR03, CA110928]+p.t@ Fl@ L@Z9/1/20048/31/20069/1/2004 to 8/31/20064/2005~zqB<88," 1@@Researchv@UGRONERJUDITHCHILDREN'S HOSPITALCOLUMBUSOHSFFNot Given\+p.T@ Fl@L@Z200220042002 to 20044/2005{pkg]H@88,"@@@Research@UGRONERJUDITHCHILDREN'S HOSPITALCOLUMBUSOHRWJF40678X[+p.j@ F@Lb@Z10/1/200012/31/200310/1/2000 to 12/31/20034/2005xqkg]H@88,"@@Research@UGROFFJANETUNIVERSITY OF TEXAS HEALTH SCIENCES CENTERHOUSTONTXRWJF40674~@WT@F@LX@Z10/1/20009/30/200410/1/2000 to 9/30/20044/2005{rF?88,"O@`@Researchl@UGRIFFINKENNETHWEILL MEDICAL COLLEGE OF CORNELL UNIVERSITYNEW YORKNYNCIR03, CA096467X+p.@F@L@K9/1/20028/31/20059/1/2002 to 8/31/20054/2005wJA88,"q@ @Researchh@UGREGORYCINDYBEHAVIORAL RESEARCH, INC.ALBUQUERQUENMNIDAR43, DA016045 @W@F@L@K6/1/20031/31/20046/1/2003 to 1/31/20044/2005ztpcHA88,"@@Research@UROSSINGMARYFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWACDMRPBC010602@6t@Fp@L@K200120042001 to 20044/2005|xoGA88,"LVALfThis study proposes a randomized controlled trial to test the addictive effects of fetal ultrasound and motivational enhancement to best practice counseling for prenatal smoking cessation in low-income women. Biochemical validation of smoking will be measured at baseline, 34 weeks gestation, and six weeks postpartum.Drug use is common among pregnant women, yet only an estimated 32% to 42% of prenatal care providers routinely ask prenatal patients about their use of drugs. Prenatal visits afford a unique opportunity for providers to educate women about prevention, and to detect, drug use during pregnancy. To facilitate efficient use of provider resources, we have developed a computerized interactive survey interview (CASI), the Pregnancy Information Program (PIP) that has been well received in multiple ethnic/racial pregnant populations, and more importantly, shown to evoke more honest responses regarding drug use and other socially stigmatized behaviors that impact birth outcomes. The program will be updated, to integrate current diagnostic standards and new information about motivational interventions, to expand domains of use to clinicians, and to exploit computer advancements including audio and video. For this Phase I project, we propose to develop a commercial quality CD ROM prototype of the entire instrument, with revised scoring and reporting, ethnic/racial sensitivity, redesigned input screens, and motivational feedback customized to the respondent's readiness to change. Phase II funds will allow extensive validation studies of the revised instrument's ability to promote behavior change from the initial to the third trimester of pregnancy.LVAL+p.YContemporary school-based smoking prevention programs that combine refusal skills training with techniques to enhance general personal and social competence can be highly effective in reducing adolescent smoking. While etiology research has shown that social resistance skills are important in keeping young people away from smoking, little work has focused on how social competence (e.g., assertiveness, communication skills) and personal competence (e.g., cognitive and behavioral self-management skills) are protective in terms of youth smoking. The etiological mechanisms remain particularly unclear among youth in high-risk settings. Furthermore, national survey data show that prevalence rates for adolescent smoking differ according to ethnicity, gender, and geographic location. Thus it is important to determine if competence-based etiological models can account for the initiation and escalation of adolescent smoking among different subgroups of adolescents. A primary goal of the proposed research is to develop, test, and refine several etiologic models that focus on the role of social and personal competence skills in adolescent cigarette smoking, and to examine these models among two longitudinal samples of middle school students: a largely white, suburban sample and a predominantly minority, inner-city sample. This goal will be accomplished through secondary analysis of untreated control students who participated in one of two school-based drug abuse prevention trials. The proposed research aims to elucidate how competence skills influence the initiation and escalation of cigarette smoking during the critical middle-school years. For example, mediational analyses will examine the roles of affective self-regulation and perceived social benefits of smoking as factors that explain how poor competence leads to youth smoking; and moderational analyses will examine whether good competence skills buffer the effects of other salient risk factors for tobacco use. The hypothesized models will be cross-validated LVAL among subgroups of the two longitudinal samples including by ethnicity and gender. Because different etiologic factors may contribute to varying levels of cigarette smoking, prediction of experimental versus heavy smoking will be investigated among subgroups of students. Several multivariate statistical techniques will be used including multiple linear and logistic regression, structural equation modeling, and latent growth modeling. The long-term goals are to improve our knowledge regarding the development of tobacco use among youth of different backgrounds, and to ultimately refine and improve smoking prevention programs for diverse youth populations.XLVAL F rAGE Adult DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Buproprion RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN Pregnancy Postpartum Partner/Spouse MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse COMMUNITY Health Care Provider ECONOMICS Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumADDICTION Relapse COMMUNITY Health Care Provider ECONOMICS Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PostpartumAGE Child Fetus/Prenatal COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumLVAL+p.To refine and pilot an intervention incorporated into home health visits to new mothers who quit smoking during pregnancy, to prevent relapse to smoking and quickly intervene with mothers who resume smoking within 6 months after delivery. Research Design: Quasi-experimental with non-concurrent, non-randomized samples. The smoking relapse rate of the intervention group will be compared with baseline relapse rate of a natural history sample established prior to the intervention. Study Population: Women who quit smoking during pregnancy, and who remain smoke free for at lest 7 days prior to delivery. The population will be enrolled at the Ohio State University Hospital Post-Partum Service. Intervention (if appropriate): The intervention has four components over time, and is based on cognitive-behavioral theory. The components occur at the following times: at the postpartum recruitment contact (Component 1), first home visiting Nurse contact within 1 week of delivery, (Component 2), within 1 month of delivery, by home visit or telephone call (Component 3), and within 3 months after delivery by home visit or by telephone call (Component 4). Home visits or phone calls will be determined by the usual Home Visiting Nurse criteria -- if mother/infant dyad warrants home visits 3 or 4, then intervention will occur at that visit; if they don t require home visits, then intervention will occur by phone from the Home Health Nurse. Outcome Measures (If cessation or reduction, how defined): Maintenance of smoke-free status will be measured at 3 and 6 months post intervention. Maintenance is defined as self-report of not resuming smoking since quit date during pregnancy. Participants who report not resuming smoking will have their saliva tested for cotinine to confirm recent smoke-free status. The other main outcome measure is the cost of the intervention, to be measured by personnel time in successfully completing the intervention.&LVAL+p.6Purpose: To refine and pilot an intervention incorporated into home health visits to new mothers who quit smoking during pregnancy, to prevent relapse to smoking and quickly intervene with mothers who resume smoking within 6 months after delivery. Research Design: Quasi-experimental with non-concurrent, non-randomized samples. The smoking relapse rate of the intervention group will be compared with baseline relapse rate of a natural history sample established prior to the intervention. A Role for Visiting Nurses in Preventing Postpartum Relapse Study Population: Women who quit smoking during pregnancy, and who remain smoke free for at lest 7 days prior to delivery. The population will be enrolled at the Ohio State University Hospital Post-Partum Service. Intervention (if appropriate): The intervention has four components over time, and is based on cognitive-behavioral theory. The components occur at the following times: at the postpartum recruitment contact (Component 1), first home visiting Nurse contact within 1 week of delivery, (Component 2), within 1 month of delivery, by home visit or telephone call (Component 3), and within 3 months after delivery by home visit or by telephone call (Component 4). Home visits or phone calls will be determined by the usual Home Visiting Nurse criteria -- if mother/infant dyad warrants home visits 3 or 4, then intervention will occur at that visit; if they don't require home visits, then intervention will occur by phone from the Home Health Nurse. Outcome Measures (If cessation or reduction, how defined): Maintenance of smoke-free status will be measured at 3 and 6 months post intervention. Maintenance is defined as self-report of not resuming smoking since quit date during pregnancy. Participants who report not resuming smoking will have their saliva tested for cotinine to confirm recent smoke-free status. The other main outcome measure is the cost of the intervention, to be measured by personnel time in successfully completing the intervention. LVAL+p.^This proposed study will build upon the extensive epidemiologic database and specimen repository derived from an ongoing bladder cancer study entitled "Genetic Susceptibility to Bladder Cancer: A Molecular Epidemiologic Approach" (R01 CA74880, applicant: Xifeng Wu). This parent grant includes a multidisciplinary group of researchers using a molecular epidemiologic approach in a case-control study with the common goal of identifying inter-individual differences in susceptibility to tobacco-induced bladder carcinogenesis. Recent evidence has suggested that sensitivity to benzo[(]pyrene diol epoxide (BPDE), the metabolic product of benzo[(]pyrene (B[(]P), a constituent of tobacco smoke, is a constitutional phenomenon and is a risk factor for several tobacco-related cancers such as lung, head and neck, and bladder cancers. There is a need for further elucidation of the molecular targets of BPDE. Loss of chromosome 9p material is one of the most frequent genomic alterations in bladder cancer. In addition, alterations of 9p21 and p16 are frequently seen in the epithelial cells of chronic smokers. The specific aims of the proposed study are: 1). To determine whether BPDE-induced chromosome aberrations on 9p21 are more common in the cultured peripheral blood lymphocyte (PBLs) of 200 bladder cancer patients than those of 200 controls matched to the cases on sex, age ( 5 years) and ethnicity. Our working hypothesis is that 9p21 BPDE sensitivity may reflect inherited genetic susceptibility of a specific locus to carcinogens in tobacco smoking, that chromosome 9p21 may be the molecular target of carcinogens contained in tobacco smoke, and that individuals with such aberrations are at an increased risk for bladder cancer. 2). To determine frequency of spontaneous 9p21 aberrations occur in cells in urine from 50 cases of bladder cancer patients and whether there is a correlation between level of 9p21 aberrations in lymphocytes and corresponding urine samples. Our working hypothesis is that aberrations in PBLs accur LVAL ately reflect changes in the target tissue. 3). To assess the associations between the genetic marker and age, sex, cigarette smoking status, and nutrition status by integrating epidemiologic data with the molecular cytogenetic data. These data are being routinely collected in the parent grant. The proposed susceptibility marker may be useful as biomarkers to identify high-risk populations that could then be targeted for intensive smoking-cessation programs and could be enrolled into chemoprevention trials.LVAL+p.`Cigarette smoking is the leading cause of preventable morbidity and mortality for women in the United States. Pregnancy is a pivotal event of young adulthood for many women. This is confirmed by the observation that women are much more likely to quit smoking around the time of pregnancy than at any other. Unfortunately, women who quit during pregnancy have extremely high rates of relapse during the months immediately following delivery. There are several reasons why post-partum women are at high risk of relapse including: decreased motivation, depression, stress, sleep deprivation, and concerns about the loss of weight gained during pregnancy. Conversely, there are many reasons to think that the perinatal period is an important opportunity to influence a woman s lifetime smoking behavior including: parenthood and a growing sense of responsibility, more frequent contact with the health care system, and less severe nicotine cravings because a woman has already been smoke-free for several months. Behavioral intervention during pregnancy has not been associated with an increase in post-partum tobacco abstinence. Recent studies suggest that bupropion is effective therapy for smoking cessation. There are several reasons that bupropion may be an effective therapy to prevent relapse post-partum, including mood stabilization, decreased fatigue, decreased tobacco craving, and increased weight loss. To date, there is no literature examining the use of bupropion or other anti-depressants as part of an intervention to prevent post-partum relapse. In the proposed IDEA Award program, we will conduct a series of exploratory studies to examine the feasibility of incorporating bupropion into an innovative treatment program to prevent post-partum smoking relapse. The results of this work will be used to design a randomized controlled clinical trial to prevent post-partum smoking relapse that will incorporate pharmacotherapy in addition to a behavioral intervention. The proposed project will address the follow8LVALHing Specific Aims: (1) To define an appropriate target population for a pharmacologic intervention to prevent post-partum relapse to tobacco use, we will quantify the amount of bupropion in breastmilk of 20 women who are lactating but not breastfeeding. The results of this Aim will determine whether it is safe to administer bupropion to post-partum women who are still breastfeeding or contemplating breastfeeding or whether it is necessary to wait until a woman is no longer breastfeeding. (2) To inventory, categorize and evaluate behavioral smoking cessation and relapse prevention interventions for pregnant and post-partum women. (3) To obtain explicit information about how best to target a multi-faceted intervention to prevent post-partum smoking relapse, we will conduct interviews with a multi-ethnic sample of 50 women. Each woman will be surveyed twice: once during pregnancy and the then again 6  8 weeks postpartum. These surveys will examine: (a) The prevalence and duration of breastfeeding among a multi-ethnic sample of women who have quit smoking during pregnancy. (b) A woman s perception of her risk of relapse. (c) The acceptability of a pharmacologic intervention during the post-partum period. (d) The acceptability of a variety of behavioral interventions (e.g., content, format, intensity) for these women and their household members. Pregnancy is an important opportunity in young adulthood to reduce a woman s lifetime exposure to tobacco. If women can be converted from pregnancy-quitters to long-term quitters this would significantly reduce their lifetime exposure to tobacco as well as reducing the exposure of their children to environmental tobacco smoke. The results of the proposed research will lead directly to an innovative, multi-faceted, targeted intervention to prevent post-partum relapse in a multi-ethnic cohort of women.LVAL+p.bThere is considerable evidence that insulin and/or insulin-like growth factors (IGFs) can increase risk of colorectal neoplasia. Epidemiologic risk factors for colorectal neoplasia are similar to those for insulin resistance syndromes, and prospective studies have shown both diabetes and higher levels of IGF-1 to be associated with colorectal cancer risk. No previous studies have included direct measures of insulin resistance, nor have any included complete ascertainment of colorectal neoplasia by direct examination of the entire colorectum. This study will assess the relationship between insulin resistance and colorectal neoplasia by taking advantage of a unique opportunity to examine a multi-ethnic cohort on whom prior measures of insulin sensitivity have been made. The Insulin Resistance and Atherosclerosis Study (IRAS) is a cohort study supported by the National Heart Lung and Blood Institute. IRAS examined 1628 people of average age 55 in 1991-1994 for atherosclerosis risk factors. The cohort, assembled in four clinical centers (Alamosa, Co., Los Angeles, Oakland, and San Antonio) was established to be multi-ethnic (34 percent Hispanic, 28 percent African American, and 38 percent non-Hispanic white), bi-gender, and varied in diabetes risk. In 1998-1999 over 85 percent of the surviving cohort was re-examined. Both of the examinations have included measures of self-reported risk factors for atherosclerosis (diet, physical activity, tobacco use, family history) as well as anthropometry and, most importantly, oral glucose tolerance testing and frequently-sampled intravenous glucose tolerance tests (FSIGT). The FSIGT is a sensitive and specific measure of insulin resistance. All surviving cohort members (estimated 1518) will be invited to have a screening colonoscopy. Feasibility data indicate that 1000 will agree to have a colonoscopic exam, among whom we estimate 240 (range 206- 274) will have adenomas. Mucosal biopsies will be taken from the cecum and rectum of all subjects, and all adenomas will b"LVAL2e removed and examined for histologic features, Ki-ras mutations, proliferation, and apoptosis. Serum samples will be assayed for insulin, IGF-1, IGFBP1, and IGFBP3 levels for all cohort members at both the time of colonoscopy, as well as at the time of two earlier examinations (1991-4 and 1998-9) using stored serum samples. This study offers the advantage of the availability of prospective measures of glucose tolerance, insulin resistance, measurements of most colorectal neoplasia risk factors, and the availability of stored blood samples from a multi-ethnic and bi- gender cohort. Complete colorectal visualization of this entire cohort will enable unbiased estimates of colorectal neoplasia risk related to these factors. This study therefore offers a time-efficient and a cost-efficient method to test the hypothesis that colorectal neoplasia risk is increased substantially by factors related to insulin resistance, and to examine the biologic mechanisms whereby that risk is increased.LVAL AGE Adult Older Adult DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use WOMEN Hormones Hormone Replacement TherapyDISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Hormones MISCELLANEOUS Weight Gain/ExerciseLOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Cancer Mechanisms ECONOMICS Cost of Intervention/Prevention LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Nicotine Replacement Therapy PSYCHOLOGICAL Other Psychological RESEARCH1 Animal Studies RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Nicotine WOMEN Parent/MotherCOMMUNITY General Partnerships Health Care Provider LOCATION National PREVENTION/TREATMENT Quitline Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumAGE Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use WOMEN Pregnancy Parent/MotherDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesZ LVALj Objective/Hypothesis: The primary hypothesis is that regular tea consumption, of either black or green tea, by subjects with chronic obstructive lung disease (COPD) and 25 or more pack-years of smoking history will induce (1) an increase in plasma catechins and (2) a decrease in the DNA and lipid oxidative stress status as measured by 8-hydroxy-deoxyguanosine (8-OHdG), 8-F2 Isoprostanes (8-epi-PGF2), Malondealdehyde (MDA), ethanes, and Nitric Oxide (NO). LVAL Maternal smoking, particularly during pregnancy, is a risk factor for early childhood wheezing and/or asthma. Little is known about the mechanisms that link maternal smoking and abnormal lung development and/or function. However, smoking is known to alter cytokine expression in smokers, and several mediators with proinflammatory actions in adults function as growth factors during development. We propose that the link between maternal smoking and postnatal lung dysfunction is an alteration in the expression of mediators affecting pulmonary organogenesis. Our central hypothesis is that maternal tobacco smoking increases the expression of proinflammatory mediators that act as growth factors in the lung during gestation. Although many mediators are probably affected by maternal smoking, we will focus on one proinflammatory chemokine, eotaxin, as a paradigm for effects of maternal smoking on lung development. While eotaxin is associated with adult asthma, the function of eotaxin in the developing lung is not known. We will use eotaxin as a candidate mediator to test our central hypothesis, addressing three specific aims. The first aim is to confirm that eotaxin and its receptor, CCR3, are expressed in specific temporal and anatomic patterns within the developing lung, and that these patterns differ between lungs exposed to tobacco smoke byproducts and lungs without such exposure. The second aim is to determine whether activation of transcription factors is the mechanism of the increased expression of eotaxin, a chemokine that has been shown to be transcriptionally regulated, in lungs exposed to tobacco byproducts. The third aim is to investigate whether maternal smoking alters lung growth and/or differentiation through an eotaxin-responsive mechanism.R LVALb In 1998, a trilateral partnership among three large not-for-profit healthcare systems was formed in 1998 to promote smoking cessation services for women during the preconceptional, prenatal, and post-partum periods. The intervention is a standardized program consisting of tobacco treatment resources, training, office support, and referrals to the California Smokers Quitline. The Smoke-Free Families mini-grant funds are being used to produce a technical assistance manual with sample materials and recommendations for other health care systems that want to implement similar activities.LVAL+p.hThe purpose of this TTURC proposal is to examine tobacco exposure reduction methods to treat smokers who have been resistant to conventional methods of intervention or who have not been previously targeted. Reduction of tobacco use will be examined both as a potential transitional goal toward cessation, or as an endpoint for refractory smokers. The center grant proposal involves five research projects and three cores. The five projects vary from animal studies to human clinical trials. Dr. Paul Pentel will use animal models of nicotine self- administration to study the use of high dose nicotine (doses producing plasma nicotine concentrations exceeding those experienced by smokers) as a treatment strategy. The combined use of high dose nicotine and the antagonist mecamylamine, and the effects of high dose nicotine on tobacco carcinogen activation will also be evaluated. Dr. Dorothy Hatsukami will conduct short-term, tightly-controlled human behavioral pharmacology studies that examine different methods of reducing toxic exposure to tobacco. These methods include nicotine replacement products and behavioral methods to reduce the amount of cigarettes smoked. Drs. Larry An, Harry Lando and Anne Joseph will examine exposure reduction treatment methods in targeted populations unable or unwilling to become abstinent or who are on the trajectory towards nicotine dependence. The targeted populations to be examined will vary across the life span including mothers who smoke, adolescent experimental smokers and medically compromised smokers. Research on each population will have unique as well as common methods for assessment and treatment with the primary outcome measures being the reduction in tobacco use and toxicity, the degree to which these treatments facilitate abstinence, and the cost- effectiveness of these approaches. The Core facilities will include Biomarker, Administrative, and Design and Analysis Cores. Drs. Stephen Hecht and Sharon Murphy will be co-directors of the Biomarker Core. This Core will p LVAL rovide measurement of biomarkers for tobacco, nicotine and carcinogen exposure and the capability to phenotype individuals according to their metabolism of nicotine. The Design and Analysis Core will be responsible for data input, monitoring and statistical analyses and for performing the economic and policy analyses for each of the clinical studies. The Administrative Core will be responsible for the smooth and coordinated operation of the studies, the training and career development of students and faculty, and the dissemination of information. In summary, the goal of this highly interdisciplinary center grant is to systematically examine tobacco exposure reduction methods that will decrease mortality and morbidity associated with tobacco use.hLVALxPregnant drug-dependent smokers are a subgroup of substance abusers at especially high risk for health complications. Due to documented deleterious effects of drug use and smoking on both mother and neonate, effective smoking cessation interventions are warranted. The proposed research will systematically examine smoking topography, attitudes, and behaviors among substance-dependent women. The effectiveness of smoking cessation Motivational Enhancement Therapy (MET) in increasing quit rates and reducing smoking throughout pregnancy will be evaluated. The Transtheoretical Model will be incorporated as a conceptual framework for describing and predicting the change process involved in pregnancy smoking cessation. Since MET can be individually tailored to stage of change for smoking, this alternative strategy for pregnancy smoking cessation will be compared with standard care (practitioner advice) in a two-group experimental design. Data will be collected on factors related to quitting prenatal tobacco use, as well as on the interactions that occur with illicit substance use. Participants will be primarily lower socioeconomic status (SES) and minority (African-American) pregnant women from urban areas, seeking drug treatment as well as prenatal care at a comprehensive, specialized program. The specific aims of the research are: 1) To characterize smoking patterns and nicotine dependence in a sample of pregnant, treatment seeking drug-dependent women; 2) To establish pretreatment stages of change for quitting smoking during this pregnancy and their relationship to other smoking and drug use variables; 3) To determine the clinical effectiveness of a specialized intervention (MET) for increasing smoking cessation rates and impacting stage movement; and 4) To identify factors associated with quitting smoking during pregnancy. 3 h D : }]G@@ResearchX@UHYLANDANDREWROSWELL PARK CANCER INSTITUTE CORP.BUFFALONYNCIR03, CA097780.z+p.t@F@L2@w7/1/20026/30/20057/1/2002 to 6/30/20054/2005zvmH@88,"g@p@4Research@UHOVELLMELBOURNESAN DIEGO STATE UNIVERSITYSAN DIEGOCASFFNot Given4@rT@FT@Lr@wNot GivenNot GivenUncertain4/2005{vrgK@88,"8@ @Researchl@UHOLTVICTORIAFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWANICHDR01, HD0403982x+p.t@FT@Ll@w3/1/20021/31/20073/1/2002 to 1/31/20074/2005}ypH>88,"g@p@4Research@UHOFFMANDOUGLASDARTMOUTH COLLEGEHANOVERNHSFFNot GivenZ@rT@FT@Lv@wNot GivenNot GivenUncertain4/2005zojf]JA88,"~@]@Researchh@UHIGUCHILESLIECHILDREN'S HOSPITALBOSTONMANIDDKK08, DK064256@rt@FR@LF@c9/15/20037/31/20089/15/2003 to 7/31/20084/2005qjf^IA88,"`@@Researchd@UHIGGINSSTEPHENUNIVERSITY OF VERMONT STATE AGRICULTURAL COLLEGEBURLINGTONVTNIDAR01, DA014028u+p.T@Fl@L@n4/30/20013/31/20064/30/2001 to 3/31/20064/2005|JA88,"@@ y@Researchl@UHERBSTARTHURUNIVERSITY OF CHICAGOCHICAGOILNCIU01, CA062912ts+p.t@F@L@n9/30/19937/31/20039/30/1993 to 7/31/20034/2005qlh_H@88,"@@Research@UHENNRIKUSDEBORAHUNIVERSITY OF MINNESOTA SCHOOL OF PUBLIC HEALTHMINNEAPOLISMNRWJF51798@rT@FR@Lt@n9/1/20048/31/20069/1/2004 to 8/31/20064/2005}LC88,"g@p@4Research~@UHENDERSONJOSEPHDARTMOUTH MEDICAL SCHOOLHANOVERNHRWJFNot Given~@oX@FR@L@nNot GivenNot GivenUncertain4/2005xrneKC88," r@ (@Researchx@UHENDERSONBRIANUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANCIU01, CA098758fp+p.t@F@L@n6/5/20035/31/20076/5/2003 to 5/31/20074/2005~zmJC88,"@Y@Researchd@UHEINDAVIDUNIVERSITY OF LOUISVILLELOUISVILLEKYNCIR01, CA034627@oBiology and CancerDiscovery 1b Evaluation 1b@9/1/19896/30/20089/1/1989 to 6/30/20084/2005tok_E>88,"@@Research.@UHEILSARAHUNIVERSITY OF VERMONT BURLINGTONVTRWJF51801@o AddictionR@L@n9/1/20048/31/20069/1/2004 to 8/31/20064/2005zsmi]E>88,"g@p@4Research\@UHEDIGERMARYNot GivenNot GivenNot GivenNICHDZ01, HD008762d)k+p.Biology and Cancerl@L8@cNot GivenNot GivenUncertain4/2005~oh]RGA88,"@p@4Researchp@ UHAUGNANCY UNIVERSITY OF MARYLAND AT BALTIMORE COUNTYBALTIMOREMDNIDAF31, DA005980@iT@Fp@L@c9/14/2000Not Given9/14/2000 to ?4/2005}rF>88,"LVAL+p.lAs part of aerobic life, we oxidize a large pool of biomolecules to obtain chemical energy. During this process, several intermediates are formed; some are chemically unstable and are referred to as free radicals (FR). FR tend to react quickly with their surrounding biological environment; depending on the nature of the molecule attacked, different reactions can occur, i.e., lipid peroxidation, protein oxidation, or DNA oxidation products. As aerobic life has evolved, antioxidant defense systems against FR have developed. An imbalance between production of FR (oxidants) and defense systems against them (antioxidants) results in oxidative stress. This can lead to irreversible biochemical changes, with subsequent tissue damage and disease. Oxygen free radicals have been implicated in spontaneous abortions, infertility in men and women, reduced birth weight, aging and chronic disease processes, such as cardiovascular disease and cancer. While the mechanisms that relate oxidative stress with female fertility are not completely understood, recent animal and human studies have suggested that oxidative stress might have an important role in follicular growth, development of endometriosis, and regulation of angiogenesis in the endometrium. Micronutrient antioxidants, hormones and enzymatic antioxidants are able to neutralize oxygen free radicals and inhibit oxidation and, thereby, potentially reduce the risk of infertility. Numerous methods have been developed to measured lipid peroxidation products and lipid peroxidation damage in tissue, cell and body fluids. Markers of lipid peroxidation can be measured directly or by measuring any substance involved in the reaction process. Since radical species are the actual agents to injured cells, their direct measurement would be preferable for clinical diagnosis. However, radical species disappear rapidly yielding stable primary and secondary lipid peroxidation products. Although, lipid peroxidation has been related to many health outcomes, there still is large disaLVALmgreement between investigators on which method should be use to evaluate circulating levels of lipid peroxidation making it difficult to synthesize research findings. Recently, it has been demonstrated that plasma lipoprotein levels fluctuate during the course of the menstrual cycle. This cyclic fluctuation in lipoproteins has been associated with fluctuation in plasma antioxidant concentrations . Hormones, lipoproteins, a-tocopherol and carotenoids were measured simultaneously for 2-3 consecutive days in each phase of the menstrual cycle for 12 healthy women. Carotenoids were lowest during menses, with concentrations of lutein/zeaxanthin and its metabolite, anhydrolutein, higher at all three phases (early follicular, late follicular and luteal) than during menses. Plasma -carotene peaked in the late follicular phase, whereas plasma lycopene, phytoene, phytofluene and retinol concentrations peaked in the luteal phase. Circulating levels of estradiol and progesterone have also been shown to fluctuate during the follicular and luteal phase of the menstrual cycle in ovulatory women. Estrogen is a powerful antioxidant that affects oxidative stress and homocysteine levels in women. However, little is known about the relation between oxidative stress, estrogen levels and their influence on outcomes such as likelihood of conception or spontaneous abortions. Prior to evaluating this relation, it is critical to have standardized measurements of oxidative stress and to know they vary with hormone levels. The primary goals of this study are to better understand the intricate relationship between hormone levels and oxidative stress during the menstrual cycle (i.e. estrogen, progesterone, LH, etc). More specifically, we would study: (i) the intra-cycle variation of oxidative stress; (ii) the relation between hormone levels and oxidative stress during the menstrual cycle in pre-menopausal women; and (iii) influence of external factors such as cigarette smoking, alcohol consumption, and exercise on oxidative stress XLVALhand hormone levels. Study Design: A prospective longitudinal cohort study of 250 women will be conducted in a university or medical center setting. Screening tests will be performed on participating individuals to exclude women who are pregnant and or have asymptomatic chlamydia. The recruitment period will last up to one full calendar year to account for seasonal variability. The participants will be followed for 2 menstrual cycles from day 1 of the menstrual cycle to the end, taking blood and urine samples every 4 days. At each of these visits data will be collected on diet, physical activity and other environmental exposures. Urine and blood samples will be evaluated for levels of F2 isoprostanes and subproducts, conjugate dianes, fasting glucose, total cholesterol and subproducts, and serum antioxidant vitamins. Public Heath Significance: This study will elucidate the best methods to estimate oxidative stress in premenopausal women and to better understand the relation between oxidative stress and menstrual function. This study will also provide basic reference data for future studies examining the role of oxidative stress in fertility, risk of spontaneous abortion, and other pregnancy related outcomes.LVAL8 ^ADDICTION Cessation Relapse ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumDISEASE/BIOLOGY Cancer LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Hormones Hormone Replacement Therapy MISCELLANEOUS Weight Gain/ExerciseCOMMUNITY Health Care Provider LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Postpartum Partner/Spouse MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionCOMMUNITY Health Care Provider LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials TOBACCO Non-Specified Tobacco Use WOMEN PregnancyDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies STUDY POPULATION African American Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesADDICTION Withdrawal Relapse ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research STUDY POPULATION Caucasian TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumLVAL0 (This project employs an educational model, the Virtual Practicum (a model that has sound basis in learning theory and has been shown to be easily used by and acceptable to health professionals) to use technologies that permit its dissemination via CD-ROM, via broadband Internet, or via CD-ROM + dial-up Internet. This project includes an evaluation to measure the impact in eight to ten communities in New England and Minnesota of the educational program on prenatal and primary care practices' implementation of the Clinical Practice Guideline recommendations. The Agency for Healthcare Research and Quality (AHRQ), American College of Obstetrics and Gynecology (ACOG), Association for Maternal and Child Health Care Providers (AMCHCP), and the American College of Preventive Medicine are providing in-kind support to review program design and help to disseminate this program to students and practicing clinicians. Initial dissemination will be followed by expanded efforts to develop marketing relationships with relevant professional organizations representing the core audience.We hypothesize that breast cancer frequency will be higher in tobacco smokers with very slow NAT2 acetylator/rapid NAT1 acetylator genotypes, and in individuals who eat deep-fried, well-done meats.The proposed study has two aims. The primary aim is to rigorously characterize the incidence, magnitude and time course of nicotine withdrawal and craving during the antepartum period and the first 6 months postpartum. The secondary aim is to examine whether nicotine withdrawal and craving predict relapse or changes in smoking frequency in this population.LVAL+p.qThis application is one of four submitted concurrently to allow large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism. These proposals combine the resources of six large prospective cohorts from the American Cancer Society (CPS-II study), Harvard University (Harvard Cohort Studies), the IARC (EPIC study), and the Universities of Hawaii and Southern California (Multiethnic cohort); in addition, two NCI intramural cohorts (PLCO and ATBC studies) will participate. The proposed study is unique in having prospective plasma samples, genetic material, anthropometric measurements, and extensive questionnaire data on diet, physical activity, exogenous hormone use, smoking, and other lifestyle factors from over 790,000 men and women. Because of the scope and collaborative nature of this consortium, simultaneous investigation of genetic predisposition and lifestyle factors is possible, to clarify the inter-relationships between, and the relative importance of, genetic and hormonal risk factors. Specifically, this study will define SNPs and haplotypes in steroid hormone metabolizing genes, genes in the IGF pathway, and related receptor proteins. These candidate genes will be resequenced in 96 cases of advanced breast cancer, and 96 cases of advanced prostate cancer, chosen from the European, African, Latino, Japanese, and Hawaiian-origin ethnic groups. Haplotype tag SNPs will be selected after genotyping of a larger number of SNPs from a collection of 768 samples from the multigenerational CEPH (Centre d'Etude du Polymorphisme Humain) pedigrees and human diversity collection, by the Whitehead Institute for Genome Research and CEPH, and will rapidly be made publicly available. The interaction of genetic variants with hormonal, lifestyle and anthropometric factors known to be associated with breast and prostate cancer will be examined. In a subset of studies, the association of these variants with markers of brean LVAL~ st and prostate cancer risk (i.e. plasma steroid hormone levels and IGF-1 levels) will be investigated. Projects developed within the Cohort Consortium will foster continuing interactions between the genomic and epidemiologic research communities and help integrate the rapid advances in genomic research into large-scale epidemiologic studies. The ultimate goal is to provide the foundation for reducing the public health burden of these cancers.LVAL \The purpose of this study was to assess whether a behavioral counseling program can decrease a mother's smoking and reduce infant exposure to ETS at home.This project gave pregnant smokers feedback on their urinary cotinine levels, reflecting their overall exposuress to nicotine and other harmful contituents of tobacco smoke.The research proposal is a prospective cohort study to examine the association of environmental factors and the two types of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Specific aims 2 through 4 will examine the association of specific dietary factors, smoking, and exogenous estrogen therapy and teh development of CD or UC.The proposed study will pilot an intervention to mobilize social support for quitting smoking and decreasing exposure to environmental tobacco smoke (ETS) during pregnancy and the postpartum period. Correlational studies have suggested that social support is related to cessation, but interventions to mobilize support, usually among partners or coworkers, have met with little success. This study will target the pregnant woman's health confidante as a source of support. Pregnancy may be a time when the woman is more open to persuasion and the health confidante may be particularly influential since she is already a source of advice. LVAL+p.tThe data which are collected and analyzed in the Registry provide the sole comprehensive series of cases of DES-associated clear cell adenocarcinoma (CCA) for comparative and collaborative study. The specific aims are to update and enhance the data on currently accessioned cases of CCA; to maximize ascertainment of newly diagnosed cases; to add to the Registry women who have been treated but not previously accessioned, by collaborating with the DES Cancer Network (DCN - Collaborative Project A); to monitor the development of other mullcrian-derived primary cancers, such as cancer of the fallopian tube and endometrium to detect early any increase in occurrence; to serve as a source of information for treating physicians and patients; and to serve as a collaborating resource with NCI for other approved investigators who will rely on the Registry participants and/or data for research implementation. Once an expanded cohort has been established by adding all identify new cases of documented CCA, a questionnaire (approved by the Project Steering Committee) will be applied to all study participants. This questionnaire will incorporate new data for Registry as well as for the collaborating investigations. Additional topics to be investigated include extension of the age-incidence curve of CCA to older patients, updating the survival curve and investigation of factors affecting survival and recurrence including the complications of therapy. A collaborative trial through NCI will be sought to develop an improved regimen for recurrence therapy. Two additional collaborative projects are proposed. The first is a case- control study undertaken to assess risk factors for CCA among women exposed to DES, in particular, to assess the relation of oral contraceptive use, age at menarche, height, obesity, and season of birth. In addition, epidemiologic factors that may promote recurrence of CCA, in particular, the relation of height, obesity, cigarette smoking, and estrogen replacement therapy will be investigated, with ` LVALp emphasis on factors that may contribute to the development of late (greater than 8 years) recurrences. The second study will be to determine if human papillomavinus and p53 tumor suppressor gene alterations, currently linked to the natural history of non-clear cell carcinoma of the vagina and cervix, and associated with CCA.LVAL+p.vMaternal cigarette smoking is the most important preventable cause of poor pregnancy outcomes in the U.S. and a leading cause of pediatric morbidity and mortality. Approximately 30% of women in the U.S. are cigarette smokers when they become pregnant and the prevalence is greater still among less educated women. About 80% of these women smoke throughout their pregnancy. Even among those who quit, 25-30% relapse during the pregnancy and 70% within 6 months of delivery. Efficacious interventions have been developed for promoting smoking cessation during pregnancy, but cessation rates are low, especially among low-income and highly nicotine-dependent women (< 15%). Efficacious interventions to prevent relapse during the postpartum period remain to be developed. We propose to examine the efficacy of a voucher-based incentive program for promoting smoking cessation and preventing relapse during pregnancy and postpartum. This incentive program is efficacious in promoting and sustaining abstinence in cocaine and other illicit drug abusers. A recent trial suggested that vouchers may be efficacious for increasing smoking cessation among pregnant smokers. The proposed studies are designed to rigorously evaluate the efficacy of voucher-based incentives for promoting cessation and extend them to preventing relapse among pregnant women and new mothers. Two randomized trials are proposed. First, we will examine the efficacy of vouchers delivered contingent on smoking abstinence for increasing cessation rates during pregnancy and postpartum among 226 women who are still smoking at their first prenatal visit. Second, we will examine the efficacy of contingent vouchers for preventing relapse during pregnancy and postpartum among 96 women who have already quit smoking prior to the first prenatal visit. Women for both trials will be recruited from Vermont's largest obstetrical practice, which serves a large population of uninsured, low-income women. In both trials, the voucher-based intervention will be adde LVAL d to brief smoking advice delivered by physicians/midwives and compared against control conditions wherein brief advice is combined with vouchers delivered independent of smoking status. Overall, the proposed studies have the potential to contribute important new scientific and practical information on effective treatment for one of our nation's most daunting drug abuse problems.FLVAL  z^ADDICTION Withdrawal DISEASE/BIOLOGY Other Disease/Biology LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Child ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Parent/Mother MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionDISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Menstral Cycle Hormones MISCELLANEOUS Weight Gain/ExerciseCOMMUNITY Health Care Provider LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionLVAL+p.yAdenomyosis, also known as internal endometriosis, is the progressive invasion of endometrial glands and stroma from the uterine endometrial lining down into the myometrium, the inner muscle wall of the uterus. This condition is diagnosed in over 150,000 women in the U.S. annually, can be associated with severe pelvic and menstrual pain and excessive bleeding, and almost always requires hysterectomy for definitive treatment. Clinical observations have raised the hypothesis that multiparity and excessive estrogen may increase disease risk; however, there is little epidemiologic data to confirm or deny this hypothesis. Consequently, we propose to conduct a case-control study to investigate the relationships between adenomyosis and reproductive and hormonally-related exposures, including polymorphisms in genes involved in steroid hormone synthesis and metabolism. The study will be conducted at Group Health Cooperative of Puget Sound (GHC), a health maintenance organization serving approximately 500,000 people in western Washington State. Cases will be 500 female GHC enrollees 18-59 years of age diagnosed with adenomyosis between March 1, 2001 and Feb. 28, 2006. Two control groups will be used: 1) 500 women undergoing hysterectomy during the study period who are found to have a condition other than adenomyosis, endometriosis, or leiomyoma, frequency matched to cases on age, and 2) 500 women randomly selected from computerized enrollment files, also frequency matched to cases on age. Data will be obtained from cases and controls by in-person interview, anthropometric measurement and collection of a blood sample for DNA analysis; and these data will be linked with the GHC computerized pharmacy database. Subjects will be interviewed regarding factors known or suspected to be associated with uterine trauma or steroid hormone levels (including reproductive, contraceptive, and menstrual histories; obesity; exercise; diet; cigarette smoking) as well as other potential risk factors for adenomyosis. Blood samples  LVAL will be analyzed for two polymorphic genes coding enzymes active in estrogen metabolism (CYP17, COMT). Analyses comparing cases and controls with respect to reproductive and hormonal risk factors and their interactions with genetic polymorphisms will be conducted to address the specific aims.LVAL+p.{Colorectal cancer is not currently on the list of diseases identified by the Surgeon General as being caused by cigarette smoking. Although the research literature has shown that cigarette smoking is associated with non-cancerous adenomenous polyps in the colon, the relationship to colorectal carcinoma is less definitive. Recent literature that includes studies with extended follow-up times reveal associations between smoking and colorectal cancer only after this long latent period; however, numerous other studies fail to find an association. The purpose of this study is to provide additional data to address the controversy in the literature about the relationship between cigarette smoking and colorectal cancer. Given that there are an estimated 135,400 new colorectal cancer cases each year and that colorectal cancer is very treatable when caught in an early stage, further knowledge about the etiologic role that cigarette smoking plays in the development of colorectal cancer may have population-wide implications for identifying persons at higher risk for disease who may be better candidates for colorectal cancer screening and for targeting smoking cessation services to high risk populations. This proposal outlines a plan for ascertaining the cancer incidence and mortality status of 9,343 (3,965 males and 5,738 females) persons who were seen at Roswell Park Cancer Institute between 1957 and 1965, who completed a detailed epidemiologic survey that included questions about their lifetime tobacco use and other lifestyle factors including their diet and their alcohol consumption, and who also received a non-cancer diagnosis. Cancer incidence and mortality status will be obtained by linkages with the New York State Cancer Registry, the New York State Vital Statistics Department, the Social Security Death Index, and the National Death Index. Hazard ratios for colorectal cancer incidence and mortality will be compared across varying levels of lifetime cigarette consumption to assess associations between cigar LVAL ette consumption and colorectal cancer while controlling for potential confounders in multivariate Cox proportionate hazard model analyses. This dataset provides a unique resource to readily address this question since detailed epidemiologic data have already been collected on a large population and straightforward mechanisms exist to ascertain cancer and mortality status of this cohort. The primary hypothesis tested is that the risk for colorectal cancer incidence and mortality will be highest among persons with the largest lifetime consumption of cigarettes, particularly in those with more than 35 years of exposure, even after controlling for potential confounders.LVAL+p.}Prospective studies have shown that smokers whoa re vulnerable to depression are less successful at quitting and have a higher relapse rate than euthymic smokers. Seventy-five percent of smokers with a history of depression develop depression during smoking cessation, even if they are not depressed prior to quitting Nicotine, a principal component of cigarette smoke, has been suggested to have rapid-acting antidepressant effects in non-smokers. These effects of nicotine are mediated through its initial actions on a central nicotinic acetylcholine receptor (nAChR) and the downstream enhancement of serotonin (5-HT) neurotransmission. In addition, a unknown byproduct of tobacco smoke is a potent monoamine oxidase inhibitor which further enhances 5-HT function. Since cigarette smoke has potent effectors on 5-HT, synaptic markers for this transmitter may by differentially regulated in smokers versus non-smokers. Also, the emergence of depression during smoking cessation in vulnerable smokers may be a consequence of adaptive changes in 5-HT markers. In vivo imaging using radiotracers regionally selective for the 5-HT transporter and 5-HT2A receptor have demonstrated reduced numbers of these pre- and post-synaptic 5-HT markers in living depressed patients. We hypothesize that heavy cigarette smoking will induce adaptive changes in 5-HT markers in living depressed patients. We demonstrated reduced numbers of these pre- and postsynaptic 5-HT markers in living depressed patients. We hypothesize that heavy cigarette smoking will induce adaptive changes in 5-HT transporter and 5-HT2A receptor number in smokers, and that these 5-HT markers will down-regulate during smoking cessation in the subset of smokers vulnerable to depression. To test this hypothesis, we propose the following specific aims: 1) to determine the effects of smoking on 5-HT transporters and 5-HT2A receptors in euthymic smokers and non-smokers between genders 2) to determine if 5- HT-transporters and 5-HT2A receptors undergo adaptive changes duri LVAL ng smoking cessation in smokers that develop depression; and 3) to develop a radiotracer for in vivo imaging of the nAChR, so that its potential role in nicotine dependence and depression may be studied in living smokers. The results from these studies will determine if there is a difference in pre- and postsynaptic 5-HT in smokers and if adaptations in key 5-HT markers during withdrawal are correlated with the emergence of depressive symptoms in vulnerable smokers. Furthermore, these studies may elucidate a neurochemical marker which will identify a subgroup of smokers who would benefit from antidepressant treatment during smoking cessation.F  q S 3 n@@Researchh@JULIANOLAURAAMERICAN UNIVERSITYWASHINGTON DCNIDAR03, DA018709,p. AddictionT@ @9/15/20047/31/20059/15/2004 to 7/31/20054/2005tnj]HA88,"g@p@4Research@JORENBYDOUGLASUNIVERSITY OF WISCONSIN AT MADISONMADISON WINCIP50, CA084724 @|@@ V@Not GivenNot GivenUncertain4/2005|xnJA88,"@@@Researchh@JONESHENDREEJOHNS HOPKINS UNIVERSITYBALTIMOREMDNIDAR01, DA012403,p.@@@6/1/19996/30/20096/1/1999 to 6/30/20094/2005wqmbH?88," @@Research^@JONESCRAIGUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANIEHSP01, ES0095812+p.t@P@6@199920041999 to 20044/2005zviF?88,"`@Y@ResearchSPORE IN LUNG CANCERJOHNSONBRUCEDANA-FARBER CANCER INSTITUTEBOSTONMANCIP20, CA090578+p.t@@@9/19/20036/30/20089/19/2003 to 6/30/20084/2005|^WNN," }@`a@Researchp@JOHNSENLISAUNIVERSITY OF HAWAII AT MANOAHONOLULUHINCIK01, CA098753h+p.T@@@9/1/20038/31/20089/1/2003 to 8/31/20084/2005ytpfGA88,"G@+@Researchh@JHAPRABHATST. MICHAEL'S HOSPITAL TORONTOON, CANADAFICR01, TW005991+p.j@n@@7/1/20026/30/20077/1/2002 to 6/30/20074/2005yth_F=88,"@Q@}@Researchp@JAMNERLARRYUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECANIDAP50, DA013332r+p.@@@9/15/20028/31/20039/15/2002 to 8/31/20034/2005}wskG@88,"z@1@Researchn@JAMNERLARRYUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECACTRDRP6PT-3003H!+p.@F@@1/1/199812/31/20011/1/1998 to 12/31/20014/2005wskG@88,"@ @Researchh@JACOBSONSANDRAWAYNE STATE UNIVERSITYDETROITMINIAAAU01, AA015035:+p.@FR@@9/30/20037/31/20069/30/2003 to 7/31/20064/2005vokbJB88,"n@!@ResearchX@UJACKSONCHRISTINEUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILLCHAPEL HILL NCNICHDR01, HD036514R+p.@F@N@9/30/19978/31/20019/30/1997 to 8/31/20014/2005yLA88,"@{@Researchj@UJACKSONCHRISTINEPACIFIC INSTITUTE FOR RESEARCH AND EVALUATIONCALVERTON MDNCIR01, CA106316+p.@F@LN@4/1/20043/31/20094/1/2004 to 3/31/20094/2005{LA88,"@@Researcht@UINNISROBERTYALE UNIVERSITYNEW HAVENCTNIDAP50, DA013334|+p.Biology and CancerP@L@w200020042000 to 20044/2005|mgcXG?88,"LVAL+p.Initiation of cigarette smoking is prevalent among children of current nonsmokers and it significantly increases the odds of progression to habitual smoking by late adolescence. Prevention programs are needed that are appropriate for children, designed to be implemented at home by parents, and focused on anti-smoking socialization as a tool for preventing initiation of smoking. Aim I: Design and produce an intervention that enables parents who are current nonsmokers to engage in anti-smoking socialization with their 8 year old children. The intervention will apply communication, modeling, rule setting, monitoring, guided experience, and other socialization practices to modify children's perceptions of the prevalence of smoking, the acceptability of smoking, the accessibility of cigarettes, and the personal and social consequences of smoking. Aim II: Conduct a two-group, randomized controlled trial to test the intervention. Sample: A volunteer sample of 760 male and female children from single or two-parent households who will be 8 years old and in the pre-initiation stage of smoking at baseline will enroll with a nonsmoking mother, step-mother, or other female guardian. Design: The study will follow children from ages 8 through 11 (grades 3 through 6) to measure the effects of anti-smoking socialization on smoking-related outcomes. Eligible participants who complete the baseline survey will be randomly assigned to the treatment (core program plus two annual boosters) or alternative control condition. Data on core program utilization will be obtained via telephone interviews with parents 1 month post-treatment. Data on program effects will be obtained via telephone interviews with children 12, 24, and 36 months post-baseline. Primary hypothesis: Children of current non-smokers exposed to a program of anti-smoking socialization beginning at age 8 will be significantly less likely to initiate smoking than controls by age 11. Secondary hypothesis: Among children who remain abstinent to final follow-up, th LVAL ose exposed to the intervention will have significantly lower susceptibility to smoking than controls. Primary analysis: Survival analysis will test the effects of antismoking socialization on initiation of smoking. Secondary analysis: A proportional odds model will test the effects of anti-smoking socialization on susceptibility to smoking among children abstinent at final follow-up. LVAL d6ADDICTION Initiation Maintenance AGE Child Young Adult DISEASE/BIOLOGY Other Disease/Biology LOCATION National PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology LOCATION International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Initiation AGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Counter-Marketing PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother Partner/Spouse MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesADDICTION Initiation AGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Counter-Marketing PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother Partner/Spouse MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesLVAL+p.Children whose parents smoke cigarettes are at high risk for early initiation of smoking, and those who initiate smoking during childhood are at high risk for subsequent addiction to tobacco. Few programs are available that aim to prevent initiation of cigarette smoking during childhood, and none is available that aims to prevent early initiation by engaging parents who smoke in altering children's smoking-specific socialization. This project tests an innovative program to change smoking-specific socialization of children in households where parents smoke cigarettes. This continuation application requests one additional year of support for this research. Aim l: Develop an anti-smoking socialization program for parents who smoke. Through communication, modeling, rule setting, monitoring, and other socialization practices, parents influence their children's perceptions of the prevalence of smoking, the acceptability of smoking, the accessibility of cigarettes, and many other aspects of smoking. The premise of this research is that all parents, including parents who smoke, can engage in anti-smoking socialization, and that anti-smoking socialization can lower children's risk of smoking. Barriers to anti-smoking socialization include the misperception by parents that initiation of smoking is uncommon during childhood and the strong belief among parents who smoke that they lack credibility as sources of anti-smoking socialization. The program developed for this project addresses these and other barriers to involvement by parents who smoke in preventing their children from smoking. Aim 2: Using a 2-group randomized design, test the effects of anti-smoking socialization on children's susceptibility to and initiation of cigarette smoking. Sample: To date, this study has enrolled 813 mother-child pairs, where mothers were biological mothers, stepmothers, or other adult female guardians, from single- or 2-parent households, who reported smoking at baseline and whose children were in the 3rd grade at baseline. D LVAL esign: Eligible participants who completed the baseline survey were randomly assigned to the treatment (n = 408) or control (n = 405) condition. Data on program implementation and impact have been obtained from mothers using telephone interviews administered 1 month post-treatment. Interviews administered to children 12, 24, and 36 months post-baseline will be used to assess program effects. Hypotheses: Children exposed to a program of anti-smoking socialization by mothers who smoke will be less susceptible to and report less initiation of smoking than unexposed peers. Analyses: A latent transition model will test the effects of anti-smoking socialization on children's susceptibility to cigarette smoking. Survival analysis will test the effects of anti-smoking socialization on children's initiation of smoking.LVAL<$|  h  v " ^ J8&f$Discovery 1c Development 3 Delivery 2 Partnerships 3 Evaluation 1aDiscovery 1a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 3 Development 2 Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Partnerships 2 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 4 Evaluation 1aDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Evaluation 1aDiscovery 1a Development 4 Delivery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Development 4 Delivery 3 Evaluation 1aDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1c Discovery 2a Discovery 2b Development 1 Development 3 Delivery 2 Delivery 4 Partnerships 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Development 2 Evaluation 1aDiscovery 1a Discovery 1b Discovery 1c Development 2 Evaluation 1aDiscovery 1a Discovery 1b Discovery 1c Evaluation 1a Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Evaluation 1aDiscovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Discovery 2a Discovery 3 Development 1 Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1c Discovery 2a Development 1 Development 3 Delivery 2 Evaluation 1a Evaluation 1cLVAL+p.Sudden infant death syndrome (SIDS) is a leading cause of infant mortality with incidence of about 0.8/1000 live births in the U.S. and considerably higher rates in at-risk populations, including Native Americans and the Cape Coloured (mixed ancestry) community in South Africa. A recent study has implicated prenatal alcohol exposure as an important risk factor for SIDS that warrants further investigation. It has been hypothesized that medullary serotonergic network deficits may be responsible, in part, for some SIDS deaths. For the past 5 years, we have been conducting a prospective, longitudinal study on the effects of prenatal alcohol exposure in the Cape Coloured community in collaboration with researchers from the University of Cape Town School of Medicine. This research has demonstrated our ability to recruit mothers from this community; obtain valid assessments of FAS, prenatal alcohol exposure, maternal alcoholism, smoking and depression, and socioenvironmental and medical risk; and perform state-of-the-art infant neurobehavioral assessments with Cape Town infants. We have found an exceptionally high rate of alcohol abuse and dependence among pregnant women in this population and of FAS among their infants. The high incidence of both SIDS and FAS in this large metropolitan area, the readily accessible maternal heavy drinking population, and our established, productive research collaboration make Cape Town uniquely appropriate as a Comprehensive Clinical Site. The proposed cooperative agreement would expand our ongoing collaboration to include researchers in pathology and obstetrics. The aims are (1) to conduct an assessment of the incidence of SIDS and stillbirths in Cape Town, using contemporary diagnostic criteria and procedures, including neuropathological examinations of SIDS victims and controls; (2) to test the hypothesis that prenatal binge drinking increases the risk of SIDS and to evaluate that risk in relation to risks associated with prenatal maternal smoking, preterm birth, infant gLVALender and sleeping position, seasonal variation, parental education, and maternal depression; (3) to test the hypothesis that certain moderator variables-- years of drinking, severity of maternal alcohol abuse and dependence, lower maternal weight and prenatal smoking, and the absence of an ADH2*2 allelo will increase the risk of SIDS in alcohol-exposed infants; and (4) to examine whether heavily alcohol-exposed neonates will exhibit alterations in autonomic nervous system behaviors similar to those described in SIDS victims, which are known to be regulated by the medullary serotonergic system, including arousal, cardiorespiratory reflex integration, and sleep/wake patterns. This research has the potential to improve our understanding of neurophysiological mechanisms involved in SIDS and to contribute to developing interventions for mothers and infants whose behaviors indicate that they are at risk for this adverse outcome.LVAL#*R  2 R 0 t $VX:f@,SMOKING, ESTROGEN METABOLITES, AND COGNITIVE FUNCTIONEARLY TOBACCO ABSTINENCE IN HIGH RISK SMOKERSACUTE NICOTINE ABSTINENCE IN ADOLESCENTSPSYCHOSOCIAL FACTORS IN ADOLESCENT AND YOUNG ADULT SMOKINGNICOTINE'S EFFECTS ON OTHER DRUGS OF ABUSETOBACCO ABSTINENCE-INDUCED COGNITIVE DECREMENTSPOPULATION WIDE SMOKING CESSATION/PREVENTION PROGRAMNICOTINE REPLACEMENT AND OXIDATIVE STRESS IN PREGNANCYTOBACCO CESSATION PROJECT FOR NATIVE AMERICAN YOUTHMATERNAL CAFFEINE USE AND PREGNANCY OUTCOMENALTREXONE AUGMENTATION OF NICOTINE PATCH THERAPYGENE ENVIRONMENT INTERACTION IN HEAD AND NECK CANCERNICOTINE REGULATION OF THE NORADRENERGIC SYSTEMSMOKING INTERVENTIONS FOR LOW INCOME PREGNANT WOMENTOBACCO CONTROL POLICIES AND YOUTH SMOKING TRANSITIONSEFFECT OF CIGARETTE SMOKING ON PULMONARY METASTASISMAPPING THE NATURAL HISTORY OF SMOKING AND SMOKING CESSATION AMONG PREGNANT WOMEN--SUPPLEMENTAL SUPPORTSERUM COTININE LEVELS AND REPRODUCTIVE OUTCOMESASCERTAINMENT OF ENVIRONMENTAL TOBACCO EXPOSURE IN PREGNANCYEFFECT OF NICOTINE ON FETAL HEMATOPOIETIC STEM CELL MIGRATIONPREVENTION OF TOBACCO USE IN RURAL ETHNIC AMERICAN YOUTHLUNG HEALTH STUDY--LONG TERM FOLLOW-UPTHE TRANSITION TO NICOTINE DEPENDENCE IN ADOLESCENCESUBSTANCE DEPENDENCE/ABUSE IN THE U.S. POPULATIONEPIDEMIOLOGICAL/FAMILIAL ASPECTS OF DRUG USEMECHANISMS UNDERLYING FETAL GROWTH RESTRICTION CAUSED BY MATERNAL EXPOSURE TO COMPOUNDS FOUND IN CIGARETTE SMOKEDISENTANGLING PHARMACOLOGICAL AND EXPECTANCY EFFECTSPILOT: NICOTINE AND EXERCISE RELATED ENERGY EXPENDITURE IN WOMENTOBACCO USE IN OPIOID AGONIST TREATED PREGNANT WOMENCOMMUNITY BASED PREVENTION/INTERVENTION PROJECTCULTURAL PROFICIENT SMOKING AND WEIGHT CONTROL TREATMENTSTRENGTHENING MONITORING OF INDIAN TOBACCO MORTALITYVESTORS OF VULNERABILITY IN TEEN AND YOUNG ADULT SMOKINGADOLESCENT SUSCEPTIBILITY TO TOBACCO: A PANEL ANALYSISFAS, SIDS AND STILLBIRTHS IN CAPE TOWN, SOUTH AFRICALVAL+p.The major objective of this project is to model the influences of situational/contextual and trait factors on the smoking behavior of adolescents in everyday settings as well as to study the contribution of individual differences in nicotine-dependence susceptibility to patterns of adolescent cigarette smoking. Over 90% of smokers begin smoking before the age of 18, yet very little is known concerning what it is that makes adolescents vulnerable to the initiation of smoking and susceptible to tobacco dependence. For example, there is evidence that nicotine reduces aggressive behavior in animal models, but little is known regarding nicotine's effects on anger and aggression in humans. Interestingly, whether the putative anger-palliative effects of nicotine may represent a particularly salient mechanism reinforcing tobacco use among high-hostile individuals has not been studied. The goals of this project are directly related to the TRDRP's research priority to fund work that will further our understanding of the factors that contribute to the development, maintenance, and relapse of cigarette smoking. The proposal is also responsive to the goal of the IRP in its emphasis on youth. One hundred and eighty adolescents entering the 9th grade (40- never-smokers, 70-experimental and 70- regular smokers) will be signaled to fill out diaries an average of twice an hour, indicating their location and activities, the social context (such as presence of other people), whether they smoked, and consumption of food and other substances. They also will be asked to report on their moods and their degree of hunger and urge to smoke. Analysis of salivary cotinine, collected at the end of each monitoring day, will be used to validate diary reports of cigarette smoking. The self-monitoring will be done for a period of two school and two weekend days. This 4-day sequence will be repeated four times over two years: i) fall 1998; ii) spring 1999; iii) fall 1999; and iv) spring 2000. Analyses will model the stimuli and cueLVALs associated with smoking behavior and urges, as well as to examine the effects of cigarette smoking on the subjective, behavioral, and psychophysiological responses of adolescents in natural settings. We also will determine the role of trait characteristics (e.g., hostility) and gender in the above relationships. In addition, heart rate activity will be recorded continuously to determine its role as a discriminative stimulus for smoking as well as to provide an index of the physiological response to cigarette smoking. The results of this project will provide important information related to the role of trait characteristics and situational factors in the susceptibility to initiation and maintenance of smoking in adolescents. This Project, with its focus on modeling factors contributing to adolescent smoking patterns at the level of the individual (made possible by the large number of observations obtained on each subject), is designed to provide data that will be useful in explicating relationships observed in the large-scale epidemiological study (Project 2) which is designed to evaluate the interactions between trait characteristics and biopsychosocial stress indicators in determining who becomes an adolescent smoker. Together, this Project and Project 2 will aid us in designing more effective primary prevention (Project 1), as well as intervention programs that are targeted specifically for youth. Both Projects 2 and 3 focus on the importance of innate or trait factors in determining the susceptibility to tobacco-dependence. This theme is carried forward in Project 4 which is designed to address the issue of innate susceptibility to nicotine at the cellular and receptor level. Thus taken as a whole, the proposed IRP will provide new and important information related to: what makes adolescents susceptible to initiation of tobacco use and how to better account for individual differences in vulnerability (Projects 2, 3); the behavioral and psychological effects of nicotine that makes it attractive  LVALto adolescents (Project 3); the role of genetic (Project 4) and biosocial factors (Project 2) in susceptibility to nicotine dependence; and the development and implementation of effective prevention programs for adolescent populations (Projects 1, 5).LVAL+p.The major objective of this project is to delineate psychosocial, behavioral, contextual, and biological vectors of vulnerability to smoking initiation and maintenance in adolescents and young adults. Psychological dispositions such as impulsivity, hostility, and negative affectivity are associated with elevated rates of tobacco use, but little is known about how these traits influence smoking initiation during the adolescent and young adult periods or how they interact with family and peer contexts, situational influences, nicotine reactivity, and genetic makeup to enhance or impede the progression toward regular smoking. A related aim is to identify developmental trajectories for stages of smoking at the two highest risk ages for tobacco use onset: early adolescence and young adulthood. In Study l, 120 14-year old adolescents and 120 college freshmen (40 at each age in each of 3 smoking stages: never, experimental, regular) will be signaled twice each hour to complete diaries that include information about their location, activities, social context, mood, stress levels, consummatory behaviors, and urges to eat and smoke. Self-reports of cigarette use will be validated by analyses of salivary cotinine. This 4-day ambulatory recording sequence will be repeated twice each year for 4 consecutive years to provide information about developmental trajectories. We will also assess the role of gender and specific trait and behavioral characteristics in these relationships. Study 2 will examine the influence of estrogen levels on these relationships by comparing cue-reactivity and nicotine effects during the luteal vs. the follicular menstrual phases. Secondary goals include (a) examination of the moderating role of situation-behavior phenotypes on associations between specific candidate genes and tobacco use, and (b) comparisons of smoking phenotypes across the adolescent, young adult, and middle adult years. Consistent with the transdisciplinary approach, this project focuses simultaneously on several discib LVALr plinary levels of analysis (environmental, psychosocial, behavioral, neurobiological) using a shared conceptual framework. interactive links among the projects in this Center include the use of the behavior-context profiles or phenotypes identified in this project to help guide brain imaging studies- and elucidate the brain activation patterns that emerge from Project 2, and to inform the targeted antismoking strategies to be developed in Project 4.`LVAL" d`RzDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Child DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National RESEARCH Human Studies TOBACCO Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesECONOMICS Socio-Economic Status PSYCHOLOGICAL Cultural Factors RESEARCH Human Studies Clinical Research STUDY POPULATION African American TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Weight Gain/ExerciseDISEASE/BIOLOGY Other Disease/Biology ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural International PREVENTION/TREATMENT Interview/Focus Group RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Smokeless MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance AGE Child Young Adult Adult DISEASE/BIOLOGY Mechanisms Other Disease/Biology EDUCATION LEVEL High School College and Above EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle Hormones MISCELLANEOUS Sex/Gender DifferencesLVALv D  :  z r>`ZTPBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsEpidemiology and National Surveillance Awareness Risk Perception and CommunicationsBiology and Cancer Epidemiology and National Surveillance Global IssuesAddiction Epidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Addiction Interventions for Prevention and TreatmentAddiction Epidemiology and National SurveillanceBiology and Cancer Interventions for Prevention and TreatmentInterventions for Prevention and TreatmentBiology and Cancer Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and Treatment Community and Policy InterventionsEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National Surveillance Community and Policy InterventionsEpidemiology and National Surveillance Community and Policy InterventionsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Interventions for Prevention and TreatmentAddiction Epidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceBiology and Cancer Addiction Epidemiology and National SurveillanceBiology and Cancer Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National Surveillance Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentEpidemiology and National Surveillance Global IssuesBiology and Cancer Addiction Epidemiology and National SurveillanceLVAL+p.The project will aim to strengthen and expand India's Sample Registration System (SRS) to obtain reliable estimates of cause-specific mortality from tobacco smoking and chewing in various parts of India by age, gender and socioeconomic group. The SRS is the primary system for collection of Indian mortality data. It is a large demographic survey to provide annual estimates of birth, death and other fertility and mortality indicators at the national and state level. The SRS consists of 6,671 sample units (4,436 rural and 2,235 urban) covering 1.1 million households and a population of about six million. Sample units are selected from the preceding census frame to be representative of the population. The SRS sampling frame will be soon expanded to over 8,000 units, covering over seven million people. Specific goals of the project are: implementing a validated verbal autopsy instrument in the SRS so as to obtain reliable information on the cause of death (for tobacco as well as numerous other causes); determining past tobacco use for adult deaths and current use from living controls within the dead person's household (so as to provide retrospective case-control data annually); specific addition of questions to the baseline questionnaire of the SRS on tobacco and other risk factors, so as to turn the SRS into a uniquely large, reliable and representative prospective study; and follow-up of deaths by cause of a 1998 Special Fertility and Mortality Survey that obtained data on smoking from about two million adults within the current SRS sampling frame (including one million males of whom 40% would smoke). Pilot studies would begin in Andhra Pradesh, Karnataka, and Tamil Nadu, home to 191 million people and about one in six of the SRS units. The project will build sustained capacity within India's flagship mortality surveillance system to monitor a heterogeneous and growing tobacco epidemic, evaluate the effectiveness of control policies and create reliable information for individuals and policy makers. Speci,LVAL<fic steps will be taken to translate the research findings for state and national policy makers.LVAL+p.Lisa Johnsen, Ph.D. is a post-doctoral fellow at Northwestern University Medical School (NUMS) who is interested in the relationships between smoking, obesity, weight concerns, and exercise in ethnic minorities. Dr. Johnsen's immediate goals are to obtain knowledge, skills, and experiences in community-based smoking cessation, nutrition, weight concerns, and physical activity interventions for African Americans (A-A's). Her long-term career goal is to develop culturally proficient interventions to decrease rates of smoking, obesity, and physical inactivity in ethnic minorities. The career development plan consists of coursework, conferences/seminars, and mentorship in cultural proficiency; grant writing; cancer; methodology/statistics; smoking; nutrition; and exercise, with the overall goal of preparing her to become a culturally proficient health disparities researcher in cancer prevention and control. The primary mentor is Marian Fitzgibbon, Ph.D. (psychologist), who specializes in behavioral risk reduction interventions in minorities at NUMS. The co-mentors are Jasjit Ahluwalia, M.D., M.P.H. (physician/public health expert) who has extensive research and clinical experience with smoking cessation in A-A's; Ken Resnicow, Ph.D. (psychologist) who has expertise in conducting smoking and dietary interventions with A-A's using Motivational Interviewing; Elaine Prewitt, Dr.P.H., R.D. (doctor of public health) who specializes in dietary assessments and interventions for A-A's; and James Rimmer, Ph.D. (exercise physiologist) who has expertise in exercise interventions with A-A's and obese individuals. Mentors will advise Dr. Johnsen in developing as an independent and culturally proficient health disparities researcher, in obtaining a faculty position, and in conducting the proposed study. The Psychiatry Department and Lurie Cancer Center are committed to the time and resources required to assure the success of Dr. Johnsen's development into an independent researcher. Research: During Phases 1 and 2, Dr. Jl LVAL| ohnsen will explore the feasibility (Aim 1) and estimate the effectiveness (Aim 2) of a community-based, culturally proficient smoking cessation and weight control treatment for weight concerned A-A female smokers. Additional aims include estimating the effectiveness of the intervention in increasing healthy eating and physical activity, and decreasing weight concerns (Aim3); and developing/adapting measures to be culturally proficient (Aim 4).LVAL+p.This application creates a Specialized Program in Research Excellence (SPORE) in Lung Cancer at Harvard University within the Dana Farber/Harvard Cancer Center. The Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer includes investigators from all Harvard-affiliated hospitals in Boston, Harvard Medical School, and the Harvard School of Public Health. This SPORE in Lung Cancer will build on the strengths of established ongoing investigation within the DF/HCC. Five major projects are supported: Project 1 will assess the impact of inherited susceptibility to adenocarcinoma of the lung in men and women and its interaction with exposures to tobacco smoke. Project 2 will analyze the dysregulation of C/EBP alpha in lung cancer, its downstream targets, and its potential impact on the outcome of lung cancer patients. Project 3 will apply array technology to the study of human lung cancer and its relationship to murine models. Project 4 will investigate the role of cdk2 inhibitors in vitro, in vivo, and apply these finding to human trials for patients with lung cancer. Project 4 will study the role of vascular endothelial growth factor receptor inhibitors and chemotherapy in vivo, and apply these finding to human trials for patients with lung cancer. These Projects are integrated by the establishment of 4 cores. These include 1) Tissue and Pathology Core, 2) Administration, Assessment and Planning Core, 3) Biostatistics Core, 4) Genomics Core. This SPORE application outlines a Developmental Projects Program that includes our plan for selection of new projects and includes seven submitted proposals that could be supported. The Career Developmental Award Program outlines the mechanism for the identification and support of talented young investigators in lung cancer. The Developmental Projects and Career Development Award Program will provide the focus for involvement of the community in planning and financial support of the DF/HCC Lung Cancer SPORE. The goal of the DF/HCC Lung Cancer SPORE is the translation LVALof biological and technological advances into clinically meaningful advances for patients with lung cancer and subjects at risk for lung cancer.LVAL+p.Asthma is the most common chronic disease in childhood, and prevalence, hospitalization and mortality are increasing. This increase is most commonly seen in non-white, poor, inner city children. Although the causes of this epidemic are not clearly understood, lack of access to medical care, indoor and outdoor pollutants, and indoor and outdoor antigens seem important. Recent small-scale community intervention to reduce exposure to dust mites and other antigens has been shown to result in clinical improvement. Further, research is needed to evaluate community based interventions which will control a variety of antigens and pollutants. Inner city, primarily minority, children with asthma are being identified through a school based mobile asthmatic clinic, the Breathmobile, which delivers high quality, continuous care to these children. Working with school nurses and community organizations and the 3 Breathmobile units, we propose a comprehensive community-based intervention aimed at reducing asthma triggers in the home. The major goal of this study is to determine whether a comprehensive environmental health education program, enhanced by least toxic integrated pest management for cockroach control, will result in reduction in concentrations of antigens in household dust and/or improvement in clinical status among these children. The study population will consist of 300 children with chronic persistent asthma randomly selected from the 3,000 asthmatics identified by the school-based Breathmobile program. Children will be randomized into three groups: (1) 100 children will continue to receive usual care from the Breathmobile; (2) 100 children will receive usual care plus a standardized antigen-reduction strategy (STARS), a community based, family oriented environmental health training program; and (3) 100 children children will receive usual Breathmobile care plus STARS, enhanced by professional pest control and home cleaning. Exposure to environmental asthma triggers in the home will be assessed by measLVALuring concentrations of dust mite antigen, and cockroach antigen, in house dust. Outcomes of interest include change in knowledge, change in concentration of antigen in house dust, school absence, clinical assessment of asthma severity, and medication use. Co-variates to be considered include exposure to environmental tobacco smoke, indoor and outdoor air pollutants, housing characteristics (such as molds, mildew, air conditioning) and demographics (such as family size, gender, ethnicity). In years 4 and 5 of the intervention, the community based infrastructure developed in years 1-3 to support the evaluation of the strategies for reducing exposure to environmental asthma triggers will be transferred to cooperating community groups and greatly expanded to provide household asthma audits, education, and intervention service at low cost upon referral from school nurses and the Breathmobile program. To evaluate efficacy, 200 asthmatic children will be randomized into 2 groups. One will receive usual care, the other, community intervention services.LVAL,p.Prenatal tobacco exposure is associated with a number of medical and developmental consequences including low birth weight and increased mortality. In fact, prenatal smoking may be more harmful to the developing fetus than illicit drugs such as opioids, cocaine and marijuana. One group of pregnant patients that is a greater risk for both tobacco smoking and additional adverse outcomes during pregnancy and the neonatal period is pregnant methadone treated women. In contrast to a general population of pregnant women, little is known about the smoking and quitting behavior of methadone treated pregnant women and how reduction of tobacco exposure may impact the incidence of neonatal abstinence syndrome (NAS) that occurs in 55-95% of methadone-exposed neonates. This becomes especially import to determine the role that tobacco plays in the prevalence and severity of NAS since tobacco exposure alone has been associated with withdrawal symptomatology that is similar to the NAS produced by opioid exposure. Using a 2 group randomized design (tobacco abstinent contingent behavioral incentives versus non-contingent incentives n = 64 per group; total 128 subjects), a study will be conducted to assess the effectiveness of tobacco abstinent contingency management for reducing prenatal tobacco use and the incidence and severity of NAS. Tobacco use (verified by carbon monoxide and/or urinary cotinine and self report of cigarettes smoked), illicit drug use, and other psychosocial outcomes will be examined at 1 and 3 month follow-ups and 6 weeks postpartum. Birth outcomes of presence and severity NAS and physical birth outcomes including but not limited to birth weight, estimated gestational age at delivery, length and head circumference will also be compared across groups. It is hypothesized that compared to the non-contingent incentive group, the tobacco abstinent contingent intervention group will result in less tobacco use and improved birth outcomes (i.e., reduced severity of and treatment for NAS and heavier birth4LVALD weights). This project will make substantial contributions to the understanding of tobacco use and cessation in pregnant women and the role tobacco has on the incidence and severity of NAS in methadone-maintained women.LVAL0 XAGE Child Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION African American Caucasian Hispanic TOBACCO Cigarette/Other Smoking Nicotine WOMEN Parent/Mother Partner/Spouse MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance AGE Child Young Adult DISEASE/BIOLOGY Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother Partner/Spouse MISCELLANEOUS Sex/Gender DifferencesADDICTION Withdrawal LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyLVAL&On average, smokers weigh less than nonsmokers, and most smokers gain 2-3 kg of weight in the first six months of a cessation attempt. Fear of weight gain is a significant barrier to cessation attempts, particularly among women who smoke as a weight control strategy. For all its clinical relevance, little is known about the metabolic mechanisms of post-cessation weight gain or strategies to prevent it, esp. in women. This study will utilize a human indirect calorimetry chamber to assess exercise-related energy expenditure in 20 pre-menopausal women who are regular smokers. Each will participate in a pre-cessation assessment of resting energy expenditure, response to 20 minutes of standardized light exercise, and recovery time from exercise. The entire sample will then quit smoking for 72 hours, half using a 21 mg patch, half without nicotine replacement, and repeat the calorimetry assessment. The results should indicate the degree to which nicotine replacement therapy can increase exercise-related energy expenditure and/or prolong metabolic recovery time. Providing women with an active intervention to address weight gain may increase the number of successful cessation attempts, and may aid those who relapse due to fear of weight gain.LVAL,p.Tobacco smoking is a major public health problem that remains the largest preventable cause of morbidity and mortality in the United States. A greater understanding of mechanisms underlying the rewarding effects of smoking may improve our understanding of smoking behavior, and ultimately lead to better prevention and treatment strategies. There is evidence to suggest that nicotine is the primary active ingredient necessary for maintaining smoking behavior. However, non-nicotine factors also appear to play an important role in the rewarding effects of smoking. Preliminary evidence suggests that smokers' expectancies for the effects of smoking may influence the actual effects experienced after smoking (e.g., craving reduction, negative affect reduction), independent of nicotine. However, more research is needed in this area, and across a wider range of possible smoking outcomes. The primary aim of the proposed project is to continue development of a laboratory model to evaluate the relative contributions of nicotine and drug expectancies in the subjective and behavioral effects of smoking. The proposed project will utilize a 2 X 2 factorial balanced placebo design methodology, which crosses nicotine dose (nicotine vs. placebo) and dosage instructional set (told nicotine vs. told placebo), to evaluate the independent and interactive effects of nicotine and instructional set (a purported indirect measure of expectancies) on smoking outcomes. This study will also investigate gender and self-reported expectancies for nicotine as potential moderators of reactions to nicotine and instructional set manipulations. Outcomes assessed will include self-reported urge to smoke, withdrawal, mood, and a measure of behavioral performance. The results are likely to advance current knowledge of the relative contributions of nicotine and expectancies in determining the immediate effects of smoking. If expectancies are shown to be important proximal determinants of smoking outcomes and smoking behavior, further development LVAL of novel nicotine dependence prevention and treatment strategies such as expectancy challenges may be warranted. o K ' uH&@!@Researchf@OCKENEJUDITHUNIVERSITY OF MASSACHUSETTS MEDICAL CENTERWORCESTERMANHLBIR01, HL051319,,p.T@@X@3/1/19968/31/20013/1/1996 to 8/31/20014/2005tH@88,"n@@Researchl@NONNEMAKERJAMESRESEARCH TRIANGLE INSTITUTERESEARCH TRIANGLE PARKNCNCIR03, CA101527(@@@P@5/7/20034/30/20055/7/2003 to 4/30/20054/2005hKD88," @G@Researchf@MURINSUSANUNIVERSITY OF CALIFORNIA AT DAVISDAVISCACTRDRP10IT-0264L,p.Biology and CancerR@@:7/1/20016/30/20027/1/2001 to 6/30/20024/2005|tpiF?88," f@`@Research@MURAMOTOMYRAUNIVERSITY OF ARIZONA COLLEGE OF PUBLIC HEALTHTUCSONAZRWJF48118@L@n@d@3/1/20032/28/20053/1/2003 to 2/28/20054/2005xHB88,"c@%@Research^@KHARRAZIMARTINSEQUOIA FOUNDATIONBERKELEYCACTRDRP6RT-0385,p.@ @@7/1/19979/30/20017/1/1997 to 9/30/20014/2005~tlh^JB88,"@G@Researchx@KHARRAZIMARTINSEQUOIA FOUNDATIONBERKELEYCACTRDRP8RT-0115,p.@ @@7/1/19996/30/20027/1/1999 to 6/30/20024/2005~tlh^JB88,"G@@@Researchz@KHALDOYANIDISOPHIALA JOLLA INSTITUTE FOR MOLECULAR MEDICINELA JOLLACACTRDRP11IT-0020v,p.Biology and CancerR@@7/1/200212/31/20037/1/2002 to 12/31/20034/2005 yNF88,"g@p@4Researchp@KELLY KATHLEENCOLORADO STATE UNIVERSITYFORT COLLINSCONIDAP50, DA007074X,p.@ @D@Not GivenNot GivenUncertain4/2005}wseJ@88,"`~@b@ResearchL@ KANNERRICHARDUNIVERSITY OF UTAH SALT LAKE CITYUTNHLBIU10, HL0592908@|@ @@2/1/19981/31/20032/1/1998 to 1/31/20034/2005yrn^I@88,"%@@Researchh@ KANDELDENISECOLUMBIA UNIVERSITY HEALTH SCIENCESNEW YORKNYNIDAR01, DA012697,p.b@ @ \@9/30/20018/31/20069/30/2001 to 8/31/20064/2005{wmH@88,"@@Researchb@ KANDELDENISECOLUMBIA UNIVERSITY HEALTH SCIENCESNEW YORKNYNIDAR01, DA009110,p.b@@ @9/30/19941/31/20059/30/1994 to 1/31/20054/2005{wmH@88,"@ @ResearchX@ KANDELDENISECOLUMBIA UNIVERSITY HEALTH SCIENCESNEW YORKNYNIDAK05, DA000081,p.@@ @8/5/19817/31/20068/5/1981 to 7/31/20064/2005{wmH@88," @@Research@ JURISICOVAANDREAMOUNT SINAI HOSPITAL UNIVERSITY OF TORONTOTORONTOON, CANADACTCRINot GivenNot availableBiology and CancerDiscovery 1b Evaluation 1b@#7/1/20047/1/20057/1/2004 to 7/1/20054/2005A9##xLD88,"LVAL,p.This is a competing continuation application for renewal (Years #21-#25, 8/l/01-7/31/06) of a K05 Senior Scientist Award (SSA) held since 8/01/81. The overall objective of the research has been to investigate through epidemiological studies three major themes on substance use in adolescence and adulthood: developmental patterns of involvement and cessation in the use of various drugs; risk and protective factors for involvement in drugs; and consequences of using drugs. Stimulated by findings obtained in the current period of support, the goal for the next five years is to conduct a multifactorial examination of the development of nicotine dependence. Six specific aims will be pursued: (1) Describe the epidemiology and natural history of nicotine dependence and other aspects of smoking behavior, in particular the transition to daily smoking and nicotine dependence, among adolescents and young adults. (2) Identify psychological, social and biological factors that promote (risk factors) and factors that reduce the risk (protective factors) of daily smoking and the transition to nicotine dependence. (3) Specify the comorbidity of drug use and dependence with psychiatric symptoms among adolescents, in particular the sequencing and reciprocal relationships between nicotine dependence and depression. (4) Examine interpersonal influences on drug behavior, especially nicotine dependence, within and outside the family, and identify: a. the extent of familial similarity on drug behavior, including nicotine dependence, among parents and adolescents, siblings, and spouses; b. the relative contribution of genetic, shared and non-shared environmental factors to smoking onset, daily smoking and nicotine dependence among twins; c. the relative importance of selection and socialization on smoking among adolescent friendship pairs. (5) Identify pathways of progression in smoking, nicotine dependence, and the use of other drugs. (6) Identify gender and ethnic commonalities and differences for #1-#5. An overall goal is t LVAL o incorporate a biological perspective in epidemiological research. Three interrelated research programs will be pursued to achieve these aims: analyses of a national longitudinal sample of young adults (Add Health), analyses of the National Household Surveys on Drug Abuse, and the implementation of a new longitudinal study of the transition to nicotine dependence in adolescence. The research will provide understanding crucial for the development of effective prevention and treatment interventions. Components of the program represent innovative activities in epidemiological research carried out on general population samples.LVAL,p.The National Household Survey on Drug Abuse (NHSDA) represents a major effort to monitor drug use in the population on an annual basis. In addition to patterns of drug use of legal and illegal drugs, information is also collected about symptoms of drug dependence. Except for the work conducted by our research group, the data on dependence symptoms have been little analyzed. This competing continuation proposal requests 31/2 years of support to carry out further analyses of multiple waves of the NHSDA to investigate selected issues related to substance dependence on four drug classes: marijuana, cocaine, cigarettes and alcohol. During the prior six years of support, we developed proxy DSM-lV definitions of substance dependence and investigated extent of drug dependence in the population in different sex, and racial/ethnic groups, the relationships of dependence to extent of use among adolescents and adults, comorbidity of psychiatric disorders, drug and mental health treatment among adults, and parental-child similarity on marijuana use and smoking. In this next period, four issues will continue to be investigated: (1) the relationship between dependence and progression along the developmental sequence of involvement in drugs; (2) the extent of familial similarity on drug behavior between parents and adolescents, siblings and spouses; (3) the comorbidity of use and dependence with selected psychiatric disorders among adolescents; (4) the natural history of nicotine dependence. Analyses will be conducted for age, sex and ethnic specific groups, and will be based on the 1999, 2000 and 2001 surveys (N=66,706- 70,000). The samples are almost evenly divided among 3 age groups, 12-17, 18-25 and 26 years old and over. Each survey will provide a large number of nationally representative familial dyads, about 6,000 parent-child, 4,400 sibling, and 500 marital pairs. The very large national samples of youths and minorities, the inclusion of data on nicotine, and the availability of familial dyads make possible aP LVAL` ge, gender and racial/ethnic-specific analyses, comparisons across drugs, and analyses of intra intergenerational similarity on drug use in the NHSDA rarely feasible in any other study. The research will extend our understanding of the extent of serious drug use in the nation, the etiology of substance dependence, the extent of treatment needs, the transmission of drug use across and within generations, and racial/ethnic differences in patterns of use, dependence, comorbidity and familial similarity in the population. Such questions by and large have not been treated in the epidemiological literature on drug use in the general population, which has focused almost exclusively on frequency measures of drug use.LVAL,p.This revision of a proposal submitted initially on 10/1/98 requests five years of support (10/1/01-9/30/06) to investigate the transition from experimental smoking to daily smoking and nicotine dependence and the underlying risk and protective factors among white, African-American and Hispanic adolescents. The research has five major goals: (1) To identify the timing and sequence of the transition from experimental smoking to daily smoking and nicotine dependence among adolescents. (2) To identify the psychological, social and biological factors that promote the progression to daily smoking and dependence and reduce the risk. Special attention will be paid to (a) depressive symptoms, (b) conduct problems, (c) initial differences in sensitivity to tobacco, (d) cotinine levels, and (e) exposure to prenatal smoking. (3) To specify the comorbidity and sequencing between daily smoking, nicotine dependence and psychiatric disorders. (4) To identify pathways of progression from experimental smoking to nicotine dependence and the use of illicit drugs. (5) To identify gender and ethnic differences among white, African-American and Hispanic youths with respect to Aims number 1-number 4. These aims will be achieved by conducting a five-wave two-year longitudinal follow-up of 1,275 6th-10th graders and their mothers. A two-stage research design will be implemented. In Phase I, approximately 17,000 students in grades 6-10 from selected public schools will be administered a brief survey. Responses will be used to select a target sample of 1,300 experimental smokers and 200 non-smokers, evenly divided among the three ethnic groups. In Phase II, 3 annual computerized household interviews will be conducted with 1,275 participating youths and their mothers, and 2 telephone interviews with the youths six months after the first and second household interviews. At each annual interview, a psychiatric assessment will be administered to the youth and the parent about the child; a saliva sample will be collected to determine LVAL cotinine levels, validate self-reports of smoking and predict progression to daily smoking and nicotine dependence. This study represents a rare attempt to investigate prospectively the periods of risk for nicotine dependence in adolescence, the duration from onset to dependence, and the factors that explain the transition to dependence. The study is unique in focusing on the comorbidity between smoking, nicotine dependence, and psychiatric disorders among adolescents of different ethnicity. The study will generate a unique understanding of the natural history, etiology and consequences of nicotine dependence among young people.LVAL .AGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology PSYCHOLOGICAL Other Psychological RESEARCH1 Animal Studies TOBACCO Nicotine WOMEN PregnancyAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology RESEARCH1 Animal Studies RESEARCH Clinical Research TOBACCO Nicotine WOMEN PregnancyAGE Child Fetus/Prenatal COMMUNITY General Partnerships ECONOMICS Cost of Intervention/Prevention EDUCATION LEVEL Less than High School High School LOCATION Rural National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION Hispanic TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesADDICTION Initiation Maintenance AGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian Hispanic TOBACCO Non-Specified Tobacco Use Nicotine WOMEN Parent/Mother MISCELLANEOUS Sex/Gender DifferencesLVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airways, reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. Of minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600.LVAL,p.Project IV: This project will determine whether localized media campaigns aimed at rural 7th and 8th grade Mexican American and White non-Hispanic students can influence their attitudes toward tobacco use and the subsequent use of tobacco (smoking cigarettes and smokeless tobacco). The primary target will be young women, where smoking produces potentially greater damage due to harmful effects to the fetus, newborn, and infant among pregnant smoking females. However, media messages will not be focused solely on females, and effects on males are expected such as reduction of smokeless tobacco. An effective and relatively low cost media campaign would be a valuable asset for rural communities that usually do not have the financial and technical resources for costly prevention efforts. However, typical media campaigns may not be useful for rural communities who may view their problems as more limited or unique compared to urban environments. The media campaigns that will be tested, therefore, will be localized to include local smoking data, identification with local situations, and images of local landmarks. There is evidence that prevention efforts may be enhanced by the use of peers; therefore, the effect of the media campaign alone (MEDIA) will be compared with the effect of the media campaign when local peers are added as an integral part of the media campaign (MEDIA+). In these MEDIA+ communities, a team of local peers (11th grade women) will be trained to present and monitor the media campaign. In addition, they will make radio spots, be names in news releases, and will be included in local visual references. The addition of this social influence from older females will be tested for its ability to reduce cigarette use and smokeless tobacco among younger females and males, over and above effects obtained in the MEDIA condition. Both experimental conditions will be compared to a control condition in which pre- and post assessments are obtained, with no intervention. Media components that can be local| LVAL ized to rural ethnic minority communities have been developed and tested, and the training program for peer involvement in media campaigns has been tested by the investigators. The programs are designed so that, if successful, technology transfer through extension services or 4H organizations would be feasible.LVAL,p.Studies of the effects of cigarette smoking by pregnant women on intrauterine development of the offspring are foremost, since the development of the child is likely to be hindered. Infants whose mothers smoked during pregnancy have lower size and weight at birth and are not only predisposed to pulmonary and cardiovascular diseases, but also to a severe immunodeficiency. Thus, the goal of this grant application is to understand the cellular and molecular mechanisms leading to dysfunction of the immune system in children whose mothers smoked during pregnancy. Hematopoiesis, generation of mature blood cells, is vital for life: the white cells fight infections, the red cells carry oxygen throughout the body, and the platelets promote healing and prevent bleeding. The hematopoietic stem cell is a progenitor cell that generates all varieties of mature blood cells throughout life. During adult life, hematopoiesis takes place in the bone marrow. However, colonization of the bone marrow with primitive hematopoietic stem cells must occur during intrauterine development of the fetus. Thus, any changes in the ability of primitive hematopoietic stem cells to egress from the fetal liver, to immigrate into the fetal bone marrow and to establish normal hematopoiesis could be deleterious to the newborn. Nicotine is one such factor, the exposure to which could lead to serious alterations in the bone marrow development, resulting in a disruption of hematopoietic homeostasis and a changed ratio of mature cells in the blood. Indeed, we have demonstrated that newborn mice exposed to nicotine during intrauterine development have a lower number of hematopoietic stem cells in the bone marrow in comparison to control animals. Furthermore, these mice had severe immunodeficiency during the first month after birth. Based on our preliminary observations, we propose to investigate how nicotine can alter the ability of bone marrow stromal cells to produce soluble factors that mediate migration of hematopoietic stem cells, coloniz^ LVALn ation of the bone marrow and production of mature blood cells. In addition, we plan to examine whether nicotine-induced immunodeficiency in newborn mice is due to inhibition of the functional activity of the immune cells or is a result of impaired colonization of the bone marrow with hematopoietic stem cells and lower production of lymphoid progenitor cells and, consequently, mature immune cells. The proposed grant application will use the current knowledge in experimental hematology to understand the cellular and molecular mechanisms that affect embryonic development of the hematopoietic and immune systems. Studying the effect of nicotine on intrauterine development may open a new area of research, which could ultimately establish a basis for novel therapeutic approaches to the treatment of tobacco-related immunodeficiency. LVAL,p.Even though it is well-known that the health of pregnant women and their newborn offspring is damaged be tobacco smoke, little is known about who in California is exposed to tobacco smoke during pregnancy, for how long and how much. One reason for this is that California is the only state that does not have a smoking question as part of its birth certificate. The objectives of this research project are to put together a source of information to answer these and other questions about smoking. We will work together with other programs of the California Department of Health Services, the National Centers for Disease Control and Prevention (CDC), the San Diego County Health Department, 20 delivery hospitals, area medical laboratories, and numerous community clinics and doctors to do this. We will collect information from pregnant women in San Diego County during 1999-2001. Blood and urine taken from pregnant women for non-study reasons and which is left over after analysis wil1 be collected by the study, stored and later used to measure how much tobacco smoke these women were exposed to. We will obtain the blood and urine at three points in the pregnancy: at the time each woman goes in for a pregnancy test at a lab or doctors' office, at 15 19 weeks gestation when she gives blood to be screened for certain birth defects, and at birth when umbilical cord blood is taken at the hospital. While at the hospital for delivery, the mother will be asked to answer a short questionnaire (in Spanish or English) about her smoking history and her exposure to others who were smoking during the pregnancy. Participation in the study is voluntary and necessary approvals from women will be obtained for all collection activities. Over a 19-month period, we plan to collect approximately 40,000 maternal urine or serum samples collected early in pregnancy, 60,000 maternal serum samples collected in the second trimester, and 50,000 umbilical cord blood samples, live birth records and questionnaires collected at the time LVALof the birth. Approximately 6,000 blood and urine samples from over 2,000 women will be selected and sent to a special national lab for analysis. Levels of a tobacco metabolite (cotinine) in a woman's blood or urine will be measured to find out how much tobacco she and her baby were exposed to, either by smoking or by being around others who smoke. Once all of these data are linked together, we will be able to: 1) define the true pattern of tobacco smoke exposure across the nine months of pregnancy; 2) determine the characteristics of women who are most exposed to tobacco smoke; and 3) determine which of two smoking questions women most accurately respond to. If we can scientifically validate at least one of the smoking questions, then it will be recommended for use on future California birth certificates. The results of this study will be helpful in informing future research efforts as well as in shaping policies to prevent the health of pregnant women and their newborns from being damaged by tobacco smoke.*LVAL N BCOMMUNITY Health Care Provider ECONOMICS Socio-Economic Status Medicaid/Medicare LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian Hispanic TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumADDICTION Initiation Maintenance Cessation AGE Child Young Adult ECONOMICS Socio-Economic Status Cost of Intervention/Prevention Cost of Smoking EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Counter-Marketing POLICY Excise Tax RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation Withdrawal COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group Biochemical Assessments RESEARCH Human Studies STUDY POPULATION Caucasian Hispanic TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Postpartum Parent/MotherAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies Clinical Research TOBACCO Environmental Tobacco Smoke WOMEN PregnancyAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco SmokeLVAL,p.The main objective of this study is to accurately measure the impact of environmental tobacco smoke (ETS) exposure during pregnancy on a variety of pregnancy outcomes. The study population derives from over 3,000 pregnant women who enrolled in California s Maternal Serum Alpha-Fetoprotein prenatal screening program in April 1992 from a diverse eleven-county region of the state. Blood samples from these women were stored in a freezer and analyzed in a laboratory to find out how much contact the women had with ETS during their pregnancies. This information was linked to information from the live birth certificate on birth weight and other factors. Different analyses were conducted to determine how much birth weight is reduced, if at all, by being in contact with different amounts of ETS. We investigated whether there are special groups of women who are more or less exposed or susceptible to the effects of ETS. Using information from a special questionnaire given to some of the study women when they gave birth in the hospital in 1992, we identified the places pregnant women come in contact with ETS, like at home, work, or other places. Through laboratory analysis of blood, we found that the highest levels of ETS exposure were in Black women, and the lowest levels were in Mexico-born Hispanic women. Generally, higher ETS exposures were associated with being younger, less educated, and poorer. According to self-report, the home was the main location where nonsmoking women were exposed to ETS. The effects of ETS were varied. Across the range of ETS exposure, from least exposed to most exposed, we found that fetal death (after 19 weeks gestation) increased 3 times, preterm delivery (before 37 weeks gestation) doubled, low birth weight (less than 5.5 lbs) increased by 1.5 times, and mean birth weight declined by about one-fifth of one pound, or 3-4% of a baby s overall weight at birth. There was no  safe level below which ETS did not diminish birth weight. Blacks and women who consume high amounts of caffein LVAL" e may be more susceptible to the effects of ETS than other subgroups of the population, but our study had too few numbers of such individuals to be sure. These results suggest that policies be put into place or tightened to protect pregnant women and their unborn children from exposure to ETS. Further steps need to be taken to lower exposure to ETS in the home. Studies that don t use objective measures of exposure to ETS may be unable to accurately quantify the true health effects of ETS.L LVAL\ 1.To document the natural history of smoking cessation and relapse as a dynamic process influenced by differing sets of variables over time and in response to life transitions or events, e.g. delivery, motherhood, stress, depression. 2. To examine the harm reduction goals, strategies, and practices of pregnant and postpartum women who reduce their smoking intensity but not quit, and how this changes over time. 3. To gain a better understanding of how social support networks affect a woman's ability to quit or reduce smoking during pregnancy and postpartum, with a particular focus on the extent to which patient characteristics such as age, ethnicity, gravity and parity, and breastfeeding status influence provider attitudes and characteristics. 4. To document the cessation treatment practices of prenatal and maternal child health providers.LVAL,p.Smokers are more likely to die of breast cancer than are non-smokers, though they don t get breast cancer any more often. This suggests that breast cancer may behave more aggressively among smokers. The reasons for this are not clear. Studies with animals have shown that a variety of things that injure the lung, like exposure to high concentrations of oxygen or to radiation, do increase metastasis to the lung. Because smoking also injures the lung, we think it may make breast cancer more likely to spread to the lung, but this has not been directly studied. Studies in populations of patients have suggested that smoking may encourage the spread of breast cancer to the lungs, but these types of studies can only indirectly look at the association between smoking and breast cancer behavior. We propose to examine the relationship between smoking and the spread of breast cancer to the lungs more directly, in an animal model of breast cancer. We will study the effect of smoking on the spread of breast cancer to the lung by measuring the number and size of breast cancer deposits in the lung among mice exposed to cigarette smoke compared to mice not exposed to cigarette smoke. The experiments will be carried out using specialized smoke-exposure chambers that generate smoke concentrations that are comparable to those experienced by actively smoking adults. The breast cancer model in the mice is one that is very much like the human situation and that has previously been used to answer other questions about things that affect the spread of breast cancer, such as diet. We will compare both smoking and non-smoking animals, as well as a third group of animals that stops smoking after the breast cancer has grown for awhile. We include this third group because it allows us to model the situation of a woman quitting smoking at the time her breast cancer is diagnosed. If smoking does cause breast cancer to spread more easily, it will be important to see if this effect can be prevented by a woman quitting smok LVAL ing when she finds out about her cancer. Since breast cancer and smoking are both very common among women an effect of smoking on the behavior of breast cancer is potentially quite important. This is especially true if the adverse effect of smoking can be reversed by quitting smoking at the time of breast cancer diagnosis. Even if it can not be reversed, it is still important. Women smokers may be persuaded to quit smoking if they know it will make them more likely to die should they get breast cancer. Also, studies that compare women with breast cancer will need to take their smoking status into account if smoking really does make a difference in the way breast cancer behaves. LVALAdolescent smoking is of particular interest from both a research and a policy perspective because smoking initiation and early smoking habits are known to have important implications for lifetime smoking and can have important negative health consequences for an individual. The earlier in life a youth begins smoking, the more cigarettes he/she will smoke as an adult with greater incidence of negative health effects. Despite a considerable body of research on the effects of tobacco control policies on youth smoking, important research and policy questions remain. There is little evidence to determine whether the effect of tobacco control policies is to prevent smoking initiation, escalation to regular smoking, or promote smoking cessation. The primary goal of this study is to investigate the relationship between cigarette excise taxes and tobacco control expenditures and smoking initiation, prevent escalation to regular smoking, and cessation using the NLSY97, a nationally representative panel of youth. The specific aims of this study are to (1) estimate the effect of cigarette excise taxes and tobacco control expenditures on the probability that an adolescent (a) initiates smoking, (b) starts smoking regularly (escalates), and (c) who smokes, quits; and (2) investigate the possibility of differential effects of the excise tax and tobacco control expenditures by gender and by race/ethnicity for smoking initiation, escalation, and cessation. A discrete-time hazard model is used to estimate the effect of the excise tax and tobacco control funding on the probability that an individual initiates smoking, escalates to regular smoking, and, if a smoker, quits smoking. The panel data and the discrete-time hazard model allow for the control of unobserved individual and state-level effects.LVAL,p.This five year Demonstration and Education project, the Provider-Delivered Smoking Intervention Project Plus (PDSIP+), will implement and evaluate the effect of a multicomponent intervention on the smoking cessation and maintenance rates of culturally-diverse, socioeconomically-disadvantaged, pregnant women (Hispanic, Black American and Caucasian) enrolled in the Women, Infants and Children (WIC) supplemental nutrition program. Three provider channels will deliver the interventions: l) WlC nutritionists during pregnancy and postpartum; 2) obstetricians (OB) and clinic staffs during pregnancy; and 3) pediatricians (PED) and clinic staffs during postpartum. A time-efficient yet intensive patient-centered intervention protocol will be used. This intervention has been previously demonstrated to be efficacious when used by general internists and family practitioners with a general population of smokers, and to be usable by WIC nutritionists. Three paired Massachusetts WIC sites and their related OB and PED clinics within Community Health Centers will be randomized to special intervention (SI) or usual care (UC). SI sites will receive training in the patient-Centered intervention, and establish an office practice management system to support intervention, which includes a system for linking the three channels of intervention delivery. UC sites will receive no intervention. In each of the three SI sites, an organizational assessment will be completed, a Health Center Operations Board will be established to tailor implementation of the intervention in each site. Then each of the SI provider channels (WlC, OB and PED) will receive intervention training consisting of a structured group program with brief individual followup sessions. Written questionnaires will be done at baseline of SI and UC providers at post-training of SI providers, and at one year followup of both Sl and LC providers. Provider adherence to the intervention will be measured by patient exit interviews (WIC providers in SI and UC), chart audi LVAL t (SI only) and retrospective patient report in patient interviews. Eligible pregnant women will have a baseline interview during their WlC enrollment visit. A brief assessment involving smoking status (with saliva cotinine validation of reported cessation), stage of change and report of provider intervention behavior will occur at ninth month of pregnancy, 3- and 9-months postpartum. A more comprehensive assessment will be conducted at l- and 6-months postpartum. Maintenance of cessation and overall non-smoking rates will be determined at each assessment point. The results of this study will demonstrate the effectiveness of a multicomponent program of linked providers, which is feasible and generalizable to other behaviors and other settings serving low-income, multicultural pregnant women.LVAL It has been understood for some time now that mothers who smoke during pregnancy are placing there unborn child at risk for a number of cognitive and behavioral deficits, including attention deficit hyperactivity disorder. Animal models have indicated that nicotine is the primary ingredient in tobacco which can affect the brain. Experiments using these models have found that long-term treatment with nicotine causes a number of alterations at the level of the brain cell (neurons) and the overall morphology of the brain. Among these changes is dysregulation of the noradrenergic system, one of the neurotransmitter systems which allows neurons to communicate with one another and send signals throughout the brain. The cerebellum is one area of the brain which receives input from the noradrenergic system and is the region of focus for our studies. The aim of the proposed experiments is to determine the effects of nicotine on the noradrenergic system in the cerebellum. Is nicotine able to alter development of the cerebellum through the noradrenergic system, and if so, how? Using animal models treated with acute and prenatal/early postnatal chronic nicotine, we will address this question by examining alterations in nicotine-stimulated noradrenaline release in the cerebellum and subsequent disruptions in the migration of neurons during development. The proposed studies will provide a better understanding of the specific mechanisms by which behavioral and cognitive disorders are produced by early exposure to nicotine and will further emphasize the health risks of prenatal nicotine exposure as a consequence of maternal tobacco use.  k ) M?&g@@@ResearchZ@!KRISHNAN-SARINSUCHITRAYALE UNIVERSITYNEW HAVENCTNIDAP50, DA013334D!,p. Addictionl@@Not Given2003? to 20034/2005xrncRH88,"@q@ResearchP@ KRISHNAN-SARINSUCHITRAYALE UNIVERSITYNEW HAVEN CTNICHDR01, HD037688N!,p.Biology and Cancer Addictionn@n@9/30/19985/31/20039/30/1998 to 5/31/20034/2005zsocRH88," @`@Researcht@KOVALJOHNUNIVERSITY OF WESTERN ONTARIOLONDONON, CANADANCICNot GivenF@b@@&@7/1/20047/1/20067/1/2004 to 7/1/20064/2005~xldE?88,"@@@ResearchT@KOURIELENAMCLEAN HOSPITALBELMONT MANIDAR01, DA012014X!,p.j@n@@9/15/19998/31/20049/15/1999 to 8/31/20044/2005zkeaWF?88,"@@@ResearchEPIDEMIOLOGY OF OVARIAN AGEKLINEJENNIENEW YORK STATE PSYCHIATRIC INSTITUTENEW YORKNYNIAR01, AG015386N!,p.t@T@@5/1/19983/31/20055/1/1998 to 3/31/20054/2005d\UU,"@ 7@Research^@KLEYKAMPBETHEAVIRGINIA COMMONWEALTH UNIVERSITYRICHMONDVANIDAF31, DA017437 @@@@9/29/20039/28/20079/29/2003 to 9/28/20074/2005zvlJB88,"  `@4@Researchh@KLESGESROBERTUNIVERSITY OF MEMPHISMEMPHISTNNHLBIR18, HL053478z,p.b@@"@2/1/19951/31/20022/1/1995 to 1/31/20024/2005tmi`IA88,"   @^@Researchl@KLESGESLISAUNIVERSITY OF TENNESSEE HEALTH SCIENCES CENTERMEMPHISTNNICHDR03, HD037225@|@@@1/1/199912/31/20021/1/1999 to 12/31/20024/2005wGA88,"  @ y@Researchf@KLECANDEBRAUNIVERSITY OF NEW MEXICO ALBUQUERQUE CONTROLLER'S OFFICEALBUQUERQUENMNCIR03, CA083352~,p.T@@@8/3/19997/31/20038/3/1999 to 7/31/20034/2005 G@88,"  g@p@4ResearchV@KLEBANOFFMARKNational Institute of Child Health and Human DevelopmentBETHESDAMDNICHDZ01, HD002520,p.Biology and CancerT@@Not GivenNot GivenUncertain4/2005 IC88,"   @@Researchb@O'MALLEYSTEPHANIEYALE UNIVERSITYNEW HAVEN CTNIDAP50, DA013334,p.|@@P@9/30/19998/31/20049/30/1999 to 8/31/20044/2005tnj^MB88,"@@@@Researchh@OLSHANANDREWUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILLCHAPEL HILL NCNCIR01, CA090731,p.t@P@@7/18/20016/30/20067/18/2001 to 6/30/20064/2005uH@88,"@G@Research^@O'LEARYKATHRYNUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECACTRDRP9DT-0115 @Biology and CancerDiscovery 1a Evaluation 1bn@7/1/20006/30/20027/1/2000 to 6/30/20024/2005!zvnJA88,"LVAL,p.The major goal of the proposed study is to comprehensively evaluate the role of genetic susceptibility in the etiology of squamous cell carcinoma of the head and neck (SCCHN; including oral cavity, pharynx, and larynx). SCCHN provides an ideal model for the investigation of gene-environment interaction in cancer given its strong and highly prevalent risk factors, tobacco and alcohol. Polymorphisms in genes representing metabolism (activation and detoxification) of carcinogens, mediators of oxidative stress, and DNA repair may help to clarify dose-response relationships needed for risk assessment, elucidate low dose exposure effects, pinpoint specific carcinogens that act as part of complex mixtures, and to identify susceptible subgroups of individuals most likely to benefit from interventions to reduce exposure. The proposed North Carolina population-based case-control study including 1,700 cases and 1,700 controls will have the ability to more precisely define the nature of the gene-environment interactions related to the risk of SCCHN. This will be the largest study of head and neck cancer ever conducted in the United States. North Carolina is an excellent setting to conduct such a study given the large biracial population, relatively high prevalence of tobacco use, and the research team's experience with conducting population-based molecular epidemiologic studies of cancer. The previous gene-environment studies have yielded generally inconsistent results with respect to several metabolizing enzyme polymorphisms. These studies have been limited by their relatively small size (typically fewer than 200 cases), hospital-based design and examination of a small number of enzymes. The size and population-based design should allow us to more confidently confirm or reject associations raised in previous studies. Finally, the study size will permit us to consider selected gene-gene exposure interactions and examine important subgroups defined by age, gender, race, and tumor site. The systematic collection ofJ LVALZ tumor blocks will also facilitate future studies of "downstream" somatic alterations of tumor suppressor genes and oncogenes. The proposed study should contribute knowledge on gene-environment interactions for cancer of the head and neck, but also for other tobacco- and alcohol-related cancers and possibly cancers of unknown etiology.LVAL,p.*Current pharmacological treatments for smoking cessation including nicotine replacement therapies and buproprion, are modestly successful in assisting smokers to quit. However, new treatments are needed. In particular, the problem of weight gain with smoking cessation is only partially reduced by current therapies. Furthermore, treatments that might address the link between alcohol consumption and smoking relapse may be particularly useful since many smokers are heavy drinkers, and this subgroup is particularly resistant to treatment. Based on our preliminary studies, we hypothesize that naltrexone, an opioid antagonist approved for the treatment of alcohol dependence, may be useful in augmenting the efficacy of transdermal nicotine replacement on rates of continuous abstinence and in preventing weight gain with smoking cessation. In the proposed study, we will test this hypothesis in 400 smokers seeking to quit smoking. All subjects will receive nicotine replacement therapy, and will be randomized to receive one of four doses of naltrexone (0, 25 mg, 50mg, or 100 mg daily) for six weeks following their quit date. Primary outcomes will be continuous abstinence during the last four weeks of treatment and weight gain. Secondary outcomes will include measures of craving for cigarettes, sweet and rich foods, and alcohol use. Through a careful analysis of data collected during the first week following their quit date, we will evaluate whether naltrexone treatment reduces the probability of continued smoking following their quit date, we will evaluate whether naltrexone treatment reduces the probability of continued smoking following a lapse in abstinence and the relationship between alcohol consumption and smoking relapse. A secondary aim of the study will be to explore predictors of response to treatment, including biochemical and neuroendocrine measures (e.g., baseline cotinine, naltrexone metabolite levels, cortisol levels), demographic characteristics (e.g., age/sex) and alcohol use history.$LVAL zX>DISEASE/BIOLOGY Other Disease/Biology LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse AGE Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Smokeless MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation Relapse AGE Fetus/Prenatal LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN PregnancyAGE Child COMMUNITY General Partnerships EDUCATION LEVEL High School MARKETING Media-Websites/pamphlets/radio PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION American Indian/Alaskan Native TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) PREVENTION/TREATMENT Biochemical Assessments TOBACCO Cigarette/Other Smoking Nicotine WOMEN PregnancyADDICTION Cessation Relapse DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy Other Pharmacological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesLVAL,p.The role of maternal caffeine consumption in the pathogenesis of adverse pregnancy outcomes is controversial. Several studies have found that women who consume caffeine are at increased risk of spontaneous abortion and fetal growth restriction compared to non-users. However, other equally well-done studies have found no harmful effects of caffeine consumption. In addition, several studies have reported that caffeine is harmful only among women who smoke. All previous studies of this question have relied on maternally-reported caffeine use; no studies have employed a biomarker for caffeine. This project first validated the use of serum caffeine and its metabolites as a marker for caffeine intake, and then studied these serum markers as a risk factor for adverse pregnancy outcome. In the validation study, serum paraxanthine was determined to be an acceptable marker for caffeine intake. As part of this project, the concentration of cotinine, a metabolite of nicotine, was assayed in the serum of approximately 450 of the women and the results compared to their reported cigarette smoking. Women were found to be very honest in reporting whether they smoked, but their serum concentration of cotinine correlated only moderately with the amount smoked. This was the case for two separate populations of women 30 years apart. In the main part of this project, the serum concentration of paraxanthine, caffeine's primary metabolite, was compared between 591 women experiencing a spontaneous abortion and 2558 women with live births who had serum drawn at the same time of pregnancy as the women with spontaneous loss. In addition, the association between reduced fetal growth and third-trimester paraxanthine serum concentrations was evaluated among these 2515 women. The mean concentration of paraxanthine was higher in women experiencing a spontaneous abortion than women experiencing a live birth (752 vs 583 ng/ml). Further analysis revealed that this may be explained by a few women with very high concentrations LVALof paraxanthine. The odds ratio for serum paraxanthine concentration greater than the 95th percentile was 1.86 (p<0.01), but intermediate concentrations were not associated with an elevated risk of spontaneous abortion. These results suggest that moderate caffeine consumption during pregnancy does not increase the risk of spontaneous abortion. Among the control women, 2515 provided a third-trimester serum sample. The mean paraxanthine concentration in this sample was higher among women who subsequently gave birth to a small-for-gestational age (SGA) infant (754 ng/ml) than among women who gave birth to appropriately-grown infants (654 ng/ml, p=0.03). There was no statistically significant association between paraxanthine and SGA birth among non-smokers (p=0.48). Among smokers, increasing serum paraxanthine concentration was associated with an increased risk of SGA birth (p=0.03).LVAL,p.Smoking prevalence among adolescents is rising despite aggressive tobacco control efforts. Students who smoke are motivated and interested in quitting, but few cessation programs show any long-term effectiveness. One of the recent advances in cessation counseling for adults is computer- assisted systems to tailor messages to gender, smoking history, and stage of changes. However, these systems have not taken full advantage of the latest technology and have not been developed or evaluated for Native American youth. The continued sacredness of tobacco and ceremonial use of tobacco in most Southwestern tribes create a unique situation when addressing the rise of abuse of commercial tobacco products among American Indian youth. The overall goal of the proposed project is to adapt, expand, and evaluate an effective computer-interactive cessation system to facilitate tobacco cessation among diverse Native American youth populations in the Southwest. This proposal is a two-year randomized controlled school-based intervention to test individualized peer counseling computer-aided cessation approaches with American Indian male and female smokers in grades 9-12. The proposed intervention will adapt and test the CD-ROM, CHATT (Computers Helping Adolescents Talk Tobacco) that was developed in a study funded by the American Cancer Society. CHATT is a computer system that features detailed smoking history, individual tailored feedback, and counseling vignettes based on the Transtheoretical Model. Using the Motivational Interviewing model, the peer counseling will facilitate the student's cessation with the computer providing guidelines for discussion of tobacco use and strategies for quitting. The current proposal will be a collaboration between the University of New Mexico's Epidemiology and Cancer Control Program, Indian Health Service's (Headquarters West Cancer Control Program, and the Gallup McKinley County School District, located in western New Mexico, which includes youth from the Navajo Nation and surroundiV LVALf ng tribes. The first six months of year one of the proposal will be devoted to the adaptation and "beta-testing" of CHATT. During the remainder of Year One and during Year Two we will conduct a randomized trial on the effectiveness of the CHATT multimedia program on cessation rates, using a pretest- posttest control group design.LVALV& d P > 2 TZ RvDiscovery 1a Discovery 1b Discovery 1c Discovery 3 Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1cDevelopment 4 Evaluation 1a Evaluation 1cDiscovery 1a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1c Development 1 Delivery 1 Delivery 2 Partnerships 1 Partnerships 3Discovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1c Discovery 2a Development 3 Development 5 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1c Development 1 Delivery 1 Partnerships 1 Evaluation 1aDiscovery 1c Discovery 2a Discovery 2b Development 3 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 2a Discovery 2b Discovery 3 Development 4 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1aDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1bDiscovery 1c Development 1 Development 2 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Development 2 Evaluation 1a Evaluation 1bLVAL6 $Many smokers report that they experience difficulty concentrating during a quit-attempt, suggesting that cognitive decrements may be a feature of tobacco abstinence. The effectiveness of nicotine replacement therapy (NRT) in ameliorating such decrements is not clear. In addition, NRT's effectiveness in ameliorating abstinence-induced cognitive decrements may differ between men and women. To examine NRT's ability to ameliorate cognitive decrements associated with abstinence, and to examine gender specific effects of NRT, male (N =64) and female (N = 64) smokers will participate in a four-session, within-subject study. In each of session, 12-hour deprived smokers will receive one of four doses of transdermal nicotine (0, 7, 21, and 42 mg) and will remain tobacco-abstinent for the next 4 hours. For the last two hours, they will smoke one cigarette every 30 min. Attention and working memory (and other outcomes) will be assessed. Results will help clarify the effect of tobacco abstinence on cognition, and will also reveal the effects of pharmacologically pure nicotine, tobacco cigarette-delivered nicotine, and gender on abstinence-induced cognitive decrements. Non-cognitive methdolological study details were described in, and are funded by, R01 DA011082 (T. Eissenberg, PI).This investigation seeks to answer to what extent 1) nicotine replacement therapy in pregnant women who quit smoking increases serum antioxidants and lowers levels of oxidative stress compared to their baseline levels while smoking, and 2) serum antioxidants and oxidative stress differ in pregnant smokers who a) are randomized to a behavioral smoking cessation program b) are randomized to a behavioral therapy plus nicotine replacement group and c) who relapse to cigarette smoking.LVAL,p.This application is a revision of a competing renewal of a collaborative smoking cessation program between the University of Memphis, the University of Minnesota, and the United States Air Force (HL-53478). We propose to extend a unique opportunity to offer a smoking cessation maintenance intervention in a population of underserved smokers who have already quit smoking for a six-week period (but are at lower risk for complete relapse). In an initial three year period, we have been successful in assessing over 32,000 Basic Military Training (BMT) recruits, randomized 75% to intervention and 25% control, delivered interventions to nearly 26,000 of these recruits, and have six week test-retest reliability on approximately 7,000 subjects. All baseline data are entered, cleaned, and with a total of only 10 missing data points. Currently, 12-month follow-up data are being finalized from troops who are now all over the globe; we have completed surveying 100% of smokers at baseline and have conducted a random sample of baseline non-smokers. Follow-up rates t one year exceed 95% of participants. Evaluation data to date suggest a clinically significant difference in point prevalent abstinence (3.0%), given a "low impact" and cost-effective intervention. Intervention effects are larger in women (relative to men) and minorities (relative to Euro Americans). Interventions developed, if found to be efficacious, will continue by members of the U.S. Air Force in the future (i.e., complete dissemination). The current proposal has a number of unique methodological strengths: (1) It offers a tailored intervention in an underserved population at risk for smoking relapse, smoking onset, and smokeless tobacco use; (2) It allows randomization of virtually an entire population over a one- year period to a specialized intervention versus standard care. Thus, sampling bias is greatly reduced in this design; (3) It ensures that 100% of those assigned to specialized intervention or standard intervention or standard care will recZ LVALj eive it. (4) The participation rate will be extremely high in this study; loss to follow-up will be minimal; and (5) We will be able to test the long-term effectiveness of our tailored intervention in a population of individuals who have quit all tobacco use for six weeks at the time of our extended maintenance intervention. Given this introduction, we propose the following Specific Aims: (1) To enhance our validated smoking cessation program by strengthening key elements of the program and by lengthening the program in Basic Military Training (BMT); (2) To validate and implement an intense, tailored smoking prevention program for non-smokers in BMT who are at high risk for smoking onset; and (3) To validate and implement a tailored smokeless tobacco intervention in a population with a high baseline rate of smokeless tobacco use.LVAL!,p.The goal of this study is to identify factors that influence ovarian age. We define "ovarian age" as the size of oocyte pool. Ovarian follicle (oocyte) counts are highest before birth and decrease as women age; similarly, the number of follicles that develop during each menstrual cycle decreases as women age. At any particular chronologic age, women vary in both the size of their oocyte pools and the number of antral (developing) follicles. These variations may reflect differences in the size of the pool at its formation or in rates of oocyte atresia. Increasing numbers of women are deferring childbearing to the later years. Since ovarian aging is accompanied by conception delay and an increased risk of infertility and trisomic conception, the identification of risk factors for accelerated ovarian aging would have significant implications for reproductive research and primary prevention. The proposed study draws on data from two already completed studies to identify risk factors for ovarian age. In the first study, ovarian age is measured by age at onset of the menopausal transition and at menopause in 494 women. In the second study. ovarian age is measured shortly after an index pregnancy by counts of ovarian antral follicles and three hormonal indicators of ovarian age-follicle stimulating hormone, inhibin B and estradiol-in 173 women. Both studies include extensive data on maternal characteristics and exposures that might influence ovarian aging. They thus provide an excellent and unique opportunity to (i) identify determinants of ovarian age in fertile women during natural cycles and (ii) examine whether determinants of ovarian age during the reproductive years differ from determinants during the menopausal transition. The specific aims are: 1. To examine whether maternal characteristics (e.g., body mass index) or exposures (e.g., smoking) are associated with ovarian age measured by (i) antral follicle counts, (ii) selected hormonal indicators, (iii) age at onset of the menopausal transition, and LVAL(iv) age at menopause. 2. To conduct exploratory studies, using data from the Oocyte study, to assess whether or not skewed X-inactivation is associated with advanced ovarian age.LVAL fHAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Nicotine WOMEN PregnancyAGE Older Adult DISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menopause HormonesADDICTION Withdrawal LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Withdrawal AGE Child DISEASE/BIOLOGY Other Disease/Biology LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Smokeless Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance AGE Child Young Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesLOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle Hormones MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Menstral Cycle Menopause HormonesLVAL!,p.This application Nicotine's Effects on Other Drugs of Abuse, investigates conditions under which nicotine may alter the reinforcing, subjective and physiologic effects of the two most widely used psychoactive drugs in the United States, marihuana and ethanol. Even though these substances are commonly used together, the medical consequences, pharmacokinetic profiles and reinforcing effects of these drug combinations are not well understood. The proposed studies will systematically assess whether nicotine pretreatment via a transdermal patch alters the pharmacodynamics and pharmacokinetics of acute marihuana and ethanol and will evaluate whether these interactions are dose- dependent. Study 1 will investigate these interactions in non-smokers in order to characterize the nature of the pharmacodynamic interactions without the possible confounds introduced by variables associated with smoking. Studies 2-5 will use moderate tobacco smokers as subjects in an attempt to replicate conditions similar to those experienced by individuals who are treating their nicotine dependence with the patch and may continue to smoke marihuana or drink alcohol. These studies will also investigate whether nicotine alters ethanol's or marihuana's reinforcing effects by using a laboratory-based drug self-administration paradigm. In addition, because there is a paucity of research studies using women as subjects, and sex-related differences have been shown in the absorption, bioavailability, distribution and metabolism of various drugs of abuse, both male and female occasional drug users will be used in the studies to identify gender differences in the effects of these drug interactions. Finally, the influence of hormonal fluctuations associated with the menstrual cycle on the observed drug interactions will be investigated by studying women at different times of their menstrual cycle. The findings from the proposed studies will provide important information on the pharmacodynamic interactions and the reinforcing effects of these| LVAL drug combinations. These findings will have direct public health implications because, since the nicotine transdermal patch is now over-the-counter, many individuals may be using it without medical supervision and at the same time using or abusing alcohol and other drugs. If nicotine increases the positive effects and decreases the negative effects of ethanol and marihuana, individuals using a nicotine transdermal patch may find these substances more reinforcing and may be more likely to increase their use, putting them at higher risk for developing dependence.LVALRelevance: Smoking is a major cause of a number of cancers, and finding ways to prevent people from smoking will significantly reduce the rates of these cancers. Dr. Koval's team has been studying more than 1,600 teenagers for 10 years to discover what factors contribute to teen smoking. A better understanding of why teens start smoking and why they stop will help in the design of more effective smoking prevention and cessation programs tailored for teens. Description: Dr. Koval's group has used questionnaires to collect information about 1,614 teenagers at the ages of 11/12, 13/14, 16/17, and 21/22. The results support the idea that teens, particularly older teens, begin smoking in order to cope with stress. The group now plans to explore the importance of stress in smoking and quitting smoking. They will also look at whether gender differences or educational choices affect the reasons teens start or stop smoking.LVAL!,p.The applicants will conduct a detailed, prospective examination of tobacco withdrawal symptoms of male and female adolescents who are either heavy users, light users or nonusers of tobacco products (including cigarettes and smokeless tobacco). In adults, physical dependence as documented by the presence of withdrawal symptoms, is known to be an important factor in the maintenance of cigarette smoking, and the intensity of nicotine withdrawal has been shown to be directly correlated to the intensity of nicotine use. It has been suggested that like adults, adolescents may also be physically dependent on nicotine. However, all the studies examining incidence of nicotine withdrawal in adolescents have been retrospective in nature, but they suggest that self-reports from adolescents indicate that they also experience withdrawal during abstinence from nicotine. The specific aims of this proposal are (1) to conduct a prospective and systematic study of nicotine withdrawal symptomatology in adolescents who differ in amount of tobacco use (heavy users, light users, nonusers) using standard nicotine withdrawal measures as well as the Clinical Institute for Narcotic Assessment (CINA) scale-(2) to evaluate gender differences in the incidence of nicotine withdrawal in adolescents, (3) to determine if adolescents experience cognitive performance deficits during nicotine withdrawal and if these deficits are greater in heavy users compared with light users of tobacco products, (4) to evaluate alterations in responsivity to both physical and mental stress during nicotine withdrawal, in heavy and light users of tobacco products, compared with nonusers of tobacco and (5) to document alterations in responsivity of the hypothalamo-pituitary-adrenal (HPA) axis and sympathetic system during nicotine withdrawal and exposure to stress. The results of this study would have substantial implications for the use of nicotine substitution and other treatments in adolescents for the pharmacological management of withdrawal, and coul LVAL d also help elucidate the role of cognitive deficits and stress in maintaining cigarette smoking in adolescents. Determining physical dependence and related changes in adolescent tobacco users may also provide valuable information regarding the process of development and maintenance of nicotine dependence.LVAL!,p.This proposal is composed of two sequential studies; the study will examine male and female smokers with and without current depressive symptoms on the clinical course (intensity, content and duration) of cigarette abstinence effects, and responses to cigarette-related cues during acute and prolonged nicotine abstinence; the second study will conduct a similar examination in male and female smoker who are either heavy or light drinkers. Alcohol dependence, major depression/current depressive symptoms and female gender have also been associated with high rates of cigarette smoking and poor smoking-treatment outcomes. In adult smokers without psychiatric comorbidity, development of nicotine withdrawal is an important factor in the maintenance of cigarette smoking (USDHHS, 1988), and the intensity of withdrawal is directly correlated with the degree of nicotine use. Retrospective studies report that smokers with a history of major depression disorder and/or alcohol dependence experience more current depressive symptoms (without current MDD) and heavy drinkers (without alcohol dependence) has not been examined. This is particularly important considering a significant percentage of smokers have depressive symptoms and are also heavy drinkers but may not meet criteria for MDD or alcohol dependence. Detailed understanding of the nicotine abstinence syndrome in these high-risk smoker could lead to strategies (behavioral and pharmacological) for effective management of withdrawal symptoms which may prevent relapse to smoking. The following specific aims will be tested 1) To compare male and female smokers, with and without current depressive symptoms, in a prospective study of the intensity, content & duration of nicotine abstinence effects during an eight-day abstinence period, and responses to cure exposure ( in vivo cigarette cues, alcohol and negative affect- inducing imagery cues) during acute versus prolonged abstinence and, 2) To compare male and female smokers, who are either heavy alcohol drinkers or  LVAL light alcohol drinkers, in a prospective study of the intensity, content & duration of nicotine abstinence effects during an eight-day abstinence period, and responses to cure exposure (in vivo cigarette cues, alcohol and negative affect-inducing imagery cues) during acute versus prolonged abstinence.LVALPrevious studies reported that cigarette smoking is associated with lower levels of endogenous estrogen in the blood and an earlier age at menopause. Smoking has also been associated with poorer cognitive function. However, the literature has not reported on the association between smoking, estrogen and cognitive function, and the information that is available on estrogen and cognitive function is inconsistent. This may be because smoking alters the breakdown of estrogen in the body causing more of it to be converted to an inactive form. If estrogen is protective against memory loss and impaired cognitive function, smoking would have an effect of decreasing cognitive function via the estrogen metabolism pathway. This will be the first study to measure estrogen metabolites in a large sample of women aged 65 and older. It will determine if smoking is related to cognitive function at baseline and to change in cognitive function over time through alterations in estrogen metabolism. We will also look at the effects of smoking and estrogen metabolism in women who develop Alzheimer s disease. Results of this study will help elucidate the mechanism by which smoking exerts an effect on a common disease and will provide further evidence that Alzheimer s disease and cognitive decline is a tobacco-related disease.y e " wP;   g@p@4ResearchP@ LESLIEFRANCESUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECANIDA1P0DA013332-0100031,p.Biology and Cancer AddictionP@@Not GivenNot GivenUncertain4/2005 yumI@88,"~@`a@Researchl@ LERMANCARYNUNIVERSITY OF PENNSYLVANIAPHILADELPHIAPANCIP50, CA0958561,p.@@P@9/15/20038/31/20089/15/2003 to 8/31/20084/2005zuqcG@88,"@@@ResearchX@LERMANCARYNUNIVERSITY OF PENNSYLVANIAPHILADELPHIAPANCIR01, CA0635621,p.|@@l@9/10/19935/31/20049/10/1993 to 5/31/20044/2005zuqcG@88,"@i@ResearchD@LEEI-MINHARVARD UNIVERSITYBOSTONMANCIR03, CA091213N@L@@H@4/15/20013/31/20034/15/2001 to 3/31/20034/2005xid`XD=88,"@@Researchr@LASHTIMOTHYBOSTON UNIVERSITY MEDICAL CAMPUSBOSTONMANCIK07, CA087724@1,p.t@R@d@8/4/20007/31/20058/4/2000 to 7/31/20054/2005zuqiG>88,"n@ y@Researchn@LASATERTHOMASBROWN UNIVERSITYPROVIDENCERINHLBIR01, HL057457@T@@ \@9/30/19977/31/20039/30/1997 to 7/31/20034/2005rkg[IA88,"^@B@Researchz@LARKEYLINDAUNIVERSITY OF ARIZONA CANCER CENTERPHOENIXAZACSTURSG-03-080-01-PBP1,p.@@ @1/1/200312/31/20071/1/2003 to 12/31/20074/2005~yulG@88," @@Researchp@LANIADO-LABORINRAFAELSAN DIEGO STATE UNIVERSITYSAN DIEGOCACTRDRP7RT-0049!,p.@@ @7/1/19986/30/20017/1/1998 to 6/30/20014/2005|xmQI88,"g@p@4Research"STUDIES OF ATOMIC BOMB SURVIVORSLANDCHARLESDIV. OF CANCER EPIDEMIOLOGY AND GENETICSBETHESDAMDNCIZ01, CP010134!,p.@@ b@Not GivenNot GivenUncertain4/2005i`ZZ,"c@@Researcht@LAMMEREDWARDCHILDREN'S HOSPITAL OAKLANDCACTRDRP6RT-0360Not availableBiology and CancerDiscovery 1a Evaluation 1b@7/1/19976/30/20017/1/1997 to 6/30/20014/2005!}skg^H@88,"`u@@Researchb@KUSHILAWRENCEUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCANIEHSU01, ES012801B!,p.Biology and CancerR@ (@7/1/20036/30/20107/1/2003 to 6/30/20104/2005 tI?88," @G@Researchv@KROETZDEANNAUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP7RT-0025!,p.Biology and CancerT@@7/1/19986/30/20027/1/1998 to 6/30/20024/2005sH@88,"@@u@Researchj@"KRITZ-SILVERSTEINDONNAUNIVERSITY OF CALIFORNIA AT SAN DIEGOSAN DIEGOCACTRDRP9RT-0034f @Biology and CancerDiscovery 1a Evaluation 1b@7/1/20006/30/20037/1/2000 to 6/30/20034/2005/'yRK88,"LVAL!,p.Smoking during pregnancy is associated with many adverse outcomes on both the pregnant woman and on her fetus and newborn baby. Some of these effects include an increased chance of premature birth, a higher rate of infant death, a slower rate of fetal growth, low birth weight of the newborn, and an increased incidence of sudden infant death syndrome. Most of these adverse effects are associated with nicotine, a major component of tobacco smoke. Nicotine is also responsible for the addictive properties of this drug. With at least 16% of women continuing to smoke throughout their pregnancy, the effects of smoking on the pregnant woman and fetus are major public health concerns. This study will investigate if and how the placenta protects the fetus from nicotine. The placenta serves as a major life support organ for the fetus. Its ability to move oxygen and nutrients from maternal to fetal blood is necessary for the normal growth and development of the fetus. It also serves as a protective barrier for the fetus against harmful compounds by preventing their passage from maternal blood. Since nicotine is such a commonly used and abused drug during pregnancy, it is important to understand how the placenta functions to prevent nicotine from reaching the fetus. Specifically, this project will examine the mechanisms by which nicotine moves across cell membranes, allowing its entry both into and out of the fetus and placenta. It is likely that, once nicotine enters the placenta, it encounters  pumps which return the nicotine back to the maternal blood, thereby protecting the fetus. We will also test whether the placenta can break down nicotine into less harmful agents. This is another possible way in which the placenta can protect the fetus from the harmful effects of nicotine (and other drugs and toxins). These studies will also determine whether the placentas of smoking women are better able to pump nicotine away from the fetus and to break nicotine down into less harmful compounds in comparison* LVAL: to the placentas of non-smoking women. This would mean that the placenta may have important ways in which it responds to not only nicotine but also other potentially harmful drugs as a means of protecting the fetus. Overall, these studies will greatly increase our understanding of the role of the placenta in regulating the exposure of the fetus to nicotine. This information is vitally important for us to decrease the health risks of smoking women and their newborn infants.LVAL$(D \ N & H ( BV>b\J| A PANEL STUDY OF QUIT SMOKING PROCESSES IN LOW-SES WOMENHEALTH BEHAVIORS AND FAMILY HISTORY OF COLORECTAL CANCERGENETICS OF VULNERABILITY TO NICOTINE ADDICTIONGENETICS OF ADOLESCENT TOBACCO USE AND DEPENDENCETOBACCO-RELATED DISEASE IN NATIVE CALIFORNIA TWINSSUPPLEMENT TO TOBACCO DISEASE IN TWINSIRON STATUS AND RISK OF CHD AND COLON CANCERPOLYDRUG ABUSE-IMAGING AND BEHAVIORPHARMACOLOGICAL AND BEHAVIORAL INDICES OF DRUG ABUSEMODELING THE RELATION OF SMOKING TO THE OVARIAN FUNCTIONBIOSOCIAL RISK FACTORS FOR CHILDHOOD BEHAVIOR PROBLEMSMODERATE ALCOHOL USE--THE HETEROGENEITY OF ABSTENTIONA RANDOMIZED CONTROLLED TRIAL OF SUSTAINED RELEASE BUPROPION FOR PREVENTION OF RELAPSE IN WOMEN WHO QUIT SMOKING DURING PREGNANCYDECIPHERING GENES AND PATHWAYS IN NICOTINE DEPENDENCEPOPULATION BASED STUDIES OF BRCA1MOLECULAR EPIDEMIOLOGY OF PANCREATIC CANCERGENETIC SUSCEPTIBILITY AND EXPOSURE TO HETEROCYCLIC AMINES IN BREAST CANCERPATTERNS AND RISK FACTORS FOR ADOLESCENT SMOKING PROGRESSIONA SIMULATION OF TOBACCO POLICY, SMOKING AND LUNG CANCEREFFECTS OF SMOKELESS TOBACCO USE ON PREGNANCYTREATING POSTPARTUM NICOTINE DEPENDENCEMECHANISM OF STRESS EFFECTS ON WEIGHT IN NICOTINE WITHDRAWALADOLESCENCE: A SENSITIVE PERIOD FOR NICOTINE ADDICTIONINITIAL SUBJECTIVE REACTIONS TO NICOTINE IN YOUNG ADULTSNICOTINE REGULATION OF DEVELOPING BRAIN CATECHOLAMINESANIMAL MODELS OF NICOTINE SUSCEPTIBILITYTARGETING ANTI-SMOKING PSAs BASED ON SENSATION-SEEKINGBIOBEHAVIORAL LUNG CANCER PREVENTION PROGRAMRISK FACTORS FOR PANCREATIC CANCERSMOKING AND GENETIC INTERACTION IN BREAST CANCER ETIOLOGYSMOKING CESSATION PROGRAM FOR LOW INCOME PREGNANT WOMENJUNTOS EN LA SALUD: CANCER PREVENTION/ SCREENING FOR LATINASFAMILY FACTORS IN SMOKING ACQUISITION AMONG LATINO YOUTHORAL CLEFTS, SMOKING AND VARIATION TOXIN BIOTRANSFORMATIONENVIRONMENTAL AND GENETIC DETERMINANTS OF PUBERTYTRANSPORT AND DISPOSITION OF NICOTINE IN THE HUMAN PLACENTALVAL!,p.There is growing evidence that early life events play an important role in the development of breast cancer, and the onset of puberty is thought be a key event in influencing subsequent breast cancer risk. If it is known that lifestyle, environmental, or genetic factors influence pubertal development, this may potentially provide another area for strategies to prevent breast cancer and promote health of young girls. In order to examine the role of environmental and genetic determinants of puberty, we propose to conduct a prospective cohort study of 400 girls who are members of the Kaiser Permanente of Northern California (KPNC) Medical Care Program. We will enroll girls who are aged 7 or 8 y at baseline, and follow them as they mature sexually. Our sampling frame will be the KPNC Infant Cohort file, which documents every birth that has occurred within KPNC since 1990. We will enroll girls who were born in and are current members of KPNC, thus enabling access to substantial clinical information regarding prenatal care, birth records, and infant and childhood clinical visits. We will recruit from girls who live in Matin County, San Francisco, and selected Alameda County communities to facilitate in-clinic exams. This population of girls is also diverse racially and ethnically. At baseline and annually thereafter, we plan clinic visits to assess Tanner Stage for breast and pubic hair development, and to collect information by interview regarding various factors that may influence age at onset of these hallmarks of puberty. We are interested in: anthropomettic factors such as weight, height, body fatness, or growth trajectory; food and nutrient intake; physical activity; and exposure to tobacco smoke and alcohol. We propose to collect and store biospecimens annually. Blood will be collected to enable investigation of exposure to long-lived organohalogen compounds including polychlorinated biphenyls and polybrominated diphenyl ethers. DNA from blood samples will be extracted and pooled for genotyping for p LVAL olymorphisms in genes related to metabolism of sex steroid hormones or exogenous exposures that may influence pubertal development. Urine will be collected to measure levels of estradiol and gonadotropins, as an alternative measure of sexual maturation. After 5-6 years of follow-up, we anticipate that about 319 and 304 girls will have transitioned through Tanner Stage 2 for breast (B2) or pubic hair (P2) development, respectively, and 151 girls will have experienced onset of menses. This provides adequate power to detect relative risk of about 1.5 for exposures with prevalence of 0.2 for B2 or P2, and about 1.7 for onset of menses. With a larger cohort or pooling of data from other Centers, we should have adequate power to detect associations or interactions with public health or clinical significance.rLVAL P .AGE Young Adult Adult DISEASE/BIOLOGY Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO NicotineAGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural National PREVENTION/TREATMENT Counseling/Behavior Therapy Support Group Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionADDICTION Initiation AGE Child LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION Hispanic TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesAGE Child Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menopause HormonesAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child Young Adult DISEASE/BIOLOGY Mechanisms Other Disease/Biology EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle HormonesLVAL!,p.The Life Span Study (LSS) cohort of 94,000 survivors of the Hiroshima and Nagasaki atomic bombings is being studied in collaboration with the Radiation Effects Research Foundation (RERF). Cohort studies are used to quantify radiation dose response and its dependence on histological subtype of tumor, age at exposure, sex, age at observation, and time following exposure. Among several new findings is the excess risk of nervous system tumors, especially of schwannoma. The data indicate that exposure to even moderate doses, i.e., less than 1 Gy, is associated with an elevated risk of nervous system tumors. A nested case-control study undertaken to clarify the role of hepatitis B and C infection in radiation-related liver cancer risk showed a synergistic interaction between radiation and hepatitis C infection. Analysis of joint effects of radiation and smoking for lung cancer demonstrated important confoundning effects of smoking on the radiation risk because of significant differences in smoking behavior among different birth cohorts in Japan. The data also showed that smoking and radiation have an additive effect on lung cancer. Analysis of updated breast cancer incidence data showed that the radiation-related cancer risk is highest among women exposed at ages 0-19 years and lowest among those exposed after age 40, with little variation by exposure between ages 0 and 20, 20 and 40, and above 40, suggesting that breast cell differentation associated with full-term pregnancy and reduced hormonal stimulation with menopause, both act to modify the radiation effect. A multidisciplinary study of hormonal assays found pre-diagnostic levels of free estradiol, both at premenopausal and post-menopausal ages, to be a significant predictor of breast cancer. A subsequent international pooled analysis of data from nine studies, including ours, found a significant level of consistency across studies in this respect. A research protocol has been approved for a new, expanded A-bomb survivor study with twice as many breasLVALt cancer cases, utilizing more recent stored serum samples and measurement of additional hormones. Following the first comprehensive LSS cancer incidence report published several yeara ago, we are preparing a new solid cancer incidence report. The new incidence series comprises over 12,000 first primary cancers, adding 3,500 new cases that occured since the first report. Among various site-specific cancer studies, case ascertainment has been completed in studies of tumors of the thyroid and ovary, and manuscripts are in preparation. Case ascertainment is nearing completion for lung cancer and in progress for lymphoid cancer. A multidisciplinary case-case approach is in progress to study genetic susceptibility to radiation-related breast and ovarian cancers. This follows the previously reported phenomenon of extremely high, dose-specific relative risks for early-onset breast cancer (before age 35), which suggests increased sensitivity to radiation among a genetically predisposed population subgroup. In this study, early and late-onset breast cancer cases are compared and BRCA 1/2 and other candidate genes in breast cancer pathways are investigated using archived tissues. Another molecular epidemiological study underway involves thryoid cancer and assesses rearrangements of RET proto-oncogenes (RET-PTC1 and 3) in relation to age at exposure and tumor latency. Construction of a database that incoroporates all previous LSS mail survey data is underway. When completed, this database will allow an easy access to a large amount of information of epidemiological interest, i.e., tobacco use, alcohol intake, diet, reproductive history, occupations, medical history, etc. Using some of these data, our recent analysis showed that green tea consumption is virtually unrelated to cancer risk.LVAL!,p.This multi-phase study examined youth and parent reports of parental prompting with prompts ranging from empty or clean ashtrays to smoking with the parent. For the youth study 3624 7th and 8th grade middle school students completed surveys. About 300 smoking parents completed surveys to identify parent-reported factors associated with parental prompting behaviors, with about 30% of parents reporting having prompted their children with at least one of the prompts. One year later, children of the 300 smoking parents and about 300 additional children who reported having no parent smokers in the initial surveys, completed follow-up surveys. Initial findings indicated that parental prompts were less prevalent than in our previous work. We also found that there were not consistent or great differences in the prevalence of prompting between Latinos and non-Latinos and that parental prompting, particularly requests that the child light the parent s cigarettes with a match or lighter was associated with children s smoking. Further, we found that Latino adolescents may be influenced by more parental prompts than non-Latinos, and finally that higher familism scores were significantly associated with lower risk of smoking, regardless of ethnicity. Concordance of child and parent reports regarding prompting showed that except for requests from fathers to smoke together, child-reported prompting prevalence was consistently higher than parents reports and the biggest discrepancies between parent and child reports were requests to clean ashtrays and bring cigarettes, the two most common prompts. This study also demonstrated a temporal relationship in the multiethnic sample of adolescents between availability of cigarettes and subsequently trying smoking. In this sample, social sources were clearly more important than commercial sources both cross-sectionally and prospectively. In the prospective study, parental prompts were not related to subsequent adolescent trial smoking among 478 multi-ethnic adolescents. The rLVALesult was unexpected, since our previous cross-sectional studies had shown several strong and consistent associations.LVAL1,p.Cervical cancer rates for Latinas are nearly twice as high as for non-Hispanic women, while the two most common cancers among Latinas are breast and colorectal. Despite the availability of tests for detecting these three cancers early, screening rates are low, often two-thirds the rates in the general population of women, and survival rates are comparatively poor. This project aims to compare and refine two methods of implementing a community health advisor, or "Promotora," program to improve breast, cervical, and colorectal cancer screening and primary prevention behaviors among a population of underserved, primarily Hispanic, women 18 and over. The program will reach women through clinics, community-based organizations, and physician offices in Phoenix and Tucson, Arizona (urban, and surrounding rural areas). In the usual care (UC) intervention, Promotoras will meet with women individually to teach information and encourage prevention behaviors and adherence to screening guidelines. In the social support group (SSG) arm of the program, Promotoras will create ongoing social groups of women to learn about cancer prevention, will foster group dynamics likely to promote desired behavior changes, and will provide a much higher level of support through the group than could be provided by the Promotora alone. We want to know if one of the programs is more successful in getting them get screened for cancer when they are due (that is, getting annual mammograms, Pap tests, FOBT, and sigmoidoscopy/colonoscopy), or if they adopt behaviors expected to reduce the likelihood of getting cancer: increasing physical activity and fruit and vegetable consumption, and decreasing household tobacco use. For both interventions, Promotoras will be trained to educate Hispanic women about primary prevention and screening for breast, cervical, and colorectal cancer using culturally appropriate materials and curriculum standardized across arms of the study. The UC and SSG interventions will reach 2,000 women. Goals: 1. Conduct F LVALV a field test of a novel theory-based Promotora intervention using social networks, social support, and diffusion of innovations concepts to further our understanding of the best practices promoting cancer screening and lifestyle changes; 2. Evaluate best practices of an extended Promotora program; 3. Increase participants' knowledge of the importance of early detection and the availability of screening and treatment for cancer, increase clinical screening for breast, cervical, and colorectal cancers, and breast self-examination; 4. Promote adoption and maintenance of prevention-oriented lifestyle changes among low-income Hispanic women with a focus on diet, physical activity, and decreasing household tobacco use. LVAL @ <2AGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Nicotine WOMEN PregnancyAGE Child Adult DISEASE/BIOLOGY Mechanisms PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH1 Animal Studies RESEARCH Clinical Research TOBACCO NicotineAGE Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesADDICTION Cessation Withdrawal DISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cancer Mechanisms LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN HormonesCOMMUNITY Health Care Provider ECONOMICS Socio-Economic Status PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials Biochemical Assessments PSYCHOLOGICAL Cultural Factors RESEARCH Human Studies Clinical Research STUDY POPULATION African American Hispanic TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumLVAL This project is a collaborative effort of physicians with experience in providing prenatal care to low income participants and researchers who have developed and refined three different program components to reduce cigarette smoking. The design is a prospective randomized pretest/posttest design with biochemically confirmed smoking status as the outcome. Posttests will be carried out at 37 weeks of gestation, six weeks postpartum and six months postpartum. Participants will be randomized to three groups. Group 1 will use an adapted version of a Quit Kit called "A Pregnant Woman's Guide to Quit Smoking" developed by Dr. Richard Windsor; Group 2 adds a Quit and Win contest used by the Principal Investigator; and Group 3 adds the use of telephone counseling based upon motivational interviewing. These materials will be made culturally appropriate for African-Americans and Hispanics. LVAL1,p.The candidate, Dr. Timothy Lash, has been committed to cancer research since the beginning of his career. He studied molecular biology, including tumor biology, as an undergraduate at the Massachusetts Institute of Technology. Upon graduating, he worked as a consultant in environmental health on projects that required dose-response assessment of environmental and occupational carcinogens. Simultaneously, he completed a Masters of Public Health and the coursework for a Doctorate of Science in Epidemiology at the Boston University School of Public Health. The curricula for these degrees included many courses directly relevant to cancer prevention and control. He has worked on research projects involving breast cancer etiology, therapy, and side-effects of therapy under the direction of the proposed mentor (Dr. Rebecca Silliman) and the proposed co-mentor (Dr. Ann Aschengrau). Dr. Lash is currently an Assistant Professor of Epidemiology at the Boston University School of Public Health. He spends 75 percent of his effort on research projects directly relevant to the proposed research plan. For example, he is the project director on a study of adjuvant tamoxifen therapy in old age. Dr. Silliman is the Principal Investigator of the project, which will provide the cohort of breast cancer patients eligible for the second proposed study. Dr. Lash also works with Dr. Aschengrau, the proposed co-mentor, on analyses of the effect of active and passive smoking on breast cancer occurrence. The most recent case-control data set in which these analyses have been performed will provide the subjects eligible for the first proposed study. The environment at the Boston University Medical Center is ideally suited for accomplishing the career development goals of this application. The research plan proposes two studies of the interaction between tobacco smoke and NAT2 or COMT genetic polymorphisms. The association between tobacco smoke and breast cancer risk is complicated. It has been hypothesized that tobacco smoke expos LVAL ure may both cause and prevent breast cancer, depending on the timing of exposure relative to reproductive milestones. The interaction with tobacco smoke exposure with the gene polymorphisms will allow tests of these hypotheses. The first study would collect buccal swabs from eligible participants of the second Cape Cod case-control study (Dr. Aschengrau was PI). Existing interview information would be combined with the polymorphism data extracted from the swabs to assess the interaction between the polymorphisms and tobacco smoke subgroups under a biologically based etiologic model of breast carcinogenesis. The second study would collect buccal swabs from participants in the study of adjuvant tamoxifen therapy (Dr. Silliman PI). A similar analytic plan would be conducted, but with a case-only design.lLVAL!8 ^  R ( @ X< fr&HXdEpidemiology and National Surveillance Awareness Risk Perception and CommunicationsEpidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentEpidemiology and National Surveillance Awareness Risk Perception and Communications Community and Policy InterventionsBiology and Cancer Addiction Interventions for Prevention and TreatmentEpidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentAddiction Epidemiology and National Surveillance Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Addiction Epidemiology and National Surveillance Global IssuesBiology and Cancer Addiction Epidemiology and National Surveillance Global IssuesBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National Surveillance Community and Policy InterventionsBiology and Cancer Epidemiology and National Surveillance Global IssuesInterventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Interventions for Prevention and TreatmentEpidemiology and National SurveillanceLVALPancreatic cancer is the ninth most commonly occurring cancer, but the fifth leading cause of cancer death in the US. It is one of the most rapidly fatal cancers, with 1- and 5-year survival of only 16 percent and 0.4 percent. As there are currently no effective treatments for this disease, prevention is of paramount importance. Only older age and cigarette smoking are well- established risk factors. The roles of other risk factors, such as pipe and cigar smoking, coffee, tea and alcohol consumption, the presence of diabetes mellitus, and physical activity are unclear. To provide more information, we propose to analyze the associations of these characteristics with pancreatic cancer risk using previously collected data. In 1962 or 1966 (1962/1966), 29,347 men and women, who were free of cancer and aged 30-79 years, returned a health questionnaire. Subjects also returned another health questionnaire in 1977. They provided a wide range of information on these two questionnaires, including data on cigarette, pipe and cigar smoking, coffee, tea and alcohol consumption, physician-diagnosed diabetes mellitus, and physical activity. Between 1962/1966 through 1993, 210 subjects died from pancreatic cancer. We request funds to collect another two years of mortality data through 1995 (given the costs constraints of the small grants program), bringing the total of pancreatic cancer deaths to an estimated 230. Power calculations show adequate power to detect moderate increases in relative risks (1.5-2.5) associated with these risk factors. This large database provides a unique and cost-effective opportunity to examine the associations of various characteristics, most of which are modifiable, with pancreatic cancer risk. Findings from these analyses will have public health significance for a highly fatal disease.LVAL1,p.In our original grant (R01CA63562), we evaluated the impact of a smoking cessation treatment which incorporated motivational feedback about genetic susceptibility to lung cancer. We found strong positive effects of genetic feedback on perceived risk, perceived quitting benefits, and fear arousal. While smokers receiving genetic feedback made more quit attempts, they were no more likely to quit than were smokers receiving standard minimal contact cessation treatment. Observing that the vast majority of smokers were unable to quit, even in the face of perceived vulnerability and heightened motivation, we became interested in the genetic basis of nicotine dependence and smoking cessation. The strongest evidence (by our group and others) supports the role of the dopamine transporter gene (SLC6A3) which regulates reuptake of dopamine at the synapse. This is consistent with a large body of data suggesting that the reinforcing effects of nicotine are due to its impact on the neurotransmitter dopamine. Thus, in this competitive renewal, we propose to extend our research by evaluating the role of SLC6A3 in the response of smokers to pharmacological smoking cessation treatment (bupropion/Zyban). We have selected bupropion because: (a) initial data from randomized clinical trials provide strong support for its efficacy as a smoking cessation treatment, and (b) bupropion has inhibitory effects of dopamine transport (the protein product of the SLC6A3 gene). The specific aims of the proposed research are: (1) to evaluate the role of genetic factors in response to standard smoking cessation treatment; (2) to evaluate the role of genetic factors in response to bupropion treatment; and (3) to evaluate the psychobiological mechanisms by which genotype and bupropion influence smoking cessation. The study will be a double blind randomized placebo-controlled clinical trial of bupropion in 600 adult male and female smokers. The factorial design includes one treatment factor (bupropion plus standard treatment (with nicotineLVAL  patch) vs. placebo plus standard treatment with patch) and one subject factor (SLC6A3 genotype, genetically predisposed vs. genetically protected). Bupropion or placebo will be delivered over a 10-week treatment period. All subjects will receive standard minimal contact cessation treatment, which includes two in-person sessions plus five brief structured phone-counseling sessions. A major innovation of this study is that we will use a behavioral economics computer paradigm to evaluate the reinforcing value of nicotine at pre-treatment and during bupropion therapy. Other mediating outcomes (mood, withdrawal) will be assessed at pre-treatment and at multiple points during treatment. The primary smoking cessation outcomes will be assessed at 1-, 6- and 12- months post-treatment. The proposed research will be the first to examine the role of specific genetic factors in response to pharmacological therapy for smoking cessation and to evaluate novel mediating mechanisms. The long-term objective is to provide information necessary to match smoking cessation treatments to individuals, based on their genetic predispositions.LVAL1,p.Cigarette smoking among young adults (ages 18-25) is an important cancer control problem. Despite increasing trends in smoking behavior, this group has been understudied with respect to anti-smoking campaigns. Although much attention has been directed to anti-smoking media campaigns for adolescents, on balance, these efforts have produced modest results. Some have argued that the theoretical underpinnings of such media-based anti-smoking prevention campaigns need to be refined if their efficacy is to be improved. Toward this end, we propose to conduct experimental research to develop and test theory-based anti-smoking video segments (referred to as PSAs) that are targeted to high and low sensation-seeking young adults. The specific aims are to: (1) evaluate the effects of the sensation value of the content of the PSAs in high and low sensation-seekers, (2) to evaluate the effects of the sensation value of the format of the PSAs in high and low sensations-seekers, and (3) to explore the cognitive, affective, and arousal mechanisms by which the different PSAs exert an impact on behavioral intentions in these two groups. Our hypotheses, experimental design, and measures are guided by theories of Communication and Health Behavior Change. Using a laboratory-based experimental design, PSAs will be developed and targeted to high sensation-seekers (HSS) and low sensation-seekers (LSS). Two aspects of the PSAs to be manipulated are sensation value of the content (the theme of the anti-smoking appeal; e.g., tobacco industry manipulation vs. second-hand smoke) and sensation value of the format (the formal features; e.g., high vs. low intensity of visual and auditory effects). Study participants will be 800 males and females ages 18-25 from the Philadelphia area who have smoked at least 1 whole cigarette in the past 6 months. A factorial design will be used to test hypotheses about the impact of 8 different PSAs: (2 per condition): (1) high sensation value (HSV)-content and format; (2) HSV-content, (LSV)-format; $ LVAL4 (3) LSV-content, HSV-format; and (4) LSV-content and format. Our analyses will focus on the following mediating mechanisms in the communication and behavior change process: (a) arousal; (b) cognitive processing and affective evaluation; (c) comprehension (free and forced recall of content); (d) changes in smoking-related beliefs, attitudes about smoking, beliefs about the consequences, prototype images and social norms; and (e) behavioral intentions and willingness. Those PSAs found to be most effective in our research will be exported to the Legacy Foundation for dissemination and large-scale evaluation.LVAL1,p.The majority of adult smokers initiate smoking as children. Most previous studies of the biological effects of nicotine have focused on adults rather on adolescence, a developmental period that is characterized by sexual maturation and by significant changes in brain structure and function. In the present proposal we will use animal models to examine the biological factors that underlie susceptibility to nicotine. In particular, we will test the following hypotheses: (l) That the balance of reinforcing/aversive effects of nicotine is greater in juveniles than in adults. (2) That individual differences in susceptibility to nicotine dependence are associated with variations in stress responsivity. Three specific aims are proposed. First, the effects of nicotine will be compared in juvenile rats aged postnatal day (p) 30 and in adults. Animals will be treated with nicotine and tested behaviorally. At the end Of some experiments animals will be decapitated and trunk blood collected for the measurement of corticosterone levels. Brains will be processed by in situ hybridization for quantitative analysis of the expression of mRNA for the immediate early gene, cfos, in specific neuronal populations. Experiments will be conducted with both male and female rats to determine whether nicotine is more reinforcing in juveniles than adults using both conditioned place preference and self adrnistration paradigms. Animals will also be tested to determine whether conditioned sensitization to the locomotor activating effects of nicotine Occurs more rapidly in juveniles than adults, and to determine whether juvenile exposure to nicotine increases sensitivity to nicotine in adults. Second, individual differences in stress responsivity will be induced by a procedure in which pups are either handled (H) or not handled (NH) for two weeks after birth. H and NH groups will then be compared as juveniles and adults to determine whether differences in stress responsivity result in different acute effects of nicotine on locomotion LVAL , plasma corticosterone and cfos expression. Differences in the reinforcing effects of nicotine in H and NH groups will also be examined, as will differences in withdrawal severity following chronic nicotine treatment. Third, the effects of nicotine on genetically distinct strains of mice will be studied. Both acute and chronic effects of nicotine in C3H andC57B1/6J mice, and in transgenic mice with alterations in selected genes, will be examined. These studies will provide critical information on the biological mechanisms underlying individual variations in responsivity to nicotine and will complement the human studies in projects I and 2.LVAL1,p.In the previous funding period, we have demonstrated that nicotine interacts directly with nicotinic receptors (nAChRs) on catecholamine neurons to stimulate norepinephrine (NE) and dopamine (DA) release in developing rat brain. We now propose a series of studies to examine the physiological and clinical relevance of these observations. We will study the species specificity of nAChR-mediated catecholamine release in C57BL/6J mice, and will use null mutant mouse strains to examine the subunit composition of nAChRs on developing NE and DA terminals. Two types of approach will be used to examine whether nAChRs on developing noradrenergic locus coeruleus (LC) terminals may be activated by endogenous ligand. We will use immunohistochemistry to establish the developmental appearance of cholinergic cells and fibers in relationship to LC and its forebrain and hindbrain terminal fields. Antibodies specific for the vesicular acetylcholine transporter (VAChT) and for dopamine beta hydroxylase (DBH) will be used to visualize developing cholinergic and noradrenergic elements, respectively. We will also determine whether nAChR activation or blockade can modify early learning in paradigms that have been shown to require activation of the LC, including early olfactory learning and somatosensory associative conditioning. Learning in each task has been shown to necessitate LC activation by tactile stimulation and electrical shock, respectively. We will test the hypothesis that peripheral administration of nicotine induces sufficient LC stimulation to facilitate learning in the absence of sensory stimuli. We will also use the nAChR antagonist, mecamylamine, to determine whether endogenous acetylcholine (ACh) influences sensory stimulus-induced LC activation on these tasks. Having established the functional roles of nAChRs in acute regulation of catecholamine release, we will examine the effects of both tonic and phasic modes of chronic prenatal nicotine exposure on the development of central catecholamine systems. OsmotLVAL ic minipumps will be used for constant infusion and self- administration for pulsatile delivery of nicotine to pregnant rats. Offspring of varying ages will be used for functional and neuroanatomical studies to determine whether prenatal nicotine exposure after the overall excitability, or nicotine-sensitivity, of NE and DA terminal fields. Behavioral tests that involve both central NE (early olfactory learning, associative somatosensory conditioning) and DA systems (locomotion, conditioned place preference, self-administration) will be used to determine whether chronic nicotine-induced changes in catecholamine system development are associated with long-term alterations in behavioral response. These combined in vitro and in vivo approaches are designed to elucidate mechanisms underlying adaptive responses of central catecholamine neurons to chronic prenatal nicotine exposure.   A  j> >--@@Researchj@LI MINGUNIVERSITY OF TEXAS HEALTH SCIENCES CENTERSAN ANTONIOTXNIDAR01, DA013783~@,p.Biology and Cancer AddictionP@x@9/28/20004/30/20099/28/2000 to 4/30/20094/2005|oC=88,",, @q@ResearchB@LIFREDERICKDANA-FARBER CANCER INSTITUTEBOSTONMANCIR01, CA078564@L@ Discovery 1b Evaluation 1b~@8/5/19995/31/20038/5/1999 to 5/31/20034/2005vqmeG<88,"++@@ResearchV@LIDONGHUIUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNCIR01, CA098380@,p.t@@@5/1/20044/30/20095/1/2004 to 4/30/20094/2005}tE<88,"**G@@@Research@LIDONGHUIUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXACSRSG-02-243-01-CCE@,p.Biology and CancerR@@7/1/20026/30/20067/1/2002 to 6/30/20064/2005 }tE<88,"))@G@Researchx@LICHAOYANGUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP9DT-0199F@,p.L@@\@7/1/20006/30/20027/1/2000 to 6/30/20024/2005zviF<88,"((N@ @Researchn@LEVYDAVIDPACIFIC INSTITUTE FOR RESEARCH AND EVALUATIONCALVERTON MDNCIU01, CA097450j@,p.@V@L@8/26/20027/31/20068/26/2002 to 7/31/20064/2005tE>88,"''g@p@4ResearchZ@LEVINERICHARDNational Institute of Child Health and Human DevelopmentBETHESDAMDNICHDZ01, HD008745@@T@@Not GivenNot GivenUncertain4/2005I@88,"&& S@ (@ResearchN@LEVINEMICHELEUNIVERSITY OF PITTSBURGHPITTSBURGHPANIDAK01, DA015396@,p.T@@,@9/30/20025/31/20079/30/2002 to 5/31/20074/2005ysocI@88,"%% @G@Researchx@LEVINEJONUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP7RT-0068p @Biology and Cancer AddictionDiscovery 1a Evaluation 1b*@7/1/19986/30/20027/1/1998 to 6/30/20024/20055- pE@88,"$$@{@Researchn@ LEVINEDWARDDUKE UNIVERSITYDURHAMNCNIDAR01, DA015756@,p.Biology and Cancer AddictionP@.@4/1/20043/31/20094/1/2004 to 3/31/20094/2005yjd`XG?88,"##j@@Research OKLAHOMA SMOKE-FREE BEGINNINGSLEUTHARDJOYOKLAHOMA STATE MEDICAL ASSOCIATIONOKLAHOMA CITYOKRWJFNot Givenn@@@@4/1/200312/31/20054/1/2003 to 12/31/20054/2005 gbXX,"""9@p@4Researchp@ LESSOVCHRISTINAWASHINGTON UNIVERSITYST. LOUISMONIDAF31, DA015268 @Biology and Cancer Addictionn@@3/5/2002Not Given2002 to ?4/2005wqmbK@88,"!![@@Researchl@ LESLIEFRANCESUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECANIDAR01, DA0106121,p.Biology and CancerDiscovery 1a Evaluation 1b^@5/1/19971/31/20065/1/1997 to 1/31/20064/2005#yumI@88,"LVALThis 12-month project is motivated by the hypothesis that individual differences in initial nicotine sensitivity in humans are associated with nicotine dependence vulnerability and are an important mediator of genetic influences on risk of nicotine dependence. This application combines (1) characterization of existing data on self-report reactions to first cigarette assessed retrospectively in a large adolescent female twin sample (Missouri Adolescent Female Twin Study, MOAFTS) and on subjective reactions to nicotine versus placebo administered by nasal spray to smoking experimenters (smoked fewer than 100 cigarettes lifetime) and measured in the laboratory (Nicotine Challenge Study); and (2) collection of new self-report data on subjective reactions to first cigarette and recalled reactions to nicotine nasal spray in order to assess validity of proposed measures of nicotine sensitivity data and the feasibility of collecting such data from genetically informative samples. If measures can be shown to have acceptable reliability and validity, to be strongly familial and to be associated with nicotine dependence vulnerability, this will lay the groundwork for including such measures in gene-mapping and other genetic studies of nicotine dependence vulnerability and will help identify potential key targets for smoking prevention and intervention. A series of individualized tutorials and formal coursework will provide necessary advanced research training in human behavior genetic of addiction to support this research plan. LVAL0 <AGE Child ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION African American Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National POLICY Regulatory Intervention RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International RESEARCH Human Studies TOBACCO Smokeless WOMEN PregnancyADDICTION Relapse DISEASE/BIOLOGY Other Disease/Biology PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Postpartum MISCELLANEOUS Weight Gain/ExerciseADDICTION Withdrawal DISEASE/BIOLOGY Mechanisms Other Disease/Biology TOBACCO Nicotine MISCELLANEOUS Weight Gain/ExerciseAGE Child Young Adult Adult DISEASE/BIOLOGY Other Disease/Biology PREVENTION/TREATMENT Nicotine Replacement Therapy PSYCHOLOGICAL Other Psychological RESEARCH1 Animal Studies TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Health Care Provider LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN PregnancyLVALThis intervention is based on recommendations and implementation suggestions from ACOG and the Public Health Service Clinical Practice Guideline Treating Tobacco Use and Dependence. A "Practice Enhancement Assistant", or PEA, will provide education, resources, and feedback to physicians and staff at each practice regarding the plan they choose to use when implementing the 5 A's. As part of the implementation plan, physicians will be offered the use of a Personal Data Assistant (PDA) to enter information on patients to track their status at each prenatal visit. One champion will be identified in each practice who will communicate the responsibilities in the delivery of the 5 A's. Quality improvement strategies such as chart audits will be implemented to provide a fast and efficient way of modifying each part of the intervention to ensure optimal implementation at each site. The utilization of the Chronic Care Model to implement the practice guidelines will allow for an effective, efficient way to improve the health of all smoking pregnant women in Oklahoma. LVAL@,p.The great majority of tobacco addiction begins during adolescence, but very little is known about the neurobehavioral effects of nicotine in adolescents compared to adults. Adolescents are still undergoing important neurodevelopmental changes on the path to adulthood. Nicotine exposure in adolescence may have lasting impacts on this late neurodevelopment. There are suggestions in the clinical literature that more heavily addicted smokers begin smoking earlier in adolescence, but the impact of nicotine self-administration during adolescence versus self-selection bias whereby people more prone to heavy addiction also begin earlier, cannot be ethically unconfounded in humans. This project is based on our hypothesis beginning nicotine self-administration during adolescence leads to greater nicotine intake and dependence than beginning in adulthood. Our preliminary data demonstrated in the rat model of nicotine self-administration that rats with adolescent-onset nicotine self-administration self-administer substantially higher total doses of nicotine than adult-onset rats, This higher rate of nicotine self-administration continues into adulthood with an approximate doubling of nicotine self-administration. The proposed experiments will determine the causal relationship between adolescent-onset nicotine self-administration and enhanced long-term nicotine self-administration with these Specific Aims. 1. Determine the pharmacokinetics and dose-effect functions of nicotine in adolescents and adult rats. 2. Determine the impact of nicotine replacement and nicotinic antagonist therapy on nicotine self-administration in adolescent-onset and adult-onset nicotine self-administration. 3. Determine the age threshold for the adult-like nicotine self-administration. 4. Determine if adolescent-onset nicotine self-administration enhances cocaine dependence. 5. Determine sex differences in adolescent-onset nicotine self-administration. Nicotine pharmacokinetic measurements in adolescent and adult rats will be used to dete LVAL rmine the effect of altered distribution and metabolism versus pharmacodynamic factors in accounting for age-related differences in nicotine self-administration. Benefits of this research include a more relevant animal model of adolescent-onset smoking, improved understanding of how adolescent-onset nicotine use potentiates nicotine intake, a cause and effect determination of the gateway hypothesis of adolescent nicotine use leading to harder drugs and the development of better treatments for adolescent-onset nicotine dependence.LVALSmoking cigarettes during pregnancy adversely affects pregnancy outcomes. Smokeless tobacco is thought to be a safer alternative to smoking because combustion products are not generated. We are studying the effects of smokeless tobacco on pregnancy outcomes in a retrospective cohort study of women in the Swedish Medical Birth Register. We will compare pregnancy outcomes of those who used snuff daily, but did not smoke cigarettes; those who smoked cigarettes daily, but did not use snuff; and those who used neither product. Associations between tobacco exposure and birth weight, preterm delivery, and preeclampsia will be examined.Smoking related diseases constitute an extremely important public health problem, in terms of both human suffering and economic cost. While many diseases caused by smoking are probably not related to the nicotine in tobacco smoke, addiction to nicotine plays a significant role in the great difficulty in stopping smoking. One of the most important factors that discourages smoking cessation is stress related gain in body weight. We propose that through its potent effects on the brain, nicotine alters the body's responses to stress, and in this way promotes weight gain during nicotine withdrawal. Through this project we will understand the changes in the body 's response to stress that occur due to nicotine withdrawal when smoking is stopped. This information will be used to aid in the development of methods to treat nicotine withdrawal syndrome, so that people can be more successful at stopping smoking. The results of this study will particularly benefit young people who are still becoming smokers in large numbers and find it very difficult to stop. It will also benefit women who are particularly susceptible to concerns over weight control. If nicotine withdrawal induced weight gain can be better controlled, smoking cessation rates should increase dramatically, benefiting countless individuals and society as a whole.LVAL@,p.This Mentored Research Scientist Development Award describes a training and research plan designed to qualify the candidate to design and conduct research on the prevention of smoking relapse during the postpartum period. Although many women quit smoking during pregnancy, approximately 70% will resume smoking within a year of giving birth. Because smoking during the postpartum period has negative effects on the health of both women and children, preventing postpartum relapses to smoking can have important public health benefits. To date, however, little is known about the causes or prevention of postpartum smoking. Changes in mood and increases in concerns about weight are common during the postpartum period, and these factors also have been related to women's smoking behavior. Thus, it is hypothesized that mood and weight concerns increase women's vulnerability to postpartum smoking relapse. To elucidate the effects of mood and weight concerns on postpartum smoking, the candidate proposes a research plan designed to: (1) assess factors theoretically related to postpartum smoking relapse; (2) develop a postpartum-specific relapse prevention program addressing factors found to relate to postpartum relapse; and (3) test the feasibility, acceptability and initial efficacy of this postpartum-specific relapse prevention program. This research plan is combined with a training plan designed to establish a strong knowledge base in the following areas: (1) the physiologic effects of nicotine and tobacco on women, (2) factors in the postpartum period that affect mood and weight, and (3) advanced longitudinal data analytic techniques. The background and skills developed during through this research and training plan will provide a cohesive framework for the candidate's future career as an independent investigator in the area of clinical research on approaches to women's smoking cessation.LVAL@,p.Because over 85% of lung cancer is caused by smoking, we focus on the effect of tobacco policies on lung cancer. We will extend a previously developed macro-simulation model, known as SimSmoke, to predict smoking-attributable lung cancer the effect of tobacco control policies on those deaths. The first major aim of this project is extending SimSrnoke to estimate and predict smoking-attributable lung cancer deaths. The model will be programmed to estimate the number of smoking-attributable lung cancer deaths to smoker and non smokers during the past ten years and predict deaths over the next 35 years, and to distinguish the number of deaths by age, gender and by racial/ethnic group, and distinguish the effects of quantity smoked and smoking prevalence. We will also distinguish the effect on lung cancer of factors other than smoking, other such as other risks and the effects of treatment. We also propose to determine the impact of tobacco control interventions on observed trends in mortality; and to determine if the interventions are having their expected population impact. Specifically, SimSmoke will be used to estimate the number of smoking-attributable deaths in the United States averted as a result of policies implemented in the last ten years, and estimate the number of smoking deaths that have been averted as a result of policies implemented in the last ten years in three states with proactive tobacco control policy. We will also consider the potential impact of policies in the future. In examining the effect of tobacco control policies, we will distinguish their effects on smoker and non-smoker deaths, their effects by age, gender, and racial/ethnic group, and their effects in terms of quantity reduction and smoking cessation. We will also add a new module to examine the effect of new tobacco products (low tar and cigarettes without certain additives) and non-tobacco products (inhalers) which may reduce lung cancer risk, and a module to consider how improved lung cancer detection and treatment maj LVALz y reduce smoking-attributable lung cancer deaths, and how they might be coordinated with tobacco control policies. A final goal of this project will be to critically examine the methods that are traditionally used to project lung cancer deaths, and determine how the estimates depend on the sensitivity to key parameters.LVAL@,p.Cigarette smoking is the number one preventable cause of death and disease in the United States. Despite increased public health knowledge about the adverse health effects of smoking, adolescents still experiment with tobacco use. Nationwide, the percentage of adolescents who smoke has increased during the1990s. The number of adolescents who started smoking increased by 30% and who started daily smoking increased by 50% between 1988 -1996. In California, the percentage of adolescents who smoke was stable from 1990 to 1993 but, since then, has been increasing. Cigarette smoking among White, Hispanic, and Asian adolescents is increasing more rapidly than that among Black adolescents. Identifying different patterns of smoking progression is an important issue because such difference have important implications for prevention and research. Adolescent smoking has been described as consisting of several stages (never smoke, preparatory, trial, experimental, regular use, and nicotine addiction), but not all adolescents smoke or progress from trial smoking to addictive use. Intentions and favorable attitudes toward use predict trial use; refusal self-efficacy may predict onset and escalation of smoking; peer and parent use appear to predict some progression beyond trial use, but predictors of addictive smoking are not altogether clear. Meanwhile, smoking prevention programs that have countered these personal and social influences have shown success in preventing onset and progression from trial to more regular use, but relatively little is known about the capacity of such programs to offset progression to addictive use. A study of the relationships of demographic, personal, and social factors to progression of smoking beyond trial use would help inform future prevention programs. This study has the following specific aims: (a) to examine patterns of smoking development Among California adolescents by gender and ethnicity; (b) to determine the relative importance of social influence, personal, and demograpLVALhic factors in predicting development of adolescent smoking; (c) to test potential interactions among social influence and demographic predictors for development of adolescent smoking; and (d) to test potential indirect effects of social influences on development of adolescent smoking mediated through personal factors. The fulfillment of these specific aims will enhance our understanding of gender and race differences of smoking development and related risk factors in California adolescents. This study will conduct further data analyses using the longitudinal data from an ongoing TRDRP funded tobacco prevention project (the Tobacco Program and Policy project, Pentz, PI) that has being been conducted among junior high school students in Orange County, California since 1997. A total of 2,335 students who completed all investigations at three time points will be analyzed. The investigated students comprise of 49.8% males and 50.2% females; 39.9% White - not Hispanic, 27.2% Hispanic, 16.2% Asian, 2.3% Black, and 14.4% others. This research will enhance our understanding of gender and race differences in smoking development, as well as explore ways to reduce tobacco dependence among diverse groups. The findings of this study will inform public health decision-making and improve smoking prevention strategies. LVAL@,p.Breast cancer is the most common cancer in women of the United States. Hereditary factors account for only a small portion of the total cases. Studies of women from different regions and of immigrants suggest that environmental factors may play an important role in this disease. However, no specific factors have been clearly linked to the cause of breast cancer. While laboratory studies in animal models and in human tissue samples have suggested that chemical carcinogens may play a role in breast cancer development, the results of human studies seeking to confirm links between breast cancer and cigarette smoking, pesticide exposure, or food-born carcinogen intake have been controversial. We have previously shown that breast tissue from women with breast cancer has a significantly higher level of genetic damage from exposure to carcinogens than tissue from women without breast cancer. We have also shown that individuals react differently to carcinogenic insults, and those who are susceptible to carcinogen exposure may be at increased risk of breast cancer. In this study, we plan to focus on a specific type of carcinogen, i.e., heterocyclic amines, in breast cancer. This type of carcinogen is present in cooked food and cigarette smoke. The most abundant of such carcinogens in cooked food is PhIP. This compound causes mammary tumors in female rats and colon and prostate tumors in male rats. PhIP has been detected in human urine and breast milk, and we recently detected PhIP-induced DNA damage in breast tissues. The levels of this damage is significantly higher in women with breast cancer than in those without cancer. Now we will further investigate the role of PhIP exposure and genetic susceptibility in breast cancer. We will begin by using a questionnaire to collect exposure information from 250 women with breast cancer and from 250 without breast cancer. We also will measure the level of PhIP-induced DNA damage in the breast, and we will determine the genetic variations in several enzymes involved in P LVAL hIP metabolism. We will determine how an individual reacts to PhIP exposure by treating the white blood cells and tissue samples in test tubes with PhIP. Then we will compare the questionnaire data and the laboratory measurements in women with breast cancer and those without the disease. We expect to demonstrate an association between exposure to PhIP and the risk of breast cancer, as well as the genetic factors that influence the outcome of this association. These results will help us determine the lifestyle factors that could be modulated and which individuals should take extra precautions to reduce their risk of breast cancer. LVAL^  pj.&DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Hormones MISCELLANEOUS Weight Gain/ExerciseAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology ECONOMICS Socio-Economic Status LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation Relapse EPIDEMIOLOGY/SURVEILLANCE Large (>=100) PREVENTION/TREATMENT Biochemical Assessments Buproprion RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumADDICTION Maintenance Withdrawal AGE Adult DISEASE/BIOLOGY Mechanisms RESEARCH1 Animal Studies TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Menopause HormonesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies In Vitro Studies Clinical Research TOBACCO Cigarette/Other SmokingLVAL@,p.Pancreatic cancer contributes 5% of the total cancer death in this country. It is a deadly disease but the etiology is poorly understood. Our long-term goal is to identify genetic and environmental factors that contribute to pancreatic cancer so novel preventive strategies can be developed. With an NCI grant support (RO3 CA84581), we have conducted a pilot hospital-based case-control study of pancreatic cancer. We have found a significant association between dietary exposure of heterocyclic aromatic amines (HCA) and increased risk of pancreatic cancer. We have also observed significant interactions of a number of drug-metabolizing genes and a DNA repair gene with smoking and HCA exposure. Furthermore we have detected a significantly higher frequency of micronucleus (MN) in peripheral lymphocytes of cancer cases compared to that of controls. The current proposal will build upon these results to further test the hypothesis that carcinogen exposure through smoking and dietary HCA intake increases the risk of pancreatic cancer, especially among genetically susceptible individuals. We will test this hypothesis in a hospital-based case control study with 400 cases of newly diagnosed pancreatic adenocarcinomas and 400 frequency-matched healthy controls. Cases and controls will be matched by gender, race, and age (+/- 5 years) and will be recruited from the UT M.D. Anderson Cancer Center. To identify the high-risk exposure group, we will assess the risk factor and exposure profile by using a risk factor questionnaire, a meat preparation questionnaire, and a food frequency questionnaire to collect information on smoking, alcohol, medical history, family history of cancer, and dietary history. Exposure levels of three major dietary HCA compounds as well as total HCAs will be determined in relation to cancer risk. We will determine genetic susceptibility to HCA exposure and smoking by examining the polymorphisms of several metabolic genes, i.e. CYP1A2, CYP1B1, CYP2E1, NAT1, NAT2, SUL1A1, UGT1A1 and GSTT1, and a  LVAL DNA repair gene, XRCCI. We will measure the level of ENU-induced DNA adducts and frequency of MN in peripheral lymphocytes of each study participants. These biological measurements will be analyzed in relation to disease status and exposure history. Results of this study are expected to shed light on the rote of carcinogen exposure and genetic susceptibility to such exposure in the development of pancreatic cancer. Such information will be valuable for the primary prevention of this deadly disease. LVALWomen at highest breast cancer risk are those with inherited mutations in breast cancer genes, such as BRCA1. We will identify BRCA1 carriers among population-based breast cancer cases and their relatives enrolled in the Cooperative Family Registry for Breast Cancer Studies (CFRBCS). Approximately 6,300 breast cancer cases and 30,000 of their relatives are being accrued; one-half are statistically sampled from 3 population-based cancer registries. Each breast cancer case has consented to respond to standard questionnaires on family history, diet, and other breast cancer risk factors. Blood specimens to generate DNA and follow-up data are also being collected on probands, affected relatives and other selected family members. This Registry of a large number of well-characterized subjects provides exceptional opportunities for genetic studies of breast cancer. Our 3 specific research aims are to use an efficient detection strategy to estimate population-based BRCA1 mutation frequency and age-specific penetrance in 2,036 CFRBCS breast cancer families. Secondly, by exchanging 220 coded samples, 3 independent CFRBCS laboratories (ours and 2 others) will test the analytical validity (sensitivity and specificity) of various mutation detection technologies. Lastly, subgroups of population-based families will be categorized by BRCA1 mutation type (truncating/non-truncating) and position, and tested for differences in frequency of cancers of the breast, ovary, prostate, and colon. These results will lead to future studies of modifying effects on BRCA1 carriers of hormone-related risk factors (ages at menarche, first full-term pregnancy, menopause, and exogenous estrogen use), smoking, alcohol use, and ionizing radiation. Our validated BRCA1 data will be submitted to the CFRBCS Central Database for investigations of early intervention strategies and cancer outcomes among BRCA1 carriers.LVAL@,p.Despite an increasingly negative attitude towards smoking and intensified public campaigns and legislation against smoking, virtually no further reduction in smoking has occurred in this country during the 1990's. Based on the 1996 National Household Survey on drug abuse, an estimated 68.8 million Americans used tobacco products. Therefore, tobacco represents one of the most widely abused substances. Nicotine is believed to be the primary addictive constituent in tobacco. Both epidemiological and molecular studies have implied that many genes respond to nicotine stimulation and there exists significant genetic differences between males and females in response to nicotine administration. Even though numerous studies have been conducted to investigate how a gene of interest is modulated by nicotine using both in vivo and in vitro systems, only a limited number of systematic studies were reported on gene expression profile during chronic exposure to nicotine. We hypothesize that distinct genes and pathways could be identified by a genome-wide functional genomic approach, such as microarray technique. Specially, the aims of this proposal are: 1) to identify novel genes associated with nicotine dependence and nicotine withdrawal in male and female adult rats using a high-density cDNA microarray generated and annotated in the laboratory; 2) to characterize several most promising genes identified from Aim 1 in detail at DNA, RNA, and protein levels with various conventional molecular techniques using both in vitro and in vivo systems; 3) to identify novel signaling pathways involved in nicotine dependence and nicotine withdrawal in rats using the pathwayfocused microarray developed in the laboratory; and 4) to implement and develop databases and statistical methodologies for managing and analyzing microarray data generated from Aims 1-3. Such a global perspective may provide new direction to develop preventive and treatment strategies to nicotine dependence and nicotine withdrawal in human smokers. The complVLVALfetion of the proposed studies will advance our understanding of complex gene expression patterns associated with nicotine dependence and nicotine withdrawal in rats and in human postmortem brain tissues.LVALTo evaluate whether bupropion given to women who have quit smoking during pregnancy is effective in decreasing postpartum relapse. We propose a randomized placebo controlled trial of 300 women to determine whether women treated with bupropion have lower rates of smoking relapse than women receiving placebo. Subjects will be recruited from the clinical practices at Brigham and Women s Hospital. Pregnant women at least 18 years of age, who have quit smoking within the year prior to delivery and have not resumed smoking will be eligible to participate. Patients with contraindications to treatment with bupropion and breastfeeding women will be excluded. Subjects will be randomized to receive bupropion or placebo. Those randomized to bupropion will be receive 150 mg by mouth twice a day for 9 weeks. The primary outcome measured is smoking cessation at 3 and 6 months. This will be measured using a urine cotinine to creatinine ratio.  s F  ~gB::@@Researchp@"MADLENSKYLISAUNIVERSITY OF CALIFORNIA AT SAN DIEGOSAN DIEGOCANCIR03, CA108360@t@@ @4/1/20043/31/20064/1/2004 to 3/31/20064/2005{pIC88,"99@@Research^@!MADDENPAMELAWASHINGTON UNIVERSITYST. LOUISMONIDAR01, DA012854`,p.@@ @5/25/20004/30/20055/25/2000 to 4/30/20054/2005tnj_H@88,"88@!@ResearchGENETICS OF SMOKING IN WOMENMADDENPAMELAWASHINGTON UNIVERSITYST. LOUISMONIDAK21, DA000272`,p.@@Z@9/30/19958/31/20019/30/1995 to 8/31/20014/2005}f^VV,"77@@Researchb@ MADDENPAMELAWASHINGTON UNIVERSITYST. LOUISMONIDAR01, DA012540`,p.t@T@@6/1/19995/31/20056/1/1999 to 5/31/20054/2005tnj_H@88,"66c@@Researchd@MACKTHOMASUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP6RT-0354`,p.t@P@@7/1/19977/30/20017/1/1997 to 7/30/20014/2005zviF>88,"55@G@ResearchL@MACKTHOMASUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP8RT-0107H, `,p.t@n@@7/1/19996/30/20027/1/1999 to 6/30/20024/2005zviF>88,"44z@^@ResearchX@MAJINGBRIGHAM AND WOMEN'S HOSPITALBOSTONMANCIR29, CA078293V `,p.t@@@1/1/199812/31/20021/1/1998 to 12/31/20024/2005qlh`B<88,"33p@@ResearchF@LUKASSCOTTMCLEAN HOSPITAL BELMONT MA.NIDAR01, DA003994`,p.Biology and Cancer Addiction@F@3/1/19925/31/20063/1/1992 to 5/31/20064/2005|mgbXF?88,"22`g@K@Researchh@LUKASSCOTTMCLEAN HOSPITAL BELMONT MA.NIDAK05, DA000343`,p.Biology and Cancer Addiction@@8/1/19977/31/20028/1/1997 to 7/31/20024/2005|mgbXF?88,"11@4@Researchp@LIUYANUNIVERSITY OF CALIFORNIA AT DAVISDAVISCACTRDRP8DT-0172@,p.t@ R@@1/1/20001/31/20021/1/2000 to 1/31/20024/2005xpleB=88,"00 ~@@Researchl@LIUJIANGHONGUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANINRF32, NR008661h@t@ @<@9/9/20039/8/20069/9/2003 to 9/8/20064/2005|xkH=88,"//`@K@Researchj@LIPTONROBERTPACIFIC INSTITUTE FOR RESEARCH AND EVALUATIONCALVERTON MDNIAAAR03, AA012764z@,p.L@ @@8/1/20007/31/20028/1/2000 to 7/31/20024/2005wH@88,"..g@p@4Research@LIEBERMANELLICEBRIGHAMAND WOMEN'S HOSPITAL, HARVARD MEDICAL SCHOOLRWJFNot Givend@j@ Discovery 1c Development 2,@N/AN/AUncertain4/2005KC88,"LVAL@,p.The purposes of the proposed project are to determine if abstainers have a higher prevalence of physical and mental illness compared to light-to-moderate alcohol drinkers and, amongst abstainers, determine if differences exist in regard to prevalence of physical and mental illness. Socio-demographic measures, lifestyle and ethnic/cultural differences will also be examined for abstainers and light-to-moderate alcohol consumers. To this end, a nationally representative data set, the National Longitudinal Alcohol Epidemiologic Survey will be used to: (1) measure alcohol use in terms of frequency quantity and binge drinking, (2) distinguish amongst those abstaining based on differences in health, smoking, ethnicity and socio- demographic measures, (3) determine amongst those abstaining if there are differences in risk of heart disease by type of abstainer; sick never drinkers, healthy never drinkers, former light, moderate, heavy drinkers, abusing drinkers, (4) determine amongst those abstaining if there are differences in risk of depression by type of abstainer, (5) determine if abstainers have higher levels of depression/mood problems than those not abstaining when controlling for socio-demographic variables, ethnicity and physical illness, and (6) determine if abstainers have higher levels of heart disease, compared to those not abstaining. Information from these activities will serve two related purposes: First, to increase our understanding of the correlates of abstention, particularly differences across age, gender and ethnicity. Second, to increase our ability to classify abstainers into etiologically meaningful categories relevant to moderate alcohol and health. Often moderate drinkers, who may also be moderate in many different measures of lifestyle and health status, are typically compared to abstainers who may have combinations of measures that are considerably less moderate, or at the least, very different. Thus, instead of measuring differences in health outcomes based on alcohol consumption Z LVALj between moderate and abstention categories, researchers frequently are comparing, for example, sick former heavy drinkers with relatively healthy moderate drinkers. Similarly, sick never drinkers might be compared to moderate alcohol drinkers. In either case, the possible beneficial effect of moderate alcohol use is obscured by other factors that may be influencing health outcomes independently from moderate alcohol use or abstention. Results from this project will allow a more insightful examination of the role of moderate alcohol in protecting against certain chronic diseases.LVALv$   n Z * 4 8Discovery 1a Discovery 2a Discovery 2b Development 5 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1c Development 2 Delivery 1 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Development 4 Development 5 Delivery 3 Partnerships 2 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 1 Delivery 2 Partnerships 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 2 Evaluation 1a Evaluation 1bDiscovery 1c Development 1 Development 3 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Discovery 2b Development 1 Development 3 Delivery 1 Partnerships 1 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 3 Development 1 Development 2 Evaluation 1bDiscovery 1a Discovery 1c Development 1 Development 2 Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bLVALThis study aims to investigate the link between early biosocial risk factors and childhood externalizing behavior problems. Specifically, the study will examine how prenatal health factors interact with postnatal psychosocial risk factors in predisposing to later externalizing behavior. The specific aims are to: (1) assess the direct effect of prenatal biological and postnatal psychosocial risk factors on childhood externalizing behavior; (2) examine the interactive effect of biological and psychosocial risk factors on childhood externalizing behavior; (3) test what factors mediate the above direct and interactive effects of biological/social risk factors on childhood externalizing behavior; (4) identify the specific components of biological and social risk factors which give rise to childhood externalizing behavior; (5) test the relationship between internalizing behavior in relation to the above risk and mediating factors in predisposing to childhood internalizing behavior. Prenatal biological risk factors include maternal smoking during pregnancy, and pregnancy/birth complications. Postnatal psychosocial risk factors include parenting, child rearing disagreements, domestic violence, and home environment. Further, the mediating role of cognitive ability, and temperament, will also be explored. Hypotheses will be tested in the context of an ongoing prospective longitudinal study of approximately 600 three-year-old male and female children using structural equation modeling. By attempting to further establish the early, modifiable health risk factors for externalizing behavior, and by examining a biosocial perspective on antisocial behavior, the proposed study aims to illustrate how the Nursing profession can potentially impact this significant societal problem as well as better inform future prevention programs.LVAL@,p.Other than its well-known carcinogenic effect, tobacco smoke might also act as a toxin to the reproductive endocrine environment in women. Menstruation and ovarian steroid patterns are primary markers of human female reproductive endocrinologic and ovarian function. Researches only involve laboratory animals or a few women have show that tobacco smoke could influence ovarian sex hormone biosynthesis. Investigation of menstruation and its hormonal bases based on large-sample-size data is limited. In fact, major difficulties in analysis and interpretation of cyclic menstrual and hormone data arise when much of the observed variability in menstrual characteristics stems from changes within women as opposed to differences between women and steroid data are curved over an entire menstrual cycle. The improvement of less-cost biological assay techniques, rapid development of computer hardware/software and considerable exploration of modern statistical inference methods allow us to model human ovarian function based on cycle-to-cycle daily diary and urine collection now. The primary goal of the research proposed is to explore methodology for investigating the influence of cigarette smoking in the presence of other host and environmental factors on the ovarian function of women based on daily diary and urinary assay data. The study data were collected previously. The importance of this existing database is that it contains information on urine specimens collected not only over an entire menstrual cycle for each of 402 women but also over several successive cycles for most of those women. The effects of cigarette smoking on ovarian steroid secretion and metabolic clearance rate (MCR) of progesterone, in premenopausal women will be assessed with control of variables we collected, such as age, race, parity, body mass index (BMI), alcohol use, caffeine consumption and physical activity. We also want to evaluate the relation of menstrual cycle length and follicular and luteal phase lengths with tobacco exposLVALure. The response variables from an individual are usually correlated since they were measured repeatedly over time. In the present proposed study, appropriate models that allow for such correlation is discussed. Menstrual characteristics will be modeled as linear functions of the smoking and other variables using the general linear mixed model (GLMM). But typical menstrual cycle measures may not be sensitive indicators of changes or disturbances in hormonal function resulting from cigarette smoke exposure. We will model curves which reflect hormone profiles over time using variants of the GLMM, which are expected to be more sensitive to such changes. The above analyses rely on the assumption of normality of the data and on having moderate to large sample sizes. We will perform a special technique, bootstrap analysis, in order to check on these assumptions and to provide inferences that are less dependent on these assumptions. The present proposed study should shed light on the mechanisms by which cigarette smoke adversely affects women's endocrinologic and menstrual function and provide new approaches for scientists in their efforts to detect more sensitively the tobacco-related health effects with respect to reproduction in premenopausal women.LVAL`,p.This is an request for a K05 Senior Scientist Award to permit the candidate to continue his career development in drug abuse research. During the past ten years as a K02 awardee the candidate has spent 80-85 percent of his time engaged in drug abuse research. His overall research goal is to use multiple tools to study reinforcing efficacy, polydrug abuse and potential pharmacotherapies for drug and alcohol abuse. The research plan is based on three currently funded R01 grants on which the candidate is the Principal Investigator and three additional grants on which he serves as co-investigator. The candidate's research directives have recently changed by focusing all of his energy on clinical research and has eliminated his involvement in non human primate research. This decision was made partly because of recommendations made during the last competitive review of his K02 application and partly because the candidate has now become a senior scientist in the field of human psychopharmacology. This change in his status in the field has prompted a shift to developing an independent research program that also will support the training of predominantly women and minority students/postdoctoral fellows. The candidate continues to use electroencephalographic activity, physiological activity, plasma drug levels and instrumental measures of subjective mood states as dependent variables to quantify the effects of cocaine, marihuana and ethanol in adult volunteers. The candidate's funded grants focus on the effects of drugs of abuse in women, and is currently studying the pharmacokinetic and pharmacodynamic effects of cocaine in individuals of different ethnic backgrounds. The candidate has made a strong commitment to research and over the next five years of his professional growth he will study the similarities between cocaine- and tobacco-related cues and their effects on brain electrical activity, quantify sex-related differences in the pharmacokinetic and pharmacodynamic response to i.v. and i.n. cocaine, evaluF LVALV ate the usefulness of nicotine and estrogen transdermal patches as potential pharmacotherapies for cocaine abuse, co-register EEG data with three dimensional MRI and study the effects of a Chinese herbal medicine, kudzu, as a possible treatment for alcohol abuse. The present application is being sought to provide the candidate with continued stability of support essential for his sustained commitment to research in the field of drug abuse and to ensure his continued high level of productivity not only as a senior scientist, but as a mentor for the next generation of drug abuse scientists.LVAL\  J0ADDICTION Initiation Maintenance AGE Child Young Adult DISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking NicotineDISEASE/BIOLOGY Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Cessation DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Young Adult Adult DISEASE/BIOLOGY Other Disease/Biology PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Adult DISEASE/BIOLOGY Other Disease/Biology PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Nicotine WOMEN HormonesLVAL`,p. In this competing renewal application (currently in its 14th year) we propose to explore the behavioral correlates of polydrug abuse in male and female adult and adolescent subjects by expanding upon our findings during the previous four years of funding. Further, we will continue to focus on changing trends in polydrug abuse, the most recent of which involves the club drug MDMA. The proposed series of experiments are connected via three major inter related themes: I) The neurobiological bases of polydrug abuse will be explored using cue-induced craving and functional magnetic resonance imaging (fMRI). Regional brain activation after exposure to cues from different modalities and drug classes will be assessed using a 4 Tesla magnet that improves spatial resolution and reveals individual differences. The activation profile of exposure to different cues in polydrug abusers will help determine whether there is significant cross-generalization among cues. II) Differences between adolescent and adult polydrug use will be measured using EEG mapping, physiology and behavioral indices during cue-induced craving procedures. As the rate of both tobacco and marihuana smoking among adolescents continues to rise, we will explore the relationship between these two drugs and the generalizability of drug-related cues in adolescents. III) Novel pharmacotherapies for polydrug abuse will be tested as traditional medication trials have focused on testing a single treatment drug. We will use new strategy of combining two medications (polypharmacy) to address the multi-faceted nature of polydrug abuse. Nicotine and selegilinepatches for combined cocaine/tobacco abuse and gabapentin for combined cocaine/alcohol abuse will be studied. A new direction for our laboratory is to study drug-taking behavior in the natural fieldenvironment using a unique wrist actigraphy and data input device to monitor sleep/wake activity, MDMA craving and actual polydrug use while subjects continue with their usual daily routines. Finally, we wil LVAL l explore the impact that the availability of MDMA has on alcohol and marihuana use in a Natural Setting Laboratory. The proposed studies will fill important gaps in our understanding of polydrug abuse including: cue-induced craving in adolescents, actual polydrug patterns, sex-related differences, brain sites associated with craving, similarities among cues, and how best to design effective pharmacotherapies for polydrug abuse. Results of these studies may also reveal why cue-induced craving has not been a good predictor of relapse as there may be significant cross generalization among the cues that can trigger relapse in successfully treated patients.LVAL`,p. The investigators propose to examine prospectively the relation between iron status (intake, body stores, and genetic susceptibility for hemochromatosis) and risk of myocardial infarction (MI) and colorectal cancer in three large cohorts. Iron intake was assessed by semiquantitative food frequency questionnaire (SFFQ) in 1980 in the Nurses' Health Study (NHS, n=121,700 women) and in 1986 in the NHS and in the Health Professionals Follow-up Study (HPFS, n=51,529 men). Blood samples were collected in both of these cohorts: from the NHS in 1989-90 (n=32,825 women), and the HPFS in 1993-94 (n=18,000 men). In addition, samples also were collected from participants in the Physicians' Health Study in 1982 (PHS, n=14,916 men). These men and women initially free of cardiovascular disease and cancer and have been followed prospectively for the occurrence of cardiovascular disease and cancer. The investigators plan to assay the samples, in a nested case-control design, for biomarkers of body iron stores (iron, total iron binding capacity, ferritin) and genetic marker of hemochromatosis, an inherited disease of iron overload (C282Y, a missense mutation in HLA-H gene). The iron-CHD/cancer hypotheses have been supported by laboratory and animal studies, but findings from small, less comprehensive epidemiologic studies are inconsistent. They propose to evaluate the individual associations of intake, biomarker levels, and genotype with risk of MI and colorectal cancer, as well as the combined effects. Further, they will evaluate other dietary and lifestyle factors that may account for or modify the association between iron and MI/colorectal cancer. The ongoing three cohorts will provide high yield follow-up participation and high quality end-point verification in addition to information on important variables (e.g., smoking, vitamin supplement use, dietary factors) for the proposed study. These analyses will take advantage of existing blood banks of these well-characterized cohorts, and part of the plasma ferritin me~ LVAL asurements (the NHS and PHS) are funded through other sources. The investigators state that hence, this application provides a well-focused, efficient cost-effective, and comprehensive approach to evaluate the hypothesized but unproven role of iron as a risk factor for future cardiovascular disease and cancer.LVAL`,p. Observations on twin subjects can often provide the most exacting and conclusive measures of the health impact of personal choice as opposed to constitution or societal influence. Insufficient twin research in America has been brought to bear on the subject of tobacco use, because there are no convenient means of identifying representative twin subjects in quantity. We propose to complete the establishment of a roster of potential subjects who are simultaneously native Californians, twins, and current residents of California, and to characterize such individuals and pairs with respect to family history, medical history, and lifestyle, including the history of tobacco use for purposes of concurrent and subsequent study. To date, about 20,000 individuals have been so characterized. We expect a complete registry to be comprised of well in excess of 65,000 well-documented individuals. When complete, this large and representative resource will be able to provide rosters of specifically chosen unique and compliant subjects for the study of all aspects of tobacco-related and other disease. Within the period of this grant we expect to begin a large comparison of the morbidity and mortality of twin smokers to their non-smoking twins. Other uses of the registry, separately proposed for support, address the personal reasons for initiating and quitting tobacco use, the genetic determinants of differences in phenotypic nicotine metabolism, the search for molecular and immunochemical measures of the residue of cumulative smoking, and the degree to which persons who take up smoking, in the presence of a family history of asthma or chronic obstructive pulmonary disease (both important tobacco-related diseases) place themselves by doing so at particularly high risk. Once established, researchers of various disciplines will be able to recruit subjects for many other analytic studies, including a wide variety of studies of tobacco-related conditions. In addition, we will link the roster of known twins with the Calif LVAL ornia Twin Registry and the California mortality files. This will allow us to identify pairs in which one death or one cancer case has occurred in order to quantify the strength of the relation between ever smoking and death/cancer when inheritance and early environment are held constant. LVAL`,p.The initial objectives of this proposal were to identify identical twin cases of bladder, renal, and pancreas cancer who smoked but who had co-twins who did not smoke, and compare the genetic characteristics of the twins with those of unrelated controls, specifically spouses. The scientific goal was to test the hypothesis that variations in a specific gene (responsible for the enzyme N-acetyl-tranferase) might be important determinants of bladder, renal and/or pancreas cancer. This enzyme competes with the enzyme responsible for turning the products of smoking into potent carcinogens, and if it works rapidly, little toxic material is created to bathe the tissues of these organs. If, on the other hand, it works slowly, as it does under some genetic conditions, carcinogens are more readily formed. Since the genetic methods in 1993 were not well developed, we initially proposed to test the functionality of the genes by collecting urine after a test dose of caffeine, known to be changed by the enzyme in the same way as the tobacco products. The twin cases had occurred in the years 1975-90. After the grant was approved, the Governor cut the research funds, and only after nearly 2 years did a limited proportion became available, although additional funds did appear in the succeeding year. We cut costs by eliminating renal cancer, giving bladder cancer priority, collecting DNA itself instead of the functional assay, and arranging for scientists at the National Institute of Environmental Health Sciences to do the genetic lab work. Unfortunately, by the time we got to the twins, many had moved or died, and others had less interest in cooperating. In addition, by the time the material was collected, the scientific interest at the NIEHS had cooled, since other studies had successfully tested the hypothesis, and the bladder cancer material remains stored there untested. In the last year of the grant and the succeeding period we tried to collect similar material from the families of twins with pancreas cancer, i LVAL n some cases diagnosed more than 20 years before. We succeeded in about a third of the available pairs, but got material from very few of the unrelated controls. Anyway, after the laboratory analysis was completed on the 26 specimens available, no evidence was found to suggest a role for these enzymes in pancreas cancer, but such a possibility could not be ruled out. LVAL`,p.Despite the importance of adolescent smoking from a public health perspective (including its association with teenage alcohol and drug involvement), and the evidence from adult twin studies for a strong genetic influence on smoking behavior, there has been little research designed specifically to understand the genetic contribution to risks of becoming a regular tobacco user, and of developing nicotine dependence, and to difficulties with quitting tobacco use. The classical twin study, comparing MZ and DZ twins reared together, is a powerful behavioral genetic design for analyzing the joint effects of genes and environment on behaviors such as the onset of regular tobacco use and transitions in the tobacco habit which are subject to rapid developmental and secular changes. Using a prospective cohort sequential design, we will ascertain cohorts of adolescent same sexed male twins, 11, 13, 15 and 17 years of age, including minority pairs, over a 2-year period, and continue to identify new cohorts of 11-year old twins in years 3, 4 and 5. Each twin and one parent or guardian (whenever possible the biological mother) will be sent a questionnaire and by telephone given an interview that includes assessments of patterns of tobacco use and nicotine dependence, alcohol use and dependence, illicit drug use, other axis I disorders, perceived tobacco, alcohol and drug use and attitudes towards use in peers and parents, and about other pertinent risk factors. There will be brief annual follow-up of the twins. Analyses will include data from an ongoing longitudinal study of female adolescent twins (AA09022; Heath, PI) using similar assessments, allowing us to examine the following issues for cigarette use in adolescent boys compared with girls: (i) genetic influences on tobacco use; (ii) possible mediators of genetic influences on use of and the development of dependence on nicotine; i.e., personality, lifetime depression and anxiety disorders, and adolescent conduct disorder; (iii) the relationship between genetiT LVALd c influences on smoking behavior, and genetic influences on alcohol and illicit drug- related problems; (iv) possible environmental mediators (e.g., perceived smoking in peers); and (v) protective factors (e.g., parental monitoring) which may modify a genetic predisposition to tobacco use and to nicotine dependence in adolescents.LVAL`,p.A Scientist Development Award (K21) is requested to allow the Candidate- to develop an independent program of research to examine in women compared with men (i) genetic influences on smoking; (ii) the relationship between genetic influences on smoking behavior, and genetic factors responsible for use of and dependence on other substances (using alcohol as a model system); (iii) possible mediators of genetic influence on use of and the development of dependence on nicotine and other substances, i.e., personality (e.g., Neuroticism and Novelty-Seeking), lifetime depression and anxiety disorders, and adolescent conduct disorder; and (iv) vulnerability and protective factors (e.g. spouse's smoking or successful cessation) which contribute to the initiation of cigarette smoking, transitions in amount used, smoking persistence and dependence. Despite the importance of smoking from a public health perspective, there has been little research designed specifically to understand the genetic contributions to risk of becoming a long-term ("persistent") smoker. Yet re-analyses of existing data have given heritability estimates for smoking persistence as high as 53-71% in women as well as men. A program of secondary data-analysis is proposed that will provide more information about the inheritance of smoking behavior, identify the most important aspects of smoking to select for genetic study, and permit necessary skills acquisition in quantitative genetic methodology. Findings will be compared from large sample questionnaire twin surveys in Finland, Sweden, Australia ("1981" and "1989" cohort twins), and the U.S. (Virginia mailed questionnaire twin survey). Further analyses will be conducted using data from telephone-interview assessments from some 6,000 twins from the Australian twin panel, and data from a longitudinal study of female adolescent pairs (in progress) that include assessments of alcohol dependence, illicit drug use, and other Axis I disorders. To implement this program of research, funds are requeste LVAL d to allow specialized training and additional mentoring in the following areas: (i) quantitative genetics; (ii) psychometric evaluation (to optimize phenotype definition for smoking research); and (iii) statistical epidemiology; as well as for (iv) exposure to genetic research on nicotine sensitivity in rodents. In the long-term, self- report interview and questionnaire data on twin pairs are limited in how far they can advance our understanding of genetic influences on smoking behavior and funds are also requested for training and/or coursework in (i) molecular genetics; and (ii) the administration of nicotine, and physiologic and biochemical measures of nicotine response; as well as for (iii) the ascertainment of a sample for use as pilot data in the preparation of grants for the future conduct of a) nicotine challenge research, and b) genetic association studies.LVAL  >vCOMMUNITY Health Care Provider ECONOMICS Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseADDICTION Cessation COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionDISEASE/BIOLOGY Cancer Mechanisms Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Adult DISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance Cessation DISEASE/BIOLOGY Mechanisms Other Disease/Biology LOCATION National International PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Nicotine WOMEN Partner/Spouse MISCELLANEOUS Sex/Gender DifferencesLVAL`,p.Despite the public health significance of smoking, and evidence from adult twin studies for a strong genetic influence on smoking behavior (heritability estimates as high as 70%), there has been little research designed specifically to identify genes that contribute to risk of addiction to nicotine in humans. We propose a large-scale gene mapping study to identify specific chromosomal locations or candidate genes that have at least a moderate effect on risk. Families will be ascertained through panels of adult Australian and Finnish twins, and a sample of spouses of Australian twins, who have been identified as having a history of heavy smoking in earlier surveys. We will conduct diagnostic telephone interviews and blood drawing on probands, their full siblings and parents, to identify sibships with at least one affected sib pair (ASP) concordant for heavy smoking, and at least one living parent (target N=400 Australian, 400 Finnish families with approximately 600 ASPs from each). A 10cM genome-wide scan will be conducted using these families, with affected sib pair methods of linkage analysis used to identify candidate chromosomal regions suggestive of linkage. A transmission disequilibrium test approach will be used to test for candidate gene effects on nicotine dependence (DSM-IV nicotine dependence criteria and a-Fagerstrom Test for Nicotine Dependence score >= 4), and for fine mapping of candidate regions. Our study will have the advantage of having not only candidate alleles from trios (two parents plus nicotine dependent offspring), but also sibships with both nicotine dependent and non-regular ("unaffected") smokers. The availability of these within family controls will increase the robustness of our inferences. Candidate genes to be tested include CYP2A6, CYP2D6, and the dopamine D1 and D2 receptor genes. A database(without personal identifiers) will be established in St. Louis that includes genotype, diagnostic, and other pertinent information, a lymphoblast cell line repository will be estaPLVAL`blished in St. Louis for cell lines obtained from Australian families; and a repository in Helsinki for DNA obtained from Finnish families, for distribution to qualified members of the scientific community.XLVALhWhile there is convincing epidemiologic evidence that a family history of colorectal cancer (CRC) is one of the strongest risk factors for developing CRC, there has been little investigation of the behavioral aspects of CRC familial risk. To date, studies of at-risk relatives of CRC patients have focused on interest in genetic testing, and to a lesser extent, CRC screening. There is a gap in the literature with regard to the patterns of health behaviors in relatives of CRC patients, even though the report of the NCI Colorectal Cancer Progress Review Group states that there is a clear need for research in this area. We propose to undertake extensive secondary data analyses using data collected from the NIH-sponsored Cooperative Family Registries for Colorectal Cancer Studies (the CFRs). We will compare individuals at varying levels of familial CRC risk: 1. High-risk (3 or more lst/2nd degree relatives affected by CRC); 2. Moderate risk (1 or 2 affected relatives) and 3. Population-risk controls (no affected relatives). The health behaviors that will be compared include CRC screening, aspirin/NSAID use, smoking, alcohol intake, diet pattern, and dietary supplement use. Since CRC affects men and women equally, we will also examine potential gender differences in these health behaviors across familial risk levels. Finally, we will explore potential clustering of health behaviors across levels of familial risk. It is important to first determine what relationships exist between family history and health behaviors before embarking on in-depth investigations of how and why those relationships exist. Thus, the results of these comparisons will be used to 1) develop testable hypotheses and 2) build on a conceptual framework that will be used to guide future in-depth behavioral studies and intervention studies of CRC prevention and familial risk.LVAL`,p.The main goals of this study are to: (1). Elucidate the smoking outcome constructs inherent to the process of change as postulated in Prochaska and DiClemente (1992) stages of change theory. Specifically, we will assess the relationships and changes over an 18-month period among five smoking outcomes: stage of readiness, motivation, self-efficacy, action, and quitting. (2). Assess how these smoking outcomes are affected by intervening events: changes in pregnancy status and exposure to organized smoking cessation interventions (delivered through health care systems and through television). We will assess direct effects of these events on smoking outcomes, as well as indirect effects through four mediating variables: life stress, social support, social pressure, and health concerns. (3). Assess the nature of the effect of SES conditions on individual smoking outcomes. We will identify which influence paths lead from SES indicators at the individual level and area of residence level to smoking outcomes. We will focus on how SES indicators interact with pregnancy and exposure to smoking cessation interventions in affecting the above mediating variables. We will conduct theory-guided analysis of existing panel data (5 waves over 18 months) from two previous studies that used comparable instruments to evaluate, respectively, a public health clinic smoking cessation program (N=872) and a media-based smoking cessation program (N=1,197) with Iow-SES women. (a) We will review/recode data for comparability and merging. (b) We will complement these data with information about the socio-economic characteristics of the Community Area where subject resided, using available Chicago Community Area and Census publications. (c) We will conduct the multiple analyses needed to answer the above questions, using multilevel structural equation models (in LISREL 8). We will conduct these analyses separately on each of the two sets of data, to take advantage of the information unique to each study and to assess the paths of i LVAL nfluence of each of the two types of interventions (health care and media). We will repeat the analyses with the two merged data sets, to assess the individual and area SES effects on smoking cessation processes on a total sample with greater variation on these variables.0 } P !ZHH @@Research\@ MCCARTHYWILLIAMUNIVERSITY OF CALIFORNIA AT LOS ANGELESLOS ANGELESCACTRDRP10RT-03331o,p.L@@@37/1/20016/30/20047/1/2001 to 6/30/20044/2005tKB88,"GG @@@$@Researchl@ MCBRIDECOLLEENDUKE UNIVERSITYDURHAMNCNCIR01, CA0890530o,p.T@@@ 5/1/20024/30/20075/1/2002 to 4/30/20074/2005{lgc[JA88,"FF`n@G@Researchf@ MCBRIDECOLLEENDUKE UNIVERSITYDURHAMNCNCIR01, CA076945N.o,p.T@@@)9/26/19976/30/20029/26/1997 to 6/30/20024/2005{lgc[JA88,"EE@@Researchl@MCALISTERALFREDUNIVERSITY OF TEXAS HEALTH SCIENCES CENTERHOUSTONTXNCIR01, CA086295,o,p.@@L@)5/25/20004/30/20055/25/2000 to 4/30/20054/2005wKC88,"DD@@ResearchCORE--SEX SPECIFIC FACTORSMAZURECAROLYNYALE UNIVERSITYNEW HAVENCTNIDAP50, DA013334 @+@@@)200020042000 to 20044/2005ve\TT,"CC W@@Research@MAYBARBARAFAMILY HEALTH INITIATIVES INC.PENNSAUKENNJRWJF47134Not available11/1/200210/31/200511/1/2002 to 10/31/20054/2005|vrfF=88,"?~BB`<@@ResearchD@MATHURSUBBIMEDICAL UNIVERSITY OF SOUTH CAROLINACHARLESTONSCNCIR21, CA092085*o,p.Biology and CancerR@@)4/1/20023/31/20044/1/2002 to 3/31/20044/2005 }ymG@88,"AA`u@@Researchl@MASSEYCATHERINESLIPPERY ROCK UNIVERSITY OF PENNSYLVANIASLIPPERY ROCKPANIDAR03, DA016328T'o,p.L@@@)7/1/20036/30/20047/1/2003 to 6/30/20044/2005uK@88,"@@:@ @Researchh@MARTINEZFERNANDOUNIVERSITY OF ARIZONATUCSONAZNHLBIR01, HL056177l%o,p.Biology and Cancern@H@ 8/10/19967/31/20068/10/1996 to 7/31/20064/2005vokcLB88,"??c@@ResearchX@MARINGERARDOUNIVERSITY OF SAN FRANCISCOSAN FRANCISCOCACTRDRP6RT-0407#o,p.L@@|@ 7/1/19976/30/20017/1/1997 to 6/30/20014/2005xteH?88,">>z@1@Researchj@MARINGERARDOUNIVERSITY OF SAN FRANCISCOSAN FRANCISCOCACTRDRP6PT-60012!o,p.L@@@ 1/1/199812/31/20011/1/1998 to 12/31/20014/2005xteH?88,"==@ @Researchd@MARCUSMARSHAUNIVERSITY OF PITTSBURGHPITTSBURGHPANIDAR01, DA004174(o,p.T@@ @ 7/1/198611/30/20047/1/1986 to 11/30/20044/2005xrnbH@88,"<<@@ResearchT@MARCUSBESSMIRIAM HOSPITALPROVIDENCERINCIR01, CA077249T`,p.T@@ @4/17/19988/31/20044/17/1998 to 8/31/20044/2005{lgcWF@88,";; f@`@Researchp@#MANFREDICLARAUNIVERSITY OF ILLINOIS AT CHICAGOCHICAGOILNCIR01, CA100680`,p.@@ @3/1/20032/28/20053/1/2003 to 2/28/20054/2005~yulIB88,"LVAL`,p.Lung cancer rates now exceed breast cancer rates as the leading cause of death by cancer among women. Furthermore, smoking prevalence rates among women are declining at a slower rate than men and approximately 23% of women still smoke. One important reason why women do not attempt and/or succeed at smoking cessation may be fear of post-cessation weight gain. However, combined smoking cessation and weight control treatments have not been successful at decreasing post-cessation weight gain or enhancing achievement of smoking cessation. Exercise offers a healthful alternative to smoking, which may allay women's fear of weight gain. Exercise facilitates regulation of body weight, moderates mood changes, aids in decreasing responses to stress, and is incompatible with smoking. The proposed study will test the hypothesis that moderate intensity exercise enhances the achievement and maintenance of smoking cessation among healthy adult female smokers. This is a randomized controlled clinical trial comparing two conditions: (a) cognitive-behavioral smoking cessation plus moderate exercise and (b) cognitive-behavioral smoking cessation with equal contact time. The treatment is delivered over 12 weeks. A sample of 224 subjects will be recruited, treated for twelve weeks and followed for 12 months. This design permits separation of the effects of physical activity from the effects of frequent contact with staff and other subjects. Smoking cessation outcome (7 day point-prevalence) will be verified by saliva cotinine. Exercise adherence will be validated by attendance at supervised sessions, exercise monitors, and maximal exercise testing. Secondary analyses of hypothesized mediators (weight and/or weight concerns, negative affect, withdrawal symptoms, self-efficacy, motivation) of the effect of moderate exercise on smoking cessation will also be examined. Successful smoking cessation in women could significantly reduce chronic disease mortality in this group. Although intensive, this kind of prograLVALm could have advantages over pharmacologic treatments and/or could be made more disseminable and cost-effective, but only if the initial results of this rigorous trial are promising.LVAL#H n p  2 ~  l jD(`>2VSTRATEGIES AGAINST HPV RELATED GENITAL DISEASES IN WOMENTELEPHONE COUNSELING PROGRAM FOR PREGNANT SMOKERS ENROLLED IN A MANAGED CARE ORGANIZATION-SUPPLEMENTAL SUPPORTWOMEN'S INTERAGENCY HIV STUDY (WIHS) IIIDNA REPAIR GENES AND BREAST CANCER RISKSMOKING CESSATION FOR WOMEN AT RISK FOR CERVICAL CANCERSMOKING CESSATION FOR LOW-INCOME PREGNANT WOMENMETABOLIC GENOTYPES AND ONCOGENIC DAMAGE IN BREAST CANCERCOLLEGE SPORTS, GENDER, AND SUBSTANCE USEBUPROPION FOR SMOKING CESSATION IN PREGNANCYSTUDY OF TOBACCO INDUSTRY DOCUMENTS: MARKETING TO WOMENNICOTINE EFFECTS ON NEUROLOGICAL DEVELOPMENTCONTEXT AND SUBJECTIVE EXPERIENCE OF EARLY SMOKINGNEUROBIOLOGY OF NICOTINE: HORMONES AND BEHAVIORSMOKE-FREE FAMILIES NATIONAL DISSEMINATION OFFICESMOKE-FREE FAMILIES NATIONAL DISSEMINATION OFFICESMOKE-FREE FAMILIES NATIONAL DISSEMINATION OFFICESMOKE-FREE FAMILIES NATIONAL DISSEMINATION OFFICEMARKETING AND COMMUNICATIONS SUPPORT FOR THE SMOKE-FREE FAMILIES NATIONAL PARTNERSHIP TO HELP PREGNANT SMOKERS QUITCADMIUM EXPOSURE AND BREAST CANCER RISKRELATIONSHIPS BETWEEN SMOKING, HOMOCYSTEINE AND FOLATEA PAN-CANADIAN RESOURCE NETWORK FOR TOBACCO CONTROL RESEARCH, POLICY, AND PRACTICE PREVENTIVE ONCOLOGY AWARD--SMOKING CESSATION AND WOMENCANCER WORRY AND HEALTH-PROTECTIVE BEHAVIORSANALYSIS OF CALIFORNIA ADOLESCENT TOBACCO DATATESTING PHARMACOLOGICAL THERAPIES FOR PREGNANT SMOKERSPARTNER ASSISTED INTERVENTIONS FOR PREGNANT SMOKERSTEXAS MULTICULTURAL REGIONAL COMMUNITY TOBACCO STUDIESDEVELOPMENT OF A COLLABORATIVE STATEWIDE APPROACH TO IMPROVING ACCESS TO CARE FOR DRUG- AND ALCOHOL-AFFECTED WOMEN AND CHILDRENEARLY DIAGNOSIS OF CERVICAL CANCERPSYCHOSOCIAL CORRELATES OF SMOKING IN COLLEGE STUDENTSLONGITUDINAL STUDY OF ASTHMA FROM BIRTH TO ADULTHOODSMOKING PREDICTORS IN MEXICAN AMERICAN YOUTHPREDICTORS OF CIGARETTE SMOKING IN LATINO ADOLESCENTSBUPROPION AND WEIGHT CONTROL FOR SMOKING CESSATIONEXERCISE TO AID SMOKING CESSATION IN WOMENLVALo,p.Although rates of smoking have declined, the decrease in prevalence has been much less pronounced in women than in men, and women are particularly vulnerable to ongoing smoking-related morbidity and mortality. One reason for gender differences in smoking cessation is concern about cessation-related weight gain among women. In the previous grant period, we tested the efficacy of two adjuncts to a standard cessation program for weight concerned women, behavioral weight control (WEIGHT) and cognitive behavior therapy to reduce weight concerns (CBT). Results of this trial have shown that CBT is a promising adjunctive treatment for weight concerned women. Specifically, 59.7% of known in the CBT condition were abstinent from smoking in post- treatment. Further, CBT yielded significantly higher abstinence rates in 3- month follow-up when compared to standard cessation only or the WEIGHT adjunct, with cessation rates of 39.4%, 23.6%, and 22.6% for the three groups, respectively. Nevertheless, abstinence rates decreased significantly during follow-up for all groups, and in the present study, we propose a randomized, double-blind, controlled trial to determine whether the addition of bupropion (Zyban) to CBT treatment for weight- concerned women will enhance longer-term abstinence. Four hundred fifty weight-concerned women smokers will be randomized to either cognitive behavioral treatment for weight concerns plus standard cessation (CBT) or standard smoking cessation only (STANDARD), and six months of either bupropion (Zyban) or placebo. Primary outcome will be rates of smoking abstinence and time to relapse across the four treatment conditions. In addition, we will determine the effects of these treatments on tobacco withdrawal, mood, and weight. Results of this investigation will provide information on the relative efficacy of CBT and bupropion alone and in combination, and the utility of drug and counseling strategies that are specifically tailored for a high- risk population. This is a competing cLVALontinuation of 2-R01-DA04174-13.<LVALN 0 lTAGE Fetus/Prenatal EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials Biochemical Assessments Nicotine Replacement Therapy Other Pharmacological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking NicotineAGE Child Young Adult Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance AGE Child EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesADDICTION Initiation Maintenance AGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION African American TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesADDICTION Cessation Withdrawal Relapse EPIDEMIOLOGY/SURVEILLANCE Large (>=100) PREVENTION/TREATMENT Counseling/Behavior Therapy Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseLVALo,p."Despite a gradual decrease in cigarette smoking rates among adults over the past 30 years, little progress has been made in changing adolescent smoking behavior since 1980. The onset of tobacco use among young adults has become much less frequent and most initiation now takes place in adolescence. There has been an unexplained decrease in smoking among African American youth from 15.7% in 1980 to 4.4% in 1993, despite minimal change in rates among White youth in the same time period (21.8% in 1980 and 22.9% in 1993). Smoking rates among African American adolescents showed that 67% reported lifetime cigarette use (Trying), 20% current cigarette use (2 1 day in previous month), and 6% frequent use (2 20 days in previous month). Defining what protective factors exist among African American adolescents may assist understanding of how to prevent smoking initiation for all youth. The long-term aim of the study proposed here is to identify those characteristics of African American youth that by predicting initiation and continued use of cigarettes will need to be addressed in culturally appropriate prevention programs to be developed in the future. Specific aims are: 1) To identify predictors of each of three stages of cigarette smoking behavior (Trying, Experimentation, and Regular Use) in a cohort of African American youth of both genders over two years of annual follow-ups; and 2) To evaluate the role of six domains of variables in predicting each of three stages of cigarette smoking (Trying, Experimentation, and Regular Use) among African American youth of each gender. The predictor domains are: (a) social environment (e.g., smoking modeling by adults and peers, normative beliefs of smoking prevalence); (b) intrapersonal characteristics (e.g., depression, risk taking); (c) knowledge about health effects of cigarette smoking; (d) attitudes (e.g., expectations about smoking and stereotypes about smokers); (e) normative beliefs about cigarette smoking (i.e., beliefs of important others regarding cigaretteLVAL smoking); and, (f) intentions to try, experiment, or smoke cigarettes. These domains of predictors were chosen because they have shown promise in previous studies of cigarette smoking onset and are susceptible to modification through short-term prevention interventions. The study proposed here comprises a longitudinal study of a randomly selected cohort of African American children. The cohort will initially include nonsmoking children of both genders aged 10 to 12 years at the time of first testing. The cohort will be randomly selected from residents in the San Francisco Bay area and will be interviewed in their homes every year for four years. The parent(s) of the children will also be interviewed at the same time as the youth. The study will utilize culturally appropriate instruments (specially developed to reflect the group's culture) that will be self-administered at home in the presence of the interviewers. All youth respondents will be asked to provide a saliva sample as a bogus pipeline and 25% of all saliva samples will be biochemically validated. The study proposed here will test the proposed passage through stages in the process of acquisition of cigarette smoking separately among boys and girls of each ethnic or racial group. In addition, at each of the three acquisition stages being studied here (trying, experimentation, regular use), a latent variables model will be tested in terms of its predictive value. LVALo,p.$The study was designed to identify predictors of each of three stages of cigarette smoking behavior (Trying, Experimentation, and Regular Use) in Latino boys and girls. Seven predictors were evaluated: (a) social environment (e.g., smoking modeling by adults, peers, normative beliefs of smoking prevalence); (b) intrapersonal characteristics (e.g., depression, risk taking); (c) knowledge about health effects of cigarette smoking; (d) attitudes (e.g., expectations about smoking and stereotypes about smokers); (e) normative beliefs about cigarette smoking (i.e., beliefs of important others regarding cigarette smoking); (f) intentions to try, experiment, or smoke cigarettes; and (g) previous or current use of cigarettes, alcoholic beverages, marihuana, or other substances. In the initial stage, our research group completed the questionnaire development and pretesting phase of the project. In order to include culturally relevant questions regarding cigarette smoking (e.g., attitudes, norms, and expectancies), open-ended interviews with 24 Hispanic adolescents and 20 non-Hispanic White adolescents were conducted. Responses were content analyzed in order to develop closed-ended items for the large-scale survey. The final structured surveys for the adolescents and their parents/guardians were pre-tested and translated. The second phase of our project started in November of 1999. This phase included a telephone survey of Hispanic boys and girls (10-17 years of age) and their parents or guardians who live in the same household. Potential participants were selected from the telephone directories within counties in the San Francisco Bay area (e.g., San Francisco, Marin, Alameda, and Santa Clara counties). Spanish-surnamed families were called and those with children within the target age range were invited to participate in the study. In each household a child and one parent or guardian were interviewed. Respondents were given a choice of the language (Spanish or English) in which they wished to respond. Each8 LVALH family was compensated $20.00 for their participation. As part of the study, we completed 2,206 interviews (1,103 Latino youths and 1,103 parents or guardians). As proposed in the second grant from TRDRP, we expect to re-interview each youth and the parent/guardian between 2000 and 2001. The survey instruments will be similar to the ones used in the first wave in order to guarantee comparability in responses and in the data. These comparisons will be of particular significance in allowing us to look at predictors of cigarette smoking in a short longitudinal analysis. The data from this study provide important indicators to be used in the design of culturally-appropriate tobacco prevention strategies for Latino youth. LVALo,p.&The major objective of this competitive renewal is to establish the principal mechanisms and risk factors that modify incidence and persistence of asthma from birth into early adult life. Specific aims are to: 1) identify factors that alter persistence and remission of asthma symptoms among young adults who developed asthma in childhood; 2) assess the role of persistent eosinophilia during childhood as a mechanism which determines progression and incidence of asthma in early adult life, and prevalence of persistent BHR; 3) measure noninvasive markers of airway inflammation in early adult life, and identify correlates of these markers, both with childhood and current asthma symptoms, BHR and immune system indicators of allergy; 4) predict early (by age 20 ) decline in lung function with reference to childhood lower respiratory tract illnesses, asthma-like symptoms, and the initiation of smoking; and 5) investigate the role of gender in incidence of and risk factors for asthma during adolescence and young adult life. More detailed knowledge of the natural history, risk factors, and mechanisms of asthma are essential for the development of effective strategies for the primary and secondary prevention of this and complex and costly disease. This project is designed to continue into early adult life our prospective investigation of risk factors for the development and persistence of asthma, and to study longitudinally assessed mechanisms associated specifically with asthma, in a multiethnic population. The children enrolled at birth in the Tucson Children's Respiratory Study are approaching a critical age during which lung growth slows, ceases, or begins to decline, and when environmental influences may be changing. Collection of questionnaire data regarding respiratory symptoms will occur in all 974 subjects still being followed at three ages: 18, 20 and 22 years. In addition, at age 20 there will be a comprehensive evaluation of respiratory health on subjects (n=400-450) who have relatively complete longh LVALx itudinal data. At that time, subjects will be tested for baseline lung function, airway reactivity (using methacholine challenge, peak flow variability and bronehodilator response), markers of airway inflammation (exhaled nitric oxide) and allergy skin test response. Blood will also be drawn for measurements of total serum and allergen specific IgE, cytokine studies, and a CBC with differential. A subgroup will provide a sample of induced sputum for assessment of percent eosinophils, cytokine studies, and total and allergen specific IgE. Linking this extensive data set to the genetic analyses conducted in related projects will provide a powerful means of addressing fundamental questions about the relative roles of environmental exposures and familial factors in the development of asthma from birth through young adult life.LVALo,p.(Cigarette smoking rates among gay men and lesbians are approximately 20-25% higher than the general population. The smoking rates among college students have increased about 27% in the past 10 years. Gay and lesbian college students may be especially at risk for tobacco use due to stressors related to their sexual minority status. In the gay and lesbian college student population, however, there is sparse research on smoking and the psychosocial factors related to cigarette use. Therefore, the specific aims of this study are: (1) to explore differences in smoking attitudes, beliefs, and behaviors among gay and lesbian college student smokers and nonsmokers and their heterosexual peers, (2) to explore differences in self-acceptance of homosexuality and mental health among gay and lesbian college student smokers and nonsmokers and their association with anti-gay victimization and psychosocial risk and protective factors, and 3) to examine differences in psychosocial risk and protective factors among gay and lesbian college student smokers and nonsmokers and their heterosexual peers. Participants will be 320 (80 gay men/80 Lesbians and 80 heterosexual males/80 heterosexual females) college students ages 18-24. The students will be recruited from two universities. Participants will complete several questionnaires to assess smoking attitudes, beliefs, and behaviors, coping styles, sex roles, and levels of perceived stress, body image, depression, anxiety, self-esteem, social support from family and friends, and nicotine dependence (smokers only). In addition to the aforementioned measures, gay men and lesbians will complete questionnaires to assess levels of victimization and self-acceptance of homosexuality. The long-range objective of this study is to identify psychosocial correlates related to smoking among gay and lesbian college students that may be incorporated into a cognitive-behavioral smoking cessation program for this population. Identification of important psychosocial issues specific to smokinLVALg in gay men and lesbians will significantly facilitate the successful development of a culturally sensitive cessation program that may be utilized on college campuses across the US.LVALz ` jEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Educational Materials Biochemical Assessments PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Postpartum Partner/SpouseAGE Child Young Adult Adult COMMUNITY General Partnerships Health Care Provider EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Counter-Marketing Media-Websites/pamphlets/radio POLICY Regulatory Intervention PSYCHOLOGICAL Social Factors Cultural Factors STUDY POPULATION African American Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Maintenance Cessation Relapse LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Hormones MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingAGE Young Adult EDUCATION LEVEL College and Above EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research STUDY POPULATION Lesbian Gay Bisexual Transgender TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/Exercise Sex/Gender DifferencesLVALo,p.Cervical cancer is a leading gynecologic malignancy with 14,500 new cases and 400 deaths yearly. Eighty to 90% of women with cervical cancer are infected with human papillomavirus (HPV). Cervical intra- epithelial neoplasia (CIN) markers the pre-cancerous stage. Ten to 20% of women develop cervical cancer. Paper smears and HPV testing have limitations in identifying women progressing to cancer, not helpful in the patients with ASCUS/AGUS (atypical squamous/glandular cells of undetermined significance) and for monitoring therapy efficacy (paucity of tissue after therapy) in recurrence. Our data-supported hypothesis is that progression of squamous cell cervical cancer from CIN is related to up-regulation of EGF-R and insulin-like growth factor-II (IGF-II) proteins in cervical epithelium, followed by significant increases in serum IGF-II levels (specific to cervical cancer; levels decrease after therapy. Our latter finding provides us with an excellent opportunity to develop a non-invasive screening test that gives an added value to pap smear and HPV testing. We propose that: Serum IGF-II levels can be used to identify patients who are at risk of developing cervical cancer and, more importantly, to monitor therapy efficacy in the patients with cervical cancer. We shall obtain serum levels of IGF-II (ELISA) in women with: 1. Normal Pap smear; 2. Abnormal Pap smear with no CIN; 3. Endometrial or ovarian cancer; 4. CIN-I, II or III pre-treatment; 5. CIN-I, II or III, post-treatment; 6. Invasive cervical cancer pre- treatment or at a time of hysterectomy; and, 7. Invasive cervical cancer (6 months and a year) post-treatment. We shall correlate the levels of IGF-II with clinical diagnosis of CIN or cervical cancer, size of neoplasm and resolution or recurrence of the disease and the smoking history. We believe that serum IGF-II test could compliment the Pap test to reduce deaths by cervical cancer. 6LVALFThe purpose of this core is to pursue and support the investigation of sex- specific factors in nicotine-dependence and treatment. The function of the core is supported by an emerging empirical literature, and by national research goals. The core will support all Center investigators, and it will be linked to other institutional programs at Yale in order to enhance transdisciplinary collaboration. Although the core will initiated independent projects, its primary mission will be cost-effective attention to sex-specific factors in current and new projects through such means as pooling data to test sex-related hypothesis, including assessments related to sex and gender issues, ensuring adequate representation of women so that sex related comparisons can be made, and taking charge of data analysis and interpretation of findings pertaining to sex differences for all appropriate Center projects. Improvement in the health of women and men depends upon new-found scientific knowledge which recognizes sex-specific effects. The core is directed toward strengthening existing research in nicotine dependence as it relates to sex and gender, and developing new, cutting-edge areas of investigation that will result in direct practical benefit. The specific aims of the core are as follows; 1) Testing sex-specific models of smoking maintenance 2) Assessing sex-specific benefits of smoking cessation. 3) Investigating the relationship of sex-specific hormonal factors to treatment response and relapse. 4) Providing support and methodological consultation to investigators examining sex and gender effects in Center projects.LVALo,p.-More than 26,000 people die each year as a result of tobacco use in Texas. To lessen the health burden of tobacco, innovative and intensive interventions are urgently needed. The tobacco suit settlement in Texas has led to an allocation of approximately $10 million/yr. for state-level tobacco control. To match per-capita expenditures that have appeared to influence behavior in other major state initiatives, the funds will be concentrated in media, community and policy activities for a single region, involving approximately one-fifth of the state population and forming a "natural" quasi-experimental design. The University of Texas School of Public Health, the Baylor College of Medicine and the Texas Department of Health (TDH) will evaluate these regional activities and investigate their processes and effects in the three major cultural groups in Texas (Anglo-, Hispanic- and African-American). Data sources will include annual telephone surveys of adults (approx. 10,000 year/with 2,200 smokers), biannual surveys of secondary school students (n=15,000/2 years), surveys of physicians, other providers, schools, other organizations and key individuals, media content tracking and other qualitative and quantitative studies to document and evaluate the implementation of media, community and policy activities. In the quasi-experimental regional studies, trends in adult and youth prevalence and related factors will be compared in statewide and regional groups. Tobacco use cessation effects in the intensive regions will be evaluated through comparative panel studies. In an experimental study limited to randomly selected panel participants, some smokers and their families will receive mail-telephone contacts from peer outreach workers to increase exposure and response to media and community activities. The research designs employed in these studies will allow us to answer questions about the effects of different intensive regional interventions on tobacco use prevalence and smoking cessation and the processes and qLVALualitative factors that are associated with the success or failure of different interventions in different ethnic and SES groups. To enhance the quality of intensive regional activities supported by the settlement funds, technical assistance will be provided through training workshops for TDH and its partners and contractors, focusing on effective multi-cultural action and the use of innovative media, community and policy interventions to address specific theoretical variables related to cessation and prevention. A publicity and peer modeling campaign will be conducted to promote individual behavior change and organizational program and policy innovation. This regional project within Texas is designed to gather evidence of effects of anti-smoking expenditures and to provide capacity development to justify later funding of similarly intensive tobacco control activities for the entire state.LVALo,p./Smoking during pregnancy increases women's risk of complications of pregnancy and numerous birth outcomes. Two-thirds of women smokers continue to smoke during pregnancy, with particularly high rates of smoking among low income and less educated women. For the majority of women, pregnancy occurs in the context of an intimate relationship that pregnant women report as their primary source of support. However, naturally occurring partner support may not be enough to assist pregnant smokers with cessation, particularly when the partner is a smoker. The proposed study is a five year randomized trial to evaluate the incremental improvement of providing a part-assisted support adjunct to state-of-the-science self-help smoking cessation interventions for pregnant smokers. Ft. Bragg military base located in Fayetteville, NC was selected as the study site because of high smoking rates, high birth rates and the majority of women who receive prenatal care are married to military personnel. Three intervention conditions will be tested in an additive design. Eligible couples who are receiving prenatal care at Ft. Bragg/Womack Army Medical Center will be identified from automated appointment logs and recruited to participate. Couples who agree (n=700) will be randomized to (1) provide advice and a self-help booklet (usual care prototype, n=233); (2) self-help guide and relapse prevention kit plus pre-and postpartum telephone counseling (enhanced self-help, n=233); or (3) enhanced self-help plus a partner-assisted support intervention that includes a couple contact session and tailored serialized written materials plus cessation materials for partner smokers (partner-assisted, n=233). Participants will be surveyed at baseline, 32 weeks of pregnancy, and 8 weeks, 6 and 12 months postpartum. Self reported smoking status will be biochemically validated late in pregnancy and at the 12 month follow-up. The primary outcomes of interest will be rates of smoking cessation among pregnant women and levels of perceivLVALed partner support for cessation at all follow-ups.LVALo,p.Smoking in pregnancy poses serious health risks to the fetus and the mother. About half of women smokers continue to smoke throughout pregnancy. Pregnant women who have the greatest difficulty quitting smoking even when provided with behavioral cessation interventions tend to be more dependent smokers who may requite nicotine replacement therapy to be successful at cessation. The proposed five-year study is designed to evaluate the effectiveness of providing over-the-counter (OTC) nicotine replacement therapy, choice of gum or patch, (NRT) to promote prepartum smoking cessation. Proposed is a two-arm design. Eligible pregnant women (N=300) will be randomized to either: Arm 1, Tailored Cognitive Behavioral Treatment (TCBT, n=150) that provides women with customized risk information about smoking and nicotine, the potential harms to the fetus and encouragement of appropriate behavioral skills building; or Arm 2, TCBT + NRT - the tailored intervention incorporating NRT information plus choice of patch or gum (n about150). The intervention will include 5 face to face contacts as part of prenatal visits and 2 telephone counseling sessions. Primary outcome measures will be biochemically validated 7-day prevalent abstinence rates at the 19-27th and 27 35th week of pregnancy. Secondary outcomes will include 7-day prevalent abstinence rates at 12 and 24 weeks postpartum, serious quit attempts, compliance with NRT, and use of materials. Saliva cotinine will be measured among all women at baseline, the 27-35th week of pregnancy, and 24 weeks postpartum. The significance of this project is that it relies on transdisciplinary collaborations to extend the science in nicotine replacement therapies to a population that could derive substantial health benefits. Moreover, the study results have immediate potential to inform clinical recommendations for integrating nicotine replacement into prenatal care.LVALo,p.2Researchers from UCLA and WestEd are collaborating to analyze three years worth of data from the California Healthy Kids Survey (CHKS), data collected from 1998 through 2001 from approximately 429,000 California teenagers. The CHKS includes measures of tobacco use, diet, physical activity, alcohol and drug use. The survey is mandated by the California legislature, to provide feedback to school districts every two years about their students' health-related behaviors. The sample of students completing the CHKS is big enough so that reliable conclusions can be drawn for less well-known ethnic groups that have not been described in earlier surveys, such as Native Americans, Central Americans, Laotians, Cambodians, Cubans, as well as students with mixed ethnic ancestry. With a third year of CHKS questionnaires being completed by June 30, 2001, it will also be possible to see how much tobacco use behaviors have changed in the estimated 300 schools whose students will have completed the CHKS both in the first and third years of administering the CHKS. This project has three specific aims: To describe tobacco use rates among California middle school and high school students at the state-, county-, and school-level. To investigate racial/ethnic differences in student tobacco use onset, beliefs about tobacco, efforts to quit smoking as well as the conditions associated with continued smoking or with long-term refusal to use tobacco. Also to investigate how much tobacco use might be associated with other health behaviors & attitudes, such as drug use, perceived harm from smoking, food choices, and concerns about weight. These associations would be compared across different racial/ethnic groups. To describe changes in tobacco use and associated behaviors and beliefs that occurred from Year 1 of the CHKS to Year 3 of the CHKS, for the 300 schools whose students have re-taken the CHKS. Analyses will proceed systematically, beginning with efforts to correct the data for missing data and then descriptive results LVALby age, gender and major ethnic identification. Methods will then be used to examine whether lifestyle patterns observed in one gender-by-ethnicity subgroup are similar to or different from the lifestyle patterns observed in other groups. Other state-of-the-art methods will then be used to examine differences in tobacco use patterns across different groups, defined by age, gender, or ethnic background. This proposed study has the potential to tell us new information about ethnic differences in youth tobacco use. It may also tell us how much tobacco use behavior is associated with predictable patterns of other health-related behaviors including eating habits, physical activity choices, alcohol and other drug use. Finally, this proposal is designed to provide a more detailed understanding of "social" or "intermittent" smoking. The overall intent of the proposed research is to identify new behaviors and environmental influences that may influence adolescent tobacco use. Innovative tobacco use reduction strategies can then use this new knowledge to encourage youth to reduce their tobacco use. Sustained reduction of tobacco use by adolescents, in turn, should yield predictably large social, quality of life, economic and health benefits for themselves and their communities. 8LVAL RCOMMUNITY Health Care Provider LOCATION National POLICY Guidelines/Best Practices RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco SmokeDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingADDICTION Cessation EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cancer MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Counseling/Behavior Therapy PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionADDICTION Initiation Maintenance Cessation AGE Child EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/Exercise Sex/Gender DifferencesLVALo,p.5Cancer is a disease feared by nearly everyone--young and old, people who have no direct experience with the disease but believe that they are at risk, and survivors concerned about a recurrence. Most behavioral research surrounding cancer has focused on non-affective factors such as perceived risk, but researchers are beginning to recognize that the way people feel--their affective reactions to cancer--plays an important role in what they do about the disease. This grant proposal deals with relationships between cognition (e.g., perceived risk), affect (e.g., worry; distress) and health-protective behaviors (e.g,, screening; smoking cessation). The overall purpose of this research is to test the feasibility and value of brief telephone therapy. We are testing the value of this approach for reducing distress and improving the quality of life for women diagnosed with Stages I-III breast cancer. I propose a five-year senior investigator award so that I may continue to develop the study of affect and self-protective behavior in the cancer arena. The award will release me from most of my teaching and service responsibilities. I plan to continue ongoing work studying coping among women diagnosed with breast cancer. In addition, I will seek new funding to address important basic and applied research questions such as: (a) how does worry affect self-protective behaviors (e.g., cancer screening) and how does worry as a construct differ from other affective responses to cancer (e.g., anxiety; depression; "cancer concern")? (b) how do thoughts and feelings about recurrence affect self-protective actions among cancer survivors?, how does advertising (i.e., cigarette labeling) influence thoughts and feelings toward smoking among adolescents, and (d) can we create worry and thereby influence persons who need to take self-protective action (e.g., smokers)? In addition to addressing new and important research questions, the senior investigator award will provide additional time for mentoring activities. The investiga` LVALp tor will serve in that capacity for clinical M.S. students with interests in health psychology and Ph.D. students in a health/social experimental psychology program at North Dakota State University in Health Psychology. Overall, this grant would enhance the investigator?s ability to conduct novel research in cancer prevention and control and to shepherd students through the process of becoming productive researchers in psychosocial aspects of cancer.  H % uE UU@G@ResearchX@METHERATERAJUUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECACTRDRP8RT-0059D,p.Biology and CancerT@ 9@?7/1/19996/30/20027/1/1999 to 6/30/20024/2005yumIC88,"TT@`@Researchd@MERMELSTEINROBINUNIVERSITY OF ILLINOIS AT CHICAGO SCHOOL OF PUBLIC HEALTHCHICAGOILNCIR01, CA080266 @Cb@:@9J@?9/30/19989/29/20049/30/1998 to 9/29/20044/2005LE88,"SSh@`J@Research`@MENDELSONJACKMCLEAN HOSPITALBELMONT MANIDAR01, DA015067A,p.Biology and Cancer Addiction@9@?3/20/20032/29/20083/20/2003 to 2/29/20084/2005}nhdZIC88,"RR @@Researchb@MELVINCATHYCECIL G. SHEPS CENTER FOR HEALTH SERVICES RESEARCHCHAPEL HILL NCRWJF51592x@@@:l@9v@?7/1/20046/30/20057/1/2004 to 6/30/20054/2005{G@88,"QQm@@Researchb@MELVINCATHYCECIL G. SHEPS CENTER FOR HEALTH SERVICES RESEARCHCHAPEL HILL NCRWJF48676x@>@:l@9v@?5/1/20037/31/20045/1/2003 to 7/31/20044/2005{G@88,"PP f@`@Researchb@MELVINCATHYCECIL G. SHEPS CENTER FOR HEALTH SERVICES RESEARCHCHAPEL HILL NCRWJF46679x@>@:l@9v@?3/1/20034/30/20043/1/2003 to 4/30/20044/2005{G@88,"OO@`@Researchb@MELVINCATHYCECIL G. SHEPS CENTER FOR HEALTH SERVICES RESEARCHCHAPEL HILL NCRWJF38601x@>@:l@9v@35/1/20004/30/20045/1/2000 to 4/30/20044/2005{G@88,"NN @@@Research@MELVINCATHYCECIL G. SHEPS CENTER FOR HEALTH SERVICES RESEARCHCHAPEL HILL NCRWJF45257Not availablej@:5/1/20024/30/20055/1/2002 to 4/30/20054/2005{G@88,"~MM @ @ResearchN@MCELROYJANEUNIVERSITY OF WISCONSIN AT MADISON COMPREHENSIVE CANCER CENTERMADISONWINCIR03, CA110796=,p.t@:T@9@38/18/20047/31/20068/18/2004 to 7/31/20064/2005GA88,"LL@G@Researchl@MCELIGOTARCHANAUNIVERSITY OF CALIFORNIA AT SAN DIEGOSAN DIEGOCACTRDRP9DT-0046;,p.Biology and CancerR@9@37/1/20006/30/20027/1/2000 to 6/30/20024/2005 }rKB88,"KK @`@Research@MCDONALDPAULUNIVERSITY OF WATERLOOWATERLOOON, CANADACTCRINot GivenNot available7/1/20047/1/20097/1/2004 to 7/1/20094/2005}vj`HB88,"?~JJ@@Researchl@ MCCLUREJENNIFERGROUP HEALTH COOPERATIVE OF PUGET SOUNDSEATTLEWANCIK07, CA0846037,p.@:@96@37/1/19996/30/20047/1/1999 to 6/30/20044/2005}tKA88,"IIR@/@ResearchX@ MCCAULKEVINNORTH DAKOTA STATE UNIVERSITYFARGONDNCIK05, CA092633t4o,p.@ @@39/27/20027/31/20079/27/2002 to 7/31/20074/2005vqmfG@88,"LVAL,p.8This project will enhance the career development of the principal investigator through a combination of educational and research activities. The goal is to develop expertise in smoking cessation with a particular emphasis on female smokers. Smoking is the leading cause of death and illness in our society. A greater understanding and emphasis on cessation in women is of particular importance, as women may have more difficulty quitting smoking than do men. Two investigations have been planned. The first is a randomized clinical trial in which women at high risk for cervical cancer (n=300) will be offered treatment based on a) the Agency for Health Care Policy and Research's (AHCPR) Clinical Practice Guideline for Smoking Cessation or b) usual care (UC). Smoking is a significant risk factor for cervical cancer and it is estimated to be responsible for nearly 31 percent of cervical cancer-related deaths. However, we are unaware of any smoking cessation trials focusing on this unique, at-risk population. Additionally, this study will be the first to test the full AHCPR treatment model, which dictates motivational and/or action- oriented treatment be offered to all smokers. To overcome several potential limitations of the model, the AHCPR's motivational intervention will be supplemented with motivational interviewing techniques proven to be effective in the alcohol treatment literature. Furthermore, with the exception of initial contact, all counseling will be conducted by phone. The specific aims of this investigation are to 1) determine if use of the AHCPR treatment model increases motivation and cessation rates among women who are at high-risk for cervical cancer, and 2) explore factors through which the intervention may impact abstinence. Project two will examine the role of depression history on the process of quitting smoking among women. Individuals with a history of depression have greater difficulty quitting smoking than do those without a history of depression. It is unclear, however, what accountLVALs for this difference. Project two will evaluate differences in several theoretically important variables (negative affect, urge, self-efficacy, and outcome expectations). Three hundred women will be stratified based on their depression history and followed for one week post-quitting. During this period, "real-time" assessments of cognitive, emotional, and situational aspects of the quitting process will be conducted using ecological momentary assessment procedures (EMA). Information will be collected via small, hand-held computers carried by the participants at all times. The primary aim of this study is to evaluate the relation between depression history and factors identified as potentially important in the quitting process, based on Marlatt and Gordon's theory of relapse prevention. If differential patterns are found between women with and without a history of depression on these factors, these variables will also be evaluated as potential mediators of smoking lapse/relapse. Such knowledge is important as it may lead to the development of more targeted, and therefore potentially more effective, cessation interventions.jLVALv  2 : \ , n  \f6~2vDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1c Discovery 3 Development 1 Development 3 Delivery 2 Delivery 3 Evaluation 1aDiscovery 1c Development 2 Development 3 Delivery 1 Evaluation 1aDiscovery 1c Discovery 2a Discovery 3 Development 1 Development 3 Development 4 Delivery 2 Partnerships 2 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2b Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1c Development 2 Evaluation 1bDiscovery 1a Discovery 1c Development 1 Delivery 1Discovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Development 2 Delivery 1 Evaluation 1a Evaluation 1bDiscovery 1a Development 1 Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1c Development 3 Development 4 Delivery 1Discovery 1c Development 3 Development 4 Delivery 1Discovery 1c Development 3 Development 4 Delivery 1Discovery 1c Development 3 Development 4 Delivery 1Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Discovery 1c Discovery 2a Development 1 Development 3 Evaluation 1a Evaluation 1bLVAL \~ F  ` l b .PhV bInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Interventions for Prevention and TreatmentBiology and Cancer Interventions for Prevention and TreatmentBiology and Cancer Interventions for Prevention and TreatmentEpidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and Treatment Community and Policy InterventionsBiology and Cancer Interventions for Prevention and Treatment Global IssuesAddiction Epidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National Surveillance Global IssuesBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentAddiction Epidemiology and National SurveillanceInterventions for Prevention and TreatmentAwareness Risk Perception and Communications Community and Policy InterventionsEpidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceInterventions for Prevention and Treatment Community and Policy InterventionsInterventions for Prevention and Treatment Community and Policy InterventionsInterventions for Prevention and Treatment Community and Policy InterventionsInterventions for Prevention and Treatment Community and Policy InterventionsAddiction Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National Surveillance Interventions for Prevention and TreatmentLVAL,p.<The relationship between cigarette smoking and increased risk of cardiovascular disease (CVD) has been well established. Studying the biological link between smoking and CVD needs further investigation. Increased blood levels of homocysteine may increase risks of heart disease. Homocysteine is an amino acid, and consuming a diet high in meat and dairy products has been shown to increase blood homocysteine levels. Studies have suggested that smokers have higher blood levels of homocysteine than non-smokers and the levels of homocysteine increase with the number of cigarettes smoked. Homocysteine levels can be lowered by consuming three vitamins: folate (mostly found in fruits and vegetables), vitamin B-12 and vitamin B-6. Folate, in particular, has been shown to substantially reduce homocysteine levels. Some studies that have reported on the link between cigarette smoking and homocysteine have not examined folate levels in smokers and non-smokers, which could alter the results. Also most studies use folate from vitamin supplements rather than from fruit and vegetables to lower homocysteine levels, and therefore the effects of consuming a high vegetable diet on homocysteine concentrations have not been widely investigated. We would like to examine blood homocysteine and folate levels in a group of female smokers participating in a randomized clinical trial. The randomized trial is investigating the effects of consuming a diet low in fat and high in vegetable, fruit and fiber on breast cancer recurrence. We will examine homocysteine and folate levels upon entry into the study and one-year after randomization into either the intensive diet group (high vegetable and fruit diet) or the control group (usual diet). We expect that the smokers in the intensive diet group will have lower homocysteine concentrations than the control group at one-year post-randomization, which will show that a high vegetable diet may be protective for smokers by reducing homocysteine. Also, we will be able to compare  LVAL homocysteine levels in smokers and non-smokers at entry into the study and one-year post-randomization. If smokers have higher amounts of homocysteine concentrations than non-smokers, regardless of their folate levels, then we could hypothesize on a possible mechanism for higher CVD rates in smokers. Thus, reducing homocysteine levels in smokers and investigating possible explanations for higher rates of heart disease in this population may provide future avenues of preventing or curbing the risk for CVD in smokers.DLVAL,p.TIn vitro and in vivo data support the carcinogenic potential of cadmium (Cd) and its role in breast cancer development. Increased human exposure to Cd has raised concern about the association between this heavy metal and risk of breast cancer. However, only one epidemiologic study has been published that addresses this emerging environmental exposure. This project aims to evaluate the association between Cd exposure and breast cancer risk using data collected from an on-going population-based case-control study of breast cancer (R01 CA47147) supplemented with proposed urine sample analysis. The main hypothesis of interest is that higher body burden levels of Cd as measured in urine are associated with an increased risk of breast cancer. Secondary hypotheses are: 1) self-reported personal smoking history and exposure to tobacco smoke are related with measured Cd and 2) age, geographic location, parity, menopausal status, occupation, consumption of supplemental minerals and food with potentially high Cd levels are related with Cd body burden. To accomplish these aims, 250 newly diagnosed breast cancer cases (identified by Wisconsin's statewide tumor registry) and 250 population controls enrolled in the parent study will be asked about their exposure to factors hypothesized to be associated with Cd body burden. This information will supplement existing questions regarding established risk factors for breast cancer. Women will also be asked to collect a urine sample at home and to mail it to the study office. Urine samples, the most relevant practical biological indicator of long-term Cd exposure, will be expertly analyzed by the Wisconsin State Lab of Hygiene to measure body burden of Cd. interview data will be merged with urine Cd level data to address the specific aims. The study team brings together expertise in breast cancer and environmental epidemiology, laboratory science, and biostatistics to efficiently address the role of cadmium in the etiology of breast cancer.LVAL This multi-component program has two aims: to promote the dissemination of existing best-practice treatments for pregnant smokers in prenatal care and to support innovative research to discover more powerful "breakthrough" treatments. The National Dissemination Office is funded to build capacity, demand and policy supports for proven interventions, and to conduct research on the systems changes needed to implement them. The National Program Office supports innovative research demonstrations with promise to produce the next generation of more effective treatments.This multi-component program has two aims: to promote the dissemination of existing best-practice treatments for pregnant smokers in prenatal care and to support innovative research to discover more powerful "breakthrough" treatments. The National Dissemination Office is funded to build capacity, demand and policy supports for proven interventions, and to conduct research on the systems changes needed to implement them. The National Program Office supports innovative research demonstrations with promise to produce the next generation of more effective treatments.This multi-component program has two aims: to promote the dissemination of existing best-practice treatments for pregnant smokers in prenatal care and to support innovative research to discover more powerful "breakthrough" treatments. The National Dissemination Office is funded to build capacity, demand and policy supports for proven interventions, and to conduct research on the systems changes needed to implement them. The National Program Office supports innovative research demonstrations with promise to produce the next generation of more effective treatments.LVAL ADDICTION Cessation AGE Fetus/Prenatal ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies STUDY POPULATION Asian Pacific Islander Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Child DISEASE/BIOLOGY Other Disease/Biology RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN PregnancyADDICTION Initiation Maintenance AGE Child EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle Hormones MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Health Care Provider LOCATION National POLICY Guidelines/Best Practices RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyCOMMUNITY Health Care Provider LOCATION National POLICY Guidelines/Best Practices RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyCOMMUNITY Health Care Provider LOCATION National POLICY Guidelines/Best Practices RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancyx LVAL This multi-component program has two aims: to promote the dissemination of existing best-practice treatments for pregnant smokers in prenatal care and to support innovative research to discover more powerful "breakthrough" treatments. The National Dissemination Office is funded to build capacity, demand and policy supports for proven interventions, and to conduct research on the systems changes needed to implement them. The National Program Office supports innovative research demonstrations with promise to produce the next generation of more effective treatments.LVAL,p.BThis is a revision of a new application in response to PA-00-045 Neurobiological and Behavioral Research on Nicotine and Tobacco Components. Nicotine activates a4beta2 nicotinic receptors on mesolimbic dopamine neurons and increases extra cellular dopamine release. The indirect dopamine agonist effects of both nicotine and cocaine are thought to be important for their abuse-related effects. However, it is likely that dopamine is only one of a constellation of neurobiological systems that may contribute to nicotine abuse as well as to cocaine abuse. The role of the endocrine system in modulating the reinforcing effects of drugs is poorly understood, but recent preclinical and clinical studies suggest that hormones may influence the abuse-related effects of cocaine, and these findings have led to novel approaches to treatment. Our preliminary studies indicate that both nicotine and cocaine stimulate anterior pituitary and adrenal hormones, and have similar pharmacodynamic and pharmacokinetic profiles. However, in contrast to cocaine, relatively little is known about the temporal relationships between nicotine-induced alterations in subjective states, hormone release patterns and increases in plasma nicotine levels, or how nicotine's effects may vary as a function of gender and/or menstrual cycle phase. We propose to conduct clinical studies of the acute effects of nicotine on the hypothalamic-pituitary-adrenal axis (HPA) and the hypothalamic-pituitary-gonadal axis (HPG) in men and women who are daily smokers and are nicotine dependent (DSM-IV criteria). Women will be studied at the follicular and the mid-luteal phases of the menstrual cycle to determine if hormone fluctuations across the menstrual cycle influence nicotine's biological and abuse-related effects. The effects of two doses of nicotine and placebo on neuroendocrine, subjective and cardiovascular measures will be studied under double-blind conditions in an own control design. Nicotine will be administered by smoking in a procedure where puff LVAL(volume, duration and frequency are measured and controlled. However, because other constituents of tobacco smoke may contribute to the effects of smoking, we propose to conduct parallel studies of intravenous nicotine. Examination of nicotine's effects on the endocrine system and correlated changes in subjective and cardiovascular measures will advance our understanding of the biological bases of nicotine's abuse-related effects, as well as its contribution to some reproductive disorders in women who smoke (e.g., early menopause and infertility). Clinical reports suggest that nicotine has anti-estrogenic effects, but there have been no comprehensive studies of nicotine's effects on the HPG axis. This question is important, because gonadal steroid hormones appear to enhance the abuse-related effects of cocaine in preclinical studies and may contribute to gender differences in cocaine's effects. We propose to study the temporal relations between nicotine's effects on gonadal steroid hormones, subjective effects and cardiovascular measures. An increased understanding of nicotine's acute effects on anterior pituitary, gonadal and adrenal hormones may suggest new strategies for the development of antinicotine medications as it has for cocaine.LVALThe broad, long-term objective of this proposal is to increase our understanding of how adolescent's subjective experience of early trials of cigarette smoking impacts upon their future smoking behavior. The Specific Aims are 1) to increase our understanding of the subjective and objective microcontexts of adolescent smoking and how they vary by age and gender, 2) to describe adolescents' patterns of acceleration and deceleration in the frequency, intensity and regularity of smoking, and 3) to determine which micro- and macro-level factors differentiate youth who eventually either escalate, maintain, or discontinue their smoking. The research design follows youths ranging widely in their smoking behavior (from recent tryers to weekend smokers), cross-sectioned by grade (8th- 10th), at semi-annual intervals for a period of 18 months. During each data collection period adolescents will provide 1) intensive naturalistic self-reports on their daily experience and smoking behavior for one week and 2) retrospective questionnaire and interview data. Employing hand-held computer self-monitoring devices, we will use a combination of random time-sampling and event sampling while adolescents go about their daily lives to capture both smoking episodes and comparison events. This ecologically valid yet systematically collected data, Capturing thousands of moments nested in 240 adolescents, can provide a heretofore unseen picture of the subjective experience of adolescent smokers and examine its relationship to changes in smoking patterns. Findings from this study have potential for informing both smoking cessation and preventive interventions for adolescents.RLVAL,p.bA particularly tragic effect of tobacco smoke is what it does to unborn and newborn babies, including how it affects their brain growth. Nicotine in a mother's bloodstream can cross the placenta to affect brain development in the fetus. Even after birth, nicotine in secondhand smoke inhaled by infants can affect their growing brains. For example, studies have shown that smoking by pregnant mothers results in babies that do not respond as well as they should to sounds around them. As a result, their abilities later on in life to hear and speak normally are hurt. Since these babies have normal input from their ears to their brain, their problems come from improper brain development. Similar problems also occur in infants who inhale secondhand smoke. It is not known why nicotine has this effect, nor is it known how much nicotine must be inhaled in order to produce these effects. This research will determine how exposure to nicotine affects the normal development of the auditory cortex (the highest brain center responsible for hearing). Scientists think that a protein called the NMDA receptor is important for the development of the auditory cortex (and similar areas for sight and touch). Recent studies have shown that nicotine affects the normal functions of the NMDA receptor. The effect is strongest during a brief period of time shortly after birth. This may be the time when the growing brain is most vulnerable to the effects of tobacco smoke. By placing tiny electrodes into brain cells to measure their activity, we will determine exactly how nicotine affects the NMDA receptor. We will also determine how much exposure to nicotine is sufficient to affect brain growth. Finally, we will test auditory functions in adult rats that were exposed to nicotine as pups, to determine how exposing babies to nicotine will affect their abilities as they age. This research will benefit the public by increasing our understanding of how nicotine affects brain function.nLVAL~The Population Dynamics Core will provide demographic information on the multicultural population of specific study areas, the region, state, and other contexts. The broad objective is to provide a longitudinal accounting of populations with rapidly changing composition and to locate specific ethnic groups in sufficient spatial detail to support localized sampling of different ethnic groups. Composition data will be specified by race-ethnicity, age, gender, immigration history (native-born or decade of immigrants' arrival), and other factors where appropriate. Specific aims include the following: organize demographic data sets for many sources (decennial census, Current Population Survey, the new American Community Survey, and others) to interface with existing and proposed surveys of tobacco use behavior; organize school-based data collected annually by race and by language of instruction for systematic linkage to 1990 and 2000 census data; prepare annual estimates of the small-area location of detailed ethnic groups of Asian or Latino heritage; prepare a population standardization matrix for adjustment of aggregate prevalence rates across time; and organize demographic data and tobacco and tobacco survey data in cohort format based on the 'double cohort' design for use with repeated surveys of immigrants and native borns.q o ` < rR=bb`@@@Researchj@ZMORGENSTERNHALUNIVERSITY OF CALIFORNIA AT LOS ANGELESLOS ANGELESCANIDAR01, DA011386[,p.t@:@9@X4/1/19993/31/20054/1/1999 to 3/31/20054/2005sJE88,"aaP@ @Researchp@ZMOOLGAVKARSURESHFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWANCIU01, CA097415@YL@:n@9@X9/10/20027/31/20069/10/2002 to 7/31/20064/2005}tLD88,"``!@@@Researchp@"MONKBRADLEYUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECANCIK23, CA087558V,p.Biology and CancerDiscovery 1b Evaluation 1b@L8/29/20016/30/20068/29/2001 to 6/30/20064/2005"|wskG>88,"__ f@`@Research@!MONGANJAMESGENERAL HOSPITAL CORP.--MASSACHUSETTS GENERAL HOSPITALBOSTONMARWJF48006Not available3/1/20032/28/20053/1/2003 to 2/28/20054/2005G@88,"?~^^p@?@ResearchP@ MINKOFFHOWARDSUNY DOWNSTATE MEDICAL CENTERNEW YORKNYNIAIDU01, AI031834T,p.t@:R@9@L3/1/199211/30/20073/1/1992 to 11/30/20074/2005}vrhIA88,"]]g@p@4ResearchN@MILLIKANROBERTUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILLCHAPEL HILL NCNCIP50, CA058223R,p.Biology and CancerR@9@LNot GivenNot GivenUncertain4/2005 wJB88,"\\`@@Researchn@MILLERSUZANNEFOX CHASE CANCER CENTERPHILADELPHIAPANCIR01, CA076644P,p.T@ :T@ 9>@L4/1/19991/31/20054/1/1999 to 1/31/20054/2005ytpbI@88,"[[G@@@Research^@MILLERSUZANNEFOX CHASE CANCER CENTERPHILADELPHIAPAACSTURSG-02-227-01-PBP @OT@ :j@ 9@L7/1/20026/30/20067/1/2002 to 6/30/20064/2005ytpbI@88,"ZZ@@Researchr@MILLERMARKWAKE FOREST UNIVERSITY HEALTH SCIENCESWINSTON-SALEMNCNCIR01, CA081330LM,p.Biology and CancerDiscovery 1b Evaluation 1b @L7/1/20006/30/20057/1/2000 to 6/30/20054/2005*"  }nF@88,"YY@@$@ResearchR@MILLERKATHLEENSTATE UNIV. OF NEW YORK AT BUFFALOBUFFALONYNIDAR21, DA016581J,p.b@ :@ 9@L5/10/20044/30/20075/10/2004 to 4/30/20074/2005{wnJ@88,"XXP@@ResearchX@MILLERHUGHUNIVERSITY OF ARIZONATUCSONAZNCIR21, CA089510H,p.T@ :@ 9@?9/5/20028/31/20049/5/2002 to 8/31/20044/2005}nie]F@88,"WW@y@/@Researchp@MIDDLESTADTSUSANACADEMY FOR EDUCATIONAL DEVELOPMENTWASHINGTON DCNCIR01, CA098342@G@ :Development 4 Development 5@:8/1/20037/31/20078/1/2003 to 7/31/20074/2005~qLE88,"VVg@@@ResearchCORE--POPULATION DYNAMICSMEYERSDOWELLUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANCIP50, CA084735 @EL@:Evaluation 1a Evaluation 1c@?Not Given2003? to 20034/2005  c[SS,"8LVALHWhen the tobacco industry targeted American women for increased consumption, they invested tremendous resources to understand and exploit the position of women in society and their resulting wants and needs. Access to the formerly secret internal industry documents makes possible a comprehensive search for and analysis of tobacco industry documents that supported the targeting of women. With experts in tobacco control, document analysis, behavioral science, marketing, and counter-marketing, the proposed research will locate and analyze behavioral and consumer research and other marketing documents to improve our understanding of how the tobacco industry markets to women. The ultimate goals of this research include informing and improving counter-marketing efforts. The research seeks: . To conduct a comprehensive, systematic search for tobacco industry documents relevant to . behavioral and consumer research on women and marketing to women; . To create a user-friendly, well indexed database of these documents and make it widely available through tobaccodocuments.org: . To review, analyze, and interpret key documents to address questions including: . What are the techniques, processes and tools the industry uses to identify promising segments of the female market and to develop marketing strategies and tactics for these segments? . What are the determinants, benefits, and appeals that are successful in getting women in general, and various subsegments of women to smoke? Which are the least successful approaches? . How does the industry attract new female smokers? Keep current smokers from quitting? . How does the industry identity, exploit, respond to, and/or influence social trends? . To develop and test counter-marketing concepts that might be effective: . To disseminate the findings on marketing and counter-marketing to academic and applied audiences.LVAL,p.ISmoking in pregnancy is associated with a variety of complications, including low birth weight (LBW), intrauterine growth restriction (IUGR), antenatal bleeding and pre-term birth (PTB). These significant health hazards could largely be prevented with successful antepartum smoking cessation. In recognizing both the success and the limitations of counseling based smoking cessation programs, we are interested in piloting the use of pharmacologic agents for reduced smoking during pregnancy. The first objective of the proposed research is to evaluate the efficacy of a pharmacologic aid for successful smoking cessation in pregnancy. The specific aims include evaluating bupropion SR's efficacy for both cessation and reduction of antenatal smoking by comparing pregnant women receiving smoking cessation counseling combined with placebo to those pregnant women who receive smoking cessation counseling combined with bupropion SR. The second objective of the proposed research is to evaluate the safety of bupropion SR used for smoking cessation in pregnancy. The specific aims include determining the adverse events and adverse effects associated with antenatal bupropion administration. Secondarily, the pilot seeks to evaluate the impact of bupropion SR on maternal well being, anxiety, depression, psychosocial variables and neonatal outcome (birth weight, Apgar scores, and neonatal intensive care unit admission rate). This research will consist of a pilot double blind placebo controlled randomized trial in which pregnant women who self-report continued smoking at the inception of prenatal care, will be randomized to one of two groups. The interventions will consist of brief smoking cessation counseling in combination with either placebo or bupropion SR. Participants will be surveyed to determine important demographic factors, psychosocial variables, and intercurrent medical illnesses, including measures of psychiatric disease, particularly concurrent depression. Maternal outcome measures will include cessa6 LVALF tion and smoking reduction rates by self-report and biochemical analysis (urinary cotinine and breath carbon monoxide analysis). The proposed research seeks to evaluate whether a pharmacologic aid (bupropion SR) administered antenatally can achieve higher rates of smoking cessation and smoking reduction without imposing serious adverse outcome.LVAL,p.KRecent research findings indicate strong associations between sports participation and adolescent health-risk behavior; for example, compared to their peers, high school athletes are at lower risk for illicit drug use, cigarette smoking, and suicide but at higher risk for binge drinking and smokeless tobacco use. These associations are in many respects gender-specific; female athletes report less sexual risk-taking than nonathletes, whereas male athletes report more. The present R21 application will extend this research to explore the effects of athletic involvement on substance use and other problem behaviors among female and male college students, examine the longitudinal effects of high school sports on young adult problem behavior, and create comprehensive new measures of athletic involvement for use in future research. Two complementary research strategies are proposed. First, cost-effective, secondary data analysis will be conducted on the Family and Adolescent Study (FAAS), a six-year longitudinal study of Western New York youth and their families (N=699) which includes self-report data on athletic participation as well as alcohol, tobacco, marijuana and other substance use, sexual risk-taking, and depression. Second, informed by findings from the FAAS, the Athletic Involvement Pilot Study (AIPS) will draw on focus group and questionnaire responses of Western New York undergraduate college student-athletes in order to design and pilot test new, multidimensional measures of athletic involvement. In its final round, the AIPS will collect data to test hypotheses about the gender-specific relationships between high school and college athletic involvement and substance use, sexual risk-taking, depression, and suicidality. This research will also serve as a basis for the development of a theory-driven R01 proposal examining factors associated with sports participation, gender, and substance use. The research has the overall aim of establishing more effective prevention and intervention strategies forTLVALd reducing young adult substance use and other related health-risk behaviors.,LVAL  X bHDISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO NicotineDISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other SmokingADDICTION Cessation DISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Nicotine Replacement Therapy PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research STUDY POPULATION African American TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseADDICTION Cessation Relapse ECONOMICS Socio-Economic Status LOCATION Urban National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumDISEASE/BIOLOGY Cancer Mechanisms RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingAGE Child Young Adult ECONOMICS Socio-Economic Status EDUCATION LEVEL High School College and Above EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Smokeless MISCELLANEOUS Sex/Gender DifferencesLVAL,p.NInteractions between environmental and genetic factors have been implicated in the etiology of breast cancer. In particular, several studies have suggested that the type of genetic damage observed in human breast tumors may be influenced by exposure to chemical toxicants. However, few attempts have been made to compare the ability of breast tissue to metabolize chemical carcinogens with the types of mutations observed at critical oncogenic loci. To better understand the etiology of breast carcinogenesis and determine the role of gene/environmental interactions in determining individual susceptibility to breast cancer formation, a prospective case-case study design will be utilized to compare mutations in the p53 gene with the genotype of affected cancer patients for 4 metabolic enzymes (CYP1A1, GSTM, GSTT, and GSTP) that play key roles in the metabolism of human environmental carcinogens. We hypothesize that those breast cancer patients containing either specific alleles of CYP1A1 that enhance the metabolic activation of environmental toxicants or genotypes of GSTs that would result in less detoxification will be more likely to have accrued genetic damage at the p53 locus, and that combinations of alleles that increase the burden of reactive electrophiles will be more susceptible to tumor initiation. Tumor tissue samples will be analyzed for genetic alterations in p53 by SSCP and gene sequencing analyses. DNA obtained from blood will be genotyped by PCR-RFLP to determine if patients harboring genetic damage to p53 more frequently exhibit metabolic genotypes that increase formation of reactive electrophiles from environmental toxicants. A prospective study design will allow use of a questionnaire to identify other potential factors (including smoking, diet, occupation, race, and reproductive history) that may modify the association between genotype and mutations to p53. As mutation at p53 has been implicated in poor patient prognosis, these studies should aid in identifying those patients at risLVALk for damage to key regulatory genes that play a role in the pathogenesis of breast cancer, and will further our understanding of the etiology and risk factors for this disease. 8LVALHSmoking is the most preventable cause of death in the United States (American Cancer Society [ACS], 1998). Yet, every year, smoking accounts for approximately one out of every five deaths, or a total of more than 419,000 deaths per year (CDC, 1993). Pregnant women who smoke are at a heightened risk not only for cancer, but also for a range of adverse health conditions, many of which can result in long-term illness for both mother and child. For example, smoking during pregnancy can cause numerous health complications for the fetus including: intrauterine growth retardation, low birth weight, congenital malformations, and an increased risk for pre- mature births and neonatal and fetal mortality. Adverse health effects continue for the mother who smokes post-delivery; they also continue for the child, since exposure to cigarette smoke can cause cancer, asthma, respiratory infections, middle ear disease, and reduced cognitive function. In addition to negative health effects, smoking related-illnesses place a significant financial burden on the health care system, exceeding $200 million per year in the U.S. The proposed study will use the pregnancy and postpartum phases as a "window of opportunity" to deliver an innovative smoking cessation intervention to reduce smoking among low-income, inner city pregnant women, and to prevent relapse post-delivery. LVAL,p.QSmoking accounts for approximately one in every five deaths in the United States, totaling more than 419,000 deaths each year. Cigarette smoking is associated with a number of adverse health effects, including an increased risk of cervical dysplasia. Minority women not only suffer from disproportionately higher rates of cervical cancer mortality, but they are also significantly more likely to smoke. Emerging guidelines recommended that patients with smoking-related prenoplastic conditions be identified as candidates for smoking cessation, at all medical visits, particularly low-income, ethnic minorities. Toward this end, the proposed study will assess the utility of a theory-driven smoking cessation intervention, based on well established cognitive-behavioral techniques, presented at a teachable medical moment (i.e., around diagnostic follow-up for an abnormal Pap smear result). Low-income inner city women (N=502) will be randomized to either a 7-session enhanced smoking cessation protocol, delivered over a 13-week period, or to a matched control condition that equates for time, attention, and format. Both groups will receive advice and tips for quitting, along with nicotine replacement therapy. In addition, the intervention group will receive a cognitive-affective smoking program, systematically tailored to the individual's attentional style (i.e., high vs. low monitoring). The control group will receive general health behavior recommendations (e.g., diet, exercise), tailored to high vs. low monitors. Participants will be assessed at baseline (prior to the diagnostic follow-up visit), on the day of the visit, and at 6- and 12-months post-visit. Assessments will include background variables (e.g. demographics), process variables (e.g., stage of change, disease status), and outcome variables (e.g., biochemical and self-reported smoking status). The proposed study will bring together two key strengths: 1) expertise in the individualized assessment and management of cervical cancer risk feedb LVAL ack; and 2) expertise in the development and implementation of smoking cessation interventions. It will apply these strengths to the delivery and evaluation of a highly transportable, readily implemented, intervention, focusing on a traditionally underserved population.LVAL,p.SThe Carolina Breast Cancer Study (CBCS) is a comprehensive, interdisciplinary investigation into the causes of breast cancer in African American and white women. A major focus of the CBCS is to understand genetic susceptibility. Our goal is to conduct the first comprehensive, population-based study of genetic risk factors for in situ and invasive breast cancer in African American and white women. Our recent results have shown that germline mutations in BRCA genes are rare in breast cancer patients. Common inherited polymorphisms in metabolism genes play a role in a much larger number of cases. To date, we have investigated hormone metabolism, carcinogen metabolism, and cell cycle control. We propose here to expand our study of genetic susceptibility to include DNA repair genes, and potential interactions between these genes and exposure to environmental factors. Our preliminary data indicates that polymorphisms in the base excision repair gene, XRCC1, and the double-strand break repair gene, XRCC3, are susceptibility genes for breast cancer. During Phase 1 of the CBCS (1993-1996), 861 cases of invasive breast cancer and 790 population controls were enrolled. During Phase 2 (1996-2000), 890 cases of invasive breast cancer, 514 cases of in situ breast cancer, and 1232 controls were enrolled. After enrolling additional controls, the total number of participants is expected to be 2265 cases and 2086 controls. African Americans comprise 44 percent of invasive cases and 21 percent of in situ cases. Controls are frequency matched to cases based upon age and race. CBCS participants complete in-depth interviews covering known and potential risk factors for breast cancer. Blood samples are collected for extraction of lymphocyte DNA. DNA samples and exposure histories are available from 2147 cases and 2021 controls. The current proposal provides for statistical and laboratory analyses using previously collected DNA samples and exposure information from the CBCS. The Specific Aims are to conduct high throughput gLVALenotyping for single nucleotide polymorphisms in genes involved in the principal DNA repair Pathways: Base excision repair (XRCC], APEI, HOGG], Pol Beta); nucleotide excision repair (XPA, XPD, XPF, ERCC1); double strand break repair (XRCC3, XRCC4); nonhomologous end joining (DNA PK, DNA ligase/); direct repair (MGMT, AGT). Main effects for each genetic locus will be estimated, as well as the combined effects of multiple genes (gene-gene interaction) and the joint effects of genetic and environmental factors (gene-environment interaction). The study will provide important information regarding genetic susceptibility to breast cancer in African American and white women, and help to clarify the role of ionizing radiation, smoking and other environmental exposures in the etiology of breast cancer. In addition, we propose to extend our data collection and obtain updated treatment and outcome information on breast cancer cases. This information will allow us to evaluate novel hypotheses related to the role of DNA repair in response to adjuvant chemotherapy and radiation treatment, and to generate pilot data for subsequent grant applications.LVAL,p.UIn collaboration with our colleagues at the other five WIHS sites and WDMAC, we are proposing to be active contributors to the research agenda described in Part A of this application which, with the expanded cohort, can substantively contribute to an understanding of HIV infection in women in the era of effective antiretroviral therapy. Although SUNY looks forward to providing completed data sets, meticulously collected and stored biologic specimens, and its investigators' expertise to the full range of issues that WIHS will confront, we believe we have particular strengths. Specifically, we have successfully served as a source for a disproportionate share of study data, biologic samples and participants in substudies and have demonstrated our ability to seamlessly incorporate additional study participants into the expanded study population. We have been uniquely successful at working to overcome barriers to recruitment and retention in both the core study and within substudies. Our investigators have a particular academic focus on obstetric and gynecologic, behavioral, epidemiologic and co- infection aspects of HIV infections in women, have demonstrated the ability to collaborate with researchers from other locations and disciplines and have committed themselves intellectually to new areas of scientific investigation in the WIHS. Finally, the scientific environment at SUNY, which has supported research into HIV infection in women for over fifteen years, augurs well for the success of the site. In order to demonstrate this site's ability to perform significant scientific analyses of WIHS data, in this application we propose to define the relationship between smoking, inflammatory markers, genetic polymorphisms and the prognosis of women with HIV. The majority of WIHS participants smoke and researchers at SUNY have found that smoking influences changes in CD4 cell count and HIV-1 RNA with smokers having a significantly higher mortality and less response to HAART. It is not known whether these effects vF LVALV ary with genetic polymorphisms. Smoking may also influence inflammatory markers of disease progression (e.g., albumin) and the course of cervical disease. We will perform a pilot study of 500 women smokers in which data will be obtained on genetic polymorphisms and selected markers of inflammation (albumin, pre-albumin and CRP). The design will be a prospective cohort of HIV-1 infected women followed for up to 10 years. The study outcomes will be mortality, the development of AIDS-defining conditions and cervical disease. Predictor variables will be cigarette smoking, genetic polymorphisms, albumin, pre-albumin and CRP. Covariates will include CD4 cell count, HIV RNA, age at enrollment and anti-retroviral therapy.LVAL,p.WThe human papillomavirus (HPV) is a significant etiologic agent in lower female genital tract neoplasia. Novel interactions with other co-carcinogens and/or immuno-deficiency lead to tumorigenesis and cancer progression. However, both the lack of adequate animal models and prospective clinical trials are impediments to the development of effective anti-HPV therapies and prevent a thorough understanding of human interactions with this virus. The objective of this proposal is to support the career development of Bradley J. Monk, M.D. Under the direction of Dr. Luis P. Villarreal, Ph.D., Dr. Monk will evaluate co-carcinogens and anti-viral agents in a recently described severe combined immunodeficiency mouse model using implanted human HPV infected epithelium, cervical intraepithelial neoplasia (CIN). Dr. Monk proposes to study the neoplastic transformation as well as the progression or regression of these cervical tissue implants. The influence of specific promoters or genotoxic compounds (e.g. hormones, nicotine) as well as novel anti-HPV agents (e.g. stimulated immune cells, anti-sense oncogenes) and nutritional supplements (e.g. indole 3-carbinol or I3C) will be studied. In addition, under the direction of Philip J. DiSaia, M.D., a Gynecologic Oncologist; Frank L. Meyskens, M.D., a Medical Oncologist with expertise in Chemoprevention; and Jeffrey S. Weber, M.D., Ph.D., a Medical Oncologist with expertise in Immunology, Dr. Monk will conduct two prospective clinical trials of novel HPV therapies. First, I3C, a compound found in cruciferous vegetables and effective in HPV related laryngeal papillomatosis, will be evaluated in patients with HPV induced genital warts in a randomized phase II trial. Second, a phase I and II study of a DNA plasmid vaccine encoding an immunogenic portion of the HPV type 16 E7 protein is planned among women with CIN. Dr. Monk will focus his career on translational research in the area of anti-HPVmodalities specifically related to female lower genital tract neoplasia. Mentors LVAL in Virology, Chemoprevention, Immunology and Gynecologic Oncology will allow Dr. Monk to investigate unique anti-viral agents both in the laboratory and in clinical settings with an emphasis on HPV immunity. This path will develop Dr. Monk into an independent investigator able to study anti-HPV therapies first in animals then in human chemoprevention trials. It is expected that Dr. Monk will have obtained extramural funding for both his laboratory and clinical studies by the end of the period of support requested.LVAL Z ^DISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Child EDUCATION LEVEL High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer LOCATION International RESEARCH Human Studies Clinical Research STUDY POPULATION Hispanic TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesLVALThis project tested the effectiveness of an individualized intervention to help women stop smoking. The intervention was incorporated into prenatal case management services for low-income African American and Hispanic women in east Texas.Using the SEER database, which covers more than 10% of the US population, lung cancer incidence trends over the period 1973-1998 will be investigated using extensions of age-cohort-period models. Specifically, it is proposed to develop models in which non-specific age effects are replaced by parametric hazard functions that acknowledge the multistage nature of carcinogenesis. At least formally, this procedure finesses the well known problem of arbitrary linear trends that plagues the traditional age-cohort-period models. Furthermore, analyses of carefully collected incidence data in large registries such as SEER using biologically-based modelscan lead to insights in to the mechanisms underlying carcinogenesis in addition to shedding light on temporal trends. With respect to temporal trends, attempts will be made to relate trends in lung cancer incidence to trends in smoking habits in the US. Tobacco smoke contains both mutagens and agents that impact cell proliferation kinetics. Thus, tobacco smoke probably acts as both an initiator and a promoter in lung carcinogenesis. One goal of these analyses is to investigate whether non-specific and birth cohort and calendar year trends can be directly linked to specific aspects of carcinogenesis, such as initiation, promotion and progression. This possibility will be investigated by incorporating tobacco consumption trends into the parameters of the multistage model. Because of the large size of the SEER database it should be possible to conduct these analyses separately by race, sex and histologic type. Finally, the estimated parameters of the optimal multistage model will be used to project lung cancer incidence trends into the future under various assumptions regarding changes in composition of cigarettes and smoking habits.LVAL#&` @ \ " & Z &lP(v .HEALTH RISK PREVENTION PROGRA FOR INNER-CITY HIGH SCHOOL GIRLSSEX DIFFERENCES IN NICOTINE REINFORCEMENT: HUMAN/ ANIMALCHRONIC AND ACUTE TOLERANCE TO NICOTINE IN HUMANS--TOLERANCE DISSIPATIONENVIRONMENTAL HEALTH IN MINORITY WOMEN/ INFANTSDRUG ABUSE PREVENTION--ADOLESCENCE AND EARLY ADULTHOODSCHOOL TOBACCO PROGRAM AND POLICY TRIALVACCINE EFFECTS ON FETAL NICOTINE EXPOSURE IN RATSSTRESS AND THE SELF-ADMINISTRATION OF NICOTINEDETERMINANTS OF SMOKING AMONG GAY AND LESBIAN YOUTHTRIAL OF ACTIVITY FOR ADOLESCENT GIRLS-FIELD CENTERREDUCING CERVICAL CANCER IN APPALACHIAEXPLORING THE ROLE OF MOOD, PROVIDER COMMUNICATION, AND RISK PERCEPTIONS ON PREGNANT WOMEN'S TOBACCO USEGENE POLYMORPHISMS IN RELATION TO CANCER IN BLACK WOMENRETARGETING MID LIFE AND OLDER SMOKERSPRIMARY CARE AND SELF HELP INTERVENTION FOR TEEN SMOKERSRESEARCH ON MATERNAL DEPRESSIVE SYMPTOMS AND POSTPARTUM SMOKINGMULTIDISCIPLINARY COLLABORATIVE TO ADDRESS THE NEEDS OF SUBSTANCE-ABUSING WOMEN AND THEIR FAMILIESPILOT STUDY--SMOKING CESSATION AND BONE REMODELING IN ADOLESCENTSNICOTINE REPLACEMENT TREATMENT FOR PREGNANT SMOKERSEFFECTS OF NICOTINE ON BONE TURNOVER IN OLDER WOMENEFFECTS OF MATERNAL SMOKING ON FETAL CATECHOLAMINE SECRETION DURING BTOBACCO DEPENDENCE AND RISK FACTORS FOR TREATMENT FAILUREDIET/ACTIVITY OF MEXICAN AMERICAN AND ANGLO CHILDRENSMOKING TREATMENT FOR SUBSTANCE ABUSING ADOLESCENTSTESTING PHARMACOLOGICAL THERAPIES FOR PREGNANT SMOKERSPARENT ASSISTED SMOKING CESSATIONBIRTH DEFECTS TREATMENT AND PREVENTION PROGRAMNIDA PREDOCTORAL FELLOWSHIP PROGRAMENHANCED CASE MANAGEMENT FOR PREGNANT, LOW-INCOME SMOKERSSMOKING DURING PREGNANCY AND BREAST CANCERADOLESCENT MEDICINE HIV/AIDS RESEARCH NETWORKNATURAL HISTORY OF TOBACCO ADDICTION IN ADOLESCENTSRISK OF ORAL EPITHELIAL DYSPLASIA IN PUERTO RICOMARIJUANA USE AND THE RISKS OF LUNG AND OTHER CANCERSLUNG CANCER IN THE US: PATHOGENESIS, TRENDS, PREVENTIONLVAL,p.\Marijuana is the most widely used illegal drug in the United States. Although marijuana use had decreased substantially since the late 1970s, it has risen dramatically since 1992 among teenagers and young adults. One possible factor contributing to this upsurge is the widespread belief that there are no chronic adverse health effects of regular marijuana use. In November 1996, California voters passed Proposition 215, which would legalize the use of marijuana for medicinal purposes. Despite scientific debate about the benefits of marijuana treatment, the public's perception seems to be that the potential benefits outweigh the risks. Nevertheless, several lines of evidence from biochemical, cellular, tissue and animal studies provide a biologically plausible basis for the hypothesis that marijuana is a risk factor for respiratory-tract cancers. Thus far, however, there is no epidemiologic evidence for this association, primarily because of the long induction/latency of human carcinomas and the infrequent use of marijuana in the general U.S. population before the late '60s. The major objective of the proposed 5-year project is to estimate the effects of marijuana use on the risk of lung cancer and upper-aerodigestive-tract (UAT) cancers among residents of Los Angeles County, ages 18-57. Secondary objectives are to assess the interaction effects of marijuana and tobacco use, to estimate the effects of other factors for which the epidemiologic evidence is inconsistent or sparse, and to initiate a molecular study by obtaining tumor specimens for cases and buccal cells from cases and controls. The proposed design is a population-based case-control study involving 600 lung-cancer cases, 600 UAT-cancer cases (395 oral cavity and pharynx, 85 esophagus, and 120 larynx), and 1,200 controls. Histologically confirmed cases will be identified by the rapid ascertainment system of the USC Cancer Surveillance Program, a population-based SEER registry for Los Angeles County. Controls will be selected according to a pre@ LVALP specified algorithm from the neighborhoods of cases; one control will be matched to each case on age, sex, race/ethnicity, and neighborhood. The major source of data will be personal interviews conducted with all subjects in their homes. Information will be collected on a variety of factors: detailed history of marijuana, tobacco and alcohol use; occupational and environmental exposures (e.g., passive smoking); clinical factors (e.g., depression and family history of cancer); diet and other behaviors (e.g., fruits, vegetables, fats, and supplements); and sociodemographic factors (e.g., SES).LVAL,p.^Oral and pharyngeal cancer incidence in Puerto Rican males is notably higher than among white males living on the U.S. Oral epithelial dysplasia (OED) is a histopathological diagnosis characterized by cellular changes and maturational disturbances. A diagnosis of OED is significant in that it is associated with an elevated risk factors for OED, and non such studies have carried out in an Hispanic population. The primary aim of this study is to estimate the association between OED and the use of smoking tobacco and alcoholic beverages in an Hispanic population living in Puerto Rico. On an exploratory basis the proposed investigation will (a) examine the presence of a dose-response relationship as regards OED and both smoking tobacco and alcohol use, (b) test for a synergistic relationship between alcohol and smoking with regard to OED, (c) evaluate smokeless tobacco, mouthwash use and dentures and OED risk factors, (d) evaluate dietary habits as risk/protective factors for OED, and (e) examine whether polymorphisms in genes that code for enzymes active will be identified in the carcinogen activation and detoxification pathways are associated with OED. OED cases (aged 20-79) will be identified by reviewing biopsy reports generated by pathology laboratories on the Island. The control series, frequency matched 1:1 to cases on age, gender, gender, and geographic region, will consist of persons diagnosed with an irritation fibrinoma via the same pathology laboratories. Environmental risk factor data will be obtained using a structured questionnaire. Oral cells will be obtained for DNA extraction and used in studies of genetic polymorphisms while paraffin-embedded tissue from cases and controls will be available for immunohistochemical and molecular analyses. Adjusted odds ratios will be obtained from logistic regression models. Information obtained from this study will further our understanding of the etiology of OED, provide possible explanations for the high rates of oral and pharyngeal cancer in Puerto RJLVALZico, and suggest opportunities for the primary prevention of OED and oral cancer.2  _ f R < Zoog@p@4Research@ZONCKENCHERYLUNIVERSITY OF CONNECTICUT SCHOOL OF MEDICINEFARMINGTONCTNCRRM01, RR006192p@tBiology and CancerDiscovery 1a Evaluation 1bT@qNot GivenNot GivenUncertain4/2005%vH@88,"nn @@Researchr@ ZO'MALLEYSTEPHANIEYALE UNIVERSITYNEW HAVEN CTNIDAP50, DA013334>@s|@:@r@q9/30/19998/31/20049/30/1999 to 8/31/20044/2005tnj^MB88,"mm@^@Researchh@ ZNADERPHILIPUNIVERSITY OF CALIFORNIA AT SAN DIEGOSAN DIEGOCANHLBIR01, HL052449o,p.L@:@9@q1/1/199512/31/20021/1/1995 to 12/31/20024/2005}ynG?88,"ll @G@Researchf@ ZMYERSMARKUNIVERSITY OF CALIFORNIA AT SAN DIEGOSAN DIEGOCACTRDRP7RT-0135m,p.j@:@9@f7/1/19986/30/20027/1/1998 to 6/30/20024/2005{wlE?88,"kk @@@$@Researchl@ ZMYERSEVANDUKE UNIVERSITYDURHAMNCNCIR01, CA089053l,p.T@:@9(@f5/1/20024/30/20075/1/2002 to 4/30/20074/2005vgb^VE?88,"jj @@ResearchB@ ZMURRAYNANCY UNIVERSITY OF TEXAS HEALTH SCIENCES CENTERHOUSTON TXNCIR03, CA086785zj,p.@:@9 @f9/30/19999/30/20039/30/1999 to 9/30/20034/2005~tH@88,"ii @@Research\@ZMURRAYJEFFREYUNIVERSITY OF IOWAIOWA CITYIANICHDU01, HD0405616h,p.@:@9@f8/17/20014/30/20068/17/2001 to 4/30/20064/2005slh]I@88,"hh`@p@4ResearchF@ZMUMFORDELIZABETHJOHNS HOPKINS UNIVERSITYBALTIMOREMDNIDAF31, DA006097@gb@:@9@f6/1/2001Not Given1/6/2001 to ?4/2005{uqfLA88,"ggg@p@4Researchr@ZMULLENPATRICAINot GivenHOUSTONTXSFFNot Given@Y@:@9j@fNot GivenNot GivenUncertain4/2005~rgb^UJ@88,"ff`<@@@ResearchT@ZMUELLERBETHFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWANCIR03, CA096434\e,p.t@:p@9d@X4/1/20023/31/20054/1/2002 to 3/31/20054/2005|xoGA88,"ee@`@ResearchZ@ZMOSCICKIANNA-BARBARAUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCANICHDU01, HD032830jc,p.t@:@9@X9/29/199411/30/20039/29/1994 to 11/30/20034/2005 {PB88,"dd @ S@Researchf@ZMOSCICKIANNA-BARBARAUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP7RT-0195!`,p.L@:@9@X7/1/19989/30/20027/1/1998 to 9/30/20024/2005{PB88,"ccK@ y@Research`@ZMORSEDOUGLASNEW YORK UNIVERSITYNEW YORKNYNIDCRU54, DE014257],p.@:l@9\@X8/1/20027/31/20038/1/2002 to 7/31/20034/2005rkg]H?88,"LVAL,p.aThe health hazards of cigarette smoking are well known. There are currently about 46 million adult cigarette smokers and 3 million adolescent smokers in the U.S. Although smoking in adults has decreased, teen smoking has not. We know that starting to smoke as a teenager is particularly risky, since almost all adult smokers began smoking as teenagers. That is, a large portion of teenagers that smoke end up being addicted to tobacco. Subsequently, the study of tobacco addiction in adolescents is key in preventing tobacco use not only among adolescents but among adults. What we do know is that one of the cigarette metabolites called nicotine is addicting and that once the body gets used to a certain amount of nicotine, it begins to crave it when it doesn't get it. That is addiction. Unfortunately, little is known about the transition period during which this type of nicotine addiction occurs. In addition, definitions for nicotine addiction among adolescents has never been well-defined. Our objective is to examine addiction in youth by closely following biologic???????????? and psychologic?????????????? measures that might directly influence the development of nicotine addiction. Following adolescents from 9th grade to 11th grade, we propose to: 1 ) examine the natural history of nicotine addiction in teenage smokers from the time they experiment with cigarettes to when they are addicted. Some of the measures we will examine include: how often they use cigarettes, changes in how much nicotine they take in over time (this will be measured by measuring the amount of cotinine, another metabolite of tobacco, in their saliva. Measuring the amount of cotinine in the saliva gives us a good idea of how much of this metabolite is in the blood. The higher amount of cotinine in the blood, the more likely the person will be addicted to cigarettes). We will also look at when and with whom they smoke cigarettes, and if they begin to develop a notion that cigarettes make them feel better than usual and that stopping makLVALbes them feel worse; 2) we will better define nicotine addiction in teenagers by comparing the changes or increases in saliva cotinine levels with how many cigarettes they smoke a day and the presence of certain symptoms that we use??????????????? when defining adults who are addicted to cigarettes and we will explore certain symptoms that might be more specific to teenagers than adults; 3) we will example specific social and psychologic????????????? influences that help the teenager keep smoking so that eventually the body become addicted. Specifically we are interested in looking at: how some teenagers may use it because they think it keeps their stress down and their weight better controlled; how some teenagers might think that quitting is worse than continuing to smoke; how doing other kinds of drugs, like drinking alcohol or smoking marijuana, might keep them smoking; how smoking at certain times, like at finals, might influence addiction; how friends and parents influence smoking; and how feeling stress and depressed might influence smoking; 4) we will also look at how gender (male or female) and race or ethnicity might influence the natural history of nicotine addiction. The study population will be approximately 1,800 9th graders of diverse racial/ethnic backgrounds from the Bay Area. Phase I (months 0-6) will consist of focus groups (that is a small group of teenager will be asked about their smoking habits), development of a questionnaire, pilot testing (making sure that teenagers understand the questions) and setting up the school sites so they are ready when we begin data collection. This phase is critical in the study since there is a lack of these self-administered (that is the person fills out the questionnaire themselves) questionnaires in teenagers regarding addiction and a lack of studies that are sensitive to cultural diversity. Phase II (months 7-9) will consist of recruiting subjects from schools and time 0 data collection including giving the questionnaire to the teenagers and col LVAL lecting their saliva for the cotinine. Phase III (months 10-36) will consist of ongoing data collection from classrooms and other alternative settings for dropouts and will include questionnaire administration and saliva sample collection at 6 month intervals.LVAL,p.dAccumulating evidence strongly associates human papillomavirus (HPV) infection with the development of anogenital cancers. The rising rate of specific anogenital cancers in HIV infected individuals has led researchers to begin the study HPV as a co-morbid infection in this group. Unfortunately, little data is available to date on HPV infections in HIV infected adults and even less information is available in adolescents. With the increased life expectancy of HIV infected persons, the rates of anogenital cancers can be expected to continue to rise. The purpose of this study is 1) to define the prevalence of HPV infection and HPV-related disease [(low and high grade squamous intraepithelial lesions) LGSIL/HGSIL] of the anogenital area (i.e. cervix, vagina, vulva,anus, penis, and scrotum) in adolescents infected with HIV and to compare the prevalence and severity of HPV disease in a group of similar high risk adolescents who are HIV negative (controls); 2) to define the natural history of HPV in HIV infected youth and to compare the rate of progression of HPV-related disease in HIV infected youth to the controls and 3) to examine the association between specific risk factors (specifically, high level HPV persistence, level of immunosuppression, substance use, hormonal influences, tobacco, and co-infections in the genital tract including Chlamydia trachomatis (CT), herpes simplex virus (HSV), cytomegalovirus (CMV), Treponema pallidum, Haemophilus ducreyi, fungal infections and Neisseria gonorrhoeae (NG) and HPV infection and the development of HPV-related disease in the anogenital tract in HIV infected youth. Methods: The 100 HIV positive and 100 HIV negative adolescents matched for similar high risk behavior (e.g. substance use, sexual behavior) collected by the Adolescent AIDS/HIV Research Network will be asked to participate. All adolescents will be asked to undergo a face-to- face interview, testing for HPV DNA, cervical, vaginal and anal cytology, CT, NG, HSV, CMV, T. pallidum, H. ducreyi, fungal infj LVALz ections, and bacterial vaginosis and colposcopic examination of the cervix, vagina, vulva, anus, penis and scrotum (gender appropriate). In addition, lavages of the cervical and anal mucous will be obtained for nicotine/cotinine assays. Patients will be asked to return every 4 months for similar examination and testing. All LGSIL will be followed. However, adolescents found to have evidence of HGSIL anywhere in the anogenital tract will be referred for treatment but continued to be followed after treatment is completed. Data analysis will emphasize the examination of differences for prevalence and disease severity of HPV-associated lesions between HIV positive and negative persons. The results from this study will be related to the prevention and education of pre-cancer and cancer lesions in adolescents infected with HIV.LVAL,p.Although cigarette smoking has been linked to the etiology of several cancers, the relationship between smoking and breast cancer remains unclear. A woman's first pregnancy represents a period of rapid breast cell growth and differentiation and thus, a period of vulnerability to the influences of smoking or other exposures. During pregnancy, tobacco mutagens and free radical formation caused by smoking may affect rapidly growing breast tissue or act synergistically with elevated estrogens to increase breast cancer risk. Because breast tissue is less differentiated at the onset of first pregnancy, it may be more susceptible to mutagenesis than in subsequent pregnancies. The proposed population-based case-control study will utilize linked vital statistics - cancer registry data to test the hypothesis that cigarette smoking during first pregnancy is related to the risk of breast cancer. The specific aims of this study are to: 1)measure the risk of breast cancer associated with smoking during a first pregnancy relative to not smoking during the first pregnancy, and 2)evaluate possible differences in the relation between smoking during first pregnancy and breast cancer by tumor estrogen receptor status. To the extent possible, the study will also evaluate a possible dose response relation between the average number of cigarettes smoked per day during first pregnancy and breast cancer risk, and measure possible differences in the relation between smoking during first pregnancy and breast cancer risk by subject characteristics such as parity at the time of diagnosis and pre-pregnancy weight. This study will be among the first to examine smoking during first pregnancy and breast cancer risk. The clarification of the role of smoking during first pregnancy in breast cancer development will aid in understanding the complex etiology of breast cancer, and may identify a specific preventive strategy to help reduce breast cancer incidence.<LVAL . VAGE Child EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingADDICTION Cessation AGE Child EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child Young Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesECONOMICS Socio-Economic Status LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments RESEARCH Human Studies Clinical Research STUDY POPULATION African American Hispanic TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Partner/Spouse LVAL This proposal is for training and research regarding the smoking behavior of a nationally representative sample of adolescents ages 12-18, surveyed as part of the National Longitudinal Survey on Adolescent Health. The analysis will examine differences among smoking youth by age, race/ethnicity, and gender. Further, this research will identify predictors of transitions to subsequent stages of smoking that could be used to target programs to adolescents most likely to benefit from them. Ancillary variables such as alcohol use will be studied in the context of mapping the natural history. The longitudinal nature of the study will subsequent examination of time-variant characteristics of the sample and their impact on predicting smoking behavior.LVAL,p.iCleft lip and cleft palate can serve as a sentinel for birth defects in general for the impact that they have on fetal and maternal health. As sentinels, they are easy to identify and require a high input of surgical and medical care, but also commonly result in long-term survival of affected individuals, even when untreated. They are common with the average frequency of about 1:1000 in most South American countries. Their etiology is complex, although it is clear that genes and genetic and environment interactions play an important role. Nutritional factors in clefts are well recognized and have been studied for over 40 years. Recent evidence that folate or B6 deficiency, as well as a role for smoking and alcohol use, suggest that environmental interventions in the form of supplementation or preventive strategies may be effective in decreasing the frequency of these birth defects. The South American birth defects registry, Estudio Collaborativo Latinoamericano de Malformaciones Congenitas (ECLAMC), has for many years provided epidemiologic information on the frequency of birth defects throughout South America. At the present time, folate supplementation has been introduced to one country in South America (Chile) and it is now possible to measure changes in outcomes of this based around the known preventive effect of folic acid supplementation for neural tube defects and the likely effect that it may have on cleft lip and cleft palate. Extensive populations of affected individuals such as those followed by the Centrinho clinic in Bauru provide high risk populations in which targeted interventions can be effectively studied. In this proposal, the applicants will use cleft lip and cleft palate as a sentinel defect to study the impact of birth defects in general on maternal, fetal and neonatal health and to carry out direct interventions on decreasing the number of these birth defects using both behavioral and medical interventions. The specific aims will include measuring the impact of the interventiona LVAL l use of folic acid supplementation on cleft lip and cleft palate and neural tube defects, measuring the impact of having a child born with a cleft on subsequent maternal, infant and family health, and finally, interventions to decrease the number of birth defects through the direct prevention strategies of smoking intervention and vitamin supplementation. The outcome of this project will be to further strengthen collaborative relationships in the area of craniofacial anomalies between Brazil and the US, to better understand the effects of birth defects and craniofacial anomalies in particular on maternal family units and to decrease the burden of these defects directly.LVAL,p.kDespite years of prevention programs targeting adolescents, adolescents continue to begin smoking, putting them at risk for an epidemic of diseases, including cancers of the lung, larynx, oral cavity, as well as COPD, CHD and stroke. Many adolescent smokers have tried to quit but there are few cessation programs available for adolescents and little research conducted on the effectiveness of adolescent cessation programs. This community-based project provides a unique opportunity to intervene with adolescent smokers who are court-mandated into a tobacco awareness and cessation program. The State of Texas instituted a new law January 1, 1998 that prohibits possession, purchase, consumption, or receipt of tobacco products by minors and requires minors to attend a tobacco awareness program upon conviction or lose their driver's license. Because these adolescents are thrown into the cessation process without their own volition, parental support for a more complete and coherent progression through the stages of smoking cessation may increase the probability that the children will be successful in smoking cessation. Parents are committed to the health and welfare of their children and have timely, constant access to them as part of an enduring relationship. Parent Assisted Smoking Cessation (PASC) is a parent education intervention designed to promote parental support for adolescent smoking cessation. The parent education intervention will be based on the Transtheoretical Model of Change (TTM), Motivational Interviewing (MI), and Social Cognitive Theory. TTM proposes that addictive behaviors change dynamically through processes specific to different points or stages in the cycle of change. Along with decisional balance and self-efficacy, these processes are strategies the individual uses to move through the stages of behavior change. PASC will inform parents about supporting these processes through parental monitoring of tobacco use and association with smoking peers, communication about tobacco, and other sZ LVALj upport behaviors. In an attempt to reduce coercive and punitive parental behaviors, and help parents tailor their communication with their child to their child's stage of smoking cessation, parents will be informed about the empathetic, non-confrontational techniques of MI. Using theory, data from smoking adolescents and their parents, and the experience of the investigative team, 12 newsletters will be developed. Newsletters will incorporate role model stories, exercises, information, and communication tips, and be tailored to the adolescent smoker's age, gender, and family structure. A pilot study will test the hypothesis that PASC results in increased smoking cessation rates among adolescents. Adolescents and their parents (N=90) will be recruited through the courts, newsletters will be mailed, and data collected by telephone.LVAL,p.Smoking in pregnancy poses serious health risks to the fetus and the mother. About half of women smokers continue to smoke throughout pregnancy. Pregnant women who have the greatest difficulty quitting smoking even when provided with behavioral cessation interventions tend to be more dependent smokers who may requite nicotine replacement therapy to be successful at cessation. The proposed five-year study is designed to evaluate the effectiveness of providing over-the-counter (OTC) nicotine replacement therapy, choice of gum or patch, (NRT) to promote prepartum smoking cessation. Proposed is a two-arm design. Eligible pregnant women (N=300) will be randomized to either: Arm 1, Tailored Cognitive Behavioral Treatment (TCBT, n=150) that provides women with customized risk information about smoking and nicotine, the potential harms to the fetus and encouragement of appropriate behavioral skills building; or Arm 2, TCBT + NRT - the tailored intervention incorporating NRT information plus choice of patch or gum (n about150). The intervention will include 5 face-to-face contacts as part of prenatal visits and 2 telephone counseling sessions. Primary outcome measures will be biochemically validated 7-day prevalent abstinence rates at the 19-27th and 27-35th week of pregnancy. Secondary outcomes will include 7-day prevalent abstinence rates at 12 and 24 weeks postpartum, serious quit attempts, compliance with NRT, and use of materials. Saliva cotinine will be measured among all women at baseline, the 27-35th week of pregnancy, and 24 weeks postpartum. The significance of this project is that it relies on transdisciplinary collaborations to extend the science in nicotine replacement therapies to a population that could derive substantial health benefits. Moreover, the study results have immediate potential to inform clinical recommendations for integrating nicotine replacement into prenatal care.LVAL,p.nApproximately 80% of adolescents treated for alcohol and drug problems also smoke cigarettes. Available evidence suggests that smoking continues at high rates following adolescent substance abuse treatment. The high prevalence and persistence of smoking among substance abusing adolescents identifies these youth as being at high-risk for tobacco-related diseases, and, therefore, an important target for tobacco intervention. However, limited information exists regarding smoking among substance abusing youth. In particular, little is currently known about how to encourage and assist smoking cessation for substance abusing adolescents. Developing effective smoking treatments for this population is important in order to reduce the long-term health problems associated with tobacco use. The main goal of the present project is to evaluate the effectiveness of a treatment designed to motivate substance abusing teens to cut down and quit cigarette smoking. This study will address 3 questions: 1) Do adolescents who receive a smoking intervention during treatment for substance abuse decrease smoking compared with those who do not? 2) Does smoking treatment have any effect on alcohol and drug use following substance abuse treatment? and 3) Will the smoking treatment have different effects for boys and girls? The proposed project is consistent with TRDRP goals of obtaining scientific information pertinent to the treatment of tobacco use and is consistent with the program emphasis on youth tobacco use. This project is designed to evaluate a smoking treatment that has been developed over the past two years as part of a project funded by the National Institute on Alcohol Abuse and Alcoholism and Children's Hospital of San Diego. The treatment is based on techniques found helpful for adult smoking cessation, and has been modified to take into account the special needs and circumstances of teens with alcohol and drug problems. The main goals of the treatment are to motivate adolescents to cut down on their smoking aLVAL,nd try to quit. The treatment provides encouragement, advice and support to assist teens in accomplishing these goals. A total of 112 adolescents in treatment for substance abuse will be recruited to participate in the project. Participating adolescents will be assigned to treatment (6 weekly meeting; delivered in a group format) or to a wait-list control condition. The wait-listed adolescents (who will be offered treatment following completion of the post-treatment interviews) will serve as a comparison group that will allow evaluation of whether the treatment is effective. All participants will be interviewed four times over an 8 month period. Teens will be asked to complete questionnaires and interviews regarding their tobacco, alcohol, and other drug use and also provide breath and saliva samples that will be used to test for nicotine use (to verify self-reported tobacco use). Results from this project will: 1) demonstrate whether the smoking treatment succeeds in decreasing cigarette use; 2) show whether changes in cigarette smoking are related to alcohol and other drug use; and 3) provide initial information as to whether the treatment is equally effective for boys and girls. The proposed project is thus intended to provide important information for designing and implementing smoking cessation treatments for alcohol and other drug abusing adolescents. LVAL,p.pThere are very few longitudinal study populations of Mexican-American and Anglo-American children and their parents which simultaneously investigate cardiovascular, behavioral and physiologic risk factors from preschool through early adolescence. Most of the studies of the determinants of diet and physical activity in children are cross-sectional. The current study population, still robust in cohort retention (nearly 68 percent after 7 years) will pass through adolescence in the next 3 years. This provides a unique opportunity to extend and combine the rich data already collected between ages 4-7, and again at ages 10-11, to the age period of [14-16] years. This study will continue the strengths of prior assessments of risk factors, health behaviors and behavioral determinants, but add adolescent-relevant measures of smoking behavior, feelings associated with depression, and peer influences; changing parental influences are also assessed. This study period will also concentrate on the influence of acculturation on these health behaviors in the Mexican-American population. This longitudinal study will add important data for investigators seeking a scientific basis for experimental manipulation of factors in intervention trials with youth of specific gender, ethnic and age characteristics. The specific aims of the study are prospective and cross-sectional, and for many of these aims, gender and ethnicity can be assessed as mediators of associations. In this study of young people and their mothers from two ethnic groups, aims of prospective analyses are to: 1. Study the determinants of physical activity and dietary intake of total fat, saturated fat, sodium, and energy, and changes in these behaviors in 4 year olds to [14-16] year olds. 2. Determine the relationships between diet and physical activity practices and physiologic indicators of risk, such as blood pressure, adiposity, body mass index, and serum lipoproteins at ages 4 to [14-16]years. 3. Describe the degree of tracking of physical activity ha LVAL bits and dietary intake of fat, sodium, and energy in 4 to [14-16] year olds. 4. Study the impact of changing acculturation on dietary and physical activity behaviors in Mexican-American parents and children from ages 4 to [14-16] years. Aims of cross-sectional analyses are to: 1. Determine the associations among physical fitness, adiposity, and smoking to CVD physiologic and behavioral risk factors in [14-16] year old Mexican-American and Anglo-American youth. 2. Examine the relationship of depression to cardiovascular risk behaviors of diet, physical activity and fitness, and smoking in Mexican-American and Anglo-American [14-16] year olds.LVAL . pADDICTION Cessation AGE Child DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN PregnancyAGE Adult Older Adult DISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO NicotineAGE Child Fetus/Prenatal LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Other Disease/Biology RESEARCH1 Animal Studies TOBACCO Non-Specified Tobacco Use Nicotine MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Child DISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies STUDY POPULATION Caucasian Hispanic TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother MISCELLANEOUS Sex/Gender DifferencesLVALv$~.6 | h V  `d Discovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 1 Development 2 Evaluation 1a Evaluation 1bDiscovery 2a Development 3 Development 5 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1c Discovery 3 Development 1 Development 2Discovery 1a Discovery 3 Development 1 Evaluation 1bDiscovery 2a Development 1 Development 3 Delivery 1 Delivery 2 Partnerships 2Discovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Discovery 2b Discovery 3 Development 3 Development 4 Delivery 2 Partnerships 2 Evaluation 1a Evaluation 1cDiscovery 2a Discovery 3 Development 3 Development 4 Partnerships 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1c Discovery 2a Discovery 2b Development 1 Development 3 Delivery 1 Delivery 2 Partnerships 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 3 Development 2 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1a Discovery 1c Discovery 3 Development 1 Development 3 Delivery 1 Delivery 2 Partnerships 2 Evaluation 1aDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1c Development 2 Delivery 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1c Discovery 3 Development 1 Evaluation 1bLVALTobacco use is one of the most significant public health issues facing our nation and the world today. Although tobacco use has declined over the past three decades, this decline has begun to level off and the remain smokers appear to have more difficulty quitting. Individuals with psychiatric comorbidity, including depression and alcohol use, as well as women find it more difficult to successful quit. In addition, adolescent smoking is on the rise and current treatments are ineffective for this important group of smokers. The goal of this center is to investigate and improve the treatment of tobacco dependence using transdisciplinary approaches to 1) understand the underlying factors associated with failure to enter treatment and poor treatment outcome, and 2) to develop and evaluate novel behavioral and pharmacological treatments that address these factors. The following specific aims will be achieved by the TTURC: 1) To galvanize research interest across different disciplines that will address the problem of tobacco dependence in these high risk groups. The theories and methods of each discipline will be brought to bear on the critical issues and the results will be synthesized at a level that transcends disciplinary boundaries. 2) To provide career development activities for graduate students, medical students, and junior investigators from different disciplines that will expose them to research on tobacco use and dependence and will potentially influence some to pursue careers studying issues related to tobacco. 3) To provide a mechanism to rapidly review and fund pilot projects that have significant promise for advancing the field. 4) To conduct a series of programmatic research studies aimed at understanding risk factors for treatment failure and developing more efficacious treatments.LVAL xThis grant provides supplemental funding for research focused on the relationships between maternal prenatal depressive symptoms (and other psychosocial factors) and maternal prenatal smoking cessation and intensity (i.e., number of cigarettes smoked). During the current study, data are being collected on psychosocial factors and smoking status at the first prenatal visit and at 30 weeks gestation. During this study, the research team will collect follow-up data at the 6- or 12-week postpartum visit and again at 6 to 12 months postpartum. The purpose of this further research is allowing the team to thoroughly measure smoking status during the postpartum period, which will greatly aid the team s findings. The findings from this research will lead to future new treatments of depressive symptoms as a way to prevent smoking relapse and facilitate smoking cessation.The aim of this study is to evaluate the effects of maternal smoking on measures of fetal well being and to determine whether smoking cessation with nicotine replacement can lessen these effects.We have begun a study to examine the effects of nicotine on bone turnover, largely based on the preliminary results of our work showing that smoking cessation reduces markers of bone resorption by 20%.Maternal smoking is the most preventable cause of poor pregnancy outcomes in the United States. This study will provide useful information on potential mechanisms by which maternal smoking may contribute to SIDS, and may provide essential data for future work in detection and prevention of tobacco-related disturbances. This study utilizes a between-subject design to compare the effects of prenatal smoking on catecholamine response to hypoxia during delivery. Forty women will be identified as smokers or non-smoking (20 per group) at 28 weeks gestational visit.i ] 0  z]A||@@u@Researchf@ZPAULJAYUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP9RT-0218P,p.L@@ rL@7/1/20006/30/20037/1/2000 to 6/30/20034/2005}nC>88,"{{@@Researchf@ZPATERUSSELLUNIVERSITY OF SOUTH CAROLINA AT COLUMBIACOLUMBIASCNHLBIU01, HL066852b,p.T@4@r@9/30/20008/31/20069/30/2000 to 8/31/20064/2005{qG>88,"zz@`a@ResearchL@ZPASKETTELECTRAOHIO STATE UNIVERSITYCOLUMBUSOHNCIP50, CA105632l,p.L@p@r*@z9/30/20038/31/20089/30/2003 to 8/31/20084/2005tokaJA88,"yy@`@Research@ZPARKELYSEGENERAL HOSPITAL CORPORATION--MASSACHUSETTS GENERAL HOSPITALBOSTONMARWJF51805D@L@Discovery 2a Evaluation 1a@z9/1/20048/31/20059/1/2004 to 8/31/20054/2005E>88,"xxm@R@Researchn@ZPALMERJULIEBOSTON UNIVERSITY MEDICAL CAMPUSBOSTON MANCIR01, CA098663,p.t@p@r @z5/1/20034/30/20085/1/2003 to 4/30/20084/2005{vriG@88,"ww 6@@ResearchL@ZOSSIP-KLEINDEBORAHUNIVERSITY OF ROCHESTER ROCHESTERNYNCIR01, CA067594f},p.T@@r<@z7/3/19966/30/20057/3/1996 to 6/30/20054/2005|wshNE88,"vv@@Researchp@ZOSSIP-KLEINDEBORAHUNIVERSITY OF ROCHESTER ROCHESTERNYNCIR01, CA080283{,p.@:@r@z9/30/19987/31/20049/30/1998 to 7/31/20044/2005|wshNE88,"uu8@`@Research~@ZORRSUEZANNEEAST CAROLINA UNIVERSITY SCHOOL OF HEALTH AND HUMAN PERFORMANCEGREENVILLENCRWJF43281@t AddictionDiscovery 2a Evaluation 1aX@z3/1/20022/28/20053/1/2002 to 2/28/20054/20051)G=88,"tt @+@Research@ZO'NEILLMOLLYWOMEN'S 12-STEP RECOVERY CENTER INC.KANSAS CITYMORWJF51436Not available7/1/20046/30/20077/1/2004 to 6/30/20074/2005{nHA88,"?~ss^@@Research@ZONCKENCHERYLUNIVERSITY OF CONNECTICUT SCHOOL OF MEDICINEFARMINGTONCTNIDAP50, DA013334x,p.Biology and CancerP@r@q200320042003 to 20044/2005vH@88,"rrG@ @Researchf@ZONCKENCHERYLUNIVERSITY OF CONNECTICUT SCHOOL OF MEDICINEFARMINGTONCTNIDAR01, DA015167v,p.|@:@r@@q7/1/20023/31/20077/1/2002 to 3/31/20074/2005vH@88,"qqg@p@4ResearchSMOKING AND PREGNANCY: CAPONCKENCHERYLUNIVERSITY OF CONNECTICUT SCHOOL OF MEDICINEFARMINGTONCTNCRRM01, RR006192@t|@:Discovery 1a Evaluation 1b"@qNot GivenNot GivenUncertain4/2005.&e]UU,"pp@`@Researchf@ZONCKENCHERYLUNIVERSITY OF CONNECTICUT SCHOOL OF MEDICINEFARMINGTONCTNCRRM01, RR006192@tBiology and CancerR@r\@q12/15/199311/30/200312/15/1993 to 11/30/20034/2005vH@88,"LVAL,p.wSmoking during pregnancy is one of the most important modifiable causes of poor pregnancy outcomes in the United States. Unfortunately, the majority of women who smoke prior to pregnancy continue to smoke during pregnancy. Even with augmented behavioral interventions, smoking cessation rates in pregnancy trials rarely exceed 20 percent. These low quit rates may be due to inadequate treatment of the physical addiction to nicotine. Indeed, medications are first-line treatment for smoking treatment in non-pregnant smokers. However, little information is available on the safety or efficacy of medications to treat pregnant smokers. This proposal will examine the utility of one first-line medication, nicotine gum, as an aid to smoking cessation during pregnancy. The specific research aims of this project are: 1. To compare smoking cessation rates and smoking reduction among pregnant smokers who are randomized to receive 2 mg nicotine gum or a matching placebo; 2. To compare nicotine gum versus placebo on surrogate measures of maternal and fetal safety (i.e., overall nicotine and tobacco exposure), and birth weight at the time of delivery; 3. To examine which subjects benefit the most from the use of nicotine gum for smoking cessation during pregnancy. Subjects will be recruited from a prenatal clinic that serves primarily a low-income, minority population. Two hundred sixty-six pregnant smokers who smoke at least 5 cigarettes per day will be randomly assigned to receive a behavioral counseling intervention and either a 6-week course of 2 mg nicotine gum or placebo for smoking cessation followed by a 6-week taper. Primary outcome measures will be 7-day point prevalence cigarette abstinence, number of cigarettes smoked per day, saliva cotinine concentrations, and measures of tobacco exposure (i.e., carbon monoxide in exhaled air, and urine anabasine and anatabine) at 6 weeks after the quit date and at 32-34 weeks gestation. Birth weight will be obtained at the time of delivery. We hypothesize tha LVAL t 1. Pregnant smokers who are randomized to nicotine gum will have double the quit rates, and will reduce their smoking to a greater degree than subjects randomized to placebo; 2. Nicotine gum compared to placebo will reduce maternal cotinine levels, carboxyhemoglobin levels, and urine anabasine and anatabine levels. Birth weights will be higher in the offspring of subjects randomized to nicotine gum compared to placebo and will be negatively correlated with carbon monoxide and urinary alkaloids at 32-34 weeks gestation; 3. The odds of cigarette abstinence will be increased primarily in subjects who smoke at least 15 cigarettes per day.LVAL,p.yEvaluation of the short-term benefits of smoking cessation in adolescents is important because the knowledge of these benefits may enhance treatment outcomes for young persons. To date, most research on the medical benefits of smoking cessation has focused on adult smokers (i.e., reduced risk for lung cancer, hear disease). Unfortunately, these health benefits may not be meaningful enough for adolescents to quit smoking. Thus the current proposal seeks to determine a potentially important benefit of smoking cessation in adolescents. Specifically, we will examine effects of smoking cessation on bone turnover in adolescent girls and boys. This information may eventually be useful for treatment of adolescent smokers, especially if it can be presented in terms of maximal bone strength and height potential. The primary aims of this study are: 1) To determine the effects of smoking cessation on biochemical markers of bone turnover in adolescents; and 2) To examine the potential mechanisms by which smoking could affect bone turnover by measuring plasma cotinine concentrations and hormone profiles. We hypothesize that smoking cessation will increase markers of bone formation in adolescent boys during their rapid growth rate. We also hypothesize that smoking cessation will decrease markers of bone resorption in adolescent girls who have completed their rapid growth phase. Additionally, we anticipate that the change in biochemical markers of bone turnover in boys or girls will be correlated with a decrease in plasma cotinine concentrations. Study subjects will be recruited primarily from an ongoing study of acute nicotine abstinence in adolescent smokers (RO1 HD 37688; P.I. Krishnan-Sarin) being conducted at Yale University School of Medicine. The present proposal will examine four groups of smokers (N=60): boys versus girls, who either quit smoking for three months or who continue smoking. Blood and urine for markers of bone formation (bone specific alkaline phosphatase, osteocalcin and C-terminal pro-collagen8 LVALH peptide) and resorption (cross-linked amino-terminal and carboxy-terminal telopeptides of collagen and deoxypyridinoline free cross-links) will be collected on all smokers at baseline, and again at the three month up visit. Anthropomorphic measurements (e.g., height and weight) will be assessed at baseline, three months, and again at one year.hLVAL  AGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Rural National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other SmokingADDICTION Cessation Relapse EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PostpartumDISEASE/BIOLOGY Cancer Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American TOBACCO Non-Specified Tobacco UseADDICTION Cessation AGE Adult Older Adult LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Quitline Educational Materials Buproprion Nicotine Replacement Therapy Other Pharmacological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Young Adult COMMUNITY Health Care Provider EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Quitline Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other SmokingADDICTION Cessation Relapse ECONOMICS Socio-Economic Status Medicaid/Medicare LOCATION National PREVENTION/TREATMENT Interview/Focus Group RESEARCH Human Studies STUDY POPULATION African American TOBACCO Cigarette/Other Smoking WOMEN PregnancyLVAL,p.|Approximately 2,145 adolescents begin smoking each day in the US; an evidence base for effective cessation interventions for this population is just beginning to emerge. Brief primary care interventions for smoking with referral to appropriate adjuncts have been shown to be effective with adults; current clinical guidelines recommend extending this intervention to adolescent patients. Although there have been recent calls to action, tobacco cessation interventions by adolescent primary care providers remain low. The current trial is a randomized controlled trial to examine the effectiveness of a brief primary care provider intervention with referral to adjuncts for adolescent smoking cessation. Preliminary data indicate greater adoption of specific smoking screening and counseling behaviors by providers in intervention conditions relative to usual care control, although adoption of the systems and clinical interventions was not universal. To the extent that this health care delivery system can serve as a structure for providing evidence-based tobacco cessation interventions to adolescents, evidence based health care provider office systems interventions need to be identified and the infrastructure for intervention needs to be disseminated. The current project has 100 pediatric and family practices engaged, half of whom are now experienced in working with the brief intervention system. Using the evidence base generated from the current trial, lessons learned in the field, and specific collaborative feedback from practices, the proposed project would identify a set of recommended best practices for primary care office implementation of adolescent smoking cessation intervention using academic detailing. (Note that other models for implementing practice-based interventions exist and similar processes are needed for each; the current project will identify and package for the field best practices for the academic detailing model which is the one with which our team has had considerable experience). The deve<LVALLlopment of such a "best practices" tool kit will provide critical infrastructure for dissemination of evidence-based cessation interventions as they emerge from the current trial and other adolescent trials underway.LVAL,p.~There are over 13 million smokers ages 50+ in the United States, who tend to be heavy, long-term smokers who are more likely to have chronic diseases caused or exacerbated by smoking. Stopping smoking can reduce morbidity and mortality from disabling diseases and conditions across the lifespan. Thus, the implications of smoking and smoking cessation for maintenance of health and independent living for older populations are considerable. Little data are available on effective treatments for smoking in this growing population. Assisted self-help interventions seem particularly appropriate to this group, who may be limited geographically or by health status in their ability to access smoking intervention services. Preliminary results from the current and preceding trials suggest that proactive telecounseling, in combination with a self-help manual and access to a reactive quitline, enhances quit rates, particularly among those using concurrent pharmacotherapy for smoking cessation. Results of other trials indicate that multiple quit attempts are often necessary to achieve smoking abstinence, and telecounseling may enhance recycling (i.e., re-quitting after a failed attempt). The proposed study will extend the scope of the current trial to examine the effectiveness of recycling smokers ages 50+ with a failed quit attempt in the past two years (recruited from the current trial and supplemented with community recruits). Two groups will be compared: 1) Minimal Intervention Control - self-help manual and access to a reactive quitline (smokers call in to the quitline for assistance); and 2) Proactive - manual and quitline along with proactive telecounseling calls (calls out to participants) to supporting re-quitting and supporting use of FDA approved pharmacotherapies for smoking cessation (nicotine replacement, bupropion, and others if they are approved during the period of study. Subjects will be followed at 6, 12, and 18 months for assessment of smoking status, health outcomes, and use of cessation resourcenLVAL~s (manual, quitline, proactive telecounseling, pharmacotherapy)LVAL#8L  4 8 ~TXDn"XDBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Addiction Epidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentEpidemiology and National SurveillanceBiology and Cancer Addiction Epidemiology and National SurveillanceAddiction Epidemiology and National Surveillance Interventions for Prevention and TreatmentEpidemiology and National Surveillance Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentAddiction Epidemiology and National SurveillanceInterventions for Prevention and Treatment Community and Policy InterventionsBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and Communications Community and Policy InterventionsInterventions for Prevention and Treatment Awareness Risk Perception and Communications Community and Policy InterventionsEpidemiology and National SurveillanceInterventions for Prevention and TreatmentEpidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentLVAL,p.Increasing evidence suggests that susceptibility to cancer may be determined in part by low-penetrance genes, such as genes involved in the synthesis and metabolism of hormones or the metabolism of toxic substances. Many of these genes have been found to be polymorphic, with different actions depending on the polymorphism. In some cases, the frequencies of polymorphisms differ by race and ethnicity. Studies of gene-environment interactions which combine genetic information with standard epidemiologic data on reproductive factors, behaviors, medication use, and other exposures have the potential to greatly advance our current understanding of the etiology of human cancer. We propose to establish a DNA repository by obtaining cheek cell samples from as many as possible of the African-American women enrolled in the Black Women's Health Study (BWHS), a prospective follow-up study begun in 1995. Every two years since entry, mail questionnaires have been used to obtain data on reproductive history, personal habits and behaviors, medication use, and the occurrence of cancer and other serious illness. A recent pilot demonstrated the willingness of participants to provide a DNA sample by mail by swishing the mouth with mouthwash, expelling it into a small container, and mailing it directly to a laboratory. The DNA yields were high, and successful PCRs were carried out. We propose to seek mouthwash samples by mail from the approximately 57,000 BWHS participants who have completed at least one follow-up questionnaire; an estimated 36,000 women will provide samples. DNA will be extracted and stored at the participating laboratory. During year 05, nested case-control analyses will be carried out of breast cancer risk in relation to several genes involved in estrogen metabolism and a gene involved in the regulation of insulin-like growth factor. The DNA repository will serve as a resource for studies of gene effects and gene-environment interactions in relation to cancer in BWHS data alone and in combined or pooled,LVAL< analyses with other large cohort studies. The BWHS will provide the largest source of data on gene-environment interactions in black women, and will contribute substantially to the data available on young women of any race. LVAL The primary aim of this study is to compare rates of relapse among women who reach an elevated threshold of depression or anxiety symptoms versus women who do not reach an elevated threshold of depression or anxiety symptoms. Secondary aims are to assess postpartum mood symptoms and smoking status to determine at what time mood symptoms increase and relapse occurs and to determine mood and other factors associated with postpartum relapse. Qualitative aims are to explore a) type of mood symptoms, b) relapse experiences, c) attributions for mood changes and/or relapse, d) coping mechanisms and support to deal with mood and/or staying quit and e) postpartum stressors.LVAL,p.The overall goal of the proposed project is to increase early detection of cervical cancer by increasing the proportion of Appalachian women, age 18 and older, who receive Pap smears at appropriate intervals, and return for follow-up care when necessary. The proposed project will be implemented in Appalachian Ohio, a mainly rural and underserved area with a population comprised of 1.5 million adults, aged 18 and older and will utilize a CBPR approach and community relationships already established in the area by Center investigators. Cervical cancer prevention is a concern for this community, thus a CAB and a consortium of local community agencies are partnering with the Center in this effort. The first phase of the project will involve surveying 1,600 randomly selected women aged 18 and older who are patients of 16 primary care practices in Appalachian Ohio. The investigators will survey these women to identify social, environmental and behavioral barriers to obtaining risk-appropriate Pap smears within guidelines. Approximately half of these women will be in need of a Pap smear and will be entered into Phase 2 of the project. In this phase, an individualized health education program will be compared to a brochure and letter in a quasi-experimental trial design among 614 women. The education program will use two innovative strategies to address barriers to cervical cancer screening in these women: 1) educational sessions will be at the individual level in the woman's home; and 2) lay health educators supervised by local agricultural extension agents will deliver the education program. Specific Aims of the proposed project are to: 1) identify social-, environmental- and individual-level barriers to obtaining Pap smears; 2) develop and evaluate a health education program to improve knowledge, to address the identified barriers to behavior change, and to motivate women in the target populations to obtain Pap smears and understand the risky behaviors associated with developing cervical cancer (interactiohLVALxn with Projects 2 and 3); and 3) evaluate, through use of a quasi-experimental trial design the impact of the health education program compared to a brochure and physician letter on the proportion of women obtaining Pap smears. Approximately 30% of the 1,600 women will be current smokers and will be eligible to participate in Project 2, thus allowing the investigators to explore the differential effect of the health education intervention to enhance smoking cessation (interaction with Project 2, aim 4). Secondary aims will relate to assuring adequate follow-up among women with abnormal test results (interaction with Project 3). If this program is successful in improving cervical cancer screening practices among this population of women, lay health educators from a variety of community organizations can be trained and supervised by community organizations to deliver similar programs to underserved women in other areas where health disparities exist.LVAL,p.The major purpose of the proposed investigation is to examine the effects of a comprehensive, school-based, community-linked intervention on physical activity and physical fitness in middle school girls. Factors that mediate the effect of the intervention will be identified, and the intervention's impact on tobacco use, alcohol use, and depressive symptomatology will be observed. A collaborative, multi-center investigation will be conducted. At each of five field centers, six middle school catchment areas will be pair-matched and randomly assigned to intervention and control groups. In the intervention catchment areas a multi-component intervention, based on an ecological model and Social Cognitive Theory, will be implemented. The school physical education curriculum will be modified to emphasize in-class participation in moderate to vigorous physical activity and mastery of behavioral skills related to physical activity. Relationships will be established between the school and at least two community organizations that will provide after- school and summer physical activity programs for girls at the school site. in addition, after-school, weekend, and summer physical activity programs for girls will be expanded in community settings. Modifications will be made in several components of the school health program to link girls to the expanded physical activity program opportunities. Girls will be exposed to the intervention during their 7th and 8th grade years. Baseline measures of physical activity, physical fitness, other health characteristics and psychosocial/environmental factors related to physical activity will be administered during the spring of the 6th grade year, and this measurement battery will be re-administered during the 7th, 8th and 9th grade years. To determine intervention effects, statistical analyses of the physical activity and fitness data will be performed using mixed- model analysis of variance, with catchrnent area (nested within treatment) taken as the unit of analysis. It is hr LVAL ypothesized that the intervention will significantly reduce the usual rates of decline in physical activity and fitness seen in girls between the 6th and 8th grades. This study will uniquely and markedly expand our knowledge of promotion, determinants, and health benefits of physical activity in middle school girls.LVALH jADDICTION Maintenance Cessation Relapse AGE Fetus/Prenatal EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National POLICY Regulatory Intervention PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION Asian Pacific Islander Caucasian Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology RESEARCH1 Animal Studies TOBACCO Cigarette/Other Smoking Nicotine WOMEN Pregnancy MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Pregnancy MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance Cessation AGE Child Young Adult ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child COMMUNITY General Partnerships EDUCATION LEVEL Less than High School PSYCHOLOGICAL Depression/Mood/Anxeity TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Weight Gain/ExerciseLVAL,p.After years of steady declines in rates of use, cigarette smoking appears to be on the rise among adolescents and young adults. Tobacco use is one behavior that both starts early and shows a more stable pattern of consumption over the lifespan than the use of other substances. For these reasons, it is vital to understand the antecedents of smoking tobacco among the young to plan effective and appropriate prevention and treatment programs. As one might expect, different subgroups of youth show greater risk for regular cigarette use. Prior work by our team and others has demonstrated that tobacco use is more prevalent among gay and bisexual men than among the general male population. Other research findings suggest that this is also true for lesbians and bisexual women, in comparison to their general population counterparts. One important area of research on vulnerability among adolescents to tobacco use has been the notion of "deviance proneness." This theoretical construct seems to potentially dovetail with our prior research findings, which suggest that there may be gay-specific factors that lead to higher rates of smoking. However, we have little information on the determinants of smoking behavior and the specific appeal of cigarettes for gay youth. This study will address this gap in knowledge. As significant work needs to be done in furthering our understanding of any gay-specific predictors of initiation of tobacco use among gay, lesbian and bisexual youth, we have proposed a qualitative study that will allow us to explore this phenomenon in depth. Open-ended interviews (both using focus groups and individual interviews) will allow us to ask participants about their history of smoking, possible factors that may be associated with their initiation of tobacco use (for example, asking about family members who smoked tobacco, peer use of tobacco, situations that were going on in their lives concurrent to the onset of regular smoking), and considerations that may be relevant to smoking cessation proLVALgrams targeting these youth (for example, asking about any quit attempts, and how they currently view their smoking behavior). We will attempt to examine both those variables that prior research has shown to be important, as well as to identify any gay-specific variables that may have influenced the use of tobacco. We anticipate that there may very well be gender-related differences in the factors described by study participants. To ensure diversity of respondents, we will select respondents (in both Los Angeles and San Francisco) who vary on several dimensions (gender, educational attainment, smoking level, and race/ethnicity). Individual interviews will provide an opportunity to gain more in-depth information on the smoking histories of younger gay and lesbian smokers, as the narratives of these interviews can provide a rich picture of the pathway from experimentation to regular use of tobacco, and the factors associated with smoking. Having an open-ended structure for these interviews permits us to explore newly emerging ideas about linkages between smoking behaviors and other life experiences or issues. We anticipate that the results of this study will provide helpful information for the development of gay/lesbian/bisexual-specific interventions to a) reduce the numbers of such youth who initiate smoking, b) address the contexts in which those who have initiated smoking may progress to regular smoking (and addiction), and c) facilitate smoking cessation in this population. The opportunity to collaborate with community service providers enables us to translate our research findings into anti-smoking campaigns and smoking cessation programs for this population in a timely fashion. LVALAlthough it is well appreciated that nicotine is a very addictive substance, the exact reasons for its addictive nature remain elusive. Evidence suggests that stress in general, and stress hormones such as corticosterone and cortisol in particular, can modulate nicotine intake. However, the relationship between stress and nicotine use is not well defined. For the first two series of studies, we propose to assess the relationship among stress, stress hormones (corticosterone in particular) and nicotine self-administration using an animal model. This modeling will allow us to determine how easy or difficult it is to start or stop the self-administration nicotine. At the same time, we will study the relationship between blood levels of corticosterone and self-administration of nicotine, as well as determine the corticosterone response to the intake of nicotine and to nicotine withdrawal. The next series of studies will determine the effects of prior stressors on nicotine self-administration. We will measure the levels of corticosterone and the corticosterone response to nicotine and determine if these are related to the degree or pattern of nicotine self-administration. Finally, studies suggest that smoking is increased in humans exposed to stressful experiences early in life (Anda et al 1999). Accordingly, we will determine if neonatal exposure can produce permanent changes in the regulation of the corticosterone secretion that may also effect adult nicotine self-administration. Taken together, the results of the proposed studies should help us to understand if, how, and to what extent, prior stress, occurring either during adulthood or during early development, effects nicotine self-administration. The results should help us to devise new strategies to prevent and treat nicotine abuse.   b :  f@ c@@Researchp@PINKERTONKENTUNIVERSITY OF CALIFORNIA AT DAVISDAVISCACTRDRP6RT-0327,p.Biology and CancerDiscovery 1a Evaluation 1b`@7/1/19976/30/20017/1/1997 to 6/30/20014/2005wslIC88,"g@@@Researchz@PICKWORTHWALLACENot GivenNot GivenNot GivenNIDAZ01, DA000356,p.j@ @r>@Not Given2003? to 20034/2005smbWLC88,"!@@@ResearchZ@PICKETT KATEUNIVERSITY OF CHICAGOCHICAGOILNIDAR03, DA014334,p.b@ Discovery 1a Evaluation 1a@9/1/20015/31/20049/1/2001 to 5/31/20044/2005rlh_HB88,"g@p@4Researchh@PICCIOTTOMARINAYALE UNIVERSITYNEW HAVENCTNIDAP50, DA013334,p.Biology and Cancer Addictionn@r^@Not GivenNot GivenUncertain4/2005qkg\KC88,"^@@Research@PETERSENRUTHUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILLCHAPEL HILL NCACSCRTG-03-074-01-PBP @@ @r@1/1/200312/31/20051/1/2003 to 12/31/20054/2005uHB88,"@@Research|@"ZPETERKINROSEMARIEFREEDOM FOUNDATION OF NEW JERSEY INC.WEST ORANGENJRWJF46993Not available10/1/20039/30/200410/1/2003 to 9/30/20044/2005tMB88,"?~@@@Researchr@!ZPERKINSKENNETHUNIVERSITY OF PITTSBURGHPITTSBURGHPANIDAR01, DA012655,p.Biology and Cancer AddictionP@r@9/1/20007/31/20059/1/2000 to 7/31/20054/2005 ztpdJA88,"g@p@4Research@ ZPERKINSKENNETHUNIVERSITY OF PITTSBURGHPITTSBURGHPANCRRM01, RR000056`@Biology and Cancer Addictionn@r@Not GivenNot GivenUncertain4/2005ztpdJA88,"`g@ (@Research^@ZPERERAFREDERICACOLUMBIA UNIVERSITY HEALTH SCIENCESNEW YORKNYNIEHSR01, ES008977 @t@@r@8/1/19975/31/20078/1/1997 to 5/31/20074/2005~zpK@88,"@@`O@Researchl@ZPENTZMARY ANNUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANIDAR01, DA003976,p.@@ rT@12/16/19858/31/200212/16/1985 to 8/31/20024/2005}ylI?88,"c@@ResearchN@ZPENTZMARY ANNUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP6RT-0184,p.@@ r@7/1/19976/30/20017/1/1997 to 6/30/20014/2005}ylI?88,"~~ S@ @Researchd@ZPENTELPAULMINNEAPOLIS MEDICAL RESEARCH FOUNDATION, INCMINNEAPOLISMNNIDAR01, DA015668,p.Biology and Cancerl@ r@9/30/20027/31/20069/30/2002 to 7/31/20064/2005 tF@88,"}}@@u@Research\@ZPECHNICKROBERTCEDARS-SINAI MEDICAL CENTERLOS ANGELESCACTRDRP9RT-0103@@Biology and Cancer AddictionP@ r0@7/1/20006/30/20037/1/2000 to 6/30/20034/2005 xtgJB88,"LVAL,p.The aim of this proposal is to study the effects of maternal immunization with a nicotine vaccine on the pharmacokinetics, neurochemical consequences, and behavioral sequelae of gestationally administered nicotine in rats. Smoking during pregnancy is associated with a wide range adverse neonatal outcomes. Animal data strongly implicate nicotine as a teratogen and a contributor to these adverse outcomes. It has recently been shown that immunization of adult male rats with a nicotine vaccine can substantially reduce the distribution of acutely or chronically administered nicotine to brain and other organs. Preliminary data suggest that vaccination of female rats can also reduce the distribution of gestationally administered nicotine to fetal brain. The proposed study will address the mechanisms by which vaccination alters nicotine distribution to the fetus, and the magnitude and consequences of this effect under a variety of dosing conditions. The pharmacokinetics of nicotine in the pregnant rat will also be studied to better understand the determinants of fetal nicotine exposure. Specific hypotheses to be tested are that 1) Maternal vaccination reduces the distribution to fetal brain of nicotine administered during gestation using a variety of clinically relevant acute and chronic dosing regimens. 2) Protection of fetal brain from gestational nicotine exposure occurs via two complementary mechanisms; a reduction in unbound nicotine distribution to the fetus, and the transfer of maternal antibody to the fetus which then binds and sequesters nicotine in fetal serum, 3) Vaccination attenuates the increase in fetal brain c-fos mRNA expression associated with chronic gestational nicotine exposure, 4) Vaccination attenuates the increase in neonatal locomotor activity associated with gestational nicotine exposure, and 5) Nicotine clearance is lower in nonpregnant females than in males, but is increased in females during pregnancy. These immunologic, pharmacokinetic, neurochemical and behavioral data 6LVALFwill be integrated to help understand the mechanisms by which vaccination alters fetal nicotine distribution, and the clinical potential of vaccination to reduce the teratogenic effects of gestational nicotine exposure.LVAL,p.Cigarette smoking among California youth has not declined appreciably despite use by schools of evidence-based prevention programs. A major question is whether school tobacco policy could be improved to help decrease smoking among youth. This project developed and evaluated a tobacco policy intervention to enhance the effects of school policy on youth smoking. Year 1 included development and piloting. Year 2 included intervention and 2 measurements. Year 3 included the final follow-up collection and analyses, and training of control group schools. A no-cost extension was used to refine the curriculum and policy resource manuals, and to prepare publications. The intervention had four components: a 3 session curriculum, a policy presentation for faculty, an administrative staff policy workshop, and a parent teacher association workshop. The research design was a 2 group design, with 19 schools in 3 districts randomly assigned to the intervention or a policy as usual control group. A total of 2617 entering 7t' grade students with active parental permission were surveyed at least once (85% response rate); 2053 had complete merged data across three waves of measurement (baseline, 6 month follow-up, 12 month follow-up; 41% white; 30% Latino; 17% Asian; 2%African American; 10% Other). Seven measures were used: student survey of tobacco use, and policy attitudes and behaviors, principal policy interview; staff surveys of student and staff policy; written district and school policy; school infraction records. Analyses included structural equation modeling of tobacco use-policy relationships; regression analyses of policy intervention effects, controlling for gender, ethnicity, and baseline values of variables; and content analyses of written policies and principal interviews. Results of structural equation modeling showed that the major mediators of change in tobacco use were changes in perceived social norms for tobacco use and support of policy (CFI>.93). Results of regression analyses showed significant proLVAL&gram effects on policy support, encouragement of friends not to smoke, perceived social norms for tobacco use, intentions to use, and lifetime and monthly smoking prevalence by 6 months; and maintenance of most effects by 1 year. There were few ethnic or ethnic x program differences: Latino students showed the highest pro-smoking environment (norms), and Asian students the lowest. Written policies showed no variation among schools or districts. Three categories of policy enforcement were generated from principal interviews (punishment, punishment + counseling, counseling + support); program schools showed more adoption of counseling + support enforcement after intervention. This project has thus far produced 12 conference presentations and published abstracts, 2 peer reviewed publications and one chapter, a doctoral fellowship grant, and 2 educational products (curriculum, resource manual). With the short timeline of this project, preparation of publications and extended analyses are expected to continue for another year on both doctoral fellowship funding and on nonfunded efforts from supervised research credits.LVAL,p.The proposed project expands long-term evaluation of an ongoing community- based drug abuse prevention program (Midwestern Prevention Project) that has emphasized intervention during early adolescence, by initiating intervention earlier in childhood. The proposed program is tailored to the changing developmental needs of children and adolescents and includes school, parent, and community components. The original community program yielded significant reductions in monthly, weekly, and daily use of tobacco, alcohol, and marijuana, and lifetime use of some illicit drugs from adolescence to early adulthood. However, process and formative evaluation research suggests a need for stronger programs that are initiated earlier in elementary school and continued at least through middle school. The study will evaluate short-term and long-term effects of comprehensive school-community programming in Indianapolis that is initiated during elementary school and is implemented from grades 4 through 7. Feeder middle schools will be stratified according to current participation in DARE and then randomly assigned from within strata to a comprehensive elementary+middle program or middle program condition, both with parent involvement and community support revised from the original community intervention to include a focus on academic and social competence, and violence as well as drug abuse prevention (N=48 elementary schools, 24 middle schools, 2400 individuals measured from all classrooms each year from the 1996 fourth grade cohort as it moves through time). Measures include annual surveys of students, parents, teachers, community leaders, and individuals knowledgeable about local policy; expired air; and school archival records on drug-related infractions, absenteeism, policy and achievement. Regression, growth curve, and causal modeling analyses will be used to evaluate program effects. The proposed project continues and expands the scope of the current project by testing the efficacy of a combined elementary and midd LVAL le school year program with parent and community components. The results of the study should yield important information about the incremental effects of a community program initiated in childhood compared to programming focused only on adolescents.TLVAL nADDICTION Maintenance Withdrawal Relapse DISEASE/BIOLOGY Other Disease/Biology PREVENTION/TREATMENT Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH1 Animal Studies TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Adult COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status Cost of Intervention/Prevention LOCATION National RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Maintenance PSYCHOLOGICAL Other Psychological RESEARCH1 Animal Studies RESEARCH Human Studies Clinical Research TOBACCO Nicotine WOMEN Menstral Cycle MISCELLANEOUS Sex/Gender DifferencesADDICTION Maintenance DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Child Fetus/Prenatal DISEASE/BIOLOGY Cancer Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research STUDY POPULATION African American Hispanic TOBACCO Environmental Tobacco Smoke WOMEN PregnancyAGE Child Young Adult Adult COMMUNITY General Partnerships ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National POLICY Regulatory Intervention PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use WOMEN Parent/Mother MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesnLVAL~There is increasing evidence that people of color are disproportionately exposed to numerous environmental hazards, including hazardous air pollutants such as polycyclic aromatic hydrocarbons (PAH) and environmental tobacco smoke (ETS). The Washington Heights and Harlem neighborhoods in Manhattan are typical of other Hispanic and African American communities in that they are located in a large sprawling metropolitan area characterized by elevated air pollution. The incidence of low birth weight is higher among African Americans living in Central Harlem and Hispanics living in Washington Heights than in Caucasians in the U.S. Cancer rates are also higher in African Americans than in Caucasians. Environmental risks to the developing infant are of particular concern, given the likelihood of increased susceptibility during this period. A molecular epidemiologic cohort study of African American and Hispanic mothers and newborns is proposed to investigate the role of PAH and ETS in procarcinogenic and developmental damage. A combination of personal monitoring, questionnaire and biomarkers in peripheral blood will be used to quantify individual exposure to the toxicants of concern. The biomarkers include PAH-DNA adducts in white blood cells (an indicator of PAH exposure and procarcinogenic genetic damage) and plasma cotinine (a metabolite of nicotine and internal dosimeter of ETS). Measures of development will be assessed in the infants at birth and at 6 and 12 months. The proposal is responsive to concerns about environmental justice and to the recommendation of the National Research Council that risk assessment and public health policy pay special attention to the protection of young infants and children.LVAL Approximately 22 million adult women and at least 1.5 million adolescent women currently smoke cigarettes. These smoking patterns result in the death of more than 140,000 women each year from smoking related diseases. These diseases have been termed "the most preventable cause of premature death in this country" (American Cancer Society: www.cancer.org/tobacco/women.html). As with many health issues, poor Americans are burdened with a disproportionate share of cancer related mortality. While smoking cessation can be addressed from a variety of levels, there is very strong evidence that a smoking cessation intervention offered through the health care system is effective at reducing rates of smoking and therefore decreasing the long-term consequences of smoking. To promote the use of this effective smoking cessation intervention in the health care system, this project will address barriers that may prevent the implementation of these services, especially for pregnant women who are poor or underserved. These include such issues as reimbursement, increasing providers' use of the intervention and improving patient's confidence in quitting. Tolerance to nicotine develops with chronic smoking and may be associated with the onset of tobacco dependence. It is unclear how quickly this tolerance dissipates after terminating exposure to nicotine. We propose to longitudinally assess responses to measure doses of nicotine by nasal spray in 30 male and female smokers as they smoke ad lib for two days (baseline), quit for six days, and then resume smoking for two days on the GCRC. We hypothesize that responses to nicotine will become larger over the six days of cessation, showing dissipation of tolerance and then be smaller during the final two days of ad lib smoking, showing reinstatement of tolerance with return to smoking.LVAL,p.Men and women may differ in factors that reinforce smoking behavior: self-administration of nicotine per se is often less robust in women, women are less sensitive to many effects of nicotine, and nicotine replacement is less effective for smoking cessation in women. Nicotine therefore may be a less reinforcing consequence of tobacco smoking in women vs. men. Other results suggest that non-nicotine aspects of smoking (e.g. sensory effects) may be more reinforcing in women. In this revision of "Sex Differences in Nicotine Reinforcement: Human/Animal" (DA 12655), we will examine sex differences in the influence of nicotine and non-nicotine factors on self-administration (SA) behavior. A unique feature of this proposal is a parallel series of studies exploring these questions using an animal (rat) model of nicotine self-administration. Procedures in the human and animal lines of research will allow independent manipulation of nicotine and non-nicotine factors. Our specific aims are to: 1) Examine differences in smoking (human) or i.v. nicotine (rat) self-administration in females as a function of menstrual/estrus cycle phase and compare this SA behavior to males. Results will determine the influence of cycle phase on SA, which may help explain observed sex differences, and critically inform the design of all subsequent research in this project as to whether cycle phase must be controlled. 2) Examine sex differences in the influence of nicotine dose on SA behavior in humans and animals. Nicotine clearly is the primary psychoactive ingredient reinforcing smoking behavior. However, nicotine may be less important in regulating this behavior in females. We will explore this possibility by determining whether self-administration behavior is less affected by manipulations of nicotine dose in females. 3) Examine sex differences in the influence of non-nicotine, drug-related stimuli on SA in humans and animals. Males' behavior may be more tightly controlled by nicotine and females' relatively more influenced by nLVALon-nicotine cues accompanying drug. Results will determine the reinforcing effect of smoking stimuli that have been largely ignored in past human research and provide directions for future study of conditioned reinforcement of smoking. Findings will clarify whether, and to what extent, nicotine and non-nicotine factors differentially reinforce SA behavior in females versus males. Similarities between species would bolster the relevance of the animal findings for human smoking reinforcement and allow an animal model by which to subsequently (and more invasively) investigate mechanisms for these sex differences. Results will increase our understanding of tobacco dependence in women and suggest approaches to developing improved smoking cessation treatments for women, among other future directions. This program may also provide directions for the study of sex differences in pharmacological and non-pharmacological reinforcement from other abused drugs, with potential relevance for broadly improving substance abuse treatment in women.LVAL!r 6 Z j & 8 f  \<F`~<SCHEDULED, GRADUAL REDUCTION FOR PREGNANT SMOKERSBEHAVIORAL EFFECTS OF NEONATAL NICOTINE EXPOSURETELEPHONE COUNSELING PROGRAM FOR PREGNANT SMOKERS ENROLLED IN A MANAGED CARE ORGANIZATIONBUPROPION FOR SMOKING CESSATION IN POSTPARTUM WOMENADDRESSING NICOTINE ADDICTION IN DRUG ABUSE PATIENTSBREAST AND PROSTATE CANCER AND HORMONE-RELATED GENE VARIANTSCIGAR SMOKING AMONG YOUNG ADULTS: FORMATIVE RESEARCHLIFETIME PASSIVE SMOKING EXPOSURE AND BREAST CANCER IN THE CTSETS EXPOSURES IN THE CALIFORNIA TEACHERS STUDY COHORTASSORTMENT AND TRANSMISSION OF ALCOHOL AND TOBACCO USEFORMATIVE QUANTITATIVE RESEARCH TO PREVENT TOBACCO USE BY LGBT YOUTHSCIGAR USE PREVALENCE: SOCIAL AND MEDIA DETERMINANTSEPIDEMIOLOGY OF P16 INACTIVATION IN BARRETTS ESOPHAGUSMOTIVATIONAL INTERVENTION FOR PREGNANT WOMEN WHO CONTINUE TO SMOKE AFTER RECEIPT OF BEST PRACTICE CESSATION STUDIESPRENATAL SMOKING CESSATION RELAPSE PREVENTION TRIALMOTIVATIONAL INTERVIEWING TO PREVENT POSTPARTUM RELAPSESIGNIFICANT-OTHER SUPPORTER (SOS) PROGRAMTEEN SMOKING PREVENTION AND CESSATION VIA CD ROM PROGRAMGENETIC SUSCEPTIBILITY, DIET AND COLORECTAL ADENOMASSUSCEPTIBILITY TO MOLECULAR ALTERATION: EPITHELIAL CELLSEFFECTS OF FAMILY SMOKING HISTORY IN NEVER-SMOKERSGENETICS OF SMOKING AND NICOTINE DEPENDENCE IN FAMILIESDEPRESSION, HPA FUNCTION, AND SMOKING ABSTINENCE IN WOMENFEAR OF WEIGHT GAIN AS A BARRIER TO SMOKING CESSATION IN WOMENDEVELOPMENTAL EXPOSURE TO NICOTINEEFFECTS OF PERINATAL NICOTINE ON THE BRAINA SMOKING RESUMPTION-PREVENTION INTERVENTION FOR PREGNANT AND POSTPARTUM WOMENENVIRONMENTAL INFLUENCES ON PERINATAL LUNG DEVELOPMENTENVIRONMENTAL TOBACCO SMOKE AND NEWBORN LUNG DEVELOPMENTPHARMACOLOGIC MECHANISMS AND TREATMENT OF NICOTINE DEPENDENCEPATTERNS OF MATERNAL SMOKING DURING PREGNANCYANIMAL MODELS OF RISK FACTORS FOR RELAPSE TO SMOKINGHEALTH SYSTEM CHANGES ADDRESSING CANCER RISK FOR REPRODUCTIVE AGE WOMENLVAL,p.As the overall number of smokers in the American population decreases, many of those that continue to smoke show several risk factors that make smoking cessation more difficult. Some of these risk factors may be environmental while others may have a genetic component. We propose to study the biological basis underlying how risk factors might lead to relapse to smoking. Some major predictors of treatment failure for smoking cessation include depressive symptoms, heavy alcohol use, and female gender. This proposal will use animal models to determine how nicotine affects biological processes related to these risk factors, and will focus on how activation or inhibition of neuronal nicotinic acetylcholine receptors (nAChRs) can affect behavioral and biochemical responses related to these risk factors. These experiments will make use of pharmacological studies in normal mice as well as experiments with transgenic (knock-out) mice lacking the beta2 subunit of the nAChR which have previously been generated. Existing nicotinic agonists cannot distinguish clearly between the various nicotinic subtypes present in the brain; thus these mice will be extremely useful in identifying which receptor subtypes mediate particular pharmacological actions of nicotine. The aims of this project are to determine whether nicotine can act as an antidepressant in the learned helplessness model of depression, to determine whether nicotine withdrawal increases susceptibility to learned helplessness during acute and chronic abstinence, to identify sex- differences in learned helplessness behavior with and without nicotine treatment, to determine the concurrent and independent effects of chronic ethanol and nicotine treatment on biochemical and behavioral responses to stress, and to determine whether chronic nicotine treatment results in changes in levels of second messenger proteins involved in signaling that are associated with motivation and effect. The techniques to be used include neurochemistry, molecular genetics and behavior LVAL al paradigms. These approaches should allow an integrated view of how chronic nicotine use and nicotine cessation affect emotional behavior, and how gender differences or alcohol use can modulate that interaction. These experiments will contribute to the scientific background necessary for designing new strategies for treatment of smokers resistant to current cessation methods.LVAL,p.Studies of maternal smoking during pregnancy have traditionally conceptualized it as a relatively stable behavior, based on the assumption that few changes will occur after the transition to pregnancy. Those few studies that have examined changes over the course of the pregnancy have examined them categorically (e.g., third trimester smoking or not). In contrast, we present preliminary evidence of substantial fluctuation in maternal smoking over the course of the pregnancy, including repeated changes in overall status (i.e., smoking or not) and in categorical status (e.g., light to moderate). While these data provide evidence of individual fluctuation, group patterns of maternal smoking during pregnancy have not been empirically identified. Lack ; of empirical knowledge about patterns of maternal smoking seriously impedes scientific progress for two reasons. First, prenatal exposure to cigarettes has serious consequences, including accruing evidence of long term consequences such as increased risk of disruptive behavior disorders. Identifying the role that maternal smoking plays in the etiology of complex, multifactorial child outcomes will require more precise specification of exposure. Second, prevailing methods of prenatal cessation intervention are frequently limited to the first prenatal visit. Classification of specific patterns of smoking behavior may inform the development of targeted interventions. The proposed project is designed to classify patterns of maternal smoking during pregnancy utilizing sophisticated methods of trajectory analysis. We propose to conduct secondary data analysis of the Maternal-Infant Smoking Study of East Boston (MISSEB), a prospective population-based study with repeated measures of maternal smoking throughout the course of the pregnancy (n=873). Group patterns of maternal smoking trajectories (e.g., late pregnancy relapse, cycling between cessation and relapse) will be modeled using a semi-parametric mixed-model approach. Specific aims of the project arLVALe to: (1) characterize patterns of maternal smoking during pregnancy, using both self-reported and biochemical measures of maternal smoking and, (2) examine the explanatory power of these patterns for predicting adverse perinatal outcomes.LVAL,p.The prevalence of nicotine dependence, its accompanying health problems, and the difficulty users have in maintaining abstinence combine to make tobacco dependence a major public health challenge for society. Clinical studies were designed to provide a better understanding of the pathophysiology and mechanisms of nicotine dependence as well as to contribute to the development of putative new smoking cessation treatments. Several nicotine delivery systems have been developed to aid in smoking cessation. Two of these, nicotine polacrilex and nicotine transdermal patches, have been approved for over the counter sales for this purpose. Other nicotine delivery systems developed for smoking cessation indications, include a nicotine nasal spray and a nicotine vapor inhaler. These systems are notable for having a more rapid delivery rate, a factor that has been associated with greater potential for abuse. Therefore, although developed as aids for smoking cessation, such systems may be abused in their own right. The pharmacodynamic and pharmacokinetic effects of a new treatment for tobacco withdrawal were studied in an outpatient protocol. We found that treating cigarettes with a corn syrup-based solution significantly reduced exposure to nicotine and CO. Further, the effects were similar in men and women. Pharmacokinetic effects of nicotine were similar in men and women indicating that gender differences in patterns of smoking and tobacco withdrawal are not due to gender differences in nicotine metabolism. The effects of befloxatone, a reversible MAO-A inhibitor were evaluated for smoking cessation therapy in a multicenter clinical trial. A preliminary evaluation of cigarettes was conducted. In another study, denicotinized cigarettes were used in a rapid smoking protocol and as a control condition in an experiment to test the influence of cues on smoking behavior. In a recent evaluation of smoking among US teenagers, we have identified risk and protective factors that predispose or prevent the initiation of cLVALigarette smoking. More recently influence of cigarette smoking on co-incident marijuana smoking among US teens was evaluated.VLVAL b  H*tADDICTION Cessation PREVENTION/TREATMENT Nicotine Replacement Therapy Other Pharmacological PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking NicotineEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Industry Counter-Marketing PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Partner/Spouse MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseADDICTION Initiation Maintenance Cessation Relapse AGE Child Fetus/Prenatal RESEARCH1 Animal Studies TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology RESEARCH1 Animal Studies TOBACCO Nicotine WOMEN PregnancyADDICTION Relapse EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity TOBACCO Cigarette/Other Smoking WOMEN Postpartum MISCELLANEOUS Weight Gain/ExerciseAGE Child Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary RESEARCH1 Animal Studies TOBACCO Environmental Tobacco Smoke WOMEN PregnancyAGE Child Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary RESEARCH1 Animal Studies TOBACCO Environmental Tobacco Smoke WOMEN PregnancyADDICTION Maintenance Cessation Withdrawal PREVENTION/TREATMENT Nicotine Replacement Therapy Other Pharmacological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesLVAL,p.Environmental tobacco smoke (ETS) is defined as the combination of sidestream smoke released from the burning end of a cigarette and that portion of mainstream smoke exhaled by smokers. Health effects associated with exposure to ETS have been clearly demonstrated, but still remain somewhat controversial. In 1993 the U.S. Environmental Protection Agency declared environmental tobacco smoke (ETS) to be a human carcinogen that kills approximately 3,000 nonsmokers a year. Young children are also affected by ETS exposure with increases in the incidence of pneumonia, bronchitis, and middle ear infection. For children with asthma, ETS exposure increases the severity and frequency of asthmatic attacks. However, the cause(s) for greater and more adverse health risks associated with ETS exposure in children compared with adults is (are) unknown. We propose to study in our laboratory the effects of exposure to ETS on the maturation and function of the lung airways during fetal and early postnatal development in rats. This species is ideal to study due to its rapid fetal and postnatal growth to adulthood over a period of approximately 70 days. We have found that ETS exposure during the fetal and early postnatal periods is associated with a significant increase in lung airway narrowing, similar to that seen in asthmatic children. Also associated with these hyperactive airways is a dramatic increase in pulmonary neuroendocrine cells (PNECs), which compose a small fraction of the cells lining the lung airways. The function of PNECs is unknown; however, they are thought to be important in the pulmonary response to substances that are inhaled into the lungs and help to regulate airway tone and function. It is our hypothesis that PNECs may be directly responsible for increased airway responsiveness (such as that seen in asthma) by either releasing bronchoconstrictive mediators or by increasing the mass of airway smooth muscle through smooth muscle cell proliferation. We propose to test this hypothesis in raLVALts using environmental tobacco smoke (ETS) with exposure occurring during critical periods of lung growth and development from fetal to early adulthood in the rat. An important observation from our laboratory has been that when rats are exposed to ETS in utero (via the mother) followed by direct exposure for the first 3 weeks of life, their lungs remain markedly hyperresponsive when measured at 8 weeks of age, despite the absence of ETS exposure for the preceding 5 weeks. The discovery of this change in the lungs due to smoke exposure in newborn rats is highly analogous to the development of childhood asthma in humans. This animal model affords us the opportunity to examine whether there is a critical period during lung development when exposure to ETS leads to increased airway hyperresponsiveness and whether changes in airway PNEC number and/or function might be responsible for these observed changes.LVAL,p.Childhood exposure to a variety of indoor air contaminants including environmental tobacco smoke (ETS) produces significant risks in asthma, airway hyperresponsiveness, and other respiratory symptoms such as cough, wheeze, and mucus production. Epidemiological studies suggest that exposure to ETS during the perinatal period may have adverse effects on lung function which can persist into adulthood. It has been estimated in the United States alone 200,000 to 1,000,000 children with asthma will have their condition worsened by exposure to ETS (USEPA, 1992). However, the mechanisms leading to this process are unknown. During the past 2.5 years, we have established a state-of-the-art inhalation system to study the effects of exposure to ETS on perinatal lung development in a nonhuman primate, the Rhesus macaque monkey. Exposure to ETS has been done using aged and diluted sidestream cigarette smoke as a surrogate for ETS. Two chambers located at the California Regional Primate Research Center Inhalation Facility have been expressly designed and configured to create conditions for passive smoke exposure to monkeys during pregnancy and early postnatal development under carefully controlled conditions. These studies have demonstrated significant alterations in lung development following exposure to ETS. These effects include changes in immune effector and inflammatory cells in the lung air spaces, alterations in pulmonary and peripheral blood cytokines and neurotrophins, alterations in the innervation and epithelial composition of the trachea, and changes in the activity and distribution of pulmonary cytochrome P450 monooxygenases and glutathione-S-transferases. All these changes are evident by 2.5 months of age in infant Rhesus monkeys. These findings confirm that ETS exposure during perinatal development significantly affects the lungs of non-human primate infants. We hypothesize that these changes represent the initial steps in the genesis of an asthmatic-like condition solely due to perinatal e LVAL xposure to ETS. We also hypothesize that critical windows of exposure are present during the perinatal period which will exacerbate this effect. We propose to test these hypotheses by continuing to study this model in the Rhesus monkey to (1) determine the effects of exposure to ETS during specific periods of perinatal development in monkeys from early gestation to 6 months postnatal age using physiologic, biochemical and anatomical measures and (2) determine if cessation of exposure to ETS following 6 months postnatal age will still be associated with persistent changes in the respiratory system. Such studies should help us to better understand the potential mechanisms by which fetal and early postnatal exposure to environmental contaminants could lead to lasting, adverse consequences in children.7 i 1 ~'e_g@p@4ResearchR@PROWSSUSANOREGON STATE UNIVERSITYCORVALLISORRWJFNot Given@T@@@Not GivenNot GivenUncertain4/2005tnj_F?88,"@@Researchp@PROKHOROVALEXANDERUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNCIR01, CA081934j,p.T@@@7/19/20006/30/20057/19/2000 to 6/30/20054/2005}NC88,"@p@4Research!SUSCEPTIBILITY TO BREAST CANCERPRINDIVILLESHEILANATIONAL CANCER INSTITUTEBETHESDAMDNCI00-C-0079@Biology and CancerDiscovery 1b Evaluation 1b@2/8/2000Not Given2/8/2000 to ?4/20054,nfYY,"@k@ @Researchh@PRINDIVILLESHEILAUNIVERSITY OF COLORADO HEALTH SCIENCES CENTERAURORACONCIK07, CA075159B @L@n@h@9/1/19972/15/20019/1/1997 to 2/15/20014/2005|ME88,"@@Researchr@ POWELLCHARLESCOLUMBIA UNIVERSITY HEALTH SCIENCESNEW YORKNYNIEHSK23, ES000354,p.Biology and CancerDiscovery 1b Evaluation 1b@9/26/19998/31/20049/26/1999 to 8/31/20044/2005)!  |xnI@88,"O@ (@Researchd@ POMERLEAUOVIDEUNIVERSITY OF MICHIGANANN ARBORMINIDAR01, DA014662,p.Biology and Cancer Addiction@r@9/1/20025/31/20079/1/2002 to 5/31/20074/2005 wqmbJC88,"@G@Researchn@ POMERLEAUOVIDEUNIVERSITY OF MICHIGANANN ARBORMINCIR21, CA081645,p.@n@r@7/1/19996/30/20027/1/1999 to 6/30/20024/2005vqmbJC88,"`H@1@Researchr@ POMERLEAUOVIDEUNIVERSITY OF MICHIGANANN ARBORMINCIR01, CA042730,p.@@r0@4/19/199112/31/20014/19/1991 to 12/31/20014/2005vqmbJC88,"_@@@Research|@ POMERLEAUCYNTHIAUNIVERSITY OF MICHIGANMIRWJFNot GivenP@@ @r@6/1/19975/31/20016/1/1997 to 5/31/20014/2005ynhddLC88,"%@@ResearchD@POLANDRUSSELLCEDARS-SINAI MEDICAL CENTERLOS ANGELESCANIDAR21, DA014680J,p.Biology and Cancer AddictionP@r@9/30/20017/31/20049/30/2001 to 7/31/20044/2005 }wsfI@88,"L@p@4ResearchT@POLANDRUSSELLHARBOR-UCLA RESEARCH AND EDUCATION INSTITUTECACTRDRP6IT-0071,@Biology and CancerR@r@1997(Cycle VI)Not Given1997 to ? (Cycle VI)4/2005 {wwI@88,"@@Research@PLETSCHPAMELAUNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL SCHOOL OF NURSINGCHAPEL HILL NCRWJF51796@T@ Discovery 1c@9/1/20048/31/20069/1/2004 to 8/31/20064/2005IA88," @@@Researchl@PINKERTONKENTUNIVERSITY OF CALIFORNIA AT DAVISDAVISCANIEHSR01, ES011634@,p.Biology and CancerDiscovery 1a Evaluation 1b`@5/1/20022/28/20075/1/2002 to 2/28/20074/2005"~wslIC88," LVAL The goals of this project 1) to trace the ways in which the tobacco industry has successfully reduced the body image issue to one of thinness in a way that has been largely unchallenged by the public health community, and 2) to help identify ways in which the public health community can respond.The proposed study in animals will determine if, indeed, we can assess the detrimental effects of nicotine exposure on the brain with this technology.The goal of this pilot study is to assess procedural feasibility and refine our relapse-prevention intervention. This study will allow us to make a preliminary determination of the effect of the intervention on smoking abstinence at 3 months postpartum, will provide us with publishable findings, and will support our efforts to obtain funding from the NIH during 2005.LVAL,p.This is an R21 application to explore the development of an animal model to study the effects of parental and peripuberal exposure to nicotine. Nicotine remains an important drug of abuse worldwide. In the United States (U.S.), tobacco use is the single leading preventable cause of death. However, despite considerable negative publicity and health warnings, approximately 25 percent of the U.S. population still smoke. Aside from producing profound behavioral effects in the adult organism, nicotine also disrupts developmental processes in many species. Recent epidemiologic data suggest that fetal exposure to nicotine increases the risk for tobacco use during adolescence and adulthood, particularly in females. In addition, 75 percent of adult tobacco users report their first tobacco use occurred when they were "youngsters" (childhood or adolescence). In order to study this issue further, as well as to develop an animal model to elucidate potential underlying mechanisms, the effects of nicotine exposure during gestation on nicotine self-administration in adult male and female rat offspring will be studied. In addition, the effects of nicotine exposure during the periadolescent period on nicotine self administration in adult offspring will be ascertained. It is hypothesized that nicotine exposure in utero will increase nicotine self-administration in adult offspring. Similarly, peripuberal exposure to nicotine also will increase nicotine self-administration during adulthood. The proposed studies will characterize the relationships between exposure to nicotine during critical periods of development and the acquisition, maintenance, extinction and re-initiation phases of nicotine self-administration. The results of these experiments should provide new and important insights on the relationships between prior nicotine exposure and nicotine-seeking behavior. In addition, since nicotine is considered as a "gateway" drug for the subsequent use of alcohol and other illicit drugs, the results of the pLVALroposed studies will lay the groundwork to further understand the factors which might increase vulnerability to drug addictions in general, and to nicotine abuse, in particular.LVAL,p.There is evidence that smoking is becoming concentrated in populations who because of various risk factors, are more likely to initiate smoking or have greater difficulty quitting. One of the best documented of these cofactors is depression. Numerous observers have noted clear manifestations of depression and dysphoria in women with a history of Major Depressive Disorder (Hx+ MDD) when they attempt to quit smoking. The long-term objective is to characterize and possibly modify response patterns that constitute a diathesis for smoking. Based on the literature and our own pilot data, we postulate that the reinforcing value of nicotine self-administration is enhanced in Hx+ MDD by the drug's affect- normalizing properties and its ability to protect against the hypothalamic-pituitary-adrenal (HPA) axis dysregulation that often characterizes episodes of depression, as indicated by elevated cortisol and ACTH levels following dexamethasone administration, an effect that is most pronounced in postmenopausal women. The specific aims are to 1) trace the time course and severity of depressive symptomatology in Hx+ MDD and Hx- MDD women smokers across different age categories when they abstain from smoking; 2) determine susceptibility to induction of depressed mood in Hx+ MDD and Hx- MDD women smokers; 3) elucidate key biobehavioral mechanisms underlying the relationship between dysphoria and use of nicotine; and 4) determine the extent to which pharmacological manipulations can relieve abstinence- induced depression/dysphoria and concomitant HPA axis dysregulation. The research design employs both within-subject and between-group comparisons in two interlocking studies, involving within-subject and between-group comparisons of women smokers and carefully assessing both psychological distress and neuroendocrinological dysfunction. STUDY I will assess the effects of nicotine vs. placebo patch during a week of smoking abstinence on cognitive and neuroendocrinological variables. STUDY II will investigate the L LVAL\ ability of the antidepressant fluoxetine vs. placebo to ameliorate depression/dysphoria and restore HPA-axis function during smoking abstinence. HEALTH IMPLICATIONS: Depression is a major women's public health problem in its own right, taking an enormous toll in terms of lost productivity and diminished quality of life. To the extent that it increases the likelihood of initiation and maintenance smoking, the health consequences are magnified---as underscored by the fact that lung cancer has now surpassed breast cancer as the leading cause of cancer death in women. A better understanding of the reinforcing effects of smoking, and the mechanisms underlying these effects in depression-prone smokers, may lead to the development of rational prevention and cessation strategies tailored to the special needs of this large at-risk population.LVAL,p.The long-range objective of the proposed project is to conduct genetic research designed to generate useful information about individual differences in susceptibility to smoking and nicotine dependence. The specific aims are (1) to crease a phenotype and genotype registry to support genetic research on smoking; (2) to identify key phenotypic characteristics for smoking by taking into account the contribution of both susceptibility to nicotine dependence and other risk factors for smoking in smoking probands and first order relatives; and (3) to re- examine recent claims of genetic association between polymorphic variations in certain candidate genes and smoking behavior. The proposed study will involve 150 probands (75 males and 75 females) who are current smokers, same-sex full siblings who are nicotine-exposed never smokers and two living biological parents willing to answer questions about smoking and risk factors and to provide blood samples for DNA analysis (total N=600) Phenotypic data gathered will include a battery of instruments assessing co-factors for smoking (e.g., depression, ADHD, anxiety); personality measures (e.g., novelty-seeking); and variables believed to be associated with likelihood of smoking initiation (e.g., experience upon early experimentation with smoking); in addition, measures of nicotine dependence will be collected in all smokers and ex- smokers. Genotypic information will consist of candidate-gene markers for smoking risk factors, DRD2, DRD4, SLC6A3 [DAT1], and SLC6A4 [5-HTT] (polymorphisms associated with increased risk of depression, attention deficit, novelty seeking, anxiety), and for nicotine dependence, nAChRbeta2 (associated with nicotine reinforcement). Cigarette smoking is associated with over 450,000 premature deaths in the United States each year--25% of all deaths-- a figure that includes more than 100,000 deaths per year from bronchogenic carcinoma. The pathophysiological consequences of the habit account for nearly 60% of all direct health costs, with exp LVAL enditures estimated to exceed one billion dollars a day. Increased knowledge about the genetics of smoking will be needed in substantial improvements in the management of cigarette smoking and consequent reduction in cancer morbidity and mortality are to be achieved.LVAL& 4 X XADDICTION Cessation ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Postpartum Partner/SpouseAGE Child EDUCATION LEVEL High School LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer LOCATION National PREVENTION/TREATMENT Interview/Focus Group Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO NicotineDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Adult DISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Other Disease/Biology PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Maintenance DISEASE/BIOLOGY Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesLVAL,p.Individual differences in initial sensitivity to nicotine may play a significant role in determining whether or not a person becomes a smoker. In people with high susceptibility, the initial response to nicotine seems to include not only aversive effects but also reinforcing consequences such as pleasurable effects and temporary improvements in affect or performance, and further exposure leads to rapid development of tolerance to aversive effects and sensitization of positive effects, resulting in nicotine dependence. The concentration of people with high susceptibility among those who continue to smoke may explain the difficulty encountered in reducing the prevalence of smoking much below 25 percent over the past decade. To manage this important public health problem more effectively, there is a pressing need to identify the individual behavioral and biological characteristics that set the stage for nicotine reinforcement as well as those factors that interfere with it. The proposed research involves comparisons of sensitivity to nicotine in people who have a positive or a negative family smoking history; never smokers have been chosen for study, rather than current or former smokers, in order to avoid the influence of extensive nicotine exposure on tolerance and sensitization. The approach is comparable to that which has been employed to study the children of alcoholics and other drug abusers. Over a five-year period, the responses of men and women with positive or negative family histories will be investigated, employing both within-subject and between group comparisons. The reinforcement potential of nicotine will be explored by determining reactivity to nicotine administration via nasal spray; subjective, physiological, cognitive, and neuroendocrine response systems will be examined to provide a multi-dimensional assessment. Determination of differences in initial reactivity to nicotine along with identification of baseline characteristics that may contribute to nicotine reinforcement, such as pe LVAL rsonality variables, psychiatric cofactors, and environmental factors, should increase the understanding of the conditions that promote or protect against smoking behavior, providing the basis for more effective prevention programs and more efficient treatment interventions.LVAL,p.The objectives for this K23 Mentored Patient Oriented Research Award are to acquire conceptual and technical skills in cancer genetics, molecular epidemiology, and patient oriented research and subsequently to apply these skills to improve the survival of patients with lung cancer or at risk for developing lung cancer. These goals will be achieved through a comprehensive program that includes formal education, patient oriented research and clinical activities. The educational program will include courses on molecular genetics, clinical epidemiology and clinical research. Regular participation in national meetings and symposia related to cancer and molecular genetics will be an essential part of the educational program. The clinical activities will be focused on lung cancer. The long-term objective for the patient oriented research project is to identify the environmental and genetic factors that are responsible for the increased incidence of lung cancer in women. Recent statistical trends and case-control studies suggest that women are more susceptible to lung cancer than men with similar tobacco exposure. The goal for this research project is to determine if biomarkers of DNA exposure to carcinogens (DNA adducts) and biomarkers of effect (loss of heterozygosity and p53 mutations) in epithelial cells are involved in lung cancer susceptibility in women. The specific aims of the project are to determine if the extent of epithelial cell DNA adducts, LOH, and p53 mutations in women is different than in men with similar tobacco exposure and to determine the effect of gender, genetic polymorphisms, and diet on the relationships among these biomarkers of exposure and biomarkers of effect. This study will evaluate 60 female and 60 male middle aged smokers. Biomarkers will be evaluated in epithelial cells from the lung, bladder and oropharynx from all individuals. Polymorphisms of CYP1A1 and GSTM1 and dietary intake of vitamins and carotenoids will be characterized. These experiments will provide important infLVALormation on how genetic and environmental factors are involved in lung cancer susceptibility in women. The definition of these mechanisms may allow the prospective identification of individuals at increased risk for developing lung carcinoma.LVAL " ~ . V   hbJJDiscovery 1c Discovery 3 Development 2 Development 3 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1c Development 1 Delivery 1Discovery 1c Discovery 2a Discovery 2b Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Partnerships 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1c Development 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 1c Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Development 2 Delivery 1 Evaluation 1aDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1bDiscovery 1c Discovery 2a Discovery 2b Development 1 Development 3 Delivery 1Discovery 1a Discovery 1c Discovery 3 Development 2 Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Development 4 Development 5 Evaluation 1a Evaluation 1cDiscovery 1a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 3 Development 5 Evaluation 1a Evaluation 1cDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 1 Development 3 Delivery 1Discovery 1a Discovery 1c Discovery 2a Development 1 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Discovery 2b Discovery 3 Development 3 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1b Discovery 3 Evaluation 1a Evaluation 1bLVALThe risk of developing colonic neoplasia may be determined by the combination of inherited susceptibility and environmental factors. This research proposal is designed to examine the main effects and interactions between genetic susceptibility factors, dietary factors, and nutritional biochemical measures on the risk of colorectal adenomas. The ultimate goal is to define genetic susceptibility factors and nutritional biochemical markers that can be used to identify a population at high risk for developing colorectal neoplasia in which to focus preventive interventions. The study will be conducted using data on risk factors for colorectal adenomas and stored serum and DNA collected at baseline from participants in the VA Cooperative Study #380. Risk factor data will be obtained from a questionnaire completed by participants at baseline containing information on family history, physical activity, obesity, tobacco, alcohol, NSAIDs, dietary intake of fat, fiber, fruits and vegetables, and calcium. DNA will be harvested and analyzed for potential genetic susceptibility factors (apolipoprotein E, NAD(P)H:quinone oxidoreductase, and glutathione-S-transferase mu genotypes). Dietary intake data from a good frequency questionnaire will be analyzed. Nutritional biochemical measures (ferritin, selenium, and cholesterol) will be analyzed from the stored blood serum. The main and interacting effects of these measures on the risk of colorectal adenomas will be analyzed in 600 cases of adenomas and 300 controls frequency matched on age, gender, and ethnicity.,LVAL<This study will explore whether different forms, or variants, of genes are related to a person's risk of developing breast cancer. The genes that are looked at have no clinical significance today, and thus will not impact your personal healthcare at this time. However, these results may help researchers better understand why some people develop breast cancer and others do not. The study will try to determine: if people with breast cancer have different gene variants from people without the disease; if these genetic differences influence a person's susceptibility to breast cancer when they are exposed to certain environmental substances, such as nicotine and estrogen; and if breast cancer that occurs in families is related to a grouping of these variants. The study will also look for certain proteins, cells, or other substances in fluid aspirated (by the use of gentle suction; no needles) from the nipple that might represent a pattern, or "fingerprint," indicating increased risk for breast cancer. Study participants will complete questionnaires on cancer risk factors, diet, and family history. A small blood sample (3 tablespoons) will be drawn for study of genetic differences between people with breast cancer and people who are cancer-free. Nipple aspirations, a noninvasive method to obtain fluid from a women's breast, will be attempted 4 to 6 times, over a 4 - 6 week period. For this procedure, the subject places a warm moist towel over the breasts for about 20 minutes. The breasts are then cleansed with a rubbing alcohol pad. The subject compresses the breast with both hands and a small plastic cup is inverted over the breast. Suction is applied to a small syringe (no needles) attached to the cup for about 15 seconds. The procedure may be repeated up to 5 times on each breast. Any drops of fluid obtained from the nipple will be collected in a glass tube.LVAL,p.recent studies indicated that the existing smoking prevention cessation strategies have failed to produce population reductions in teen smoking prevalence. This is despite significant progress in intervention development and increasing financial investments in anti-smoking activities. The investigators believe several possible explanations merit consideration for this paradox. First, effective smoking prevention programs have not been widely disseminated. Second, when adopted, teachers often fail to adhere to program guidelines. Third, teens who smoke are reluctant to identify themselves to seek cessation assistance. Fourth, smoking prevention and cessation programs often fail to account for salient individual differences among students. Finally, most existing smoking prevention and cessation programs do not utilize modern communication technologies and do not meet the demands of today's adolescents. The goal of the proposed project is to design, implement, and evaluate an interactive CD-ROM curriculum aimed at adolescent smoking prevention and cessation intervention. By interactive, we mean assessing each student individually and channeling him or her into the most appropriate intervention. The software will assess student smoking status, stages of change for smoking acquisition and cessation, level of addiction, and symptoms of depression. In this manner, recruitment of smokers is facilitated because both smoking and nonsmoking students will be asked to participate in the program and the intervention they receive will be customized to meet their individual needs. The intervention will also be tailored to gender and ethnicity. By utilizing CD-ROM the investigators hope to facilitate subjects' adherence to intervention protocols and subsequent program dissemination. The investigators hypothesize the intervention will result in: a) lower onset of smoking; b) greater smoking cessation outcomes; and c) impact on variables that mediate the process of change compared to an alternative treatment control grojLVALzup. The study design is an 18-month, group-randomized, controlled trial. Study participants will include students 14-16 years of age (10" graders at baseline) from 16 Houston area high schools.^LVALhrThis project is designed to study the relationship between breast cancer risk and exposure to passive smoke in the California Teachers Sudy (CTS) cohort.Purpose: To develop and test a brief, multi-component, motivational intervention for delivery by ultrasound technicians to smokers presenting for their routine mid-pregnancy ultrasound. Research Design: The proposed intervention will be tested using a historical usual care control group design. The control group will be impaneled in the first 7 months of recruitment. The intervention group will be impaneled in the 7 months following implementation of the cessation program. Data from baseline and postpartum interviews will be used to adjust for confounding influences and to identify the predictors of cessation. Study Population: 284 adult pregnant smokers will be recruited from the diverse membership of a large multi-specialty group model HMO. Intervention (if appropriate): The intervention consists of 10 to 15 minutes of counseling and written materials tailored to smokers stage of change and characteristics that put them at risk for continued smoking. Additionally, women will receive smoking-related health messages when presented with an ultrasound scan of their developing fetus. The intervention will be structured by the principles and techniques of motivational interviewing and provide cognitive/behavioral strategies for cessation. It will include previously identified elements of effective brief interventions. Outcome Measures (If cessation or reduction, how defined): The primary dependent variable is biochemically confirmed abstinence in the 8th month of pregnancy.This program was designed to reduce smoking among low-income, highly-addicted, pregnant and postpartum women who participate in Oregon's Special Supplemental Food Program for Women, Infants, and Children.LVAL,p.The goal of this study is to develop and test an innovative relapse prevention program for women who stop smoking during pregnancy. Pregnancy offers women one of the best opportunities to stop smoking. Nearly half of the women who were smoking prior to pregnancy take advantage of this time of change and quit smoking, mainly to protect the health of their unborn child. Unfortunately, rates of relapse after delivery are high with as many as 70% of the quitters returning to smoking within 6 months of delivery. Cigarette smoking is associated with many serious illnesses, especially those related to heart and lung disease. Although smoking carries additional risks for women of reproductive age, more than 25% of US women between the ages of 18 and 44 continue to smoke. Postpartum relapse re-exposes women to the health dangers of smoking. Further harm is done by exposing infants and children to passive smoke. Numerous studies have documented increased rates of respiratory infections, including pneumonia, bronchitis, and ear infections. More recently, passive smoke has been implicated in Sudden Infant Death Syndrome. To develop an effective program we will adapt the principles and techniques of motivational interviewing to the context of postpartum relapse. Motivational interviewing is a supportive, non-judgmental counseling style that appears to be especially useful with behaviors that are difficult to change. It helps clients weigh the benefits and costs of their behaviors. The counseling will be delivered over the telephone by trained health educators in 4 to 6 brief calls. The literature identifies the influence of powerful barriers to maintenance such as being around other smokers, having a partner who smokes, and lack of confidence in the ability to stay off cigarettes. Counselors will help women identify their personal threats to maintenance, including lack of motivation to stay off cigarettes, and will assist women in developing effective coping strategies. The content of the program wi LVAL ll be developed from telephone interviews and focus groups conducted among white, black, and Latino women who quit smoking during pregnancy. Subjects will be recruited from the diverse population of Southern California Kaiser Permanente. The effectiveness of the motivational interviewing program will be measured by comparing the bio-chemically confirmed 6-month postpartum abstinence rates among women who received the counseling program and women who did not. An effective postpartum relapse prevention program would make a significant contribution to the health of young women, their newborn infants, and other family members.LVAL 4ECONOMICS Socio-Economic Status LOCATION National MARKETING Media-Websites/pamphlets/radio PSYCHOLOGICAL Social Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Health Care Provider EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Relapse COMMUNITY Health Care Provider EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Relapse EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Biochemical Assessments PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian Hispanic TOBACCO Cigarette/Other Smoking WOMEN Pregnancy  c ? 8 G!@@Researchf@RIGOTTINANCY GENERAL HOSPITAL CORP.--MASSACHUSETTS GENERAL HOSPITALBOSTONMARWJF51794Z@T@Discovery 2a Development 2@9/1/20048/31/20069/1/2004 to 8/31/20064/2005IA88," @@Researchh@RICHTERKIMBERUNIVERSITY OF KANSAS MEDICAL CENTERKANSAS CITYKSNIDAK01, DA000450,p.j@@ <@2/5/20001/31/20052/5/2000 to 1/31/20054/2005{nIA88,"w@ (@Researchx@RIBOLIELIOWORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY RESEARCH ON CANCERNot GivenNot GivenNCIU01, CA098216f,p.t@@ @7/14/20035/31/20077/14/2003 to 5/31/20074/2005F@88,"c@@Researchj@RHODESFENWICKCALIFORNIA STATE UNIVERSITY LONG BEACH FOUNDATIONLONG BEACHCACTRDRP6RT-0426,p.L@@ @7/1/19976/30/20017/1/1997 to 6/30/20014/2005|I@88,"`@p@4Research|@REYNOLDSPEGGYPUBLIC HEALTH INSTITUTEOAKLANDCACTRDRP13RT-00184@L@Discovery 1b Evaluation 1b0@2004(Cycle XIII)Not Given1/1/2004 to ? (Cycle XIII)4/2005wokbIB88," @G@Researchj@REYNOLDSPEGGYPUBLIC HEALTH INSTITUTEOAKLANDCACTRDRP7RT-0142,p.L@T@ @7/1/19986/30/20027/1/1998 to 6/30/20024/2005wokbIB88," @i@Researchl@REYNOLDSCHANDRAUNIVERSITY OF CALIFORNIA AT RIVERSIDERIVERSIDECANIAAAR01, AA011986,p.@@@4/1/20003/31/20034/1/2000 to 3/31/20034/2005}rKB88,"`@B@Research@REMAFEDIGARYUNIVERSITY OF MINNESOTAMINNEAPOLISMNMPAATRC-2004-0020j,p.L@@@200420072004 to 20074/2005yrnaHB88,"c@@Researchh@REIMANNJOAQUINSAN DIEGO STATE UNIVERSITY FOUNDATIONSAN DIEGOCACTRDRP6KT-0117!,p.L@@:@7/1/19976/30/20017/1/1997 to 6/30/20014/2005|qJA88,"@G@Researchl@REIDBRIANFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWANCIR01, CA078828$,p.t@P@D@7/6/19986/30/20027/6/1998 to 6/30/20024/2005zvmE>88,"@@Research@QUINNVIRGINIAKAISER FOUNDATION RESEARCH INSTITUTEOAKLANDCARWJF40539 @T@Development 3 Delivery 1@10/1/20009/30/200410/1/2000 to 9/30/20044/2005 |xoI?88," @`@Researchf@QUINNVIRGINIAKAISER FOUNDATION RESEARCH INSTITUTEOAKLANDCANICHDR01, HD036719H,p.T@@@5/1/19994/30/20045/1/1999 to 4/30/20044/2005|xoI?88,"c@@Researchn@QUINNVIRGINIAKAISER PERMANENTE SOUTHERN CALIFORNIAOAKLANDCACTRDRP6KT-0206,p.T@@F@7/1/19976/30/20017/1/1997 to 6/30/20014/2005}ypI?88,"LVAL,p.Smoking during pregnancy exerts an independent, adverse effect upon numerous reproductive outcomes, and thus the reduction in the prevalence of prenatal smoking has been a national priority for the past decade. Approximately a quarter of US women smoke prior to becoming pregnant, with a third of these smokers quitting prior to the start of prenatal care - and are referred to as Spontaneous Quitters (SQs). Several studies have documented that at least 25 percent of SQs relapse prior to delivery, and therefore the health of the mother and fetus is once again jeopardized due to tobacco exposure during pregnancy. To date, randomized trials testing various interventions have failed to reduce prenatal relapse with this group. This study proposes to develop a telephone counseling relapse prevention program based on the principles of motivational interviewing to address the needs of this unique group of recent quitters. The theoretically-grounded program will be developed during a formative assessment period consisting of in-depth interviews and focus groups with a representative sample of SQs. The effectiveness of the intervention will be tested under conditions of typical clinical practice among a diverse population of prenatal patients who are members of a large HMO (Southern California Kaiser- Permanente). A total of 480 SQs will be randomly assigned to either a) usual care -- consisting of provider advice which may be offered during prenatal visits and a self-help smoking cessation/maintenance booklet; or b) usual care + the experimental telephone-based counseling intervention. The principal dependent variable will be biochemically confirmed maintenance of cessation for the duration of pregnancy. If effective, the proposed intervention offers the opportunity to decrease the prevalence of prenatal smoking among the approximate 1 million US women who annually initiate prenatal care as prepregnancy smokers. Finally, as more than 75 percent of the women who stop smoking during pregnancy are SQs andLVAL given the high rate of postpartum relapse, learning about successful maintenance during pregnancy may aid intervention efforts to prevent the return to smoking after delivery.LVAL,p.Esophageal adenocarcinoma is one of the most rapidly increasing cancers in the United States. Most patients with this cancer present when the tumor is advanced; over 90% will die of their disease. Persons with metaplastic Barrett's esophagus are at high risk of developing this cancer, estimated at 30 - 40 times that of the general population. The neoplastic progression that can be observed in serial esophageal biopsies of persons with Barrett's esophagus involves the development of genetic instability and the accumulation of multiple genetic and cell cycle abnormalities. Inactivation of the p16 tumor suppressor gene occurs relatively early during progression and is detected in approximately 85 percent of patients who develop aneuploidy and cancer. The mechanisms of p16 inactivation involves 9p21 LOH of one allele and either mutation or promoter hypermethylation of the other p16 allele. The Specific Aims of this project are to: 1) determine the prevalence of p16 abnormalities, including p16 mutation, p16 promoter hypermethylation and 9p21 LOH at each stage of histologic progression in patients with Barrett's esophagus; and 2) investigate the association of each abnormality with specific environmental exposures or host factors that are believed to increase risk for esophageal adenocarcinoma. These will include age, gender, tobacco use, alcohol use, body mass index, diet, serum micronutrient levels and use of various medications. An existing cohort of patients who represent all stages of disease and for whom interviews, anthropometry, serum, and biopsies are available will be used for these investigations. DNA content and Ki67/DNA content multiparameter flow cytometry will be used to analyze and to purify cell populations from endoscopic biopsies. The flow-purified samples will then be used to detect p16 mutations, p16 promoter hypermethylation and 9p21 LOH. LOH will be determined by automated genotyping using fluoresce-labeled polymorphic markers within and flanking the p16 locus on 9p21. Mutations in p LVAL 16 will be detected using PCR template and fluorescent automated sequencing. Promoter hypermethylation will be assayed using methylation-specific PCR and whole genome amplification according to our published protocols. Statistical approaches will include contingency table analysis, logistic regression and generalized linear mixed models. These results will lead to a better understanding of the relationships between etiologic factors and molecular mechanisms for inactivating a human tumor suppressor gene in a highly fatal cancer in vivo.LVAL,p.Although it is well appreciated that nicotine is a very addictive substance, the exact reasons for its addictive nature remain elusive. Evidence suggests that stress in general, and stress hormones such as corticosterone and cortisol in particular, can modulate nicotine intake. However, the relationship between stress and nicotine use is not well defined. For the first two series of studies, we propose to assess the relationship among stress, stress hormones (corticosterone in particular) and nicotine self-administration using an animal model. This modeling will allow us to determine how easy or difficult it is to start or stop the self-administration nicotine. At the same time, we will study the relationship between blood levels of corticosterone and self-administration of nicotine, as well as determine the corticosterone response to the intake of nicotine and to nicotine withdrawal. The next series of studies will determine the effects of prior stressors on nicotine self-administration. We will measure the levels of corticosterone and the corticosterone response to nicotine and determine if these are related to the degree or pattern of nicotine self-administration. Finally, studies suggest that smoking is increased in humans exposed to stressful experiences early in life (Anda et al 1999). Accordingly, we will determine if neonatal exposure can produce permanent changes in the regulation of the corticosterone secretion that may also effect adult nicotine self-administration. Taken together, the results of the proposed studies should help us to understand if, how, and to what extent, prior stress, occurring either during adulthood or during early development, effects nicotine self-administration. The results should help us to devise new strategies to prevent and treat nicotine abuse. The proposed study is designed to provide a picture showing which Southern Californians in San Diego County tend to smoke cigars, as well as the social status, beliefs, and actions commonly connected to cigar useLVAL. In addition to learning what percentage of the population uses cigars, the study will identify personal characteristics and attitudes often associated with cigar smokers by the media and by people in general. Finally, the research will determine the amount of passive smoke that persons are exposed to at social events held for cigar smokers. A decline in cigar consumption, noted between 1965 and 1991, has reversed in more recent years. Popular writers report that cigar smoking is now increasingly valued as a sign of affluence and social distinction, especially among highly educated young adults. A growing number of media images, social events, magazines, internet sites, and clubs focus specifically on cigars. Contrary to the common belief that cigar smoke is relatively risk-free because it is not generally inhaled, medical research has found evidence linking it with increased risk for illness including various types of cancer. Since cigar users inhale their own passive smoke, assumptions that health risks are essentially eliminated by not inhaling are probably not accurate. Little current research has formally examined who is most inclined to smoke cigars. In addition, there is little scientific information on the public perceptions, images, and beliefs connected with cigar use. We thus propose a study investigating how popular cigar use has become, and if there are differences in this popularity between men and women from various ethnic, age, and socio-economic groups. The research will also examine how frequently cigarette smokers tend to switch to cigars and the degree to which factors such as having relatives and friends who smoke cigars, positive and negative portrayals of cigar smoking in the media, assumptions about cigar smokers typical characteristics and social status, and beliefs that smoking is unhealthy, influence cigar use. In addition, the proposed study will directly assess the type of media images associates cigar smoking, including how frequently such images are linked to specifLVALic gender, ethnic, and socio-economic groups. Finally, the amount of passive smoke which tends to exist in social situations focusing on cigars will be determined. LVAL,p.MPAAT Priority: Reduce tobacco use among LGBT communities. Rationale: The paucity of information regarding patterns, risk factors, mediators, and moderators of tobacco use among LGBT youths impedes prevention programs. Aim: To complete a community identification process with formative quantitative research applicable to preventative interventions. Design: Specialized cohort study involving LGBT subjects and a comparison group of non-LGBT youths selected from the same social context. Research Questions: 1. Compared to non-LGBT youths, are LGBT youths more likely to initiate smoking at younger ages, smoke cigarettes daily in the last 30 days, and smoke more cigarettes per day? 2. a) Are lifetime, monthly, and daily smoking by LGBT youths associated with chronological milestones in LGBT identity acquisition, frequency of attending popular LGBT venues in last 5 months, perceived norms of peer smoking, sexual orientation-related stress, and substance abuse severity, when controlling demographic variables? 2. b) When controlling the relevant explanatory variables (see 2.a), does sexual orientation account for additional variance in lifetime, monthly, and daily smoking between LGBT and non-LGBT youths? 3. To what extent do LGBT participants feel able and motivated to avoid smoking cigarettes? Participants: Approximately 200 LGBT subjects and a comparison group of 200 LGBT youths. Eligible participants will be any 13-to-24 year old persons who reside in the Twin Cities. The exclusionary criteria are prior participation in the study, and age or residence outside the parameters of the study. Methods: A time-space sampling method will be used to randomly select participants from popular venues in the Twin Cities metropolitan area frequented by LGBT and non-LGBT males and females. Participants will complete brief semi-structured street interviews regarding demographic characteristics; venue attendance; sexual orientation rating; sexual milestones; sexual orientation-related stress; substance use severity; tobaccoj LVALz -related attitudes, beliefs, and behaviors; and motivation and self-efficacy for cessation. Analysis: After double entry of data SAS/STAT Version 9.0 procedures that statistically adjust for sample design characteristics will be used to examine univariate and bivariate distributions and strength of relationships among variables, and to perform linear and logistic regression analyses. Collaboration and Dissemination: The research will be conducted in full partnership between the University of Minnesota Youth and AIDS Projects, YouthLink, Minneapolis Public Schools' Out4Good Program, and St. Paul Public Schools Out For Equity Program. The data will be used to enhance our existing tobacco prevention services; and it will be disseminated nationally through scientific presentations and publications, public media, and websites.hLVAL  XAGE Young Adult EDUCATION LEVEL College and Above EPIDEMIOLOGY/SURVEILLANCE Large (>=100) MARKETING Industry Media-Websites/pamphlets/radio PSYCHOLOGICAL Social Factors STUDY POPULATION African American TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesAGE Child Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Environmental Tobacco Smoke WOMEN Pregnancy Menopause HormonesEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies TOBACCO Environmental Tobacco Smoke WOMEN Menopause MISCELLANEOUS Weight Gain/ExerciseDISEASE/BIOLOGY Mechanisms Other Disease/Biology ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance Cessation AGE Child Young Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies STUDY POPULATION Lesbian Gay Bisexual Transgender TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesLVAL,p.Studies of spouse similarity for alcohol and tobacco consumption find correlations that are moderate to strong in magnitude. The assessment of assortative mating for alcohol- and tobacco-related behaviors is critical for obtaining unbiased estimates of genetic and shared environmental effects in quantitative behavioral genetic studies; however, assortment effects have rarely been taken into account. Furthermore, many earlier studies of assortment lacked comprehensive testing of alternative explanations of spouse similarity to that of phenotypic assortment, including social homogamy. We propose to use a genetically informative twin-kinship design, including monozygotic and dizygotic twins, their spouses, and offspring, to resolve the mechanisms of assortment as well as models of parent-offspring transmission. The study will focus on data collected in 1977 from a population-based sample of 138 Swedish twin pairs and their spouses born between 1911 and 1935. The twin-kinship sample will be augmented with 745 same-sex twin pairs from the Swedish Adoption/Twin Study of Aging (SATSA). Assessments of tobacco and alcohol use were made by self-report questionnaire surveys. Information on other substance use (e.g., caffeine, tranquilizers) and socioeconomic indicators was also gathered. Behavioral genetic analyses will be utilized to address the following six questions: (1) What mechanisms of assortment account for spouse similarity for alcohol and smoking consumption? (2) What is the impact of assortment on estimates of genetic and environmental contributions to individual differences on alcohol and tobacco consumption under various models? (3) Is the assortment for alcohol and tobacco consumption primary or does it occur secondarily to assortment for education or other socioeconomic factors? (4) Is there a more complex phenotype of substance use on which assortment takes place? (5) What model of parent-offspring transmission accounts for familial similarity given an appropriate model of assortment? (6) To wha0LVAL@t relative extent do common genetic and environmental influences account for the bivariate relationship between alcohol and tobacco consumption? This study will also investigate potential generation and gender differences.LVAL,p.Despite strong evidence that exposure to environmental tobacco smoke (ETS) is a hazard to human health, there remain substantial and important gaps in our knowledge. Relatively little is known about the current and historical prevalence of exposure to ETS. Few studies have investigated characteristics that may be associated with ETS exposures. Furthermore, while the relationship of ETS to the development of lung cancer has been extensively researched, comparatively few studies have evaluated the contribution of ETS to the development of other diseases of concern. The specific aims of this research are designed to directly address these limitations in our knowledge. Our aims are: (1) to characterize patterns of historical ETS exposures in the home, in the workplace and in other settings for various time periods and birth cohorts; (2) to investigate the relationship of ETS exposures to other risk factors that may be important to health outcomes of concern; and (3) to conduct a preliminary short-term assessment of the association between reported historical ETS exposures and targeted health outcomes of interest, including cancer incidence and acute asthma episodes. The study proposed here is an analysis of data collected as part of the California Teachers Study (CTS) from a cohort of 133,000 female California professional school employees who have completed detailed questionnaires concerning personal and family medical history, diet, physical exercise, environmental exposures, reproductive history, alcohol consumption, and active and passive smoking. The data collected from the CTS surveys are unique among large studies, such as this, in the availability of extensive lifetime ETS exposure -- encompassing exposures in the home, workplace and in other settings during childhood and each subsequent decade of life. Information on the quantity and quality of exposure in each of these settings and time periods was collected as well. Health outcome data will be obtained from linkage to California's statewide c$LVAL4ancer registry and hospital discharge data sets. Information on environmental risk factors will be obtained both by questionnaire and by linkage of the cohort to census and various statewide environmental databases. Many studies of ETS-related health risks have relied only on exposure from a smoking spouse and have been limited in their ability to adjust for other risk factors of interest. Additionally, most research on the influence of ETS on the risk of cancer has focused on exposures in the home as adults; very little is known about cancer risk associated with childhood ETS exposures. In contrast, we will have information on ETS exposures in the home, workplace and in social settings throughout each person's lifetime. Thus, we will be able to examine risks associated with exposures at different ages and in all types of settings. Through the use of data collected by the CTS questionnaires, we also will be able to adjust our estimates of risk associated with ETS exposures to account for a host of other factors that may play a role in the development of cancer or exacerbation of asthma. Our research objectives are directly related to the ultimate goal of reducing the use of tobacco. Understanding the patterns and correlates of active and passive smoking is critical in planning targeted public health interventions. Establishment of baseline exposure profiles is necessary to evaluate future initiatives to reduce ETS exposures. Furthermore, a greater understanding of diseases related to ETS exposures could lead to more health protective legislation regulating exposures and greater public awareness of the consequences of tobacco use - both effectively working to reduce exposures to ETS and ultimately the prevalence of active smoking. LVAL,p.Cigar use in California nearly doubled during the 1990s, and the most dramatic increase occurred within the 18- to 24year old population (Gilpin & Pierce, 1999). This project investigated the nature and scope of the rise in popularity of cigar smoking among young adults, and sought to identify factors influencing their cigar-smoking behavior. Accordingly, the project had 3 specific aims. First, an initial pilot study sought to identify how beliefs about cigars, as well as perceived obstacles and facilitators to smoking, influence cigar-smoking behaviors among young adults. Informed by the qualitative data obtained from the pilot study, a second, longitudinal study was designed to achieve the second and third aims. Due to the increased promotional activities for cigars that coincided with the upsurge in their use (U.S. Department of Health and Human Services, 1998), the project's second aim was to analyze the ways in which beliefs about smoking and exposure to tobacco-related media are related to cigar-smoking behavior in young adults. Finally, the project sought to examine how positive and negative portrayals of smoking in the media, in addition to beliefs, attitudes, and social norms, are related to cigar smoking behaviors in this population. The longitudinal study extends the results from the pilot study by documenting cigar use in a non-cigar-smoking sample of approximately 300 first- and second-year college students over the course of two years. Results suggest differences in the frequency of occasional and regular cigar use by gender, race/ethnicity, and cigarette-smoking history. First, men were more likely than women to report having tried cigars. African-Americans were the most likely to become regular cigar smokers; ironically, they were less likely than their peers to report regular cigarette use. Regular cigarette smokers were more likely than non-smokers to have experimented with cigars during the two years of the study. In addition, occasional and regular cigar smokers differed in termsLVAL( of their beliefs regarding cigars. Beliefs regarding the pleasure enhancement aspect of cigars were most strongly associated with regular cigar smoking, while beliefs regarding the social benefits were most strongly associated with occasional cigar smoking. In addition, participants who had smoked a cigar in the previous 12 months were more likely to report exposure to cigar-related media in movies, magazines, and posters. Moreover, a significantly greater proportion of those who reported that they were presented with a positive image of cigars in these three media types were more likely to report having smoked a cigar in the previous 12 months. The results of this project have several implications for intervention efforts aimed at curbing the cigar use of young adults. The present findings corroborate the results of previous studies (e.g., Centers for Disease Control and Prevention, 1997, 2000) that African-Americans appear to be the most vulnerable population for regular cigar use, and particular emphasis should be placed on this group for preventive efforts focused on encouraging the cessation of regular cigar use. Also, since there was a positive correlation between experimentation with cigars and positive images of cigars in the media, media emphasizing the possible negative social consequences of cigar smoking, such as others not wanting to be around cigar smokers because of the smell, and the unsightly staining of teeth and hands, may help to discourage young adults from experimenting with cigars. In addition, the strong association between cigar experimentation and regular cigarette smoking highlights the importance of efforts aimed at preventing tobacco use in general within this population. Finally, as suggested by the U.S. Department of Health and Human Services, (1998), efforts aimed at encouraging cigar makers to adhere to the same marketing code utilized by cigarette makers, in which the use of sex and celebrity is forbidden, may help to reduce cigar use among young adults. LVAL,p.This application is one of four submitted concurrently to allow large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism. These proposals combine the resources of six large prospective cohorts from the American Cancer Society (CPS-II study), Harvard University (Harvard Cohort Studies), the IARC (EPIC study), and the Universities of Hawaii and Southern California (Multiethnic cohort); in addition, two NCI intramural cohorts (PLCO and ATBC studies) will participate. The proposed study is unique in having prospective plasma samples, genetic material, anthropometric measurements, and extensive questionnaire data on diet, physical activity, exogenous hormone use, smoking, and other lifestyle factors from over 790,000 men and women. Because of the scope and collaborative nature of this consortium, simultaneous investigation of genetic predisposition and lifestyle factors is possible, to clarify the inter-relationships between, and the relative importance of, genetic and hormonal risk factors. Specifically, this study will define SNPs and haplotypes in steroid hormone metabolizing genes, genes in the IGF pathway, and related receptor proteins. These candidate genes will be resequenced in 96 cases of advanced breast cancer, and 96 cases of advanced prostate cancer, chosen from the European, African, Latino, Japanese, and Hawaiian-origin ethnic groups. Haplotype tag SNPs will be selected after genotyping of a larger number of SNPs from a collection of 768 samples from the multigenerational CEPH (Centre d'Etude du Polymorphisme Humain) pedigrees and human diversity collection, by the Whitehead Institute for Genome Research and CEPH, and will rapidly be made publicly available. The interaction of genetic variants with hormonal, lifestyle and anthropometric factors known to be associated with breast and prostate cancer will be examined. In a subset of studies, the association of these variants with markers of brean LVAL~ st and prostate cancer risk (i.e. plasma steroid hormone levels and IGF-1 levels) will be investigated. Projects developed within the Cohort Consortium will foster continuing interactions between the genomic and epidemiologic research communities and help integrate the rapid advances in genomic research into large-scale epidemiologic studies. The ultimate goal is to provide the foundation for reducing the public health burden of these cancers.`LVALD  ,JzAGE Adult Older Adult DISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH1 Animal Studies TOBACCO Nicotine WOMEN PregnancyADDICTION Cessation Relapse ECONOMICS Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Quitline RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionEPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Postpartum MISCELLANEOUS Weight Gain/ExerciseADDICTION Cessation Withdrawal LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Asian Pacific Islander Caucasian TOBACCO Cigarette/Other Smoking WOMEN Hormones MISCELLANEOUS Sex/Gender DifferencesLVAL,p.Kimber P. Richter, Ph.D., M.P.H., is a behavioral psychologist with training in public health who will use the MRSDA to develop expertise in addressing nicotine addiction among persons in drug abuse treatment, an estimated 80 percent of whom smoke. The proposal combines her behavioral background in drug abuse prevention, drug abuse treatment, and cardiovascular disease risk reduction with a new focus on smoking cessation. This plan outlines the training and research experience she will need, over the next 5 years, to develop and launch a fully independent career addressing nicotine addiction among persons in drug abuse treatment. Career Development: Activities include training in the chemistry of the nervous system, advanced biostatistics, training in addictions treatment and research, a week-long internship with a nicotine/drug addictions researcher, and an intensive bioethics course. Research Program: The goal of the proposed research program is to better understand smoking behaviors and nicotine dependence among persons in treatment for chemical dependencies, and to identify acceptable and potentially effective methods for reducing cigarette smoking in this population. Specifically, the plan involves three studies that address five research questions. Study 1 examines key issues in smoking cessation from the patient's point of view. It consists of a series of two focus groups among each of four subgroups of clients in methadone maintenance treatment (MMT) and other drug dependency programs. These 8 sessions is will identify clients' a) interest in quitting, b) barriers to quitting smoking, c) successful strategies used to quit smoking, d) strategies used to avoid illicit drug use that might be adapted for smoking cessation, and e) treatment preferences for quitting smoking. Study 2 is a descriptive study examining interactions in patterns of cigarette use and methadone maintenance. Twenty-one methadone patients will use electronic monitors to record the frequency and timing of their cigarette consuDLVALTmption. Data on methadone timing and dose, as well as carbon monoxide levels and psychological measures of nicotine craving and withdrawal, will be collected and analyzed to assess whether methadone dose and timing are associated with surges in cigarette consumption and smoking urges. Study 3 is a pilot study examining the feasibility and potential efficacy of a multicomponent intervention on smoking cessation. Sixty MMT patients will be randomly assigned to treatment (nicotine inhaler and motivational interviewing) or control (placebo inhaler and comparable staff contact). Primary outcomes include quit rates and avg. daily cigarette use. Pilot data will allow determination of sample sizes for a full-scale intervention trial, and will be used to assess the effects of variables such as age, gender, methadone dose on treatment effects. The research plan uses exploratory, descriptive, and intervention research to address fundamental issues of nicotine addiction. Each study stands on its own, but is designed to build on the findings of the prior study. This research may serve as a model for systematic research on nicotine addiction in patients with other drugs of dependence or who are in other drug abuse treatment modes.LVAL In this proposal we test the role of oxidative stress in the pathophysiology of preeclampsia. Oxidative stress generates free radicals that injure tissues, especially vascular endothelial cell function as components of oxidized LDL (ox-LDL), alter endothelial cell structure and function. Data from our lab and others support alterations of endothelial cell function as a component of the pathophysiology of preeclampsia. In addition, preliminary data from our group indicates potential generation of pro oxidants by preeclamptic placenta. We demonstrated increased xanthine oxidase/dehydrogenase, an enzyme which can generate superoxide, in invasive cytotrophoblast from preeclamptic women. We recently demonstrated material in the blood or plasma of preeclamptic women that increases ascorbate oxidation in vitro. We propose to characterize the activity. Whether these findings indicate cause or effect or are an epiphenomenon cannot be answered by available data. We propose definitively testing a causal role. We will study circulating markers of oxidative stress before, during and after preeclampsia.A pilot randomized double-blind placebo-controlled trial will test the feasibility of conducting a full-scale trial of the efficacy of bupropion SR vs. placebo in nonlactating postpartum women who smoked >1 cigarette in the last month of pregnancy and want to stop smoking. Subjects will be recruited postpartum while hospitalized after delivery. Outcomes will be assessed at 2, 4, 8, and 12 weeks postpartum. The study will estimate achievable enrollment and retention rates; estimate the effect size of the drug on tobacco abstinence; assess the tolerability of bupropion in postpartum women; and allow refinement of recruitment, retention, intervention, and assessment protocols.LVAL,p.The purpose of this study is to test whether offering pregnant smokers a proactive telephone counseling program throughout pregnancy and for 2 months postpartum increases the rate of smoking cessation and of tobacco use reduction, at end of pregnancy and 3 months postpartum, compared to a "best practice" control. Research Design: This study is a randomized controlled clinical trial to compare the effectiveness of an enhanced version of an existent smoking cessation telephone counseling program for pregnant women with a "best practice" control. Study Population: The study population is pregnant women smokers enrolled in the Tufts Health Plan. The goal is to recruit 434 women over a 29-month enrollment period. Eligibility criteria include (1) being in the 1st or 2nd trimester of pregnancy, (2) having smoked >1 cigarette in the past week, (3) having access to a telephone and (4) the ability to speak English. Intervention (if appropriate): The intervention condition will include: 1) A mailed pregnancy tailored manual; 2) Proactive, stage-based telephone counseling by a trained smoking counselor on a standardized schedule for the remainder of pregnancy (an initial 15-20 minute call and up to 6 subsequent 10-15 minute calls). Counseling will incorporate motivational enhancement, skills training, problem-solving, and relapse-prevention strategies; 3) Mailings sent to the obstetrical provider (informing him/her of the patient s participation and reminding provider to advise nonsmoking at each visit). Chart stickers and self-help materials will also be provided. After delivery, similar letters will be sent to the obstetrician and the infant s pediatrician; 4) Stop-smoking advice from the obstetric provider. Outcome Measures (If cessation or reduction, how defined): Smoking cessation at the end of pregnancy is the primary outcome. Smoking status outcomes will be assessed by telephone at the end of pregnancy (28-34 weeks) and 3 months postpartum. Saliva samples will be collected from self-reported n LVAL onsmokers at each follow-up point to verify nonsmoking status. Self reported nonsmoking will be considered validated if saliva cotinine value is <20 ng/ml. Secondary outcome measures will include participant s health care utilization and costs (including those incurred during pregnancy and by the infant during months 0-3), which will be obtained from Tufts HP claims data. Intermediate outcomes will include number of quit attempts (defined as >24 hours of self-reported abstinence) and stage of readiness to quit smoking.  c A  T05@K@Researchn@ RUGGIEROLAURIEUNIVERSITY OF RHODE ISLANDKINGSTONRINCIR01, CA071098,p.T@@t@7/1/19967/31/20027/1/1996 to 7/31/20024/2005ytpfJB88," @@Researchj@ROSSINGMARYFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWANCIR01, CA078784p @@@@2/21/20006/30/20042/21/2000 to 6/30/20044/2005|xoGA88," 1@^@Researchf@ROHRBAUGHJOHNWASHINGTON UNIVERSITYST. LOUISMONIAAAP50, AA011998h,p.Biology and Cancer Addiction@&@1/1/200212/31/20021/1/2002 to 12/31/20024/2005 vok`IC88,"`~@b@ResearchL@ROGERSROBERTUNIVERSITY OF PITTSBURGHPITTSBURGHPANHLBIU10, HL059276:@@@Z@2/1/19981/31/20032/1/1998 to 1/31/20034/2005yrnbH@88,"@@Research@RODRIGUEZ-THOMPSONDIANABRIGHAM AND WOMEN'S HOSPITAL--HARVARD MEDICAL SCHOOLBOSTONMASFFNot Givenf@j@@>@200020042000 to 20044/2005SL88," 2@@@Research^@ROCCAWALTERMAYO CLINIC COLLEGE OF MEDICINEROCHESTERMNNINDSR01, NS033978,p.t@n@ @6/1/19965/31/20016/1/1996 to 5/31/20014/2005~wshG?88,"@@@ResearchL@ROBINSONLESLIEUNIVERSITY OF MEMPHISMEMPHISTNNHLBIR01, HL050723@L@@t@9/30/19931/31/20059/30/1993 to 1/31/20054/2005unjaJB88,"g@p@4Research\@ROBERTSJAMESUNIVERSITY OF PITTSBURGHPITTSBURGHPANCRRM01, RR000056@Biology and CancerDiscovery 1a Evaluation 1b@Not GivenNot GivenUncertain4/2005 xrnbHA88," @@u@Research@RITT-OLSONANAUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP10DT-0162j,p.t@"@@7/1/20016/30/20037/1/2001 to 6/30/20034/2005}ylID88," }@`a@Researchn@RISCHHARVEYYALE UNIVERSITYNEW HAVENCTNCIR01, CA098870,p.L@!Discovery 1b Evaluation 1b2@9/1/20038/31/20089/1/2003 to 8/31/20084/2005{lgcXG?88,"`@%@Researchb@ RILEYWILLIAMPERSONAL IMPROVEMENT COMPUTER SYSTEMSRESTONVANICHDR43, HD038147Not available9/24/19999/30/20019/24/1999 to 9/30/20014/2005{woH?88,"?~@@u@Research`@RILEYEDWARDSAN DIEGO STATE UNIVERSITY FOUNDATIONSAN DIEGOCACTRDRP9RT-0012`,p.Biology and CancerR@@7/1/20006/30/20037/1/2000 to 6/30/20034/2005}ynG?88,"@@Research@RIGOTTINANCY GENERAL HOSPITAL CORP.--MASSACHUSETTS GENERAL HOSPITALBOSTONMARWJF40667,p.T@ @ @10/1/20009/30/200410/1/2000 to 9/30/20044/2005IA88,"LVAL,p.Cigarette smoking during pregnancy has been associated with higher rates of spontaneous abortions, intrauterine growth retardation, and an increased risk for birth defects. In addition, behavioral problems, such as hyperactivity, decreased attention, and lower IQ in the offspring of smoking mothers suggest that nicotine also has negative effects on the development of the brain. In fact, research suggests that nicotine exposure during development may have more detrimental effects on the developing brain than other drugs of abuse, such as cocaine. However, the exact cause and effect relationship between maternal smoking and the negative effects of nicotine on the human brain is difficult to study because of several confounding factors such as: nutrition, the mother s health and social environment, and the potential presence of other toxic substances. In many ways the development of many mammalian brains is similar to the development of the human brain. Therefore, one can utilize animal models of nicotine exposure to better our understanding of nicotine's effects on the developing fetus because of the strict environmental control available. The previous submission of this application focused on developing an animal model of nicotine exposure during the equivalent of the last trimester of pregnancy, the time when the brain is undergoing a period of rapid development. The potential toxic effect of nicotine exposure during pregnancy was evaluated using brain wave measurements [electroencephalography (EEG) and event-related potentials (ERPs)] and behavioral tests. Differences in the brain wave measurements were found in the hippocampus, a brain area crucial for learning and memory. Behaviorally, the animals were overactive, an effect consistent with damage to this brain area. The experiments proposed in the current application utilize this third trimester model and are designed to assess alterations in other behaviors that rely on the integrity of this brain area. Furthermore, we will explore how early nicott LVAL ine exposure influences chemical systems in the brain, as well as, anatomical changes in the hippocampus. These studies may help to identify which brain systems may be particularly affected by early life nicotine exposure, and lay the foundation for identifying the causes of tobacco-related problems in the newborn.LVAL,p.In the US in 2001, there were about 29,000 new cases of cancer of the pancreas, and nearly that number died from it, making it the 4th most frequent cause of cancer death, after lung, breast/prostate and colorectal cancer. Over the lifetime, more than 1% of the population is affected, with blacks having a bit higher rates than whites. Survival with this cancer is dismal: one year about 20-30%, and 5-year, about 5%. Most patients present with advanced disease, and the standard treatments do not much alter the progressive, fatal course. Aside from major-gene causes underlying perhaps 5% of cases, the one known risk factor for pancreatic cancer is cigarette smoking, which doubles the risk. Studies of dietary factors have not been entirely consistent but do suggest associations of higher risk with animal product intake and lower risk with consumption of fruits or vegetables. This application describes a new hypothesis on the etiology of pancreatic cancer, and provides a substantial body of laboratory and epidemiologic evidence in support of it. To examine this hypothesis, we will conduct, in the state of CT, a population-based case-control study to examine infectious, genetic, dietary, lifestyle and medical history factors. In total, 600 pancreas-cancer cases aged 35-79 years will be identified prospectively via the ultra-rapid program of the Rapid Case Ascertainment Shared Resource at Yale. About 600 randomly selected population controls will be frequency matched to the cases by age and gender. Controls will be identified using enhanced random-digit dialing methods. All subjects will be interviewed in person by trained interviewers using a standardized, structured questionnaire that will include sections on tobacco use and medical history, a standard food frequency/supplements questionnaire, and questions about other factors specific to our hypothesis. A small blood sample will be drawn for use in testing for exposure to certain infections, and for four DNA polymorphisms relevant to our hypothesis. Avera LVAL ge daily intake of dietary nutrients will be calculated from the diet histories, and uni- and multivariate analyses will be used to estimate relative risks for comparison of the cases with the controls. The factors to be examined here have received little attention with respect to pancreas cancer, and the proposed study will evaluate them systematically in a vigorous, large-scale and integrated project.LVALf T | T$:h8hJTRANSPLACENTAL PANCREATIC CARCINOGENESIS BY NNKPRE AND POSTNATAL CIGARETTE EXPOSURE AND INFANT REGULATIONPREVENTION OF SMOKING RELAPSE IN WOMENCERVICAL CANCER AND HUMAN PAPILLOMAVIRUS (HPV) INFECTIONDYNAMIC MODELS OF ADOLESCENT DRUG USE PREVENTIONCOPING DURING SPONTANEOUS SMOKING CESSATION IN PREGNANCYADVERSE PREGNANCY OUTCOMES: GENETIC/ ENVIRONMENTAL CAUSESLUNG HEALTH STUDY--LONG TERM FOLLOW-UPHPV SPECIFIC CELLULAR IMMUNITY IN CERVICAL INTRAEPITHELIAL CELLSTOBACCO-FREE NURSES: HELPING NURSES QUITEFFECTS OF PRENATAL NICOTINE EXPOSURE ON NICOTINIC RECEPTORSRISK FACTORS FOR ATTENTION DEFICIT/HYPERACTIVITY DISORDERA COHORT STUDY OF ACTIVE AND PASSIVE SMOKING IN KOREAA RANDOMIZED CONTROLLED TRIAL OF SUSTAINED RELEASE BUPROPION FOR PREVENTION OF RELAPSE IN WOMEN WHO QUIT SMOKING DURING PREGNANCYFRAMING MESSAGES FOR SMOKING CESSATION WITH BUPROPRIONJAIL OUTREACH PROJECT FOR INCARCERATED WOMENSTUDYING PREDICTORS OF SUCCESSFUL SMOKING CESSATION IN PREGNANT WOMENSTAGE-BASED, EXPERT SYSTEM-DRIVEN, SMOKING CESSATION PROGRAM FOR LOW-INCOME PREGNANT WOMENDEVELOPMENT AND FORMATIVE EVALUATION OF MOTIVATIONAL ENHANCEMENTS FOR A STAGE-BASED EXPERT-SYSTEM DRIVEN SMOKING CESSATION INTERVENTION FOR LOW-INCOME PREGNANT WOMENA NEW PERSPECTIVE ON THE QUITTING PROCESS: LOOKING INWARD, OUTWARD, AND FORWARDACCELERATING PROGRESS OF SMOKING CESSATION IN PREGNANCYEPIDEMIOLOGY OF SMOKING CESSATION--GENETIC INFLUENCESCLOSE ASSOCIATION BETWEEN ALCOHOL AND CIGARETTE USELUNG HEALTH STUDY--LONG TERM FOLLOW-UPA RANDOMIZED CONTROLLED TRIAL OF SUSTAINED RELEASE BUPROPION FOR PREVENTION OF RELAPSE IN WOMEN WHO QUIT SMOKING DURING PREGNANCYEPIDEMIOLOGY AND GENETICS OF PARKINSONS DISEASESMOKING ONSET IN A BIETHNIC POPULATIONPRENATAL EXPOSURES AND PREECLAMPSIA PREVENTIONTHE EFFECT OF DEPRESSION AND PEER INFLUENCES ON SMOKING INITIATIONCASE-CONTROL STUDY OF PANCREAS CANCER ETIOLOGIC FACTORSLVAL,p.Cigarette smoking is related to countless physical maladies, and is responsible for huge health care costs in the United States. Prevention efforts to date have had only moderate success. Understanding the predictors of smoking initiation in young adolescents in a multiethnic sample can assist in the creation of better prevention campaigns. Several authors in recent years have suggested that depression causes teens to begin smoking (eg, Breslau, Peterson, Schultz, Cilcoat & Andreski, 1998). Depressed teens are thought to start smoking to deal with their sad feelings. However , recently published studies suggest that smoking causes depression (Goodman & Capitman, 2000; Wu & Anthony, 1999). To gain a more complete understanding of the relationship between smoking and depression, third variable influences should be explored. Looking at additional influences on the relationship may help uncover underlying mechanisms and that in turn will elucidate better means of prevention. Patton and colleagues (1998) suggest that a third variable of interest may be peer influences. This study explores how depression could lead to peer associations that encourage smoking in young adolescents. This study will use social network analyses to aid in the defining of peer influences and in the exploration of how peer clusters can influence smoking patterns. Social Network Analyses reveal peer group members, can identify which students lack friends at a school, and which students are particularly well liked. Several models will be explored to evaluate the relationship between depression and peers and smoking initiation. Traditional survey data on peers (Perceived Social Norms and number of peers that smoke) will be used along with a social network approach to look at actual peer influences and peer group associations. One possible mechanism is that depressed teens become isolated because they have difficulty making friends. Because they feel isolated they may smoke to deal with feelings of loneliness. Students at the periphej LVALz ry of a social network, referred to as an isolate, will be identified in a given school. Another possible mechanism that puts students at risk may be that depressed students are drawn to groups of friends or cliques that are at risk for smoking. Social network analyses will allow for the identification of cliques and by linking the members to their individual survey data, we will be able to find out which members of the clique smoke. Also, it is entirely possible that teens could associate with peers that put them less at risk for smoking or depression. Certain types of peer associations may be protective. Cliques that are compromised of members that don't smoke and have low levels of depression may prove to be protective influences. It is expected that each of these relationships may differ by ethnicity and by gender. \LVALB vDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesADDICTION Relapse EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments Buproprion RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumDISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance Cessation AGE Child Young Adult ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use Nicotine WOMEN PregnancyAGE Child LOCATION Urban National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesLVAL@  , v " r  * z  b"D,JbdBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Addiction Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Addiction Epidemiology and National Surveillance Interventions for Prevention and TreatmentEpidemiology and National Surveillance Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceAddiction Interventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentEpidemiology and National Surveillance Interventions for Prevention and Treatment Awareness Risk Perception and CommunicationsAddiction Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National Surveillance Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National Surveillance Global IssuesAddiction Interventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentAddiction Epidemiology and National SurveillanceInterventions for Prevention and TreatmentBiology and Cancer Addiction Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National Surveillance Interventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceLVAL" Purpose: To evaluate whether bupropion given to women who have quit smoking during pregnancy is effective in decreasing postpartum relapse. Research Design: We propose a randomized placebo controlled trial of 300 women to determine whether women treated with bupropion have lower rates of smoking relapse than women receiving placebo. Study Population: Subjects will be recruited from the clinical practices at Brigham and Women's Hospital. Pregnant women at least 18 years of age, who have quit smoking within the year prior to delivery and have not resumed smoking will be eligible to participate. Patients with contraindications to treatment with bupropion and breastfeeding women will be excluded. Intervention (if appropriate): Subjects will be randomized to receive bupropion or placebo. Those randomized to bupropion will be receive 150 mg by mouth twice a day for 9 weeks. Outcome Measures (If cessation or reduction, how defined): The primary outcome measured is smoking cessation at 3 and 6 months. This will be measured using a urine cotinine to creatinine ratio. Specific aims: (1) To track participants of the Memphis Health Project (MHP), a study that has followed primarily low income, minority youth since the 7th grade, prospectively for four years post-high school, in order to assess the extent of young adult onset and cessation in this biethnic population. (2) To determine the predictors of smoking onset, not only in early onset smokers but also in late onset smokers as well. (3) To determine the predictors of conversion of experimental smoking to regular, adult patterns of smoking. (4) To identify the predictors of cessation for both early onset and late onset smokers.LVAL,p.Parkinson's disease (PD) is a common and disabling condition in the expanding elderly population of the US and worldwide. Its etiology remains unknown and both genetic and environmental factors have been suspected. The long-term goal of the proposed studies based in different sampling is to clarify the etiology of PD and to identify means to prevent it. Three independent but related studies based on different sampling and measurement strategies are proposed. The hypotheses tested derive directly from our current work and preliminary findings. A case control study will include 800 cases of PD referred to the Mayo clinic from a 120 mile radius or from a 5 state region and 800 controls free pf PD and parkinsonism matched by age (+ 2 years), sex and region of residence. Controls from the general population will be identified from health care financial administration lists for cases aged 65 years or above and through random digit dialing for cases below 65 years. Exposures will be accessed through direct telephone interview, and will include tobacco, coffee, and alcohol use; markers of novelty seeking behavior; and, for women, use of estrogen replacement therapy after menopause and other reproductive and estrogen related factors. A first historical cohort study will test the association between unilateral and bilateral oophorectomy before menopause and PD in an established population based cohort. The study will include 2,533 women who underwent oophorectomy in 1950-1987 while residing in Olmsted County, MN and 2,533 women of the same age and residence who did not undergo oophorectomy. A second historical study will test the association between personality traits measured by the Minnesota Multiphasic Personality Inventory (MMPI) and PD in an established research cohort. This study will include 8,775 persons who underwent MMPI testing in 1962-1965 while residing in Minnesota. The proposed case-control study is strong because it has adequate statistical power to confirm our preliminary findings on the role o$ LVAL4 f estrogen in PD and to explore the link between substance use and novelty seeking behaviors in PD. All interviews with case and controls will be direct, the proposed oophorectomy cohort study is strong because of its cohort design, its population-based sampling, its adequate statistical power, and because of the expected high rate of follow-up through both passive and active strategies. The proposed MMPI cohort study is strong because of its cohort design, its adequate statistical power and because of our extensive experience with tracing and interviewing individuals. These three studies will contribute greatly to understanding the causes and possible prevention of PD by exploring novel hypotheses and by using innovative methods.LVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long- term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airways reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600. LVAL,p.Substantial evidence points to a close association between alcohol and cigarette use. A sequence of laboratory challenge studies is aimed at the general hypothesis that cigarette smoking may be causally involved in excessive drinking by decreasing the acute sensitivity to the intoxicating effects of alcohol, thereby promoted increased consumption and risk of addiction. This general hypothesis is consistent with strong evidence from animal studies of cross-tolerance between the two drugs, and with findings from a reanalysis by our group of alcohol challenge data in a Australian twin sample showing that an acute dose of alcohol produced less intoxication in smokers than in non-smokers. Measurement domains will be the same as those shown effective in prior studies, with principal emphasis on measures of balance using advanced dynamic posturography procedures (and complementary oculomotor tests). In addition subjective measures of drug effects will be obtained. Cardiorespiratory responses will be measured because of their sensitivity to nicotine as well as alcohol. The hypothesized cross- tolerance will be investigated in three studies of male and female social drinkers, ages 21 through 25. Experiment 1 will be a study of 4- hour deprived smokers in which controlled cigarette smoking will be combined with acute alcohol challenges, for comparison with conditions in which the substances are given individually or neither is administered. In an additional session, the effects of nicotine administered by nasal spray (NNS) will be assessed for comparison with smoking. It is hypothesized, consistent with prior animal and neuropharmacological evidence, that nicotine spray will produce effects similar to those seen with smoking on the critical posturographic and oculomotor measures. Experiment 2 will be similar to Experiment 1, except that nicotine spray will be given to no-smokers to allow acute effects to be identified. Experiment 3 will investigate moderate drinking MZ and same-sex DZ twin pairs discordant for l LVAL| nicotine dependence, to provide a direct and controlled test of the hypothesis that undeprived chronic smokers are intensely affected by a challenge dose of alcohol. Twins will be studied in two sessions, one with alcohol plus placebo NNS, and a second with alcohol plus NNS. A second aim from this study is to test for a possible genetic component to the cross tolerance, in the form of smaller intra-pair differences in MZ than in DZ twins. The findings from these experiments will provide critical evidence regarding a potential important contributor to excessive drinking. LVAL r(DISEASE/BIOLOGY Cancer LOCATION National PREVENTION/TREATMENT Educational Materials Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal COMMUNITY Health Care Provider ECONOMICS Socio-Economic Status LOCATION National TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Fetus/Prenatal ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyEPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionADDICTION Maintenance Cessation EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingADDICTION Withdrawal AGE Young Adult Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms LOCATION National PSYCHOLOGICAL Social Factors TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Sex/Gender DifferencesLVALThere are two overall goals of this project: (a) to identify predictors of successful quitting in pregnancy; and (b) to identify predictors of successful maintenance of postpartum abstinence.Cigarette smoking remains the single most preventable cause of cancer mortality in the United States. However, although most current smokers report a desire to quit, the decline in adult use of tobacco has slowed in recent years. These observations highlight the need for new insights into determinants of smoking cessation. Available data support a role of genetic influences on smoking behavior; these effects may be most evident in populations, such as the United States, with relatively strong social pressures against smoking. The goal of the proposed study is to examine genetic influences on smoking cessation. Among 700 female participants in a smoking cessation trial, we will assess the relation of polymorphisms of genes involved in the neurologic activity or metabolism of tobacco and nicotine with the likelihood of being a non smoker at the end of the trial and when re-contacted several years later. Of particular interest are genes involved in dopaminergic neurotransmission in the mesolimbic "reward" pathway of the brain, as the addictive effects of tobacco and nicotine operate primarily through this system. Blood specimens collected in the proposed study will, in addition to enabling the work currently proposed, form a resource for future genetic studies of smoking cessation as new and relevant polymorphisms are identified and characterized. Increased understanding of genetic influences on the ability of motivated, healthy individuals to quit smoking may lead to improvements in success rates of smoking cessation efforts. In the future, such knowledge may allow the identification of subgroups of individuals who are most likely to benefit from particular pharmacologic interventions.LVAL,p.Smoking continues to be the most preventable cause of death and disability in the United States. As many as 87 percent of lung cancer deaths are secondary to smoking, as well as 30 percent of all cancer deaths. The mortality trends in lung cancer rates for women are rising more rapidly than for men and lung cancer is the leading cause of death from cancers in women. Given the mortality trends in lung cancer for women and the link to their smoking patterns, cancer prevention efforts should focus on targeting high risk female mothers as well as take advantage of teachable moments to best accelerate progress toward smoking cessation in women. Economically disadvantaged pregnant women are both more likely to smoke prior to becoming pregnant and less likely to quit during pregnancy than other women of childbearing age. Even when they do quit during pregnancy, they are likely to relapse postpartum. Therefore, pregnancy and the postpartum period is an important window of opportunity for interventions to motivate these women and accelerate their progress toward smoking cessation. Reducing smoking in pregnancy and postpartum would serve to reduce health risks for two individuals, mother and child, thereby, promote the cancer prevention objectives set forth in Healthy People 2000. The proposed project is a collaborative effort of the Cancer Prevention Research Consortium at the University of Rhode Island and the Women and Infants Hospital of Rhode Island, a teaching hospital of Brown University Medical School. The proposed study is designed to evaluate the impact of an innovative stage-based individualized, interactive intervention (Individualized Intervention) on smoking cessation compared with a stage-matched self-help approach (self-help Intervention) and a standard care condition. The Individualized and self-help Interventions will be based on existing theoretical concepts and behavior change techniques of the Transtheoretical Model. The target population will be low-income culturally diverse pregn LVAL ant women attending public maternity clinics. The proposed study will involve a prospective randomized, three-group, repeated measures design. Information gained from the project data will help determine the efficacy of this innovative smoking cessation intervention, identify the impact of the intervention on intermediate or process variables, and provide insight into the influence of pregnancy and delivery on readiness for changing smoking behaviors. The benefits of promoting smoking cessation programs during pregnancy will not only have a long-range impact on the individual, but also on the overall health of the family.  j N K L V `~@b@ResearchL@SCANLONPAULMAYO CLINIC COLLEGE OF MEDICINEROCHESTERMNNHLBIU10, HL0592948@@@~@2/1/19981/31/20032/1/1998 to 1/31/20034/2005~wshGA88,"@@@Research@SASTRYJAGANNADHAUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNCIR01, CA077378,p.t@Discovery 1b Evaluation 1b@D8/1/19995/31/20048/1/1999 to 5/31/20044/2005{L@88,"@y@ @ResearchR@SARNALINDAUNIVERSITY OF CALIFORNIA AT LOS ANGELES SCHOOL OF NURSINGLOS ANGELESCARWJF41056 @@ j@@8/1/20037/31/20068/1/2003 to 7/31/20064/2005F?88,"@@u@Researchx@SARGENTPETERUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCACTRDRP9RT-0101 @Biology and CancerDiscovery 1a Evaluation 1b<@7/1/20006/30/20037/1/2000 to 6/30/20034/2005-%sHA88," @@Researchr@SANDLERDALENot GivenNot GivenNot GivenNIEHSZ01, ES049034,p.t@ T@@199920041999 to 20044/2005~oh]RGA88,">@@Researchj@SAMETJOHNATHANJOHNS HOPKINS UNIVERSITYBALTIMOREMDNCIR03, CA094771,p.j@ @@4/19/20023/31/20044/19/2002 to 3/31/20044/2005xsodJ?88,"g@p@4Research@SAMELSONRENEEBRIGHAMAND WOMEN'S HOSPITAL, HARVARD MEDICAL SCHOOLNot GivenNot GivenRWJF40665@j@ Discovery 1c Development 2@42 MONTHSNot GivenUncertain (42 MONTHS)4/2005#~IB88,"g@@Researchl@SALOVEYPETERYALE UNIVERSITYNEW HAVENCTNIDAP50, DA0133346,p.@ @J@Not Given2004? to 20044/2005}nhdYHA88,"`@@ResearchX@RYANMARTHAHOMELESS PRENATAL PROGRAM INC.SAN FRANCISCOCARWJF39731Not available8/1/20007/31/20048/1/2000 to 7/31/20044/2005yufF>88,"?~@`@Research@ RUGGIEROLAURIEUNIVERSITY OF ILLINOIS AT CHICAGO SCHOOL OF PUBLIC HEALTHCHICAGOILRWJF51804Not available9/1/20048/31/20059/1/2004 to 8/31/20054/2005JB88,"?~Z@@Research@ RUGGIEROLAURIEUNIVERSITY OF ILLINOIS AT CHICAGO SCHOOL OF PUBLIC HEALTHCHICAGOILRWJF47472T@T@Discovery 1c Development 3l@12/1/20028/31/200412/1/2002 to 8/31/20044/2005"JB88,"g@p@4ResearchJ@ RUGGIEROLAURIEUNIVERSITY OF RHODE ISLANDRIRWJF40673@T@N@:@33 MONTHSNot GivenUncertain (33 MONTHS)4/2005wpjffJB88,"@`@Research@ RUGGIEROLAURIEUNIVERSITY OF ILLINOIS, INSTITUTE FOR HEALTH RESEARCH AND POLICYCHICAGOILRWJFNot Given~@b@n@l@9/1/20048/31/20059/1/2004 to 8/31/20054/2005JB88," LVAL4 To evaluate whether bupropion given to women who have quit smoking during pregnancy is effective in decreasing postpartum relapse. Specific aims of this project are to develop motivational enhancements and conduct formative evaluations based on the use of fetal ultrasound assessment, carbon monoxide measurement, and urine cotinine measurement in ethnically diverse, low-income pregnant women attending public maternity clinics.The primary goal of our programmatic line of research is to develop effective interventions for low-income pregnant women. This pilot study builds on our ongoing work by developing and testing motivational enhancements designed to increase the impact of our pregnancy-tailored stage-based multicomponent, multichannel, repeated contact intervention program. LVAL,p.Perhaps one of the reasons why smoking continues despite the well- documented benefits of quitting is the persuasive messages encouraging smoking cessation tend to focus on the costs of smoking rather than on the benefits of not smoking. These messages are usually designed to elicit feelings of threat or fear by presenting the negative consequences of smoking. On the other hand, messages emphasizing the benefits of smoking cessation may be more motivating for cessation. In general, appeals aimed at persuading individuals to perform a particular health behavior can be framed in different ways. Gain-framed messages present the benefits that are accrued through adopting the behavior (e.g., "If you stop smoking you will find you have more energy"). Loss framed messages covey the costs of not adopting the requested behavior (e.g., "If you do not stop smoking, you will find that you are often out of breath"). Although these two messages convey essentially the same information about smoking cessation, in certain circumstances, one of these messages may be more influential. Across a wide range of studies of health behaviors, gained-framed messages appear to be more appropriate when encouraging a prevention behavior (i.e. smoking cessation), but loss- framed messages appear to be more appropriate when encouraging a prevention behavior (i.e. smoking cessation), but loss-framed messages appear to more appropriate when encouraging a prevention behavior (i.e. smoking cessation), but loss-framed messages appear to have more impact when encouraging an early-detection (screening) behavior (i.e. mammography). The primary goal of this project is to investigate whether gain-versus loss-framed messages are more influential in encouraging individuals to complete a six-week trial of bupropion SR therapy for smoking cessation and in smoking cessation itself. We hypothesize that gain-framed messages will be more effective in promoting smoking cessation with bupropion SR than loss-framed messages, even though many of the slog LVAL ans, warnings, and other print information directed toward smokers are loss-framed. A secondary aim of the study will be to examine the relative value of gain framed and loss framed messages in relationship to characteristics of the smoker, including history of cancer, gender, depression, and alcohol use. Finally, the durability of message framing effects will be evaluated using data from three and six month follow-ups.LVALX rLAGE Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use WOMEN PregnancyDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Health Care Provider LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Interview/Focus Group Educational Materials PSYCHOLOGICAL Social Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology RESEARCH1 Animal Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child DISEASE/BIOLOGY Other Disease/Biology ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Parent/MotherDISEASE/BIOLOGY Cancer Other Disease/Biology ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International PSYCHOLOGICAL Cultural Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesADDICTION Relapse EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments Buproprion RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingLVAL,p.Although 50 years of research findings have causally linked active and passive smoking to cancer and other diseases, further epidemiologic research on the risks of tobacco smoking is still needed. One specific need is for studies in countries other than the developed, western countries where the majority studies have been conducted to date. Most of the world's smokers live outside of the western countries, primarily in Asia where a majority of males are smokers in many countries. Background disease rats and distributions of lifestyle risk factors are notably distinct in these populations, particularly in comparison with populations of previously studied western males. The majority of women, largely non-smokers, and children in Asian countries are exposed to environmental tobacco smoke (ETS). This small grant application requests support to establish a cohort study of active and passive smoking and risk for cancer and other diseases among persons receiving health insurance coverage through the Korean Medical Insurance Corporation (KMIC). The KMIC provides coverage to civil service workers, teachers, and their dependents in the Republic of Korea (South Korea). The total population insured by the KMIC is substantial, accounting for 11% of the country's 43 million residents in 1990. The insured then included approximately 1.2 million workers and an additional 3.4 dependents. A cohort study will be developed using the database of the KMIC. Risk factor information is collected in biennial medical examinations, which are required for the insured workers and are voluntarily completed by dependents. The data collected in the biennial examinations covering smoking and other lifestyle risk for disease and findings from routine laboratory work are also available. Outcomes are tracked through the hospital record system and also by mortality matches. Family members of the insured can be identified through record linkage using the unique identification number of the insured. In an effort to advance understanding of LVALsmoking and cancer and other diseases in Asian countries, as well as among Asian Americans, investigators at the Yonsei University and the Johns Hopkins University School of Hygiene and Public Health plan to collaborate in developing and then using this epidemiologic resource to carry out a major program of research on the risks of active and passive smoking in Korea. The Yonsei University has access to the KMIC cohort and already has shown its potential in several reports on cancer and cardiovascular disease. The Johns Hopkins group adds expertise in cohort studies and smoking. This application requests support to establish a comprehensive database in support of the cohort study and to carry out analyses on active and passive smoker and cancer. During the two years of support requested in this small grant application, data will be abstracted from medical records on key exposure variables from exams carried out in 1992 and 1993, providing lifestyle and laboratory data for cohort expected to number approximately 1.6 million adults. Mortality will be tracked from 1992-2003 and inpatient encounters, coded by diagnosis, will be identified for 1998-2003. To demonstrate the potential of the study, an investigation will be carried out on active and passive smoking and lung cancer risk. We intend to set data collection in place to maintain and extend this cohort. The large size of this cohort and the unusually strong possibility for data linkage makes the KMIC population a unique and cost effective study opportunity. This cohort study would have the potential to generate powerful evidence to describe the risk of smoking in a population with distinct background disease rates and distribution of lifestyle risk factors relative to western populations previously studied. LVALZ t B H *6<`Discovery 1a Discovery 1c Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2a Discovery 2b Discovery 3 Development 3 Delivery 2 Partnerships 2 Evaluation 1aDiscovery 1c Development 1 Development 3 Delivery 2 Partnerships 2Discovery 1a Discovery 1c Discovery 2a Discovery 2b Development 3 Delivery 2 Evaluation 1aDiscovery 1a Discovery 1c Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Development 1 Development 2 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 3 Development 2 Delivery 1 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1aDiscovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 3 Development 2 Evaluation 1aDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Development 2 Development 3 Delivery 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 2b Discovery 3 Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2b Delivery 2 Evaluation 1cDiscovery 1a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bLVAL,p.The prevalence of and risk factors for Atention Deficit Hyperactivity Disorder are being investigated in a population-based study carried out in Johnston County, North Carolina. Through the cooperation of the Johnston County schools, all elementary school age children in the county were studied. With parental permission, teachers completed behavior rating evaluations for children in their classroom. All children classified as potentially having ADHD according to teacher responses or reported by parents to be taking medications were eligible for further study, along with a random sample of all other children. Parent interviews obtained information on child behavior, prenatal and childhood exposures, parental occupational exposures and other factors potentially related to risk for ADHD. The pilot study combined parent and teacher information to estimate the prevalence of ADHD among elementary school children. Two-stage screening used DSM-IV criteria. Teachers completed behavior-rating scales on all children and then parents of potential cases were administered a structured telephone interview. 362 of 424 (85%) children in grades 1-5 in four schools were screened. We estimated the prevalence of medication treatment for attention deficit-hyperactivity disorder (ADHD) among elementary school children in a North Carolina county. We asked parents of 7333 children in grades 1 through 5 attending 17 public elementary schools whether their child had ever been given a diagnosis of ADHD by a psychologist or physician and whether their child was currently taking medication to treat ADHD. The primary aims of the project are 1) to describe the prevalence of ADHD and how it varies by age, race, gender, and SES, 2) to test the hypothesis that preterm and post-term births are at higher risk for ADHD and 3) to evaluate the role of maternal smoking, maternal occupation, maternal alcohol consumption and pregnancy complications as risk factors for ADHD. In the results for the first year of the study, according to parental 8LVALHreports, 43 children (12%) previously had been diagnosed with ADHD by a health professional. Thirty-four children (9%) were taking ADHD medication. Forty-six children met study case criteria for ADHD based on combined teacher and parent reports. After adjusting for non-response, the estimated prevalence of treated or untreated ADHD combined was 16% The prevalence estimate based on the full sample is lower, but still greater than published reports based on DSMIV criteria. In the overall study, parents of 6099 children (83%) provided information on medication use. Of these, 607 children (10%) had been given an ADHD diagnosis, and 434 (7%) were receiving ADHD medication treatment (71% of the diagnosed children were receiving medication). Treatment rates varied by sex, race/ethnicity, and grade. If treatment patterns observed in this study are representative, the public health impact of ADHD may be underestimated. The lead investigator for this project left NIEHS for a position at the University of New Mexico. Work on this project is continuing, but at a slow pace. In the past year, a paper on the psychometric properties of the diagnostic scales used in this population-based effort has been drafted. The ability of these scales to identify children with ADHD is being contrasted with results from a more individualized physician-based approach. In addition, an overall prevalence estimate is being determined using information from all study participants, and attention will now shift to identifying prgnancy-related factors as well as environmental exposures (e.g. lead) that may contribute to risk of ADHD. Dr. Rowland (former NIEHS lead investigator) is developing a proposal to follow the children who were studied to evaluate persistence of symptoms and outcomes among children with various subtypes of ADHD, and will be seeking grant support for such an effort.LVALCigarette smoking is a highly addictive behavior. The chemical in cigarettes that gives tobacco users their  kick is nicotine, and this chemical has a number of effects on the brain. The target of nicotine is a family of protein molecules called  nicotinic receptors. The real purpose of these molecules isn t to respond to nicotine but rather to respond to a chemical  transmitter that some nerve cells in the brain use to communicate with each other. Nicotine interferes with this communication, enhancing some connections between nerve cells and depressing others. Nicotine has both rapidly-acting and long term effects on its receptors; it is the long term effects that probably lead to our becoming addicted to nicotine. To understand these effects, it is important to study the receptor molecules with which nicotine interacts. I am doing this by looking at whether long-term exposure to nicotine changes the number of receptors in the brain and whether it alters the way those receptors work. I will expose rats at around the time of birth to low levels of nicotine for a few weeks, to mimic the exposure they might have received if their mother had  smoked. I will then examine the nicotinic receptors in these rats to learn how they have been affected by this long-term exposure to nicotine. This research will hopefully tell us more about the effects of maternal smoking on the unborn child.$LVAL4Smoking among nurses, an estimated 16-18 percent, continues to be significantly higher than that of other health professionals. Smoking threatens the health of nurses, causes dissension in the work site, and negatively affects nursing interventions in tobacco control. This grant will focus on increasing awareness of tobacco use and quit resources among nurses, removing barriers to successful quit attempts, and assisting nurses who smoke to quit. The three primary aims are to: (1) expand nurses' understanding of tobacco use and tobacco control; (2) support and assist smoking cessation efforts of nurses (RNs and LPNs) and nursing students; and (3) enhance the culture of nurses as advocates for tobacco prevention and control. Specific project activities will include the development and launch of a media campaign targeting nurses who smoke, development and dissemination of nurse-specific cessation resources (Internet, counseling, etc.), and development and implementation of training modules for nursing leadership to increase supportive quit environments. This project will be considered successful if it results in a well designed media campaign, a user-friendly and accessible Web resource for nurses, and increased quit attempts by nurses. LVAL,p.Epidemiological studies have clearly established that human papillomas (HPV) infection is a major risk factor for cervical cancer. A number of individuals undergo remission either spontaneously or after clinical intervention, while others, particularly those exhibiting immudeficiency, seem to proceed to develop invasive cancer. It is important to understand the immunological basis for the clinical remission of HPV-associated cervical neoplasia for designing proper intervention strategies. We have determined cell-mediated immunity (CMI) responses specific to synthetic peptides from E6 and E7, the two major oncoproteins of high risk type HPV (HPV-16), in a subset of patients attending the colposcopic clinic. These patients underwent excisional or ablative treatment for cervical intra epithelial neoplasia (CIN) at least six months prior to enrolling in the study. Significant differences were observed in proliferative responses directed against peptides from both the E6 (p=0.002) and E7 (p<0.001) between women without cytological or histological evidence of CIN (disease-free group) and those with a histological diagnosis of recurrence for CIN. Additional pilot studies on in vitro cytokine production mediated by the E6 and E7 peptides, showed a predominant TH1-cytokine profile in women from the disease-free group, while women with disease recurrence exhibited TH2-cytokine responses. On the other hand, none of the women in any of the study groups exhibited circulating antibodies reactive with the E6 and E7 peptides used in the study. Based on our results showing significantly high levels of HPV-peptide-specific TH1 responses in disease-free patients only, we hypothesize that HPV-specific CMI directed against the E6 and E7 oncoproteins is important for protection/recovery from HPV-associated CIN. To test this hypothesis, we propose to conduct a prospective cohort study of women positive for high-risk HPV types and treated for CIN by loop electrosurgical procedure. Our goals are to identify HPV peptides that  LVAL* can potentially serve as markers of protective immunity and for inclusion in immunotherapeutic and/or immunoprophylactic vaccine formulations against HPV-associated CIN. We will assess the pattern of the HPV-specific immunological responses over time, in particular CMI against E6 and E7 peptides corresponding to high-risk HPV types. We will also determine as to whether an association exists between the immune responses and additional HPV-related factors (persistence of infection and HPV type), and other risk factors associated with CIN such as smoking, sexual behavior, intrinsic and extrinsic hormonal factors.LVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long- term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airways reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600.LVAL,p.Life begins in utero typically. Prenatal environmental exposures, coupled with each zygote's genetics and epigenetic imprints, trace a life history path of health outcomes. The central theme of the Pittsburgh Specialized Center of Research on Sex and Gender Factors Affecting Women's Health is the "Genetic And Environmental Causes Of Adverse Pregnancy Outcomes." This major, but still under investigated, priority for women's health urgently requires multidisciplinary research both for the health of adult women and also for the health of developing fetuses and infants. For women, recurrent spontaneous abortions (RSA) are devastating. We have identified transgenerational transmission of a 'miscarriage gene' that may be an extreme example of deviant genomic imprinting. The implications for fetal outcomes are also of great importance, since in utero development of the fetus, both female and male, establishes the very foundation of the infant, adolescent, and adult. Three research projects along with two research cores and an administrative core are proposed under the directorship of Gerald Schatten, Ph.D. and Sarah Berga, M.D., Clinical Director. Project I, "Pregnancy Loss: Genomic Imprinting and Skewed X-Inactivation" (J. Richard Chaillet, MD, Ph.D., P.1), investigates DNA methylation defects in mice responsible for genomic imprinting as well as skewed X-chromosome inactivation, responsible for RSA in women, Project 11, "Epigenetic, Genetic and Environmental Regulation of Pregnancy in Primates" (Gerald Schatten, Ph.D., P.I. and Steve Caritis, MD, Co-P.I.), imaging primate pregnancies and inflammatory responses, addresses sex-specific genomic imprints in genetically controlled and experimentally-manipulated pregnancies. Project III (Julie DeLoia, Ph.D., P.I.), "Maternal and Fetal Consequences of Tobacco Smoke Exposure", analyzes the consequences of smoke exposure in pregnant women and in murine models to understand the interaction of 'genetic variants that jeopardize fetal development and pregnancy.LVAL( The Imaging Core A performs noninvasive micro-PET and MRI imaging with specific probes, including transgenic MR11PET reporters. The Pregnancy Core B establishes and maintains pregnancies through conventional and artificial reproductive technologies (ART) in non-human primates and mice. The Administrative Core fosters intra- and inter-SCOR cooperation to facilitate and accelerate basic and clinical research. The multi-disciplinary, interactive, and collegial environments the new Pittsburgh Development Center at Magee-Women's Research Institute right on the contiguous campuses of the University of Pittsburgh and Carnegie-Mellon University, and brings together accomplished teams of clinical and basic investigators inspiring innovations in non-invasive imaging of pregnancy outcomes. Taken together, this comprehensive investigation will answer major women's health problems regarding the dynamic interplay among fetal and maternal genetics, sex-specific genomic imprints and consequences of our first environmental exposures. As such, it is an appropriate and complementary contributor to the ORWH's new SCOR program.  n kW'@^@Researchn@SHAPIRODAVIDUNIVERSITY OF CALIFORNIA AT LOS ANGELESLOS ANGELESCANIDAR21, DA011903 -p.@@ @9/30/199812/31/20029/30/1998 to 12/31/20024/2005~qHA88,"`z@@ResearchX@SCHWINNTRACIINTERSYSTEMS, INC.NEW YORKNYNIDAR44, DA013305f -p.@@ @8/10/20037/31/20058/10/2003 to 7/31/20054/2005pjf\HA88,"@@u@Researchn@SCHWARTZSTEPHENFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWANIDCRR01, DE012609h  -p.t@P@ n@9/1/19986/30/20039/1/1998 to 6/30/20034/2005|sKB88,"@@Researchp@SCHWARTZSTEPHENUNIVERSITY OF WASHINGTONSEATTLEWANHLBIR01, HL056931p  -p.Biology and CancerP@ @9/15/19988/31/20049/15/1998 to 8/31/20044/2005yrneKB88,"@@ResearchF@SCHWARTZANNWAYNE STATE UNIVERSITYDETROITMINCIR01, CA087895f -p.t@p@ >@6/13/20015/31/20066/13/2001 to 5/31/20064/2005qlh_GB88,"Z@@<@ResearchR@SCHUSTERCHARLESWAYNE STATE UNIVERSITYDETROITMINIDAR01, DA010492Z -p.j@@@4/20/19973/31/20024/20/1997 to 3/31/20024/2005vplcKB88,"@ @Research^@SCHULLERHILDEGARDUNIVERSITY OF TENNESSEEKNOXVILLETNNCIR01, CA042829n @Biology and CancerDiscovery 1b Evaluation 1b@9/1/19863/31/20079/1/1986 to 3/31/20074/2005zuqfMB88,"O@@Researcht@SCHUETZEPAMELABUFFALO STATE COLLEGEBUFFALONYNICHDR15, HD039645,p.Biology and CancerR@@9/1/20026/30/20059/1/2002 to 6/30/20054/2005unjaJB88,"@@u@ResearchL@SCHMITZJOYUNIVERSITY OF TEXAS HEALTH SCIENCES CENTERHOUSTONTXNIDAR01, DA008888(,p.j@@:@6/1/19946/30/20036/1/1994 to 6/30/20034/2005{rFA88,"@V@@Researchp@SCHIFFMAN MARKNATIONAL CANCER INSTITUTEBETHESDAMDNCIZ01, CP010124p,p.Biology and CancerDiscovery 1b Evaluation 1b@10/25/20029/30/200310/25/2002 to 9/30/20034/2005 xsoeJD88,"%@@Research`@SCHEIERLAWRENCEUNIVERSITY OF NEVADA AT LAS VEGASLAS VEGASNVNIDAR01, DA015337,p.@.@T@9/30/200110/1/20039/30/2001 to 10/1/20034/2005}ynKA88,"!@@Researchp@SCHEIBMEIRMONICAUNIVERSITY OF KANSAS MEDICAL CENTERKANSAS CITYKSNINRR15, NR007735>,p.b@R@@9/1/20018/31/20049/1/2001 to 8/31/20044/2005~qLD88," S@/@Researcht@SCHATTENGERALDMAGEE-WOMEN'S HEALTH CORPORATIONPITTSBURGHPANIEHSP50, ES012359,p.t@Discovery 1a Evaluation 1b@9/30/20027/31/20079/30/2002 to 7/31/20074/2005 |xlJB88,"LVAL,p.Up to 30 percent of pregnant smokers spontaneously quit smoking during pregnancy. Unfortunately, the effects of cessation are short-lived with relapse rates reaching up to 70 percent within three to six months following delivery. In spite of established behavioral interventions and pharmacotherapies discovered in the past ten years, the prevalence of smoking in pregnant women, as well as relapse in the postpartum period, remains very high. Gaps in our knowledge exist about the efficacy of coping strategies used by pregnant women to successfully quit smoking. This exploratory study will assess the smoking cessation strategies used by low-income women attending publicly funded prenatal clinics who spontaneously quit smoking during pregnancy and after delivery using quantitative and qualitative methods. The specific aims are to: (1) Describe the coping strategies that low-income spontaneous quitters use during pregnancy and the early postpartum period, (2) Compare the self-efficacy to quit smoking of low-income spontaneous quitters with that of low-income pregnant smokers, and (3) Clarify the relationship between coping strategies and self-efficacy among low-income spontaneous quitters during pregnancy and the early postpartum period. Two county health prenatal clinics will be used to recruit 30 participants for the sample of spontaneous quitters and 150 women will be recruited for the sample of continuous smokers. Data collection for the sample of spontaneous quitters will include face-to-face interviews with participants and questionnaire data collected twice during the pregnancy and once at six-weeks postpartum. For participants who continue to smoke during pregnancy, data collection will be done once and include written questionnaire information. Data analysis methods will include descriptive statistics, Pearson Product Moment correlations, mixed linear modeling and qualitative content analysis. Triangulation of the qualitative and quantitative data will enhance the validity of the findings. LVAL This study will address a critical gap in our knowledge of the primary strategies used by women to remain abstinent from cigarettes. New insights on the key factors associated with successful abstinence will be used to enhance this window of opportunity that pregnancy provides for women smokers.LVAL &AGE Child Fetus/Prenatal DISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Postpartum Parent/MotherADDICTION Cessation Relapse DISEASE/BIOLOGY Cardiovascular/Pulmonary EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingAGE Child ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation Relapse ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumLVAL,p.This two-year investigation is designed to increase our understanding of the precise etiologic and developmental processes that influence adolescent alcohol and other drug use. The proposed study significantly extends a program of prospective research to determine the efficacy of Life Skills Training (LST), a school-based, competence enhancement, drug abuse prevention program targeted to middle school populations. Secondary analyses will be conducted using data from three randomized, school-based, prevention trials including a study of primarily white middle-class youth (N=5800), one containing predominantly Hispanic youth (N=3500) and a third comprised mainly of black inner-city youth (N=5900). Evidence has been obtained from each sample regarding the efficacy of the LST intervention in reducing cigarette, alcohol, and marijuana use with follow-up assessments conducted anywhere from three to six or more years following implementation. An essential next step is to conduct manipulation checks to determine if the reductions in drug use are brought about in the manner hypothesized and whether a multi-component intervention strategy is essential to achieve this goal. The study will specifically focus on determining the relative efficacy of three theoretically driven prevention approaches including: social skills/social competence, personal skills and self-management, and normative education (including strategies to alter cognitions regarding the social acceptability of drug use and information regarding the harmful effects of drug use). A primary analytic focus includes the use of structural equation modeling to test mediation as well as hierarchical linear modeling to control for potential clustering effects that arise from randomization of schools to experimental conditions. An important feature of this research is the use of multiple datasets that share a common assessment of key psychosocial risk mechanisms involved in the etiology of adolescent drug use and the ability to test alternative risk mechan LVAL isms that may operate specifically in ethnic minority populations. This study has the potential of informing prevention science with regard efficacious intervention strategies that extend to a wide range of ethnic groups during the critical and formative years of adolescence.LVAL,p.The focus of this research is to define the natural history of human papillomavirus (HPV) infection and cervical neoplasia, particularly cofactors that explain why cervical HPV infection (a common sexually-transmitted agent) persists and progresses uncommonly to high-grade neoplasia. Accompanying prevention research on HPV diagnostics attempts to improve cervical cancer screening, while projects on HPV immunology are on the forefront of worldwide etiologic and preventive vaccine development efforts (see closely associated HPV vaccines project. The Portland cohort study of 24,000 women was completed in 2001 but specimen testing and data analyses continue. Using a new HPV DNA test, Hybrid Capture 3, we are evaluating HPV viral load measurements at enrollment and risk of developing cervical precancer and cancer. As a follow-up to our finding of an increased risk of cervical precancer and cancer among oncogenic HPV-infected women who smoke versus those who don?t smoke, we in collaboration with Miriam Poirier (NCI) are measuring smoking-related DNA adduct formation in tissues from these women. Among oncogenic HPV infected women, we will also examine the effects of NSAID use and the development of cervical precancer and cancer. The largest active projects are the Guanacaste cohort analyses and the ALTS clinical trial, both in the testing and analyses phases. Several data analyses are projected for the Guanacaste Project for FY 2004, for example: 1) All aspects of HPV DNA, cytology, and visual appearance of the cervix among the 10,000 women during the 7 years of followup, 2) Evaluation of the role of inflammation in the development of high-grade cervical neoplasia, 3) Examining the relationship of cervical immune profiles and the development of high-grade cervical neoplasia, 4) Age patterns of type-specific prevalent HPV infections, 5) Determinants of HPV16 seroconversion and loss of seroconversion, and 6) The acquisition of sexually transmitted infections and the onset of cervicitis after sexual debut. dLVALt More than 20 analyses are underway for the ALTS trial of 5,000 women with abnormal cytology followed for 2 years. There are several ancillary projects underway as part of our investigations in Guanacaste. For example, there is a new study called the Cervical Immunity Study of ~500 women who either exited the Guanacaste Study with oncogenic HPV infection or had newly identified CIN2+ within Guanacaste. The primary goal of the study is to examine the relationships of cervical immunity to HPV clearance, persistence, and the development of CIN2+. The field effort is ongoing and is expected to be completed in 2004 with specimen testing and data analyses to ensue. Projects to identify immune genes and the role that innate immunity plays in HPV infection and progression to cervical neoplasia are being sought. Research continues on identifying and validating biomarkers of risk of progression is being conducted. This includes the validation of p16INK4a as a biomarker of oncogenic HPV infection and cervical disease, and the identification of novel tumor suppressor genes found to be methylated in cervical neoplasia. A new study has been launched to comprehensively identify biomarkers of risk at each progressive disease stage, aimed to identify the molecular events that are necessary and sufficient for progression to cervical cancer LVAL,p.Cigarette smoking is a prototypic case of drug dependence and a dominant cause of coronary artery disease (CAD). In the past several decades, women's rates of CAD and other smoking-related diseases have increased in proportion to their increased exposure to tobacco smoking. Effective smoking cessation interventions have the enormous potential of reducing smoking prevalence and improving women's health. The proposed studies provide a direct and logical extension of our previous research evaluating smoking cessation and relapse prevention (RP) treatments in health-compromised women. Our ongoing work fails to provide strong evidence of RP's superiority over a comparison treatment, and underscores the need to develop more potent interventions to prevent relapse in this refractory population. We propose to do this by combining RP with a new effective and safe pharmacologic intervention. Two parallel, double-blind, placebo-controlled studies will be conducted, each employing a 2 X 2 factorial design that crosses medication (bupropion 300 mg/d vs. placebo) and therapy (RP vs. Discussion Support). Women who smoke will be randomized into one of the four treatment combinations. The 7-week trial will involve weekly clinic visits at which time participants will receive medication doses and individual therapy. The integrated treatment of RP and bupropion 300 mg/d is expected to increase significantly the probability of abstinence and produce improvements in other relevant domains, including self-efficacy, coping, craving, and depressive symptomatology. Study 1 will enroll 104 women with stable CAD. Study 2 will enroll 104 women with significant CAD risk factors, but without diagnosis. The studies are technically rigorous and scientifically innovative. An analogue role-play test will be used to examine coping skills acquisition as a function of treatment and as a predictor of outcome. To verity treatment fidelity we will use written therapy manuals, trained therapists, and adherence checking systems.LVAL Appropriate procedures to safeguard against adverse events will include initial medical evaluation, baseline ECG, daily recording of pill taking and cardiac symptoms using an electronic medication dispensing and diary unit, weekly measurement of vital signs and side effects, and regular contact with the study psychiatrist and cardiologist. The primary dependent measure will be smoking status, validated by saliva cotinine. Assessments at 3-, 6-, 9-, and 12-months following maintenance treatment will be used to evaluate the relative durability of treatment effects. In summary, this research will contribute new theoretical and empirical information concerning the independent and interactive effects of two proven interventions, and shed light on the processes by which these interventions work. We expect that this study will result in the development of an efficacious treatment for smoking in medically at-risk women, and will therefore have major implications for health and health care costs related to drug dependence and medical disorders.LVAL,p.The purpose of this study is to investigate the impact of pre- and postnatal exposure to cigarettes and associated risk factors on infant regulation. Regulation during infancy is defined by the ability to modulate autonomic processes by maintaining physiological homeostasis as well as the ability to modulate responsiveness to both nonsocial and social stimuli. Difficulties with these regulatory processes may interfere with attentional processes and the infant's ability to successfully cope with sensory challenges from the external environment. While several studies have indicated that prenatal exposure to cigarettes is associated with altered regulatory functioning in neonates, it is unclear whether these effects persist beyond the neonatal period. Furthermore, the impact that postnatal exposure to cigarette smoke has on regulatory processes has received almost no attention. This study will examine the possibility that early exposure to cigarettes may impact regulation beyond the neonatal period through several pathways. The first is the direct teratological impact of prenatal cigarette exposure on regulatory processes. The second potential pathway is the impact of exposure to environmental cigarette smoke (passive smoking) on regulatory processes. A third pathway may be through the impact of maternal cigarette use on growth outcomes that, in turn, influence infant reactivity and regulation. The protocol consists of examining mother-infant dyads at 2 weeks of age and again at 7 months of infant age. The final sample will consist of 60 infants who were prenatally exposed to cigarettes, 60 infants who were passively exposed to cigarette smoke and 60 infants who were not exposed to cigarettes either prenatally or postnatally. Assessments of physiological (vagal tone) and behavioral reactivity and regulation will be conducted at both assessment points. In addition, mother-infant interactions and the quality of the caregiving environment (quality of home environment and maternal psychopathology) LVAL will be assessed. The study will provide information about potential teratogenic effects of cigarette exposure on regulatory processes. It will also allow a preliminary examination of potential pathways to dysregulation. Such knowledge may have significant implications for prevention programs designed to ameliorate regulatory disturbances among children exposed to cigarettes.LVALhb $ AGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco UseAGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN HormonesADDICTION Cessation EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Nicotine Replacement Therapy Other Pharmacological PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Fetus/Prenatal DISEASE/BIOLOGY Cancer Mechanisms RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Non-Specified Tobacco Use WOMEN PregnancyLVALThis is a revised competing continuation proposal to study transplacental pancreatic carcinogenesis induced by coadministration of ethanol and the nitrosamine carcinogen NNK in a hamster model. Pregnant hamsters are administered 10% ethanol in drinking water from day 5 through day 15 of gestation and are then given a single intratracheal dose of 50 mg/kg NNK on day 15. The offspring develop adenocarcinomas of the exocrine pancreas with 50% incidence (males) and 77% incidence (females) as well as pancreatitis and marked acinar and ductular cell hyperplasia. Dr. Schuller proposes to investigate the mechanisms of carcinogenesis in this model. The general hypothesis to be tested appears to be that through a combination of b adrenergic actions and in situ bioactivation to reactive intermediates, NNK initiates pancreatic tumorigenesis. The specific aims are 1) to investigate the role of the b-adrenergic receptor pathway in the initiation and development of pancreatic tumors; 2) to investigate the modulation of NNK metabolism and DNA adduction in fetal liver and pancreas by ethanol, 3) to identify mutations induced in K-ras and p53 genes in hamster pancreatic tumors; 4) to investigate the roles of individual cytochrome P450 enzymes in the bioactivation of NNK in fetal pancreas in vitro and in vivo; and 5) to investigate the ability of the nonsteroidal antiinflammatory agent sulindac to modulate pancreatic carcinogenesis. It is proposed that these studies will serve as the basis for developing effective strategies for prevention of cancer in the children of smokers. LVAL -p.As smoking prevalence in the United States has declined, the proportion of current smokers with concomitant psychiatric disorders has increased. Depression, anxiety disorders, and other forms of drug abuse or dependence occur in approximately 33% of cigarette smokers (Breslau, Kilbey & Andreski, 1991). This proportion is even higher in treatment populations (Hall et al, 1993; Glassman et al, 1990; Glassman, 1993). Because these individuals may have greater difficulty quitting smoking, more attention must be given to how to help them achieve smoking abstinence. The proposed study will examine the effect of pretreating smokers with the antidepressant fluoxetine before a standard, state-of-the-art smoking cessation program including cognitive-behavioral therapy and transdermal nicotine patches. [Fluoxetine was selected based on its use in prior research in smokers, its low side effect profile, and its potential to attenuate weight gain associated with cessation.] Participants will be 225 normal, healthy cigarette smokers with or without a history of Major Depressive Disorder (MDD) or current dysphoric symptoms. Participants will be randomly assigned to a treatment group: (1) placebo; (2) 20 mg fluoxetine; and (3) 40 mg fluoxetine. This randomized, placebo-controlled trial involves 14 weeks of fluoxetine (or placebo), 10 weeks of standard transdermal nicotine replacement therapy (6 weeks on 15 mg, 2 weeks on 10 mg, and 2 weeks on 5 mg nicotine patch), and 6 weeks of cognitive-behavioral group therapy with follow up visits at six weeks, eight weeks, ten weeks, three months, six months and one year after the quit date. Fluoxetine will be started four weeks before, the group therapy two weeks before, and nicotine patch on the quit date. The study will examine whether fluoxetine dose dependently improves quit rates and latency to relapse in these participants. It is expected that fluoxetine will be most efficacious in those with a history of MDD or current depressive symptoms. [Two proposed mechanism[s] for fz LVAL luoxetine's effect [will] be examined: reduction of negative affect experienced [prior to and] during smoking cessation [and/or reduction of nicotine craving]. If fluoxetine safely and effectively suppresses negative affect associated with smoking cessation, a new tool will be developed to help those least likely to initiate or maintain abstinence. This could potentially save hundreds of thousands of lives each year in the United States.LVAL#h2 l  P " 4 p48nV.XDRUG USE AND LATENT STRUCTURE OF ADOLESCENT MENTAL HEALTHRESPONSE TO HYPOXIA AND NUTRITION DURING DEVELOPMENTSOCIALIZATION AGAINST SMOKING UPTAKE IN PRE-ADOLESCENTSPEER GROUP NETWORKS AND ADOLESCENT SMOKINGADOLESCENT RISK REDUCTION IN THE PEERS AND PARENTSPHYSICAL ACTIVITY AND WEIGHT CONCERNS: ADOLESCENT GIRLSUNDERSTANDING AND PREVENTING COLLEGE SMOKINGQUANTITATIVE GENE EXPRESSION IN HUMAN LUNG EPITHELIUMCORE-MOLECULAR EPIDEMIOLOGY AND ECOGENETICSADENOCARCINOMA OF THE LUNG: ROLE OF NNK SUSCEPTIBILITYFETAL NICOTINE EXPOSURE EFFECT ON PRIMATE LUNGNICOTINE AND ALPHA7 NICOTINIC RECEPTOR IN LUNG DEVELOPMENTEFFECTS OF PRENATAL EXPOSURE TO NICOTINE ON PRIMATE LUNG DEVELOPMENTDRUG ATTITUDES AND BEHAVIOR ON THE US/MEXICO BORDERINFORMATION PLANNING FOR HEALTH KNOWLEDGE ASSESSMENTTELEPHONE-DELIVERED PEER SUPPORT TO HELP PREGNANT WOMEN STOP SMOKINGBREAST CANCER PROTECTIVE BEHAVIORS AMONG LOW-INCOME, ETHNICALLY DIVERSE WOMEN: THE ROLE OF BIOPSYCHOSOCIAL FACTORSPROGESTERONE AND THE EFFECTS OF NICOTINEPROGESTERONE TREATMENT ON EFFECTS OF STIMULANTS IN FEMALESNEUROBEHAVIORAL EFFECTS OF PRENATAL COCAINE AND NICOTINE EXPOSUREPOOLED ANALYSIS OF PROSPECTIVE ONCOLOGY ACADEMIC AWARDFETAL AND ADOLESCENT NICOTINE EFFECTS ON CNS 5HT SYSTEMSPROSPECTIVE STUDIES OF PANCREATIC CANCER EPIDEMIOLOGYBEHAVIORAL GENETICS OF NICOTINE DEPENDENCEEXPRESSION OF GRPR AS A RISK FACTOR FOR LUNG CANCERVITAMIN B6 ADEQUACY, SMOKING, AND DNA DAMAGEMOLECULAR EPIDEMIOLOGY OF SECONDARY LUNG CANCERMOLECULAR EPIDEMIOLOGY OF HUMAN BREAST CANCERMOLECULAR EPIDEMIOLOGY OF BREAST CANCER: DEVELOPMENT AND VALIDATION OF ACETYLATION METHODS FOR CARCINOGEN-DNA ADDUCT DETECTIONEXTERNAL AND INTERNAL CUES FOR SMOKING IN EVERYDAY LIFEDRUG ABUSE PREVENTION AMONG ADOLESCENT WOMENORAL CANCER--DNA POLYMORPHISMS IN CARCINOGEN METABOLISMCOMMON VARIANTS IN CANDIDATE GENES AND PREMATURE MI RISKADENOCARCINOMA OF THE LUNG IN WOMENFLUOXETINE IN SMOKING CESSATION TREATMENTLVAL -p. In 1998, 80,000 women in the US were diagnosed with lung cancer and incidence rates, particularly of adenocarcinoma, continue to increase among women. Many pieces of evidence suggest that there are gender differences in susceptibility to tobacco carcinogens. Several studies have shown that DNA adducts, p53 mutations, CYP1A1 expression in the lung, and GSTM1 null genotypes are more frequent in females than in males. Reasons for differential susceptibility by gender might be explained by variations in metabolic enzyme functioning or hormonal differences. Some of the same enzymes involved in the metabolism of carcinogens in tobacco smoke are involved in the metabolism of estrogen. The goals of the proposed study are two-fold. First, we will evaluate the role of tobacco smoke and estrogens in determining risk of adenocarcinoma of the lung among women. Secondly, we will evaluate the role of estrogen receptors and c-erbB-2 in lung tumors to further understand the pathways through which estrogen may be acting in the lung. The specific aims are: 1) To conduct a population-based case-control study of the contribution of tobacco exposure, estrogen use, and reproductive history in determining risk of adenocarcinoma of the lung in women. 716 cases will be identified through the Metropolitan Detroit Cancer Surveillance System of the Karmanos Cancer Institute (a SEER participant). An equal number of controls will be selected through random digit dialing. 2) To determine if genotype at the metabolic enzyme loci CYP1A1, CYP1B1, CYP17, CYP19, GSTM1, GSTP1, COMT, and NQO1 are associated with risk of adenocarcinoma of the lung in women. These enzymes are active in both the metabolism of tobacco smoke carcinogens and the synthesis and metabolism of estrogens. 3) To examine gene-gene and gene-environment interactions, focusing on tobacco and estrogen effects. 4) To determine estrogen receptor status (alpha and beta) and c-erbB-2 levels in the lung tumors of women with adenocarcinoma and evaluate risk associated with tobacn LVAL~ co exposure, estrogen use, reproductive history, and genotype at metabolic enzyme loci by tumor characteristics. The proposed study represents a focused approach to defining the contribution of genes and environments in risk of adenocarcinoma of the lung in women. The interview component of the study will provide data about individually measured environmental risk factors. Genotypes have been chosen which impact on biologically effective dose of tobacco carcinogens and estrogens in the lung. The study of tumor characteristics will provide insight into mechanism of action. This large, population-based study should provide clues for important prevention and therapeutic strategies for lung cancer.LVAL -p. Inherited factors play a role in the pathogenesis of myocardial infarction (MI), and there is growing interest in identifying common genetic susceptibility markers that interact with common environmental exposures to contribute to the occurrence of MI in the population. The preliminary data address the contribution of common genetic and environmental factors to the risk of MI among women under 45 years of age. Those data show that common polymorphisms in genes coding for two clotting factors, coagulation Factor V and coagulation Factor II, are risk factors for MI only among cigarette smokers in this sample. These relationships, and others observed, provide strong evidence of gene-environment interactions between thrombotic and atherosclerotic factors in early-onset MI. The plan is to extend this work to investigate the relationship of common putative susceptibility genotypes to the occurrence of early-onset MI in both men and women. One intent is to determine whether the risk of early-onset MI is related to interactions between environmental factors (e.g., cigarette smoking, exercise, alcohol consumption) and common polymorphisms in genes coding for thrombotic factors (coagulation Factor V, coagulation Factor II, plasminogen activator inhibitor-1, and beta-fibrinogen) and atherosclerotic factors (the adhesion molecule E-selectin and metalloproteinase stromelysin-1; the lipid metabolism enzymes paraoxinase, lipoprotein lipase, cholesterol ester transfer protein; and the apolipoproteins apolipoprotein E and apolipoprotein B). Additionally, there are plans to determine whether the risk of early-onset MI is related to interactions between plasma lipoprotein(a) levels (which are largely genetically determined) and environmental risk factors and/or polymorphisms in the candidate genes. Interactions among candidate polymorphisms will also be assessed. Cases will be all 18-49 year old male (n=386) and 18-59 female (n=386) residents of King, Pierce and Snohomish counties, Washington State, newly diagnosed withdLVALt a first, non-fatal MI during a 3.25 year period. Demographically similar controls (n=772) will be ascertained and recruited through random digit telephone dialing. Cases and controls will be interviewed in person to assess medical and behavioral characteristics related to MI risk. A venous blood sample will be obtained and processed into aliquots of plasma and white cells. DNA extracted from the white cells will be tested using the polymerase chain reaction (PCR), PCR/restriction fragment length polymorphisms (RFLP), and oligonucleotide ligation assays to determine the genotypes of interest. Plasma will be tested for lipid, lipoprotein, and homocysteine concentrations. Analyses will address both the overall association between the genotypes and MI risk, along with posited gene-environment and gene-gene interactions. In addition to providing powerful tests of the Specific Aims, this large study will provide a unique resource for testing future hypotheses regarding the role of common genetic susceptibility factors in the pathogenesis of early-onset MI among both men and women.LVAL -p. In the United States, nearly three-quarters of the oral cancer cases are attributable to tobacco and/or alcohol consumption. Oral carcinogens derived from these exposures include N-nitrosamines, polycyclic aromatic hydrocarbons, aromatic amines, heterocyclic amines, and acetaldehyde that are activated and detoxified by enzyme systems in vivo to intermediates with high and low propensity, respectively, to bind covalently to DNA. Growing evidence indicates that inter-individual variation in the activity of many of these enzyme systems is at least in part under genetic control. In this proposed population-based case-control study, the investigators will test the hypothesis that oral cancer risk is associated with polymorphisms in the genes for enzymes that contribute to an individual's ability to activate and/or detoxify tobacco carcinogens. The specific enzymes (genes) of interest are glutathione-S-transferase M1 (GST-M1) glutathione-S-transferase P1 (SST-P1), microsomal epoxide hydrolase (EPHX), cytochrome p450 2E1 (CYP2E1), alcohol dehydrogenase type 3 (ADH3), N-acetyltransferase types 1 and 2 (NAT1, NAT2), and NAD(P)H:quinone oxidoreductase (NQ01). Cases will be 345 18-65 year-old western Washington male and female residents diagnosed with a first oral cancer between 1985 and 1994; controls will be 526 18-65 year-old residents of the same geographic area selected through random digit telephone dialing and frequency matched on age and gender. All cases and controls have been recruited into two oral cancer case-control studies during which the investigators obtained: (1) in-person interviews eliciting extensive tobacco and alcohol consumption histories, and other risk factor information, and (2) a sample of exfoliated oral tissue from which genomic DNA has been extracted and stored for the majority of subjects. During the proposed activity, they will extract DNA from oral tissue of remaining subjects and conduct molecular analyses on DNA specimens to determine the presence of putative high risk genotypl LVAL| es for the genes of interest. Cases and controls will be compared with respect to the frequency of DNA variants, both overall and among sub-groups likely to vary in exposure to carcinogens (e.g., heavy vs. light smokers). The investigators state that the results of this study will contribute to accumulating knowledge regarding the role of genetic susceptibility to environmental carcinogens in determining cancer risk. They further note that in the future such information could provide the basis for both enhanced individual risk assessment, as well as targeted behavioral interventions to reduce exposures among individuals at particularly high risk of developing tobacco and alcohol-related cancers.LVAL -p.Building upon Phase I, Phase II research will develop and test a gender-specific, computerized drug abuse prevention program for early adolescent girls. The prevention program will address risk and protective factors associated with tobacco, alcohol, and other substance use among American adolescent girls within a cognitive problem-solving approach. Once created, prevention content will be programmed onto a CD-ROM for delivery. The CD-ROM will lend itself to self-instruction and will engage girls through original graphics, voice-over and music audio tracks, and interactivity of decision-making responses, behavioral choice selection paths, and skills rehearsals, all presented in context of a previously tested five-step, problem-solving sequence. Field work for Phase II will occur in New York City public middle schools. Ten schools will be randomly assigned to each of two study arms: intervention and control. Consenting seventh-grade female students in all schools will complete a pretest outcome measurement battery, and those in the intervention schools will interact with the initial 10 sessions of the CD-ROM drug abuse prevention program. Posttest measurements in all schools will be followed by booster sessions for intervention schools and two semiannual outcome measurements for all schools. Students in intervention schools will complete the CD-ROM program in computer facilities under the supervision of regular school staff aided by members of the investigative team. Each session will last roughly 20 minutes. Independently, girls will interact with the program, finishing one session per week. Process measures during intervention delivery will quantify the quality of girls' interactions with the prevention, generate dose-response data for analytic blocking purposes, and provide feedback on essential parameters of intervention and experimental control. Outcome effects will be assessed by multivariate behavioral and psychosocial measures. Should the CD-ROM intervention prove effective, we will ensure thatnLVAL~ it is compatible with a variety of personal computer platforms and disseminate the program through licensing and royalty arrangements with publishers of health education materials for youth.LVAL -p.The pharmacologic basis of smoking has received a lot of attention with development of nicotine replacement for smoking cessation. Long-term abstinence achieved by nicotine replacement has been modest, suggesting that smoking involves non-nicotinic factors. The behavior of smoking is subject to conditioning processes and comes under the control of external and internal stimuli that serve as cues for smoking. The main objective of this project is to expand our knowledge of the cues associated with smoking in everyday settings. Data on these associations will be provided by smokers using a diary to monitor their location, activity, moods, and social setting during two work and two nonwork days at times they smoke and at control non-smoking occasions. In addition, subjects will wear devices that record heart rate and physical activity continuously during each day to determine how these measures are associated with smoking. In a second set of four days of recording, subjects will wear either a nicotine or a placebo patch to determine how associations between smoking and the diary and physiological measures are affected by added nicotine. We will also determine the role of smoking rate, gender, nicotine dependence, personality and other characteristics in the above relationships. The specific aims are: 1. To evaluate the stimulus control of smoking in everyday situations using ambulatory methods. 2. To determine whether stimulus control differs as a function of smoking rate, gender, and individual differences in nicotine dependence, hostility, and other characteristics. 3. To evaluate the consistency of stimulus control of smoking from day to day and as a function of social context (work, nonwork days). 4. To evaluate the effects of added nicotine administered by patch compared to a placebo on the stimulus control of smoking and the relation of these effects to gender, smoking rate, and nicotine dependence. 5. To explore the role of heart rate and physical activity level in association with smoking. 6. To * LVAL: explore the role of personality traits (hostility, anxiety, depression) and other characteristics in the above rdationships. Participants in the study will be 60 men and 60 women heavy and moderate smokers. This research should add to our knowledge of non-nicotinic factors in smoking and help in the design of more effective smoking cessation programs.rLVALN  xzADDICTION Maintenance AGE Young Adult Adult DISEASE/BIOLOGY Mechanisms LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Hormones MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingADDICTION Maintenance DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender Differences,LVAL<We propose to establish a new assay for the detection of carcinogen-DNA adducts, use it for the first time in humans, and rigorously validate it to prove its utility for human breast tissue analysis in epidemiological studies. This assay is novel because it uses a new chemical postlabeling method and quantitates adducts by accelerator mass spectroscopy (an ultrasensitive 14C detection unit). We will develop and rigorously validate the assays using benzo(a)pyrene- (BPDE) and 4-aminobiphenyl (4-ABP)-related adducts as prototypes. Then, we will learn the variability for DNA adduct levels in the population as it relates to age, gender, race, and smoking in breast tissues from 235 donors (200 women, 35 men). From a subset, 30 matched blood samples will be used to determine the relationship of breast levels (i.e., the target organ) to blood (i.e., the surrogate tissue). From another subset, 30 matched liver samples will be used to determine the ratio of adducts in the breast to liver, where most metabolic activation in the body takes place. From another subset of 30 individuals, we will assess the relationship between total breast tissue and dissected epithelial cells. Finally, in these 235 subjects, we will perform assays for genetic polymorphisms, to assess the association of "at risk" genetic variants with higher breast adduct levels. The method also improves in vitro cell culture studies of low-level carcinogen exposure because of its sensitivity. To show this, we will use a study p53 induction in cultured primary breast cells, establishing the variability in the population for p53 induction from carcinogens.w x M ? * g@p@4Research@SOLOMONLAURAUNIVERSITY OF VERMONTBURLINGTON VTSFFNot Given@*T@'@@+Not GivenNot GivenUncertain4/2005upl_HA88,"@@@Research@SOLERHOSANNAFLORIDA STATE UNIVERSITYFLCDMRPBC001055@*T@'@@ 200020032000 to 20034/2005wmfbbH?88," }@ (@ResearchP@SOFUOGLUMEHMETYALE UNIVERSITYNEW HAVENCTNIDAR01, DA014537)-p.@'@@ 9/1/20035/31/20079/1/2003 to 5/31/20074/2005pjf[JB88,"g@p@4Researcht@SOFUOGLUMEHMETUNIVERSITY OF MINNESOTAMINNEAPOLISMNNCRRM01, RR000400@(|@'@D@ Not GivenNot GivenUncertain4/2005ztpcJB88,"g@1@Research@SOBRIANSONYAHOWARD UNIVERSITYWASHINGTON DCNIGMSS06, GM008016%-p.Biology and CancerP@@ Not Given2001? to 20014/2005slh[HA88,"@}@Researchl@SMITH-WARNERSTEPHANIEHARVARD UNIVERSITYBOSTONMANCIK07, CA078548#-p.t@@@ 9/7/19988/31/20039/7/1998 to 8/31/20034/2005vqmeQF88,"!@@Researchp@ SLOTKINTHEODOREDUKE UNIVERSITYDURHAMNCNIDAR01, DA014247!-p.Biology and CancerR@b@ 9/1/20015/31/20059/1/2001 to 5/31/20054/2005}nhd\KA88,"@@@Researchj@ SKINNERHALCYONNORTHWESTERN UNIVERSITYCHICAGOILNCIK07, CA109361\-p.t@@@ 7/15/20046/30/20097/15/2004 to 6/30/20094/2005uplcJA88,"@@ResearchT@ SIREVAAGERIKWASHINGTON UNIVERSITYST. LOUISMONIDAR01, DA014374 -p.@p@@8/5/20015/31/20068/5/2001 to 5/31/20064/2005tnj_HB88,"g@p@4Researchf@ SIEGFRIEDJILLUNIVERSITY OF PITTSBURGHPITTSBURGHPANCIP50, CA090440p -p.t@P@@Not GivenNot GivenUncertain4/2005xsocIC88,"@i@ResearchX@ SHULTZTERRYWASHINGTON STATE UNIVERSITYPULLMANWANCIR03, CA089722 -p.Biology and CancerP@@4/1/20013/31/20034/1/2001 to 3/31/20034/2005vqmdG@88,"`@B@Research^@SHIELDSPETERGEORGETOWN UNIVERSITYWASHINGTON DCNCIR01, CA092705 -p.t@T@@1/15/200312/31/20071/15/2003 to 12/31/20074/2005upl_HA88,"g@p@4ResearchZ@SHIELDSPETERGEORGETOWN UNIVERSITYWASHINGTON DCNCIZ01, BC005761j @Biology and CancerDiscovery 1b Evaluation 1b@Not GivenNot GivenUncertain4/2005upl_HA88,"z@1@Research@SHIELDSPETERGEORGETOWN UNIVERSITYWASHINGTON DCCDMRPBC980583 @Biology and CancerDiscovery 1b Evaluation 1b@199820011998 to 20014/2005wpl_HA88,"LVALThe etiology of breast cancer for the most part, remains unknown. Some risk factors for breast cancer have been elucidated, which are mostly related to hormonal status or family history. Yet, these risk factors explain only a portion of the variability in disease incidence. We have been studying the role of genetic variation and gene-environment interactions for breast cancer. With our collaborators, we have focused both on hormonal and non-hormonal risk factors. We previously reported an association for smoking and breast cancer in women who had a decreased ability to detoxify tobacco smoke constituents through the NAT2 gene, as well as some weaker effects for two other genes. Among the most important findings this year, our data indicates that there is a relationship of breast cancer to genetic variation in the superoxide dismutase gene. This gene plays a role in the maintenance of reactive oxygen species in the mitochondria. By itself, the gene was predictive of breast cancer risk, and we found that the risk decreased in women who ate more foods rich in antioxidants. Thus, women have the option of modifying their susceptibility based upon their dietary behaviors. Separately, we have tested and validate the p53 sequencing methodology for the Affemetrix chip technology. More than 100 human breast cancers were sequenced by the method and by direct sequencing, with excellent concordance. We are now applying the method to several breast cancer case series. - breast cancer, Cigarette smoking, Epidemiology, Genetic Susceptibility, - Human Tissues, Fluids, Cells, etc.LVAL -p.Several studies indicate that women with breast cancer who undergo radiotherapy are susceptible to secondary lung cancer, whether they are smokers or nonsmokers. However, all studies to date have methodological limitations and have been small. Also, none have used molecular markers, which can improve exposure assessments or elucidate mediating mechanisms. Over time, radiotherapy methods have changed and doses to the lung have lessened. On the other hand, prevalence of smoking has increased among women in the western world. The identification of lung cancer risk is important in the context of the debates for benefits of radiation therapy in good prognosis tumors or older women. Thus, a study of breast and secondary lung cancer is needed to improve dosimetry assessments for radiation induced lung cancer, with and without an interactive effect of smoking. Also, studying a unique population of women who have had both breast and lung cancer can provide new insights into carcinogeneis and cancer risk. In order to do this, we are proposing a population-based study using the Swedish Cancer Registry (SCR) and determination of radiation doses to the whole lung and side of the lung where the tumor subsequently develops. Reliable smoking data will be available. Our specific aims are to: 1) determine risk factors for secondary lung cancer in women treated with radiotherapy for breast cancer using complementary nested case-control and case-only study designs (n=559 cases and 559 matched controls); 2) to determine p53 inactivation pathways, (i.e., mutational spectra and loss of heterozygosity) in lung tumors of women with a prior history of breast cancer (n=402) and; 3) to determine the frequency of p53 inactivation pathways in breast tumors of women who did and did not develop lung cancer, and compare them to the frequency of p53 inactivation pathways in the lung tumors (n=342 cases and 342 controls). The first aim will allow us to identify risks. The second aim will provide information about the mechanistic relatiR LVALb onship of radiotherapy to lung cancer and may identify a unique spectrum for radiation-related lung cancer. The third aim considers the combined occurrence of breast and lung cancer in a woman as phenotype of susceptibility for multiple primary cases. This study provides unique opportunities. Using the SCR and the unparalleled ability to obtain tissue blocks dating back to the 1950's, we can provide new data to understand risk in the context of molecular markers, especially because we will be able to retrieve the tumor blocks from both the breast and lung cancer from the same women.LVAL -p.We propose to obtain information on the relationship between vitamin B-6 (B-6) intake and cigarette associated with DNA damage and cancer. Preliminary data reveal that vitamin B-6 inadequacy increases uracil incorporation in DNA. Furthermore, smoking reduces vitamin B- 6 status and increases oxidative damage to smoking in men and women by studying functional measures of vitamin B-6 and folate metabolism which are DNA. A controlled diet study will be conducted in men and women, during which 16 subjects (8 smokers and 8 nonsmokers) will be moderately depleted of vitamin B-6 (0.5 mg B-6/d for 28 d), and then repleted using two levels of vitamin B-6 intake (1.3 and 2.1 mg/d, respectively) for successive 28d periods. Venous blood will be collected from fasting subjects weekly; 24h urine collections will be obtained daily. Vitamin B-6 metabolite concentrations [i.e., pyridoxal phosphate (PLP), pyridoxamine phosphate, pyridoxal, pyridoxine and 4-pyridoxic acid] will be determined in plasma and erythrocytes, and PLP concentrations measured in lymphocytes. Activities of erythrocyte alanine and aspartate aminotransferase will be assessed with and without added PLP. Urine will be analyzed for 4-pyridoxic acid. Lymphocytes collected on day 1 and at the end of each experimental period will be analyzed for DNA uracil content, strand breaks, and apurinic/apyridiminic sites. Lymphocyte serine hydroxymethyltransferase (SHMT) activity will be analyzed in the presence and absence of excess PLP. Relationships among vitamin B-6 status, measures of disturbances in DNA composition and smoking will be assessed. The vitamin B-6 intake which optimizes functional measures related to DNA damage and cancer prevention in men and women, smokers and nonsmokers, will be evaluated. This study will permit carefully controlled evaluation of the responsiveness of traditional and novel (i.e., lymphocyte DNA composition and SHMT activity) biochemical status measures to alterations in dietary vitamin B-6 intake and smoking, thereby providin$LVAL4g recommendations for vitamin B-6 intake based on functional endpoints related to cancer prevention.LVAL -p.Gastrin-releasing peptide receptor (GPCR) mediates cell proliferation in the airway through its ligand, gastrin-releasing peptide (GRP), an important mitogen in the lung. Project 1 of the Lung Cancer SPORE will investigate the hypothesis that expression of GRPR in human airway cells is a predisposing risk factor for lung cancer. We further hypothesize that there is a sex difference in human GRPR expression, that may in part be responsible for sex differences in susceptibility in human GRPR expression, that may in part be responsible for sex differences in susceptibility to tobacco carcinogenesis.. Our preliminary data suggest GRPR expression is frequent in the airway cells of non-smoking and short-term smoking males. GRPR expression is also more frequent in cells cultured from long-term male smokers compared to male non- smokers and male short-term smokers. Preliminary evidence further suggests GRPR airway cell expression is found disproportionately in individuals with lung cancer. A corollary of our hypothesis is that GRPR expression may be modulated by both estrogens and nicotine. Estrogens may modulated GRPR expression through estrogen receptor beta expressed on lung fibroblasts and bronchial epithelial cells, while nicotine may modulate GRPR gene expression in the lung through nicotinic acetylcholine receptors on these cell types. We seek to obtain evidence for our hypotheses and its corollary by carrying out four Specific Aims: (1) demonstrate an increased frequency of expression of GRPR mRNA in the airway cells of individuals with elevated risk for lung cancer through a case-control population study to calculate sex- specific odds ratios for association of GRPR gene expression with a diagnosis of lung cancer; (2) quantify expression of GRP in different populations of cells found within airway biopsies of males and females without prior cell culture; (3) examine induction of GRPR expression in human lung fibroblasts and human bronchial epithelial cells from males and females by exposure to nicotid LVALt ne and estrogen, alone and in combination; and (4) examine expression of four other genes that may contribute to lung cancer risk in the same population as in Specific Aim One: gastrin releasing peptide (the ligand for GRPR), Estrogen Receptor alpha, Estrogen Receptor beta, and the GRPR-related gene, Neuromedin B receptor.LVAL -p.This proposed project, which is submitted by a new investigator, will examine genetic influences on biological responses to nicotine in women using a pharmacogenetic paradigm. Specifically, this project will: (i) determine whether there are substantial genetic influences upon reactivity to nicotine in non-smokers, and (ii) examine the relationship between level of reactivity, progression to regular smoking and risk for dependence. Genetic influences upon nicotine reactivity will be determined within the context of a laboratory nicotine challenge protocol which will provide subjective, physiological and performance-based measures of nicotine responsivity in twin pairs stratified by smoking status. Monozygotic (MZ) and dizygotic (DZ) correlations in twin pairs concordant for non-smoking will be used to estimate the contributions of genes, shared environment and within-family environmental differences in experience to variability in measures of nicotine reactivity. Twin pairs can also be observed in smokers. The relationship between nicotine reactivity and risk for dependence will be evaluated by estimating the correlations, stratified by zygosity, of the responses to nicotine in non-smoking twins drawn from smoking-discordant twin pairs with the level of dependence evidenced by the smoking co-twin. Dependence will be defines as score on the modified Fagerstrom FTND Dependence scale. To enhance statistical power, same-sex full siblings of smoking twins will also be tested whenever available. Previous epidemiological studies have indicated that at least some factors influencing smoking dependence appear to be substantially heritable. Data obtained from the proposed project may facilitate the elucidation of critical (phenotypic) differences in biological responses to nicotine. These results could subsequently be used to inform future studies examining the genetics of smoking dependence and persistence and may also impact the development of appropriately targeted smoking prevention and cessation interventioLVALns.LVAL-p.The goal of this award is to build upon my experience in cancer and genetic epidemiology to develop an independent program of research in cancer epidemiology focusing on pancreatic cancer. A three-phase approach combining educational development and mentored research is proposed to achieve this goal. Phase 1 will expand my understanding of the biology and pathogenesis of pancreatic cancer through didactic work and mentored research in cohort and nested case-control studies of pancreatic cancer risk in relation to iron, HFE gene polymorphisms, and Vitamin C consumption. Additional cohort analyses of latitude, calcium, vitamin A, and vitamin D consumption will include sub-classification of pancreatic cancers based on p21 and p27 expression in tumor samples. This work will provide a framework of preliminary results to support future research proposal, and develop my understanding of pancreatic cancer biology as a foundation for developing and investigating novel hypotheses. In phase 2 I will develop advanced skills in mathematics and statistical theory through courses and mentored research will determine the role of cigarette smoking and other established risk factors for pancreatic cancer in initiation, proliferation, and transformation phases of pancreatic tumors by re-analyzing cohort data using an innovative hazard function analysis linked to a mathematical multi-step model of carcinogenesis. Moreover, the feasibility of applying analyses based on multi-step models of carcinogenesis to case-only studies of the age at diagnosis of cancer will be determined. Through phase 3 I will develop local data resources in support of future research proposals by working with clinical and basic science collaborators to expand the epidemiologic questionnaire module of an existing pancreatic cancer patient database. The planned educational development and mentored research in this proposal will expand my understanding of pancreatic cancer biology, develop competency in developing novel methods, and provide essentialxLVAL data resources in support of a career in cancer research.,LVALd  HDISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status LOCATION National PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Partner/Spouse Menstral Cycle Menopause Hormones MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseADDICTION Maintenance Withdrawal DISEASE/BIOLOGY Other Disease/Biology LOCATION National PREVENTION/TREATMENT Other Pharmacological PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle MISCELLANEOUS Sex/Gender DifferencesADDICTION Maintenance EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Other Pharmacological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Menstral Cycle HormonesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH1 Animal Studies TOBACCO Nicotine WOMEN Pregnancy MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology PREVENTION/TREATMENT Nicotine Replacement Therapy RESEARCH1 Animal Studies TOBACCO NicotineDISEASE/BIOLOGY Cancer LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy MISCELLANEOUS Sex/Gender DifferencesLVAL-p."We have developed rodent models of prenatal nicotine exposure that simulate the plasma levels found in smokers or in users of the transdermal nicotine patch, and have demonstrated that nicotine itself is a neuroteratogen that elicits synaptic functional changes appearing after an extended period of apparent normality. These effects target catecholamine systems and we have preliminary data indicating involvement of 5HT systems as well. Brain development continues into adolescence, the period in which nearly all smokers begin smoking, and we have developed a comparable rodent model of adolescent nicotine administration; again, catecholamine systems are targeted and we have preliminary data for 5HT. It is clear that a subset of smokers are using tobacco to self-medicate for depression; additionally, adolescent smoking is associated with higher incidence of subsequent depression. These findings lead to the current hypothesis: namely that nicotine, during a critical period of brain development, alters the set-point for 5HT activity, at the level of presynaptic function, at receptor signal transduction cascades, or both. This will be pursued in fetal and adolescent nicotine exposure models, utilizing neurochemical, cell signaling, and behavioral approaches. Aim 1. To determine how prenatal nicotine exposure alters 5HT synaptic function and behaviors known to be targeted in models of 5HT dysfunction. Evaluate development of 5HT projections, using nerve terminal markers, 5HT turnover, and the ability of acute nicotine challenge to release 5HT; studies conducted from birth to adulthood. 5HT signal transduction assessed with receptor ligand binding and linkages to adenylyl cyclase. Aim 2. To determine whether the critical period for nicotine- induced alterations in the programming of 5HT function extends into adolescence. We will assess 5HT synaptic function and behaviors during adolescent nicotine treatment and withdrawal, using the same endpoints as studied with the prenatal nicotine model. Aim 3.  LVAL To determine whether prenatal nicotine exposure alters the response to subsequent adolescent nicotine administration. Animals exposed prenatally to nicotine will receive adolescent nicotine treatment and the response of 5HT systems and behavior will be assessed, along with catecholaminergic responses and nicotinic receptors known to be affected by adolescent nicotine.LVAL-p.$Candidate: Stephanie Smith-Warner received her doctoral degree in epidemiology, with a focus on nutritional epidemiology, from the University of Minnesota. She has been involved with the conduct of several types of epidemiologic studies and has experience in the areas of study design, questionnaire development, data management and data analysis. Dr. Smith-Warner is interested in strengthening her research background and development as an independent researcher in the fields of cancer epidemiology and nutritional epidemiology. Environment: Dr. David J. Hunter, the current Project Leader of the Pooling Project, has agreed to be the sponsor for this proposal. Dr. Hunter has extensive experience in mentoring graduate students and postdoctoral fellows in diverse areas of study. In addition, the Principal Investigators of the individual studies included in the Pooling Project are enthusiastic about expanding their collaboration to evaluate diet and lung cancer associations. Finally, faculty in the Nutrition Department at the Harvard School of Public Health actively collaborate with scientists in other departments and institutions. This multifaceted, collaborative environment provides unique opportunities for furthering Dr. Smith-Warner's research training. Research Proposal: This proposal builds upon the existing Pooling Project of Prospective Studies and Cancer to evaluate associations between diet and lung cancer, a leading cause of mortality worldwide. Pooling data from multiple studies will permit more precise estimation of the associations and more standardized categorization of exposures and covariates. From the eight studies comprising the Pooling Project for these analyses, approximately 1,753 female and 1,945 male lung cancer cases were ascertained prospectively. The association between lung cancer and fruits and vegetables will be evaluated to determine whether specific fruits and vegetables, rather than total consumption, are most strongly related to lung cancer risk. Due to the recent controvers LVAL y surrounding the association between B-carotene and lung cancer, the relationship with individual carotenoids will be assessed. Relationships with vitamins A, C and E, fat, cholesterol and alcohol also will be evaluated. A methods development aim is to use new analyses of diet diversity and diet indices to examine the effects of total diet, rather than individual components. For each exposure effect modification by smoking status and gender will be examined. These analyses will take full advantage of extensive data already collected in the individual cohorts to provide a powerful analysis of the relation between diet and lung cancer.LVAL-p.&Multiple drug use among female cocaine abusers is common during pregnancy. Estimates are that 85% of pregnant cocaine users also smoke cigarettes; while use of alcohol, marijuana, amphetamine an tranquilizers decreases between the first and third trimesters, tobacco use does not. Despite the frequency of their combined use, there has been no systematic study of the effects of prenatal cocaine and nicotine exposure. However, use of either drug alone during pregnancy is linked with pregnancy complications, impaired growth and subtle behavioral abnormalities, maternal smoking is also a marker variable for long-term intellectual impairment. The proposed research will determine the behavioral sequelae of prenatal exposure to cocaine and nicotine, either alone or in combination, in offspring using a rat model developed in our laboratory. The working hypothesis is that exposure of the developing brain to non-teratogenic doses of these drugs will disrupt the structural and functional organization of the CNS, which in turn will alter behavior in the offspring. The model involves the daily subcutaneous administration of 20 mg/kg of cocaine and/or 5 mg/kg of nicotine by osmotic pump on gestation days (GD) 8 through 21. Both pair-fed and saline-treated dams will serve as controls. Plasma levels of cocaine, nicotine and their major metabolites will be determine in dams on GD 15 and mothers and pups at birth; dopamine and DOPAC levels will be assayed in several brain region in offspring at various ages. Using a split-litter design, males and females from the 5 prenatal treatment conditions will be tested in a variety of behavioral paradigms. A longitudinal (from 1 week to 15 months of age] approach will be used to: 1) identify the behavioral domains (cognitive, emotional/motivational and motor) affected by prenatal cocaine and nicotine exposure; 2) determine whether combined drug exposure exacerbates or ameliorates the behavioral effects of either drug alone; 3) investigate whether these changes represent a delay iRLVALbn the rat of development, a later appearing alteration in functional capacity of the adult, or an induction of premature senescence; and 4) assess the possibility of gender-specific effects. These experiments will provide some of the first longitudinal data on the effects of prenatal exposure to cocaine and/or nicotine on both male and female offspring, and should begin to establish a consensus about the nature of the behavioral abnormalities produce by gestational exposure to these two drugs. The use of a large battery of behavioral tests, and the choice of the prenatal exposure window and drug doses most frequently used will allow for the replication and extension of the work of several laboratories and facilitate the resolution of conflicting findings regarding the effects of prenatal exposure to either drug alone. As the behaviors targeted also reflect cognitive and/or performance deficits reported in the clinical literature, the outcome of this research may serve as a guideline for determining the relative risks of combined use of these two drugs during pregnancy to the offspring. The identification of deficits as transient of long-term and the domains affected may impact the choice of treatment options. LVAL"J N B F j  J*BH"~Addiction Interventions for Prevention and TreatmentEpidemiology and National Surveillance Interventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentInterventions for Prevention and Treatment Global IssuesBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Global IssuesCommunity and Policy InterventionsCommunity and Policy InterventionsEpidemiology and National Surveillance Interventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceAwareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentBiology and Cancer Addiction Interventions for Prevention and TreatmentInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Addiction Epidemiology and National SurveillanceInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentAddiction Epidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsEpidemiology and National SurveillanceEpidemiology and National SurveillanceEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentInterventions for Prevention and TreatmentBiology and Cancer Addiction Interventions for Prevention and TreatmentBiology and Cancer Interventions for Prevention and TreatmentLVALThe main goals of these pilot studies are to obtain pharmacokinetic data for progesterone treatment in female nicotine and cocaine users and to investigate the safety and tolerability of progesterone treatment in conjunction with cocaine administration. The first study will be an open trial in which six female smokers who are in the early follicular phase of their menstrual cycle will be enrolled. Subjects will be given a single mg dose of micronized progesterone and multiple blood samples will be obtained to measure the plasma levels of progesterone. For the second study, cocaine dependent women who are in the early follicular phase of their menstrual cycle will have 2 experimental sessions. Subjects will be administered a single dose of micronized progesterone (200 mg), or placebo on each of two experimental sessions. Starting 2.5 hours after progesterone or placebo treatment, three doses of smoked cocaine (0.4 mg/kg) will be administered. We hypothesize that administration of 200 mg of progesterone will achieve plasma progesterone concentrations similar to those found in the luteal phase of the menstrual cycle, 3-30 ng/ml.LVAL-p.Although women represent close to half of the smokers in the U.S., how sex and phase of the menstrual cycle affect nicotine dependence is not well understood. Studies suggest that women, compared to men, may be less sensitive to the subjective and reinforcing effects of nicotine. The menstrual cycle phase may affect smoking behavior and the severity of tobacco withdrawal symptoms in female smokers. These sex and menstrual cycle effects could be due to fluctuations of female sex steroid-hormones, estradiol and progesterone, within the menstrual cycle. In a pilot study with overnight abstinent female smokers, we have observed that progesterone treatment attenuates the subjective effects of the first cigarette and craving for cigarettes. We conjecture that the attenuation of nicotine's reinforcing effects by progesterone may contribute to the observed sex and menstrual phase effects on nicotine dependence in humans. The goal of this proposal is to extend our preliminary findings by systematically examining the effects of progesterone on smoking behavior, tobacco withdrawal symptoms and subjective rewarding effects of smoking. This will be a double-blind, placebo-controlled study in which male and female smokers will be randomly assigned to one of the 3 treatment conditions: placebo, low (200 mg/day) or high dose (400 mg/day) of progesterone for four days. Subjects will abstain from smoking for the first 3 days of the treatment period, followed by an ad lib smoking session on day 4. We hypothesize that progesterone treatment, dose-dependently, will reduce smoking behavior, attenuate tobacco withdrawal symptoms, and subjective rewarding effects of smoking in both male and female smokers. By characterizing the progesterone effects on nicotine dependence, this study may provide a better understanding of the mechanisms which mediate the sex and menstrual cycle phase effects on nicotine dependence.:LVALNLThis study examined the use of a novel community-based peer support system for women who wanted to quit smoking during pregnancy.Variations in exposure and/or vulnerability to behavioral, psychosocial, and environmental risk factors and resources contribute to ethnic differentials in breast cancer protective behaviors that include preventive (smoking, alcohol, diet, exercise) and detection behaviors (clinical and breast self-exams). The purpose of this research is to study ethnic models of breast cancer protection behaviors in order to identify cultural as well as logistical barriers to these behaviors. Hypotheses: (1) The practice of breast cancer preventive behaviors is directly related to breast cancer detection behaviors; (2) adjustment for the practice of breast cancer preventive behaviors weakens and modifies the relationship between bio-psychosocial, structural, and cognitive factors and breast cancer detection behaviors; (3) bio-psychosocial, structural, and cognitive factors explain a substantial portion of the ethnic differentials in breast cancer protective behaviors; and (4) the extent to which bio-psychosocial, structural, and cognitive factors predict breast cancer protective behaviors differs by ethnicity.vLVAL4 \DISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Nicotine WOMEN PregnancyAGE Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Nicotine WOMEN PregnancyAGE Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary RESEARCH1 Animal Studies TOBACCO Nicotine WOMEN PregnancyECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban Rural National PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies Clinical Research STUDY POPULATION Caucasian Hispanic TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesCOMMUNITY General Partnerships ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Educational Materials RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Womens Group LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Support Group Biochemical Assessments RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN PregnancyLVAL-p.-The Centers for Disease Control has identified 6 priority areas that contribute to 70% or more illness, of the disability, and death of adolescents and young adults, and the development of chronic disease with advancing age. The priority areas are tobacco use, unhealthy dietary behaviors, inadequate physical activity, alcohol and other drug use, sexually transmitted diseases, and behaviors that may result in violence and unintended injury. Enhancing school-based health education programs to address those 6 priority areas is an objective outlined in Healthy People 2010, and the Institute of Medicine has recommended that more attention be given to assessment as a means to assure an effective health education curriculum. Yet standardized assessment of health knowledge regarding the 6 priority areas is not occurring in nearly all states due to a dominant focus on such subjects as math, reading, and science. Given this dilemma other mechanisms for standardized health knowledge assessment need to emerge. The overall objective of this project is to develop plans for a model health knowledge assessment and information management system at a community-based health education center that services 80,000 students yearly, and is one of 40 such centers nationally. Through a multidisciplinary team of educators, researchers, and public officials 3 Specific Aims will be accomplished: 1) plans will be developed for a model information management system that when fully implemented will provide classroom teachers with a composite of their students' knowledge on the 6 priority areas, track changes in student knowledge, and allow for the exporting of the assessment services to other health education centers nationally, 2) plans will be developed for the cross-linking of selected Indiana students' knowledge specific to the 6 priority areas with other data sources pertaining to students' demographics (e.g. socioeconomic indicators, race, gender) and performance on standardized academic tests, and 3) based upon the planning pP LVAL` rocess a grant will be submitted to public and private agencies for implementation of the information management system. The Specific Aims will be completed through a Steering Committee and 5 working groups (i.e. Health Education/Educational Psychology, Information Management and Technology, Geographic Mapping, Human Subjects Compliance, External Liaisons). Those working groups will collectively realize 9 predetermined Outcomes to complete the Specific Aims.  , gB@@ResearchT@STANTONCASSANDRAMIRIAM HOSPITALPROVIDENCERINCIK07, CA0956236F+-p.b@ '@7&@E5/1/20044/30/20095/1/2004 to 4/30/20094/2005rmi]LA88,"g@p@4ResearchPERSONAL MEANING OF SMOKINGSTANTONBONITAWEST VIRGINIA UNIVERSITYMORGANTOWNWVRWJF40676@0b@ '@7@E24 MONTHSNot GivenUncertain4/2005f^UU,"`@@Researchd@STANTONBONITAWAYNE STATE UNIVERSITYDETROITMINIMHR01, MH0692290C+-p.@ '@7d@;6/1/20045/31/20096/1/2004 to 5/31/20094/2005tnjaIA88," @@Researchp@SPRUIJT-METZDONNAUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANIDDKK01, DK059293\A+-p.L@ '@7.@;7/1/20016/30/20047/1/2001 to 6/30/20044/2005}pMF88,"@@ResearchX@SPRUIJT-METZDONNAUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP9KT-0191>+-p.L@'@7@;7/1/20006/30/20017/1/2000 to 6/30/20014/2005}pMF88,"`u@Y@Researchj@SPIVACKSIMONWADSWORTH CENTERALBANYNYNCIR01, CA106186<+-p.Biology and Cancerl@7@;7/1/20036/30/20087/1/2003 to 6/30/20084/2005zkfbZHA88,"g@p@4ResearchV@SPITZMARGARETUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNIEHSP30, ES007784!8+-p.L@'@7z@;Not GivenNot GivenUncertain4/2005xI?88,"\@@Researchn@SPITZMARGARETUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNCIR01, CA0557695-p.t@'@7f@+9/30/19914/30/20099/30/1991 to 4/30/20094/2005xI?88,"@@Research\@SPINDELELIOTOREGON HEALTH AND SCIENCE UNIVERSITYPORTLAND ORNICHDR01, HD037131 3-p.Biology and CancerDiscovery 1a Evaluation 1bd@+2/1/19991/31/20052/1/1999 to 1/31/20054/2005(   }ynHA88,"G@+@Researcht@SPINDELELIOTOREGON HEALTH AND SCIENCE UNIVERSITYPORTLAND ORNHLBIR01, HL066118f1-p.Biology and CancerDiscovery 1a Evaluation 1b@+7/1/20026/30/20077/1/2002 to 6/30/20074/2005(   }ynHA88,"g@p@4Research@SPINDELELIOTOREGON HEALTH AND SCIENCE UNIVERSITYPORTLAND ORNCRRP51, RR000163$ @0Biology and CancerDiscovery 1a Evaluation 1b$@+Not GivenNot GivenUncertain4/2005  }ynHA88,"%@`@Researchf@SPENCERICHARDUNIVERSITY OF TEXAS AT AUSTINAUSTIN TXNIDAR01, DA014794 @/L@'@0@+9/30/20018/31/20059/30/2001 to 8/31/20054/2005{uqhI@88,"@ @Researchh@SOTHMANNMARKINDIANA UNIVERSITYINDIANAPOLISINNLMG08, LM008354,-p.@'@@+9/30/20049/29/20069/30/2004 to 9/29/20064/2005snj\HB88,"@LVALPThe objective of this study is to improve knowledge and understanding of disparities in drug use and related attitudes, perceptions, and behaviors concerning drug use and drug treatment utilization among Hispanic and non Hispanic populations living in proximity to the U.S./Mexico border. This is a geographic area in which the mainstream culture is heavily bicultural, a pattern which is expected to typify an increasingly large segment of the West and Southwest regions of the United States during the next decade. Knowledge gained in this study is expected to benefit service planners who would anticipate need for current and future service strategies to better respond to the problems and needs of Hispanic and bicultural populations. Specific aims are 1) to describe the prevalence of substance use, abuse, and dependence, and the demographic and social correlates of use among households living on the border, and to measure the changes in prevalence that have occurred during the past six years since a similar study was done; 2) to investigate the role of acculturation in explaining differences in substance use within the Hispanic border community; and 3) to determine border residents' attitudes and behaviors related to the utilization of treatment services and the correlates of these attitudes and behaviors. These questions will be addressed through an in-person survey of 1200 adults living in households: 400 from the El Paso metropolitan area, 400 from the Rio Grande Valley metropolitan area, and 400 from colonias (rural, unincorporated communities often characterized by lack of basic public services).LVAL"To examine the personal meaning and social implications of smoking and smoking cessation and how this meaning might impact the decision to discontinue smoking for pregnant, nulliparous adolescents and their male partners.The deleterious effects of maternal smoking during pregnancy are well established. Maternal smoking is the major preventable cause of intrauterine growth retardation and prematurity. Perhaps less well appreciated, is the recent, strong evidence, that smoking during pregnancy directly and adversely affects lung development. Respiratory problems associated with in utero tobacco exposure include decreased lung function, increased respiratory diseases and increased incidence of sudden infant death syndrome (SIDS). Given the unfortunate prevalence of smoking during pregnancy and the resulting serious consequences, it is of major importance to understand the mechanisms underlying smoking-induced changes in the newborn. We have begun to investigate this by administration of nicotine to timed-pregnant rhesus monkeys. In preliminary studies we have demonstrated that exposure of pregnant rhesus monkeys to a nicotine dose consistent with that of smokers alters fetal airway development and that related effects can be reproduced in fetal monkey lung organ culture. Immunohistochemistry shows wide expression of nicotinic receptors in developing lung and nicotine appears to alter the pattern of receptor expression. Preliminary data further suggests that some of the effects of nicotine, acting though nicotinic receptors, may be mediated by antagonism of the mitogenic effects of peptide growth factors such as GRP. From these studies will come the first description of the effects of chronic nicotine exposure on lung function, a determination of the extent to which these effects are reversible, and a beginning understanding of the mechanisms underlying these effects.LVAL-p.2According to the latest statistics from the CDC in 1999, 12.3% of American women smoked during pregnancy, translating to over 400,000 smoke-exposed infants. Smoking during pregnancy is the largest preventable cause of low birth weight, premature delivery, neonatal morbidity, and mortality. Indeed it has been estimated that 10% of all fetal and neonatal deaths are due to smoking during pregnancy. Perhaps less well appreciated is the recent, evidence that smoking during pregnancy directly and adversely affects lung development as manifested by altered pulmonary function and increased respiratory illness in children born of smoking mothers. Remarkably, how smoking produces these effects is unknown. While the cause of pulmonary damage caused by maternal smoking is likely to be multifactorial, it is the basic hypothesis of this application that part of the effect of maternal smoking on lung is mediated by nicotine transported across the placenta to interact with alpha7 nicotinic receptors in developing lung. Our preliminary evidence indicates 1) that alpha7 nicotinic receptors are highly expressed in developing lung; 2) that prenatal nicotine exposure alters alpha7 nicotinic receptor expression in lung; and 3) that collagen gene expression is markedly up-regulated in areas of altered alpha7. Suggesting that nicotine's effect on collagen is mediated by alpha7 receptors, prenatal nicotine exposure has no effect on collagen gene expression in the lungs of cx7 knockout mice. In exciting preliminary data, nicotine inhibits fibroblast proliferation from cells isolated from wildtype neonatal mouse lung, but has no effect on proliferation of fibroblasts from alpha7 knockout mice. This suggests that some of the growth retardation caused by smoking during pregnancy may be mediated by the interaction of nicotine with alpha7 receptors. In this application, using alpha7 knockout and alpha7 gain of function mice, we propose to first demonstrate a link between the effects of prenatal nicotine exposure and alpha7 nAChR, tn LVAL~ hen using cultured pulmonary fibroblasts and epithelial cells begin to determine the mechanism by which nicotine produces these effects. Based on our preliminary data and epidemiologic data on human infants, we will focus on 3 aspects of smoking's effects on lung development: pulmonary function as measured by active and passive tests, cell growth, and collagen expression. From these studies will come some of the first explanations of the molecular mechanisms that underlie the effects of smoking during pregnancy on lung development. These findings will also potentially point to ways to block some of those effects of smoking during pregnancy as well as assist in fighting smoking during pregnancy.LVAL-p.4The deleterious effects of maternal smoking during pregnancy are all too well established. Maternal smoking is the major preventable cause of intrauterine growth retardation and prematurity. Perhaps less well appreciated, is the recent, overwhelming evidence, that smoking during pregnancy directly and adversely effects lung development. Respiratory problems associated with in utero tobacco exposure include decreased lung function, increased respiratory diseases and increased incidence of sudden infant death syndrome (SIDS). Given the unfortunate prevalence of smoking during pregnancy and the resulting serious consequences, it is of major importance to understand the mechanisms underlying smoking-induced changes in the newborn. Our preliminary data suggests that nicotine itself is one of the factors responsible for the changes in pulmonary function observed in neonates born to smoking mothers. In this application we propose to use the rhesus monkey to characterize the effects of chronic exposure to low levels of nicotine throughout pregnancy on lung development and subsequent pulmonary function. Whole animal studies will be complemented with in vitro studies to begin to determine the molecular mechanisms underlying nicotine's effect on lung. In preliminary studies we have demonstrated that exposure of pregnant rhesus monkeys to a nicotine dose consistent with that of smokers alters fetal airway development and that related effects can be produced in fetal monkey lung organ culture. Immunohistochemistry shows wide expression of nicotinic receptors in developing lung and nicotine appears to alter the pattern of receptor expression. Preliminary data further suggests that some of the effects of nicotine, acting through nicotinic receptors, may be mediated by antagonism of the mitogenic effects of peptide growth factors. Thus we specifically propose to 1, Determine the basis for nicotine's actions by determining the time course and cell specific expression of nicotinic receptor subtype expression in fetal  LVAL monkey lung; 2, Characterize the effect of fetal exposure to nicotine on lung development and function by functional, morphometric, immunohistochemical and molecular analysis; and 3, begin to determine the mechanism underlying nicotine's actions by use of fetal monkey lung organ culture. From these studies will come the first description of the effects of chronic nicotine exposure on lung function; a determination of the extent to which these effects are reversible; and a beginning understanding of the mechanisms underlying these effects. Definitive knowledge of the effects of nicotine on lung development would provide an important additional tool in smoking control and will begin to better explain the link between maternal smoking and altered neonatal respiratory function.LVAL-p.6To date our research on susceptibility to tobacco carcinogenesis has focused on the polycyclic hydrocarbon, benzo[a]pyrene, as an in vitro mutagen challenge for functional assays of DNA damage and repair. The tobacco-specific nitrosamine, NNK, is a selective inducer of adenocarcinoma (AC) of the lung, now the leading histologic subtype in the US. We therefore propose to build upon the infrastructure created from our parent grant, "Ecogenetics Study of Lung Cancer" to extend our research to a detailed assessment of susceptibility to NNK, incorporating functional assays of DNA damage and repair and specific polymorphisms in NNK-relevant metabolic and repair pathways. We will enroll 500 patients with newly diagnosed, previously untreated AC of the lung, from M. D. Anderson Cancer Center who are residents of Harris County, Texas, or the seven contiguous counties. Controls (n=500) will be frequency-matched to the cases on age, gender, ethnicity and smoking status (never, former and current) identified from Houston's largest private multi-specialty physician group encompassing a network of 23 clinics. By following the same design for data collection and control selection in the renewal, we can combine previously recruited AC cases (n= 600) and controls (n=600) from the parent grant with this renewal study for epidemiologic and genotype analyses, and thereby achieve time and cost efficiency and statistical power. Epidemiologic analyses will focus on smoking, diet (micronutrients such as isothiocyanates and folate intake), and family history. We propose to apply a panel of functional assays of DNA damage and repair, using activated NNK acetate (NNKOAc) as the in vitro challenge mutagen in the host cell reactivation, comet and micronucleus assays. We will evaluate frequencies of polymorphisms in genes involved in the following carefully selected pathways: metabolic activation and detoxification of NNK; repair via the alkyltransferase pathway; methylation genes; and p53. In a subgroup of cases for whom tumor ti LVAL" ssue is available (estimated 300 patients), we will evaluate genetic (mutations in K-ras) and epigenetic changes (CpG island methylation in the promoter region of select genes). Analyses will focus on diet-gene, gene-environment, genotype/phenotype and surrogate tissue/target tissue genetic and epigenetic correlations. The unifying theme is that susceptibility to the genotoxic effects of NNK is an important determinant of lung AC risk. Identification of high risk smokers has potential for primary and secondary preventive initiatives. This research is also applicable to other sites since tobacco-specific nitrosamines are causative agents in esophagus, pancreas and oral cavity cancers, and are the most prevalent carcinogen in snuff products.pLVALv N T &  n `8&Discovery 1c Discovery 2a Discovery 2b Discovery 3 Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2a Discovery 2b Discovery 3 Development 1 Development 3 Delivery 1 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1c Discovery 3 Development 2 Delivery 1 Evaluation 1aDiscovery 1c Development 3 Delivery 2 Partnerships 2 Evaluation 1aDiscovery 1c Development 4 Delivery 3Discovery 1c Development 4 Delivery 3Discovery 1c Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDelivery 1 Delivery 2 Partnerships 1 Partnerships 2Discovery 1c Discovery 3 Development 2 Development 3 Delivery 2 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 2 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Discovery 3 Development 2 Development 3 Delivery 1 Delivery 2 Delivery 3 Partnerships 2 Evaluation 1aDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1c Development 3 Delivery 2Discovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Evaluation 1aDiscovery 1a Discovery 2a Discovery 3 Evaluation 1aDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1aDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Development 1 Development 3 Delivery 2 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 2b Evaluation 1a Evaluation 1cDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bLVAL+-p.9The overall goal of this research core is to develop and validate genetic markers for cancer susceptibility. By incorporating molecular genetics and cytogenetics into population studies, the investigators hope to gain insights into the complex interactions between genetic and environmental determinants of cancer. Of particular interest are the low penetrance genes that may modulate one's response to environmental exposures and contribute to the etiology of sporadic cancers. Specific aims include maintaining and expanding communication and scientific interaction among Core and other Center members, as well as non-Center members; strengthen current and promote future research activities in the area of genetic susceptibility to environmental disease; stimulate and facilitate intra- and inter-Core grant renewals and new investigators-initiated grant proposals; and serve in consultative and collaborative roles across research and facility cores to include concept development, study design, human tissue procurement and environmental data collection. Major areas of research focus in this Core encompass: 1) the assessment of phenotypic markers of DNA damage and repair as markers of susceptibility to carcinogenesis, 2) the evaluation of polymorphisms in select metabolic and DNA repair genes and DNA adducts in the etiology of lung, bladder, breast, and pancreatic cancers, and 3) the development of statistical models for cancer risk assessment by combining biomarkers and for genotype-phenotype and surrogate-tissue marker correlation. Intra-Core 4 and inter-Core collaborative studies being conducted or completed include the following: 1) a case-control study of lung cancer examining cytogenetic and molecular determinants of tobacco carcinogenesis, 2) a study of genetic and environmental determinants, including phytoestrogen intake, of prostate cancer progression, 3) a genetic epidemiologic study of gliomas in relation to family history and genetic susceptibility markers, 4) a study of microsatellite instability aLVAL:nd the risk of bilateral breast cancer, 5) a study of genetic polymorphisms, epidemiologic risk factors and differences in breast cancer survival among different ethnic groups, 6) a study of DNA adducts, P53 mutation spectrum, oxidative DNA damage and breast cancer risk among premenopausal women, 7) a study of molecular genetics of hereditary nonpolyposis colorectal cancer, 8) a study of modifier genes that influence age-associated risk of colorectal cancer, 9) two studies evaluating environmental and genetic determinants of advanced prostate cancer, 10) studies of second malignancies after treatment for hairy cell leukemia, acute myelocytic leukemia, 11) a study of cutaneous malignant melanoma and non-melanoma skin cancer, 12) a study of linkage and linkage disequilibrium, methods for traits, 13) a study of genetic susceptibility of bladder cancer, 14) a study of mutagen sensitivity and progression in Barrett's esophagus, 15) a study of the genetic, hormonal and behavioral determinants of obesity, 16) a pilot study of breast and colorectal cancers among Egyptians and organochlorine pesticides exposures, and 17) a pilot study to examine associations of mutagen sensitivity, oxidative damage and DNA adducts in lung cancer. The stated long term goal of this Core is to develop a validated risk model for cancer, such as lung cancer, to take into account simultaneously the effects of numerous genetic and environmental factors and the nature of subgroups (women, never-smokers, young subjects, ethnic minorities, etc). Future plans include the use of funds from the Tobacco Settlement for the State of Texas to establish an archival laboratory for the long-term storage and tracking of biological specimens and a centralized genotyping core. It also plans to expand in the area of nutritional epidemiology, and in its molecular epidemiologic studies to include brain and lymphoid malignancies. Future plans also include the development of a genotyping chip, in collaboration with Genometrix, expansion of the CRED websiLVALte and implementation of multivariate statistical analysis to the large database that will be generated by incorporating chip technologies into studies.LVAL 66LOCATION National PREVENTION/TREATMENT Educational Materials RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesAGE Child LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseADDICTION Initiation AGE Child Young Adult EDUCATION LEVEL College and Above EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies Clinical Research STUDY POPULATION Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/Exercise Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco UseLVAL+-p.=Only one in ten current or ex-smokers contracts lung cancer over a lifetime. Lung cancer prevention and early detection strategies all require the identification of a high risk subgroup of tobacco-smokers upon which to focus intensive smoking cessation, chemoprevention and early disease screening efforts. Identifying this high risk subgroup is the long-term objective of this laboratory. Tobacco smoke's composition includes polyaromatic hydrocarbons, nitrosamines, and aromatic amines. Therefore, plausible candidate susceptibility genes may be hypothesized to include those genes encoding enzymes involved in initial carcinogen bioactivation and inactivation, and those involved in quenching in-situ-generated reactive oxygen species, in the lung epithelial cells of first contact with tobacco smoke. Expression of these genes in defined, smoke-exposed lung epithelium has been understudied as it relates to lung cancer risk. Our general hypothesis is that carcinogen and antioxidant metabolizing enzyme expression levels in lung epithelium, by quantitative assays, will identify smokers at high risk for lung cancer. With this laboratory's development of RNA-specific real-time quantitative expression assays for phase I and II carcinogen and oxidant metabolism enzymes, applied to laser microdissected human lung epithelium, it is now feasible to quantify cancer-relevant gene induction in the target cells of interest. Therefore, the specific aims are to 1) Quantify gene expression and interindividual expression differences of selected carcinogen-metabolizing enzymes and antioxidant enzymes in laser capture microdissected, in situ-exposed human lung epithelium, 2) Compare the observed differences with sensitive biomarkers of tobacco smoke exposure (plasma nicotine and cotinine) and an intermediate biomarker (p53- mutation frequency, spectrum, and methylation) and 3) Correlate the gene expression and p53 data with lung cancer case versus control status in multivariate models. We therefore will quantitatively define carLVALcinogen and oxidant metabolizing gene expression - related susceptibility to lung cancer, for future adaptation to broad population screening strategies.LVAL+-p.?In 1981, it was estimated that only 8.2% of college students smoked. By 1998, approximately 28.5% of our college students were reporting regular tobacco use. Similar increases have been found in both private and public institutions, in two year and four year colleges and universities, religious and secular institutions, small and large institutions, in urban and rural institutions, and across gender and ethnicity. Although the precipitous rise in tobacco use has been documented by several independent agencies, prevention programs at the college level are few and far between. Furthermore, most college prevention programs that have been documented have not been able to show significant effects of their prevention and/or cessation efforts. This project was designed to help researchers and health educators understand the processes and mechanisms driving this alarming rise in tobacco use on college campuses across the nation, in order to design evidence-based, relevant and effective prevention and cessation programs for college populations. We were especially interested in developing a knowledge base on why college students are taking up smoking, because research has shown that the best prevention programs are based on solid knowledge of what motivates the population in question to smoke. We thought that stress, low self-esteem, and functional meanings attached to smoking (for example: smoking as a means of weight control, smoking as a means of stress reduction, smoking to conform to norms of peer group) would be major influences on smoking behaviors in college populations. We also thought that there would be gender and ethnic differences in reasons why college students take up or avoid smoking. Our focus was on Mexican American, Chinese, and Caucasian college students. We proposed to examine motivating factors through interviews and questionnaires at three institutions, a private university, a state university, and a community college. Our final aim was to develop and test a model that would describe whLVAL@y college students start smoking and how these reasons for smoking differ between cultures and across genders. The model would serve as a basis for the design of evidence-based college level interventions in the future. To date, the first year of the project has been completed. Interviews have been conducted with Chinese students in Mandarin by a trained research assistant, and are being transcribed. Interviews with Caucasian students and Mexican American students are near completion. A 21-page survey was mailed out to two of the three participating institutions (private university and community college). We are in the final stages of IRB approval at a state university, and questionnaires are ready to be mailed out. Data has been entered for the first two colleges, and preliminary analyses are very promising. In particular, meanings of smoking behavior (the theory and the scale were developed by the PI) seem to explain why college students smoke quite well. Different meanings are important for girls than for boys, and we are examining the data now for cultural differences. We have shown in previous research that prevention programs designed to change specific meanings of behavior can be very successful. We were also able to show in earlier research on nutrition that when meanings are changed through targeted prevention programs, behavior also changes. Originally, this project was conceived of as a three-year project. Because of the nature of the funding (a New Investigator award), when the Principal Investigator received additional NIH funding, it was necessary to terminate the project after this first year. However, because of the importance of the emerging findings and the PI's deep commitment to the research, new funding will be sought in the coming year in order to continue this important project. Using the knowledge gained from this research, we hope to be able to develop state-of-the-art evidence-based tobacco use prevention and cessation programs suited to California's highly diverse collegLVALe population. LVAL+-p.BPhysical inactivity increase risk for obesity, breast cancer, cardiovascular disease, osteoporosis, and type 2 diabetes. Obesity has been directly related to weight concerns and negative body image in adolescent girls, putting them at risk for eating disorders, lowered self-esteem, and depressive symptoms. Further, physical inactivity has been directly related to smoking uptake in adolescents. Compelling evidence now suggests that marked decline in physical activity in girls occurs during early adolescence. However, the documented decline in physical activity is not well understood, and existing theories have consistently failed to describe or predict adolescent exercise patterns. In previous work the Principle Investigator has developed the Theory of Meanings of Behavior, and shown that this is an important psychological element that explains behavioral changes in dietary changes in dietary patterns and sleeping habits in adolescence. In the current proposal, we hypothesize that this new theory will help to explain the decline in physical activity in adolescent girls and provide an innovative approach for interventions that will increase physical activity. This study proposes 1) an in-depth study of the determinants of physical activity in adolescent girls as well as an investigation of the mechanisms that link physical activity to various outcomes, focusing on how long girls interpret the meanings of physical activity, and 2) the development of culturally sensitive intervention to improve physical activity in Hispanic and Caucasian adolescent girls. Dr. Spruijt-Metz's short-term training goals are to acquire skills in body composition research, physical activity and nutrition in children and adolescents, and in advanced statistics. Her long term career goal is to become an independent researcher with an integrated program in adolescent health. The University of Southern California provides an outstanding environment for physical activity and health promotion research in children and adolescents. Thex LVAL department of Preventive Medicine has long fostered the careers of young scientists. The ability of the P.I. to interact with the sponsor, Dr. Goran, in addition to Dr. Anderson-Johnson, Dr. Stacy, Dr. Chou, and other excellent scientist at USC will promote her continued development as an independent researcher.LVAL+-p.DHIV/AIDS remains a significant problem in the Caribbean in general, the Bahamas in particular. With an estimated 4% of adults infected with HIV, the Bahamas has the highest annual incidence rate of AIDS in the English speaking Caribbean. In response, investigators from the United States and the Bahamian Ministry of Health/Princess Margaret Hospital developed and implemented a theory-based, face-to-face adolescent risk reduction intervention, "Focus on Youth in the Caribbean" (FOYC) which was found through two pilot-tests to significantly increase condom use among sexually active females two months post intervention and to alter the perceptions and intentions among males and females. Subsequently, in response to a request from the Bahamian Ministry of Health, the US-Bahamian research team developed a complementary parental intervention, "Caribbean Informed Parents and Children Together" (CImPACT) which was designed to improve parent-adolescent communication regarding safer-sex. Feasibility testing of CImPACT demonstrated that parents could be recruited and enrolled through the schools, would participate, and could be tracked longitudinally. During the pilot testing of both FOYC and CImPACT, relevant assessment instruments were validated for use in the Bahamas. Accordingly, this proposal seeks funding to conduct a three-cell controlled, randomized trial among 900 sixth grade adolescents (ages 11 to 13 at baseline) and their parents from 15 Bahamian elementary schools to assess the differential impact on adolescent risk behavior of: 1) an adolescent risk reduction intervention plus a parent control intervention (FOYC plus control); versus 2) a combined parent and adolescent risk reduction intervention (FOYC plus CImPACT); versus 3) an attention-control for youth and parents (control plus control) to assess both short-term (six months) and long-term (12, 18, 24, and 36 months) intervention effect. The primary outcome domain will be adolescent sexual risk behavior, including a) initiation of sex, b) sex wi LVAL thout a condom and c) protected sex. Secondary outcome domains will be substance abuse, including tobacco, alcohol and drugs, and, two sets of mediating variables: a) youth perceptions of risk and protective behaviors organized by the constructs of the guiding model of behavioral change, Protection Motivation Theory; and, b) parent and adolescent perceptions of parental monitoring and parent-adolescent communication.LVAL\ 6 pRfAGE Child Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology RESEARCH1 Animal Studies TOBACCO Nicotine WOMEN PregnancyAGE Child EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother MISCELLANEOUS Sex/Gender DifferencesAGE Child EDUCATION LEVEL Less than High School LOCATION National PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Parent/Mother MISCELLANEOUS Sex/Gender DifferencesADDICTION Initiation Maintenance Cessation AGE Child EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking Non-Specified Tobacco Use Nicotine WOMEN Pregnancy Partner/Spouse MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionLVAL+-p.GThis K07 proposal in cancer prevention, control, and population sciences will enable the applicant to build on our existing knowledge of individual-level pathways and trajectories of tobacco use by examining contextual factors and group level processes to yield more comprehensive understandings of the etiology of tobacco use. Peer groups play a critical role in the initiation and progression of adolescent smoking. Most studies of youth smoking have used the individual as the unit of analysis and peer smoking has been measured by adolescent report of their friends' smoking. The conceptual framework and methodology of social network analysis utilizes peer-nomination data to construct friendship links that allow patterns of relationships among individuals to be determined and interpreted within the context of the larger social environment. This methodology has been underutilized as a mechanism for understanding the development of health behaviors in youth and few studies exist that have used the peer group as the unit of analysis to understand social influences and youth tobacco use. The research design comprises two studies, each aimed at understanding the social context in which peer group membership is related to youth smoking. Study 1 will use existing data from the National Longitudinal Study of Adolescent Health to examine whether influence on smoking occurs within the context of adolescent peer groups across two time points. Potential moderator variables such as gender, ethnicity, and parental variables will be examined. Study 2 will involve two years of novel data collection that will focus on vulnerabilities to prosmoking socialization influences in a sample of pre-adolescents in one social network system of an ethnically diverse urban middle school. The goals of the career development plan are to broaden conceptual and analytic knowledge of social network analysis as it can be applied to peer group formation and stages of cigarette smoking in youth and to develop innovative methodologies to bri LVAL dge the analysis of individual and group level data. This training plan is intended to provide mastery of skills in group level analyses and promising new methodology that will enable the applicant to develop an independent program of cancer prevention research. The long-term objectives are to translate knowledge derived from studies of contextual influences on the etiology of tobacco use into culturally sensitive, developmentally appropriate, and novel prevention interventions that reinforce protective influences in youth's social environments.LVALUtilizing a longitudinal design and drawing subjects from an ongoing study, this investigation will examine the underlying socialization mechanisms that protect children from smoking uptake in early adolescence and will evaluate a model of direct and indirect effects of parental and peer anti-smoking protective influences on pre-adolescents. While important social influences on smoking initiation have been identified in previous research, an adequate understanding of specific protective socialization mechanisms for children from different ethnic backgrounds remains elusive. Approximately 291 pre-adolescents (ages 9-13) will be recruited and followed for 18 months through primary care clinics in an urban children's hospital. As part of an existing research protocol, parents and children will complete measures at three time points of smoking status, parental socialization practices, perceived peer use, exposure to tobacco products from parents and friends, and general parenting practices. Preliminary cross- sectional analysis of baseline data will be conducted to examine independent socialization predictors of smoking uptake. In addition, multiple group comparisons of a longitudinal model of indirect and direct socialization influences on smoking uptake will be conducted for different gender and ethnic groups. a X K >. V:z@1@ResearchD@ OTENGSTAMMYUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECACTRDRP6PT-3005_:-p.D@'N@7@Y1/1/199812/31/20011/1/1998 to 12/31/20014/2005~vrjF?88,"`~@b@ResearchL@OTASHKINDONALDUNIVERSITY OF CALIFORNIA AT LOS ANGELESLOS ANGELESCANHLBIU10, HL059293T@^@'@7 @Y2/1/19981/31/20032/1/1998 to 1/31/20034/2005rIA88,"c@@Researchf@OTALBOTPRUDENCEUNIVERSITY OF CALIFORNIA AT RIVERSIDERIVERSIDECACTRDRP6RT-0039#[:-p.Biology and CancerR@7&@Y7/1/19976/30/20017/1/1997 to 6/30/20014/2005 |qJ@88," 1@@Researchp@OSWENSONKARENPARK NICOLLET INSTITUTENot GivenNot GivenCDMRPBC022320 @Zt@'Discovery 1b Evaluation 1bd@Y200220052002 to 20054/2005~wlaHA88,"^@@ResearchMAINE PRENATAL COLLABORATIVESWARTZSUSANMAINE MEDICAL CENTERPORTLAND MERWJFNot GivenZ@XX@'l@7@R1/1/200312/31/20051/1/2003 to 12/31/20054/2005{e^VV,"`@@Researchl@OSWARTZLYNNEOREGON CENTER FOR APPLIED SCIENCE, INCEUGENEORNCIR44, CA077986 @WT@'@7@R2/1/20011/31/20052/1/2001 to 1/31/20054/2005{woG@88,"@@ResearchH@OSWANGARYSRI INTERNATIONALMENLO PARKCANIDAR01, DA016427~U:-p.@'@7@R7/15/20044/30/20097/15/2004 to 4/30/20094/2005|mgcWD>88," M@ @Researchn@OSWANGARYSRI INTERNATIONALMENLO PARKCANCIR01, CA071358S:-p.@'@ 7@R1/3/19977/31/20091/3/1997 to 7/31/20094/2005{lgcWD>88," @^@Researchv@OSWANGARYSRI INTERNATIONALMENLO PARKCACTRDRP7PT-2002P:-p.@'@ 7T@R1/1/199912/31/20021/1/1999 to 12/31/20024/2005yogcWD>88,"g@p@4Research@OSTRETCHERVICTORUNIVERSITY OF MICHIGANANN ARBORMISFFNot Given@T@'N@ 7n@;Not GivenNot GivenUncertain4/2005wrncKC88," @S@Researchj@OSTOTTSANGELAUNIVERSITY OF TEXAS HEALTH SCIENCES CENTERHOUSTONTXNCIR03, CA084805M:-p.T@'@ 7h@E9/30/19999/29/20029/30/1999 to 9/29/20024/2005}tH@88,"@ @Researchr@"STORRCARLAJOHNS HOPKINS UNIVERSITYBALTIMOREMDNIDAR01, DA016323K+-p.b@'l@ 7@E4/1/20043/31/20074/1/2004 to 3/31/20074/2005uok`F?88,"c@@Researchh@!STARKRAYMONDCOLUMBIA UNIVERSITY HEALTH SCIENCESNEW YORKNYNICHDP01, HD013063@JBiology and CancerDiscovery 1a Evaluation 1b@E8/1/19796/30/20058/1/1979 to 6/30/20054/2005&{wmH?88," !@p@4Researchn@ STANTONCASSANDRAMIRIAM HOSPITALPROVIDENCERINCIF32, CA088457b @Hb@ '@7@E8/26/2001Not Given8/26/2001 to?4/2005rmi]LA88,"LVALThe central theme of this Program is based on the axiom that, during early stages of development, organisms are uniquely vulnerable to environmental challenges that constrain the physiological and behavioral phenotypes that are manifest throughout the rest of the life span of the organism. Understanding the mechanisms that confer risk or resistance to these challenges is the fundamental goal of the work done in all of the projects. The first Project, "Activity and Responses to Hypoxia/Nicotine in Development" examines the risks conferred on the developing fetal baboon by nicotine in smoking cessation programs for pregnant women and in understanding postnatal vulnerabilities of these infants for SIDS, attention deficits, and other neurobehavioral disorders. The second project, "Activity and Responses to Nutrient and Oxygen Supply" focuses on nutritional challenges experienced by the growth restricted fetal lambs and by very low birth weight infants during their adjustment to extra- uterine life. Knowledge of the short-term physiological responses and adaptations to variation in nutrient supply are the logical starting point for understand the long-term risks associated with inadequate nutrition early in life. The third project, "Perinatal Nutrition and Mechanisms of Adult Disease", addresses the long-term consequences of nutrient deprivation early in life. Research focuses on changes in placental and fetal gene expression that represent proximal steps associated with nutrient programming, the role of endogenous versus exogenous factors in stabilizing the programmed phenotype and how later nutrition and growth serve to amplify effects of fetal programming. An administrative, statistical and computer Core and molecular/bioanalytical Core support the needs of the research.LVAL+-p.LWith cross-classification used to probe for possible male-female and child-adolescent variation, recently published evidence on the mental and behavioral disturbances of young people seems to confirm dimensional models of anxiety and depression (Wadsworth et al., 2001) as well as attention problems (Hudziak et al., 1999). In this new R01 project, the main goal is to investigate youth drug use as it relates to latent structure of mental and behavioral disturbances across age strata in adolescence (12-13,14-15,16-17 years), with due consideration for different drug types (inhalants; club drugs like ecstasy; marijuana; tobacco; alcohol) and levels of drug involvement. Once the underlying latent class structures have been elucidated, and class memberships have been assigned based on the best-supported class structures, the applicant will turn to regression models to probe research questions pertinent to (a) the co-occurrence of adolescent drug involvement and disturbances of the mental life, behavior, and social adaptation, (b) probing for variation in the latent structure across subgroups defined by race-ethnicity to perhaps aid in understanding health disparities that affect minority subgroups, and (c) the clustering of the class members within local areas of residence within the United States, with a specific focus upon analyses that will probe how drug use might sustain delinquent peer groups. The data are from 13,831 youths (age 12-17) recruited after nationally representative sampling for the National Household Survey on Drug Abuse (NHSDA) in 1994-1996. For the NHSDA, the youths completed standardized modules on drug involvement, as well as a survey adaptation of Achenbach's Youth Self Report (YSR). The YSR is perhaps, the most. widely used instrument for measuring youth disturbances in the mental life, behavior, and socxal adaptation. In sum, the plan of research is one that exploits an untapped research opportunity to learn more about adolescent drug taking as it relates to disturbances of the men LVAL tal life, behavior, and social adaptation. The plan involves the use of two relatively recent biostatistical developments in the form of latent class regression and alternating logistic regression models, which are innovative approaches to the study of research questions that previously have not been asked in large-sample epidemiological studies of national scope.LVAL:-p.NAdverse health effects of cigarette smoking on pregnancy outcomes are significant and costly. Despite the well-publicized risks, almost one-quarter of women continue to smoke throughout pregnancy. Further, women from disadvantaged backgrounds are over-represented among pregnant smokers. Innovative smoking cessation interventions are needed to increase quit rates in pregnant smokers, particularly in low socioeconomic populations. The proposed study evaluates the feasibility and efficacy of theoretically innovative prenatal smoking cessation intervention based on Motivational Enhancement Therapy (MET). A randomized, controlled, pretest/posttest, between groups design will be employed to compare MET with usual care for reducing smoking rates among pregnant women. Sixty-seven pregnant smokers, at least 16 years of age and attending a university-based, public clinical will be assigned to each of the two groups. In addition to achieving higher abstinence rates, we expect that the MET intervention will produce significant changes in several domains of function (e.g. coping, self-efficacy, readiness to change). Smoking outcomes will be assessed via objective (saliva cotinine analyses) and self-report measures. Logistic regression procedures will be used to examine posttreatment smoking group differences. Repeated measures analysis of variance will be used to evaluate treatment related changes in other domains of functioning. MET strategies and techniques are implemented using an empathic, non- confrontational yet directive counseling style to enhance motivation and reduce ambivalence about change. The MET intervention consists of four counseling sessions and one stages of change based, personalized feedback letter delivered over 8-weeks. The first counseling session will occur at the clinic during a woman's first prenatal visit with the three subsequent sessions being conducted by telephone. Therapy manuals, trained counselors, competency checks, and adherence rating scales will be used to veLVALrify treatment fidelity. This research will contribute important theoretical and empirical information concerning the efficacy of a new and innovative intervention for pregnant smokers and will provide the basis for larger effectiveness trials.LVAL% d B < |  P|n8l ZjLSMOKING RELAPSE PREVENTION AMONG POSTPARTUM WOMENINDIVIDUALIZED RELAPSE PREVENTION AMONG WOMEN SMOKERSPERINATAL DEPRESSIVE SYMPTOMS AND SMOKINGGENDER, RACE, ETHNICITY AND SMOKING INITIATION AND CESSATIONMOTIVATIONAL COUNSELING AND IMMEDIATE BIOFEEDBACK (DIPSTICK)PRENATAL SMOKING AND AGGRESSION IN TWINSEXPOSURE OF CHILDREN WITH ASTHMA TO HOUSEHOLD ETSPRENATAL SMOKING AND PRESCHOOL BEHAVIOR PROBLEMSEXERCISE INTERVENTION FOR DEPRESSED SMOKERSEFFECT OF SMOKE AND GENDER ON BRONCHIOLAR INJURY AND REPAIRPRENATAL TOBACCO SMOKE AND EXPRESSION IN AIRWAYSGENDER, MENSTRUAL CYCLE, AND SMOKING CUE REACTIVITYSUSCEPTIBILITY TO SMOKING AMONG ADOLESCENT NEVER SMOKERSINTERVENTION TARGETING TOBACCO USEEFFECTS OF PASSIVE SMOKING AND PREGNANCYSMOKING DURING PREGANCY: NEWBORN AND MATERNAL GENETIC DAMAGETREATING CHINESE SMOKERS WITH INTERACTIVE EXPERT SYSTEMSSMOKING AND DEPRESSION IN CHINESE VS. NON-CHINESESENHANCING SUPPORT FOR WOMEN AT RISK FOR HEART DISEASERESOURCE KIT FOR ADOLESCENT TOBACCO CESSATIONDEVELOPMENT OF RESOURCE KIT FOR ADOLESCENT CESSATIONNICOTINE AND CENTRAL ALPHA 2 ADENOCEPTORSINCENTIVES PLUS BUPROPION FOR SMOKING IN SCHIZOPHRENICSSMOKING CESSATION AMONG WOMEN OF CHILD-BEARING AGEHYPERSENSITIVE DISORDERS OF PREGNANCYGENE ENVIRONMENT INTERACTIONS IN WOMEN WITH BREAST CANCER AND SECONDARY LUNG CANCERIDENTIFYING HIGH LEVERAGE TOBACCO POLICIES AND RESEARCHCOMPREHENSIVE TOBACCO POLICY MODELLUNG HEALTH STUDY--LONG TERM FOLLOW-UPFERTILITY, SMOKING, AND EARLY MAMMALIAN DEVELOPMENTPREDICTORS OF LYMPHEDEMA FOLLOWING BREAST CANCER SURGERYPHARMACOLOGICAL AIDS FOR INTERACTIVE SMOKING CESSATIONIMPACT OF SMOKING CESSATION ON SLEEPTREATMENT OF NICOTINE DEPENDENCE IN HEALTH CARE SETTINGSEGREGATION ANALYSIS OF PATTERNS OF TOBACCO USE IN FAMILIESQUIT FOR KEEPS - TAILORED GUIDE TO GIVING UP SMOKING FOR PREGNANCY AND BEYONDMOTIVATIONAL ENHANCEMENT THERAPY FOR PREGNANT SMOKERSLVAL:-p.QThe proposed study will examine the extent to which hereditary factors operate alone or in combination with environmental factors to determine whether adolescents are likely to experiment with tobacco or become regular smokers. The data to be used in this study derive from 763 adolescents, their parents, and their siblings. As part of the "SMOFAM" study being conducted by the Oregon Research Institute (ORI), these study participants have provided information about their substance use, including tobacco, at 12 assessments over the past 14 years. In addition, they provided information about the many psychological and environmental factors that are known or hypothesized to be related to smoking. In Study 1 of this Integrated Research Proposal, we will combine existing data from ORI with in-depth measures of nicotine dependence (collected by the Statistical Core), cotinine clearance data (Study 3), and genetic data (Study 2) to (1) determine and combine descriptions of nicotine addiction in young smokers and their families; (2) analyze family data to determine whether nicotine addiction as defined in 1 above have parent-offspring patterns suggestive of genetic influence; (3) use the Transmission Disequilibrium Test (a recent approach to determining genetic associations) to determine the presence of genotype-nicotine addiction associations in ever-smoking children; (4) use a variation of the TDT to examine the data for evidence of gene-environment interactions in determining susceptibility to tobacco use; 5) identify independent and joint genetic and environmental factors that predict the speed with which young people transition from experimentation with tobacco to regular use; 6) identify subgroups of young people based on unique combinations of genetic and environmental risk factor profiles and who differ with respect to the age at which they experimented with tobacco and then began to smoke on a regular basis. The successful completion of this analysis will provide evidence on: 1) both the limits and  LVAL" extent of genetic involvement in the susceptibility to become a regular smoker in young adults, and 2) the extent to which genetic and environmental risk factors operate independently or jointly to determine the susceptibility to becoming a regular smoker, the speed with which young people become regular smokers, and the age at which they become regular smokers. BLVAL 2ZCOMMUNITY Health Care Provider LOCATION National MARKETING Media-Websites/pamphlets/radio POLICY Guidelines/Best Practices RESEARCH Human Studies TOBACCO Non-Specified Tobacco Use WOMEN PregnancyAGE Adult LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials Nicotine Replacement Therapy Other Pharmacological RESEARCH Human Studies Clinical Research STUDY POPULATION Caucasian TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Withdrawal Relapse DISEASE/BIOLOGY Other Disease/Biology LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Buproprion Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Cessation AGE Adult COMMUNITY Health Care Provider EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Quitline Educational Materials Buproprion PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use Nicotine MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesAGE Child Young Adult Adult DISEASE/BIOLOGY Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine WOMEN Parent/Mother MISCELLANEOUS Sex/Gender DifferencesLVAL:-p.TThe purpose of this revised application is to expand and continue the research begun in the previous funding period, Treatment of Nicotine Dependence in an HMO Setting, in which 1,524 individuals enrolled in a health care system received treatment with bupropion SR and behavioral counseling and were then followed for 12 months after their target quit date to determine smoking status. The results of this study demonstrate that: (1) an effectiveness trial can be conducted in a large health care system; (2) 150 and 300 mg doses of bupropion SR are equally effective for smoking cessation at 12 month follow-up; (3) proactive telephonic based (PTB) treatment is more effective than a tailored mailing (TM) program; (4) female gender, lower education, and higher levels of depression are independent risk factors for post-treatment smoking; and (5) there is substantial heterogeneity in treatment outcome among women and men at one year follow-up. In addition, cost-effectiveness analyses showed that 150 mg bupropion SR is more cost effective than the 300 mg dose from both the payer (i.e., employer) and societal perspectives. The next generation of this research program will evaluate the effectiveness of three different intervention approaches in combination with 150 mg bupropion SR: a proactive telephone-based (PTB) tobacco cessation program, a web-based (WB) tobacco cessation program, and a combined PTB+WB program. Participants (n=1,200) will be randomized to one of the three behavioral treatment conditions, receive an eight week course of 150 mg bupropion SR, and then followed at various points throughout a 12-month period to determine indices of medication adherence, treatment utilization, point-prevalent smoking outcomes and continuous nonsmoking. The specific aims of this project are: (1) To determine the relative effectiveness of each version of the behavioral treatment in combination with 150 mg bupropion SR; (2) To determine group differences in adherence to both the bupropion SR and behavioral conditions; LVAL (3) To examine heterogeneity in responsiveness to the three treatment conditions with Classification and Regression Tree (CART) Analysis; (4) To characterize process variables related to recruitment, implementation, barriers to treatment, exposure to intervention, satisfaction with treatment, treatment contamination, and program maintenance; (5) To determine the cost-effectiveness of the different delivery modes offered in the proposed trial; and (6) To disseminate the results of the proposed trial to the adult GHC consumers (approximately 500,000), providers, and other key stakeholders in GHC's integrated care model (n=1,400). LVAL:-p.VThe vast majority of attempts to quit smoking end in failure due to many reasons including the presence of aversive withdrawal symptoms. Given the health consequences of continued smoking, treatment ineffectiveness leads to substantially elevated morbidity and mortality, with immense financial and human cost. One of the commonly reported symptoms, sleep disturbance by itself, can act as an amplifier of many of the other symptoms, as sleep disturbance in other medical conditions and in experimental situations has been found to produce dysphoria, difficulty thinking, and drowsiness. Bupropion, an agent effective in assisting smoking cessation, also has sleep disturbance as a commonly identified self-reported side effect with prevalence estimates of from 30-50 percent among quitting smokers. Likewise, the use of transdermal nicotine is associated with reported sleep disturbance, especially when used over 24 hours. Combination treatment of bupropion and transdermal nicotine has been shown to produce sleep disturbance in nearly 50 percent of cases, compared to 20 percent of quitting smokers using a placebo. The world' s literature on smoking cessation and objectively measured sleep disturbance is based on fewer than 80 subjects. We propose to utilize a randomized, four-group design with repeated measurements of withdrawal and sleep disturbance to evaluate the effect of smoking cessation following treatment with behavioral counseling in combination with either placebo bupropion and nicotine patch, active bupropion, active patch, or combined active bupropion and patch in male and female smokers. Subjects will be followed for a period of twelve months to determine abstinence (confirmed by expired-air CO). A key aspect of the research design is the use of newer definitions of arousal that may more accurately reflect the true extent of sleep disruption following smoking cessation. The specific aims are to: 1) characterize the effect of smoking cessation on sleep using state-of-the-art techniques in measurement VLVALfof central and autonomic nervous system arousal, in a sample larger than the total number of smokers studied in sleep laboratories to date; 2) determine the impact of currently recommended smoking cessation treatments on sleep and sleep disturbance; 3) evaluate the impact of smoking cessation treatments on daytime sleepiness and mood; and, 4) assess the effect of sleepiness and mood disturbance on relapse. The following hypotheses will be tested: 1) Smoking cessation will be associated with disturbed sleep, increases in EEG and autonomic arousals from sleep, and a relative shift to sympathetico-vagal balance during the sleep period; 2) The use of bupropion and transdermal nicotine will lead to further increases in sleep disturbance over and above those seen with smoking cessation; 3) The cessation-related and treatment-related increases in sleep disturbance will be positively related to an increase in daytime sleepiness and negative mood, and decreased daytime performance; 4) The cessation-related increase in sleep disturbance, daytime sleepiness, and negative mood will positively correlate with relapse within twelve months; 5) The negative impacts of pharmacotherapy treatment for the withdrawal effects of smoking cessation will be greater in women than in men. The results of this project will be particularly important for the development of targeted treatment approaches designed to ameliorate sleep disruption as part of an overall smoking cessation strategy.LLVAL\Pharmacological aids such as nicotine replacement (NR) products and buproprion (Zyban) have been demonstrated to be efficacious under FDA-specified conditions. However, despite the improved success in stopping smoking associated with using such products, many people either do not use them or do not use them properly. The primary aims of this project are to develop and test a tailored multimedia intervention designed to improve smoking cessation success by: a) motivating cigarette smokers to use pharmacological aids such as NR products and Zyban, b) assisting them in choosing the type of pharmacological aid best suited to them, and c) ensuring that they employ optimal technique for the use of the chosen pharmacological aid. In Phase I, a complete NR/Zyban intervention segment tailored for the older, Caucasian, female subpopulation was produced for use with our previously developed interactive multimedia smoking cessation programs. The efficacy of the segment was demonstrated in a randomized-control trial. In Phase II, we will develop pharmacological intervention materials explicitly tailored to the characteristics and needs of eleven other sub-populations (using three dimensions: age, race/ethnicity, and gender). The pharmacological intervention materials developed in Phase II will be disseminated in both kiosk and Internet/intranet formats.LVALThe project will implement a Clinical Practice Collaborative, with the primary objective of enhancing interventions with pregnant smokers during prenatal care. Teams will have the mutual goals of sharing information, goal setting and problem solving. Project staff will introduce the PHS Guidelines and provide technical assistance in quality improvement processes and monitoring outcomes. In the pilot phase, social marketing experts from the Sutton Group will conduct formative evaluation with the pilot practices, as well as be involved in the first Collaborative group. Emphasis will be placed on practical strategies that can be integrated into routine practice, and tracking progress in the real world of busy, complex clinical practice settings. The project aims to improve interventions by raising clinical staff self-efficacy, promoting a team approach, improving delivery system design, and using patient self-management tools.LVALv V AGE Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION American Indian/Alaskan Native TOBACCO Cigarette/Other Smoking WOMEN PregnancyDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN HormonesECONOMICS Cost of Intervention/Prevention Cost of Smoking LOCATION National POLICY Guidelines/Best Practices Regulatory Intervention Other Policy TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesECONOMICS Cost of Intervention/Prevention Cost of Smoking LOCATION National POLICY Excise Tax Guidelines/Best Practices Regulatory Intervention TOBACCO Non-Specified Tobacco UseDISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesAGE Fetus/Prenatal RESEARCH1 Animal Studies TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN PregnancyDISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingLVALStudy Design: This is a case-control study with enrollment of 200 cases and 200 controls. Cases will be identified at their lymphedema consult in the physical therapy centers and will be eligible if they have had unilateral axillary surgery for breast cancer, no known metastatic disease present, and are able and willing to give consent. Using the oncology registry, controls will be identified from patients who have had breast cancer surgery and have not developed lymphedema. The severity of lymphedema and the amount of interference with daily life will be assessed with the Measure of Arm Symptom Survey (MASS, version 2), a patient-completed survey. Potential lymphedema risk factors including diabetes, hypertension, cigarette smoking, past shoulder injury, flexibility exercises, strength training exercises, medical procedures, arm/hand infection or injury, airline travel, body mass index, and occupation will also be evaluated with the MASS, version 2. Health-related quality of life will be evaluated using the Short-Form Health Survey (SF-36). Treatment risk factors including number of lymph nodes removed, number of positive lymph nodes, type and amount of radiation therapy, adjuvant therapy, surgery type, and tumor location will be obtained from oncology registry data.LVAL:-p.\Human reproductive health is affected by smoking. We propose to characterize the effects of tobacco smoke on reproduction, identify the toxicants in tobacco smoke that affect reproduction, understand the mechanism of action of these toxicants, and develop methods to control or prevent their effects. Specifically, active smoking increases the risk of infertility, spontaneous abortion, and ectopic pregnancy. These reproductive disorders/diseases have increased in the past several decades. In the United States, as many as 1 in 6 couples are infertile. Ectopic pregnancy, which is the leading cause of maternal death during the first trimester and which is almost always fatal to the fetus, has quadrupled in the United States since 1970. Our previous work has shown that both the oviduct and corpus luteum of females are targets of mainstream (MS) and sidestream (SS) cigarette smoke. The oviduct and corpus luteum are important reproductive organs; impairment of their function by smoke could cause infertility, spontaneous abortion, and ectopic pregnancy. We propose to characterize the effects of MS and SS smoke on the oviduct and the corpus luteum, determine if the effects can be reversed, identify the toxicants in smoke that produce these effects, and begin to clarify the mechanism of action of the toxicants. Most work will be done using the hamster as a model, some parallel experiments will be done on human oviducts, and some experiments will be done on cultured human endothelial cells Oviducts. To characterize the structural and functional effects of MS and SS on the living oviduct, hamsters will be placed in smoking machine experiments, and the target cells in their oviducts will be evaluated using electron microscopy and physiological tests. Any para-meter that is affected by smoke exposure will then be examined in a reversal experiment to determine if  giving up smoking restores the normal condition. Finally, human oviducts from nonsmokers, active smokers, and passive smokers undergoing electLVAL]ive surgery will be studied to characterize the structural and functional effects of smoke on the human oviduct Corpus luteum. Our previous work shows that MS and SS smoke inhibit blood vessel development in corpora lutea. Our second goal is to study this effect in more detail. We will characterize the structural effects of smoke on the hamster corpus luteum and on a chick membrane used to assay blood vessel development. Finally, we will determine how the genes which regulate blood vessel development are affected by smoke. The genes which are affected by the toxicant will be sequenced and their expression will be studied in the corpora lutea of hamsters in smoking machine experiments. Results from these studies may influence smoking behavior in young women of child-bearing age. Young people are more likely to stop smoking if they know its effects are imminent (childbearing) rather than remote (death). Our video tapes showing the rapid response of the reproductive organs to smoke inhalation will be made available for educational purposes and may deter young women from smoking. Our video laparoscopy technique may become widely established for toxicology testing; this technique has the potential to be applied to other organs, routes of delivery, toxicants, and to males. The toxicants in smoke, once identified, could be removed form cigarette smoke by appropriate filters, thereby decreasing the toxicity of smoke to women unable to stop smoking during their reproductive years. Passive smokers are often unaware of the dangers of smoke exposure. Our experimental designs compare MS and SS smoke and thus will provide much needed data on the influence of passive smoking on reproductive events. Finally, our studies will benefit other branches of medicine. Results on the oviduct may apply to other organs having ciliated cells and smooth muscle cells, such as the respiratory system, and studies on the corpus luteum will contribute to understanding blood vessel development at other sites, such as in  LVAL wounds, the endometrium, the placenta, and the embryo/fetus. In addition our studies on blood vessel development may augment our understanding of diseases affected by blood vessels such as solid tumor growth, and rheumatoid arthritis. In summary, data obtained in this study will lead to health improvements for pregnant women and their fetuses, and will have a positive impact on the reproductive health of our species. LVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long- term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airways reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate in this study. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600.LVAL:-p.`Thc purpose of this research is tO determine the u~ost econornicully efficient combination of future tobucco control policies and interventions in the I]S and California ? that is. those policie8 expected ~o yield the greatest health gains given the economic ;esources consun~cd. To accomplish tl~is, we will co~nparc the societul costs and health henefits of raising excise taxes on tobacco with other me~sures such as anti?tol~acco media campai~t~s, sci~ool~based education, or encouraging physicians lo advise their putients to stop s'~oking. To calculate the costs and benefits of each intervention we will develop ;, computer simnlation model called the Cotnprehensive Tobacco Policy Model (C::THM>. l'he n~ode] will sin~ulate what is likely to happen to sonne populution if ;J policy is chan;c`1. For example, the model would simulate the effect of raising excise taxes by $1.50 pcr pack. In pe~forming the sin~ulation, the model woul In addition to simu1nting what happens to thc cunent populalion, it will n160 capture the effects of current policy changes on subsequenl generations. For example, if taxes are raised then fewer women will smoke during their pregnancy nnd so there will l~e fewer cases of low thth weight and other sn~oking?induced health problems in infants. Tn addilion, children would be exposed lo less environ~nental tobacco smoke in the home. Infants and children will live longer, be healthier, and n~ight l~e less likely to take up sn~oking then~selvcs. ln addition, the costs uf treating their smoking?induced illnesses vvould oe seved. The ~nodel would simulate all of these second?generation effects as wcil. When accessing the costs and be~efits of a'~y tobacco control intervention, we also will keep tracl; of who pays and who benefits so lhat we can report the distributione1 consequences of any inter~ention. The CoMprehcnsive Tobacco Policy Model will also be used to sug~cst how any new inf~sion of funds (~.g' from a future Tobacco Settlement) n~ight be ;~Ilocated so as to reach tl~e goaE0 LVAL@ of maxin~i%ing the health and eco~omic returns on investn~ent. As the name in~plies, the Co~uprehensive Tobacco Policy Model is intended to be just that ?~ comprehensive. It will be designed, not only to ans~ver the research queslions posed here, but to infonn questions of tobacco policy more ge~ierally. In addition to making it t~exibic, we plan to make the model availal~le and designed so tl~at it is useable by a diverse group of decision makers. The user?friendly ~node, will be fully documented and placed on the world wide web so 1hat it can inforn~ policy now and into lhe foreseeahle fut~rc. LVAL:-p.bThe primary objective of this research is to inform the development of high-leverage tobacco policies and research. High-leverage policies are those that maximally improve public health or dramatically reduce the economic burden of tobacco use. High-leverage applied research is designed to reduce uncertainty about the critical factors upon which real policy decisions depend. There are many policies and interventions that might reduce tobacco use. Short of performing expensive time-consuming studies, it is difficult to know which policy options are most promising. In the present research, we take a progressive approach toward informing policy. We will develop a rigorous system dynamics computer simulation model which will harness available science to predict the public health and economic consequences of any change in tobacco use in any demographic population and geographical area. Our approach to informing policy is unique in that we abstract away from the myriad of specific policy options to answer more fundamental questions. For example, we will determine which demographic groups are likely to realize the greatest public health gains for a fixed change in tobacco use. This will help decision makers to understand the tradeoffs between policies directed at the young vs. the old, men vs. women, or different racial/ethnic groups. We will also contrast the long term public health and economic consequences of efforts aimed at preventing tobacco use with efforts aimed at the reduction or cessation of tobacco use. To help communities prioritize scarce resources, the model will predict public health gains in all 50 states as well as counties and cities within those states. In addition, we will simulate the long-range outcomes of alternate approaches to safer cigarettes over different time-frames. These include lowering the nicotine content of cigarettes, removing carcinogens, improving access to non-tobacco nicotine delivery devices, and various combinations. Finally, through determining the sensitivity of o LVAL utcomes to uncertain model parameters, we will identify those parameters that may prove to be good candidates for future high-leverage research. By synthesizing available scientific evidence into a single model, documenting it carefully, and making it available through a user-friendly interface on the Internet, we hope to aid decision makers faced with difficult policy choices.   y d A +o3@G@ResearchP@OTURTELTAUBKENNETHLAWRENCE LIVERMORE NATIONAL LABORATORYLIVERMORECACTRDRP8RT-0072lwJ-p.Biology and CancerR@o@q7/1/19996/30/20027/1/1999 to 6/30/20024/2005uMD88,"@G@Researchz@OTUCKERJAMESLAWRENCE LIVERMORE NATIONAL LABORATORYLIVERMORECACTRDRP8RT-0070HNuJ-p.Biology and CancerDiscovery 1a Evaluation 1b@q7/1/19996/30/20027/1/1999 to 6/30/20024/2005&~zoG@88,"@@@Researchp@OTSOHJANICEUNIVERSITY OF CALIFORNIA AT SAN FRANCISCOSAN FRANCISCOCANIDAK23, DA000468JrJ-p.j@t@o@q8/16/20007/31/20058/16/2000 to 7/31/20054/2005qF>88,"g@p@4Researchd@OTSOHJANICEUNIVERSITY OF CALIFORNIASAN FRANCISCOCACTRDRP8KT-0012@pj@!'@o@qNot GivenNot GivenUncertain4/2005{so`F>88,"@@Researchj@OTOOBERTDEBORAHOREGON RESEARCH INSTITUTEEUGENEORNCIR01, HL062156J @p@ 'p@o@i4/12/19993/31/20044/12/1999 to 3/31/20044/2005vqmeJA88,"@@@ResearchZ@OTOBORGMARYTOBORG ASSOCIATES, INC.WASHINGTON DCNCIR43, CA091630F @n@'@7Z@i8/1/20014/30/20028/1/2001 to 4/30/20024/2005upl_F@88,"`@@Researchh@OTOBORGMARYTOBORG ASSOCIATES, INC.WASHINGTON DCNCIR44, CA091630 @m@'@7@i8/1/20004/30/20068/1/2000 to 4/30/20064/2005upl_F@88,"g@1@ResearchR@OTIZABIYOUSEFHOWARD UNIVERSITYWASHINGTON DCNIGMSS06, GM008016kJ-p.Biology and Cancer AddictionP@7@iNot Given2001? to 20014/2005slh[H@88,"@+@Researchn@OTIDEYJENNNIFERBROWN UNIVERSITYPROVIDENCERINIDAR01, DA017566 @jT@'@7^@i9/30/20036/30/20079/30/2003 to 6/30/20074/2005rlh\J?88,"o@@Researchd@ OTHOMPSONBETIFRED HUTCHINSON CANCER RESEARCH CENTERSEATTLEWAFICR03, TW005894gJ-p.r@'@7@i5/15/20034/30/20065/15/2003 to 4/30/20064/2005}ypHB88," @@u@ResearchJ@ OTHADHANIRAVIBRIGHAM AND WOMEN'S HOSPITALBOSTONMANHLBIK08, HL003804eJ-p.t@'Discovery 1a Evaluation 1b^@Y7/1/19986/30/20037/1/1998 to 6/30/20034/2005 yrnfHB88," 1@@Research@ OTENNISMEREDITHGEORGETOWN UNIVERSITYWASHINGTON DCCDMRPBC020117@dB@'Discovery 1b Evaluation 1b@Y200220052002 to 20054/2005yrnaJ@88,"@@@Researchn@ OTENGSTAMMYUNIVERSITY OF CALIFORNIA AT IRVINEIRVINECANIDAP50, DA013332a:-p.D@'N@7@Y200020032000 to 20034/2005|vrjF?88," LVAL Objective/Hypothesis: We hypothesize that there will be a difference in the p53 mutational spectra of breast and lung tumors from women with radiotherapy but not in breast and lung tumors in women with no radiotherapy. We also hypothesize that there are differences related to smoking status. There may be differences in methylation of specific genes that affect lung cancer risk after radiotherapy and differences in estrogen receptor expression between radiation treated smokers and nonsmokers.LVALJ-p.fCandidate: Ravi I. Thadhani received his M.D. in 1991 from the University of Pennsylvania. He then completed his internal medicine residency and served as Chief Medical Resident at the Massachusetts General Hospital. In 1995 he entered the Harvard School of Public Health and will complete the Masters' Program in Clinical Effectiveness by June 1997. He is interested in an academic research career studying modifiable risk factors of hypertensive disorders of pregnancy. Sponsor and Environment: Meir J. Stampfer, M.D., D.PH. has trained numerous investigators in the field of cardiovascular and nutritional epidemiology, areas in which he has published extensively. He is co-investigator of the Nurses' Health Study I and Nurses' Health Study II, which are based at Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School. Dr. Stampfer is quite familiar with the research methods proposed in this project, and as a Professor of Epidemiology at the Harvard School of Public Health, he will also oversee Dr. Thadhani's formal education. Research: The applicant plans to examine prospectively the association between pre- and early-pregnancy risk factors and the subsequent development of transient hypertension of pregnancy or preeclampsia in two large cohorts: Nurses' Health Study II and the North Dakota WIC program. The following dietary hypotheses will be tested: pre- and early-pregnancy high intake of omega-3 fatty acids, antioxidants, and calcium reduces the risk of developing hypertensive disorders of pregnancy. Two non-dietary hypotheses will be tested: elevated serum cholesterol prior to pregnancy increases the risk, and smoking, which has been associated with a reduced risk, may not be associated with a reduced risk after adjusting for potential confounders. Diet in both cohorts will be measured by validated semiquantitative food frequency questionnaires developed at the Channing Laboratory. All cases will be verified by review of medical records. We expect 650 incident cases in the Nurses'  LVAL Health Study II cohort (from 1991-2001) and 800 incident cases in the North Dakota WIC cohort (from 1995-2002). Because both cohorts are part of ongoing efforts, performing this study will be very economical. Furthermore, approximately 16% of women in the North Dakota cohort are of Native-American background, thus allowing us to evaluate a relatively under-studied segment of the population. Known risk factors for hypertensive disorders of pregnancy are either difficult or impossible to alter. The goal will be to identify dietary and non-dietary risk factors that may be amenable to modification prior to or early in pregnancy.LVALJ-p.hThis research will be done primarily in La Pintana, Chile in collaboration with Klaus Puschel of the Catholic University of Chile as an extension of NIH Grant # CA74968. Smoking is a major problem in the developing world. In Chile, for example, nearly 50% of men and women smoke. The problem is particular acute among women of child-bearing age, where over 47% of women are smokers. In this proposed project, we will build on research being conducted in the parent project in the Yakima Valley of Eastern Washington. The Valley is largely Hispanic, many of its residents are of low socio-economic status and have few years of education. In the parent project, we have developed many activities and materials for low literacy level, monolingual Spanish speakers. In this proposed developmental study, a comprehensive smoking cessation program will be implemented in a public health clinic serving individuals in a poor suburb of Santiago, Chile. The program will be directed toward women of child-bearing age. Clinic smoking cessation activities will be supplemented with activities in the community. Because this is a developmental study, evaluation will not involve a randomized trial; however, we have added a control clinic, also located in La Pintana, to provide information on the secular trend in a similar population during the time of this study. A cohort of women of child-bearing age who smoke will be accrued in two clinics in the suburb. In one clinic, smoking cessation activities will be directed toward the women who smoke, while "usual practice" toward smokers will continue in the other clinic. Quit rates at 3 months, 6 months, and 12 months will be documented in the cohort in both clinics. We propose to train health care providers to counsel their pregnant patients and mothers of young children who smoke to stop smoking by using the NCI "5 As" program and motivational interviewing (MI). The health care provider intervention will be supplemented with other clinic activities, such as availability of self-help qu, LVAL< it materials, a non-smoking environment, a Quit & Win contest, signage, and other activities deemed appropriate by a Community Advisory Board convened for this project. The primary outcome will be change in smoking cessation rates among a cohort of women of child-bearing age identified and recruited from the El Roble Clinic compared to smoking cessation rates among a cohort of similarly aged women recruited through the Santiago de Nueva Extremadura (SNE) Clinic. Long-term smoking cessation is defined as self-reported 6 months of continuous cessation. Short-term cessation is defined as seven day cessation at the 6 or 12 month follow-ups. We have ample power to detect a 7.5 percentage point difference in smoking cessation rates.LVAL x6DISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseLOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesEDUCATION LEVEL High School LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials PSYCHOLOGICAL Cultural Factors RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesADDICTION Withdrawal DISEASE/BIOLOGY Mechanisms LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Nicotine MISCELLANEOUS Sex/Gender DifferencesADDICTION Maintenance Cessation DISEASE/BIOLOGY Other Disease/Biology ECONOMICS Cost of Smoking EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Buproprion PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesCOMMUNITY Health Care Provider ECONOMICS Socio-Economic Status LOCATION International PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials RESEARCH Human Studies Clinical Research STUDY POPULATION Hispanic TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Parent/MotherLVALThere is a high prevalence of cigarette smoking among people with schizophrenia, but few smoking treatments have been developed for these patients. Laboratory and clinical studies have begun to delineate environmental and biological factors that affect smoking in schizophrenics. Recent laboratory feasibility studies have shown promising results with contingent monetary reinforcement for smoking reductions. Similarly, several smoking treatment studies in schizophrenics have shown promising results with bupropion- SR. Our long-term goal is to develop an effective, feasible, research-based smoking cessation program for smokers with schizophrenia. In this laboratory-based feasibility study, we will evaluate 128 male and female smokers with schizophrenia who are interested in quitting smoking in the future, using a 2 x 2 between groups factorial design. The primary aims are: (1) to evaluate the efficacy of a novel contingency management procedure for shaping smoking abstinence by reinforcing salivary cotinine reductions, compared to non-contingent reinforcement; (2) to evaluate the efficacy of 300 mg/day bupropion-SR, compared to placebo; (3) to evaluate the efficacy of combining contingent reinforcement for smoking reductions with bupropion, versus either intervention alone. Secondary aims are (1) to evaluate whether gender or individual differences in nicotine dependence and motivation moderate responsivity to each intervention; (2) to evaluate whether abstinence is related to changes in psychiatric symptoms, extrapyramidal symptoms or cognitive functioning. This study will provide significant information regarding the efficacy and feasibility of using a combination of contingency management and smoking pharmacotherapy to treat smoking in schizophrenics.LVALJ-p.lNicotine, the primary psychoactive gent in tobacco, interacts with specific neurotransmitter systems including the noradrenergic system. Noradrenergic neurotransmission is mediated by several receptor subtypes including alpha2-adrenoceptors. Nicotine-alpha2-adrenoceptors interactions may not only be responsible for some of the beneficial effects of nicotine, but may also be involved in nicotine dependence and nicotine withdrawal symptoms. Indeed, smoking cessation may be facilitated by clonidine, an alpha2-adrenoceptor agonist. However, clonidine's adverse effects preclude its use as a first-line treatment in smoking cessation. Various subtypes of alpha-2 adrenoceptors with distinct central distribution have been identified. Chronic nicotine administration results in increased density of cortical alpha2-adrenoceptors. However, it is not know whether alpha2-adrenoceptors in other discrete brain regions are also affected by nicotine. More importantly, no information is available on interactions between nicotine and specific alpha2-adrenoceptor subtype(s). This information is critical in identifying specific alpha2-adrenoceptor subtypes as potential targets for the development of novel agents in treatment of nicotine dependence and/or withdrawal. Thus, we propose to establish the specificity, time-course, duration, and dose-response relationship between nicotine administration/withdrawal and central alpha 2-adrenoceptors. Furthermore, since gender differences in the effects of nicotine and clonidine have been observed, both male and females will be studied. Nicotine will be administered to rats by osmotic mini-pumps. Autoradiography will be used to quantify alpha2-adreneceptor subtypes plasma levels of nicotine and cotinine (a major nicotine metabolite) will be determined by gas chromatography/mass spectrography and will be correlated with receptor binding data. These studies will significantly enhance our understanding of nicotine-alpha2-adrenoceptor interactions in the brain and will set the stage for LVAL(further characterization of this interaction which may lead to novel pharmacotherapy in smoking cessation.lLVAL|Five hundred thirty-four counties in 18 states are home to 29,497,852 persons and grow tobacco. Data indicate youth in these areas use tobacco earlier and use it more frequently. Tobacco communities have a unique perspective based on the cultural, social, and economic import of tobacco which requires a sensitive approach to adolescent cessation efforts. This project will develop a culturally congruent Resource Kit for Adolescent Tobacco Cessation in Tobacco-Growing Communities. The project will target tobacco-using males and females in high school. Based upon formative research conducted in tobacco-producing communities, Toborg Associates will develop a cessation curriculum, related health education materials, and short videos. In a randomized controlled pre-test/post-test study, Pacific Institute for Research and Evaluation (PIRE) will assess the efficacy of the curriculum and related materials. PIRE will randomize 20 NC schools in large tobacco-growing communities into experimental and control conditions, enrolling an average of 24 tobacco using youth in each school. Toborg Associates will conduct a pre-test prior to the intervention and implement the full curriculum in the experimental schools as well as an intervention that controls for attention and content in the control schools. At the end of the 6-week intervention, PIKE will conduct a post-test of youth in both conditions and biochemically validate self-reports concerning the use and non-use of tobacco. PIRE will conduct a follow-up survey at three months after post-test and again biochemically validate self-reports.LVALFive hundred thirty-four counties in 18 states are home to 29,497,852 persons and grow tobacco. Data indicate youth in these areas use tobacco earlier and use it more frequently. Tobacco communities have a unique perspective based on the cultural, social, and economic import of tobacco which requires a sensitive approach to adolescent cessation efforts. This project will develop prototypes of a culturally congruent, age-appropriate, gender-specific Resource Kit for Adolescent Tobacco Cessation in Tobacco-Growing Communities. By the end of Phase II, the Kit respectively will address males and females in the 12 to 14 and 15 to 17 age groups. Based on findings and relying on sound cessation science, the firm will develop in Phase II a uniquely designed cessation program and supplemental materials for these youth. In Phase I, one module of the cessation program and complementary materials will be developed for girls aged 12 to 14 who use tobacco and live in tobacco-raising communities. Staff will conduct focus groups to understand how these girls perceive tobacco and cessation. Staff will interview key informants for their perspective. We will conduct feasibility tests with the young women and cessation professionals from tobacco-raising communities. We will document our research in a monograph. PROPOSED COMMERCIAL APPLICATION: The Resource Kit will be marketed extensively through the 18 states where tobacco-growing counties are home to 29 million Americans. The many health departments, community-based organizations, hospitals, health clinics, and school in these communities will provide a rich market. Several tobacco states have set aside funds for youth tobacco cessation. 6LVALt ^ |  Z \ blt"~,p z~Discovery 1c Discovery 2a Development 1 Development 3 Delivery 2 Delivery 4 Partnerships 4 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2a Development 1 Development 3 Delivery 2 Evaluation 1aDiscovery 1c Development 1 Development 3 Delivery 1 Partnerships 1Discovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1b Evaluation 1cDiscovery 1a Discovery 1b Discovery 3 Development 1 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Development 1 Development 2 Delivery 1Discovery 1a Discovery 1b Discovery 2a Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1c Development 3 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Development 3 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Development 3 Delivery 1 Evaluation 1aDiscovery 1a Discovery 2a Evaluation 1aDiscovery 1a Discovery 2a Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Development 1 Development 3 Partnerships 2Discovery 1c Development 1 Evaluation 1aDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1bDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Discovery 3 Evaluation 1a Evaluation 1cDiscovery 1c Discovery 2a Discovery 2b Discovery 3 Development 1 Development 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 1 Development 3 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Discovery 2b Discovery 3 Development 1 Development 2 Development 3 Evaluation 1a Evaluation 1cDiscovery 1a Discovery 1c Development 1 Evaluation 1afLVALzThis study examined whether the number of women who start smoking again after the birth of their babies could be reduced by using brief interventions when they received their routine healthcare.In this study, we choose to specifically recruit Chinese, the largest ethnic group of the Asian Pacific Islander community, as an initial step to increase our understanding in smoking behaviors in relation to depression.The overall goal of this project is to test a practical, theory- based intervention to achieve long-term behavior change for women with Type 2 diabetes at high risk for developing coronary heart disease (CHD). Epidemiological and clinical studies suggest that diabetes is associated with increased risk for CHD that is greater in women than in men. CHD is a major cause of death and functional limitations in women, but the vast majority of CHD studies have primarily involved middle-aged men. There is convincing research evidence that healthy lifestyle behaviors, including low-fat diet, physical activity, stress management, smoking cessation, and social support, can reduce CHD risk. We will conduct a randomized trial to compare short-term (6-month) outcomes in women receiving usual care compared to a modified Ornish-type comprehensive lifestyle management (CLM) intervention. After 6 months, women in the CLM condition will be randomized to one of two approaches for providing support either lay-led group support or personalized computer-based support - to evaluate these strategies in enhancing longer-term maintenance of effects. Outcomes will include multiple CHD lifestyle behaviors (e.g., dietary intake, exercise levels, stress management, smoking cessation), physiological risk factors associated with CHD (e.g., serum lipids, hypertension, weight, vascular reactivity), HbA1c and quality of life (e.g., depression, functioning).LVAL hAGE Child EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Industry Counter-Marketing PREVENTION/TREATMENT Interview/Focus Group PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesAGE Child EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesDISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms Other Disease/Biology PREVENTION/TREATMENT Biochemical Assessments RESEARCH1 Animal Studies TOBACCO Environmental Tobacco Smoke Nicotine WOMEN PregnancyAGE Child Fetus/Prenatal DISEASE/BIOLOGY Mechanisms LOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Maintenance PSYCHOLOGICAL Depression/Mood/Anxeity Cultural Factors RESEARCH Human Studies Clinical Research STUDY POPULATION Asian Pacific Islander TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesADDICTION Maintenance Cessation LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies Clinical Research STUDY POPULATION Asian Pacific Islander TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesLVALJ-p.sThis K23 mentored patient-oriented research application will support the career development of the candidate in the area of nicotine dependence and tobacco control, particularly targeting smoking cessation efforts to the ethnic minority populations. Drs. Sharon Hall and Neal Benowitz of the University of California, San Francisco will serve as the primary and secondary mentors. The objective for this 5-year proposed program is to provide training and hands-on experience in designing and conducting clinical trials, cross-cultural research and methodology, and clinical pharmacology knowledge and applications. The overall goal of this research is to design and test efficacious smoking cessation programs that can successfully treat a large minority group, Chinese American smokers. This study will transfer the interactive expert system technology in smoking cessation to Chinese American smokers and test the efficacy of the intervention using a randomized clinical trial in this population. It will also examine the effectiveness of proactive versus reactive recruitment approaches, which will guide implementation of smoking cessation intervention in this population. Participants will be randomized to either to a control condition receiving a standard self-help manual, or experimental condition receiving a stage-matched manual and 3 personalized expert-system reports over 6 months. Assessments will occur before randomization at baseline, 3, 6, 12, and 18 months. It is hypothesized that research participants receiving the experimental smoking cessation intervention will be more likely to be abstinent, report at least one quit attempt, and to significantly reduce in smoking rate (verified by continine) than those in the control condition at 12 and 18 months. The proactive recruitment approach is hypothesized to be more effective in reaching smokers who are not ready to quit smoking. Depression symptoms, negative affect, acculturation and gender differences in association with smoking behaviors and nicotine depen LVAL dence in the Chinese population will be examined. Pilot work focusing on enhancing smoking intervention for this population will be conducted based on the findings of the proposed clinical trial. This research and career development program will yield significant knowledge for effectively treating Chinese American smokers, and will build a solid foundation to prepare the candidate to be an independent clinical research scientist.LVAL B& ^ " l L  * ,|lEpidemiology and National Surveillance Awareness Risk Perception and CommunicationsEpidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and TreatmentBiology and Cancer Addiction Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National Surveillance Interventions for Prevention and TreatmentInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Addiction Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentEpidemiology and National SurveillanceAddiction Epidemiology and National SurveillanceInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National Surveillance Awareness Risk Perception and CommunicationsEpidemiology and National SurveillanceInterventions for Prevention and TreatmentAddiction Interventions for Prevention and TreatmentLVALJ-p.vThe consequences of maternal cigarette smoking during pregnancy on both the mother and newborn are being studied. It is of particular interest to understand how smoking and inherent genetic susceptibility relate to observed chromosomal aberrations in circulating blood cells. Approximately one quarter of the population is inherently susceptible to chromosomal damage whereas the remaining three quarters are relatively resistant. It is hypothesized that sensitive populations of newborns and mothers are at increased risk to chromosomal damage by maternal smoking during pregnancy compared to relatively resistant populations. Blood samples from 470 mothers and their newborns have been collected for this study. Peripheral blood lymphocytes from the mother and the fetal side of the placenta were cultured and harvested 48 and 72 hours later to evaluate chromosomal aberrations and genetic susceptibility, respectively. Chromosome aberrations are detected using whole chromosome painting probes to visualize chromosomes 1, 2, and 4 in red and 3, 5 and 6 in green. Approximately 1000 cell equivalents (1800 metaphase cells) are being scored from the maternal and newborn samples to identify stable and unstable chromosome damage. The clastogen, bleomycin, is used to assess susceptibility to induced chromosomal damage in vitro. In addition to baseline and postpartum interview questionnaires data about smoking history, some maternal and newborn blood samples are being tested by our collaborators for two biochemical measures of tobacco exposure. The quantification of cotinine levels and 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts will reduce the risk of potential recall bias for self-reported tobacco use. Preliminary data indicate that self-reported cigarette smoking behavior prior to and early in pregnancy are highly correlated with these biochemical measures of exposure. To date, 202 mother/newborn blood sample pairs have been analyzed for chromosomal damage: 106 are from Caucasian-Americans and 96 are from ALVALfrican-Americans. Preliminary statistical analyses have been performed on a subset of these subjects, namely 97 Caucasian American and 73 African American sample pairs. The distribution of bleomycin-induced chromatid damage in both the maternal and newborn populations deviates from a normal distribution. In general, the newborn lymphocytes are more resistant to bleomycin-induced damage than the maternal cells. The most recent analyses of the data evaluated the effect of age, race, maternal smoking during pregnancy, ever smoking, passive smoking, and bleomycin sensitivity on chromosome aberration frequency. In univariate analyses, there are significant associations between maternal chromosome aberration frequencies and mother's age (p =0.05) and passive smoke exposure (p = 0.01) and these factors remain significant in multivariate analysis. In univariate analyses of data for newborn samples, bleomycin sensitivity associates significantly with chromosome damage. In a multivariate analysis, ever smoking, smoking during pregnancy, and passive smoke exposure are significantly associated with chromosome damage. We have now finished collecting the samples. In the next few months we will finish the cytogenetic analyses. We will determine if maternal and newborn populations, genetically susceptible to DNA damage, are at increased risk of chromosomal aberrations due to tobacco exposure during pregnancy. The identification of risks associated with maternal smoking during pregnancy are critical for the improvement of the health of the individual and the community.LVALJ-p.Studies in people have suggested that second-hand smoke from cigarettes can cause cancer in people who never smoked. Importantly, some of the most vulnerable non-smokers to second-hand cigarette smoke may be to newborn children. These studies, while implicating second-hand smoke as a human health threat, do not provide information on how this process occurs. Information on the way second-hand smoke causes cancer will aid significantly in our understanding of the risk this poses to the public and to children. Smoking-related cancers are believed to involve chemicals present in the smoke. Passive smoke, which is emitted from the burning end of the cigarette, contains higher concentrations of these chemicals than main stream smoke. Upon inhalation, these chemicals pass from the smoke into the bloodstream and chemically bind to proteins and the genetic material of cells, DNA, forming adducts. DNA and protein adducts have been detected in the sperm of adult men who smoke and in the placenta and umbilical cords of newborn children of women who smoke. However, there has been no information to show that second-hand smoke causes this damage. There is also no direct method to measure these adducts at levels of chemical exposure equivalent to second-hand smoke. The purpose of this work will be to specifically determine if DNA and protein adducts are formed when exposed to two chemicals present in cigarette smoke, nicotine and hydroquinone, at levels present in side-stream smoke. These chemicals are important components of the smoke. This will be possible using the novel and sensitive technique of accelerator mass spectrometry. This research will determine whether adduct levels increase with increasing dose and will help identify whether the adducts of these common components of cigarette smoke can be used to measure side-stream smoke exposure. This research will also help determine if this damage occurs in the offspring of smoking mothers.LVALJ-p.yTobacco use is a behavioral health problem that poses serious medical risks especially for patients who have previously been treated for cancer. The potential late effects of cancer treatment include the development of second malignancies and cardiopulmonary sequelae that may be exacerbated in patients who use tobacco. Our ultimate goal is to promote abstinence from tobacco use in young cancer patients. According to theories proposed to explain health behavior, persons who perceive the likelihood of a negative health outcome to be high are more likely to engage in some behavior to reduce that risk. Within this context, our study proposes to address two primary aims: 1) To examine the effects of a smoking educational/counseling intervention on a) objective knowledge, b) perceived vulnerability, and c) intention to use tobacco among youngsters previously treated for cancer; and 2) To examine the relationship between objective knowledge, perceived vulnerability, and intention to use tobacco. Ninety-six patients who have completed cancer treatment, between the ages of 10-18 years, will be randomized to either a Standard Care Control (SCC) group or a Smoking Education Intervention (SEI) group. Patients will be stratified by age, gender, race, and smoking status prior to randomization. Patients in the SCC group will be advised about the general health risks associated with tobacco use. Patients in the SEI group will receive an intervention targeting their greater vulnerability to tobacco-related health risks secondary to their cancer treatment and relative to their healthy peers. The intervention will consist of a) an educational video, b) risk counseling focused on cancer late effects, goal setting, physician feedback, and one and three month telephone follow-up and c) take-home smoking literature. Patients in both groups will be encouraged to abstain from or stop using tobacco. The impact of our intervention on patient knowledge, and self-reported perceived vulnerability and intentions will be evaluated aLVALt 6 and 12 months.  z E &  mJ&   1@@ResearchR@"OWEISMILLERDAVIDBRODY SCHOOL OF MEDICINE, EAST CAROLINA UNIVERSITYGREENVILLENCSFFNot Given @L@ tR@oV@200220042002 to 20044/2005KD88,"   f@@Researchx@!OWEDENMARGARETJOHNS HOPKINS UNIVERSITYBALTIMOREMDNIDAF31, DA015942 @b@ t@ o@3/1/200310/27/043/1/2003 to 10/27/044/2005xrncI?88,"   1@@Researchx@ OWEBBDAVIDPHILADELPHIA DEPARTMENT OF HEALTHPHILADELPHIAPARWJF40670f@T@ tDiscovery 1c Development 1@200220042002 to 20044/2005zvhE>88,"   @@`@ResearchP@OWARDMICHELLEUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANIDAF31, DA006076 @t@tp@ or@5/1/20024/30/20045/1/2002 to 4/30/20044/2005|xkH>88,"  @-@@Researchb@OWAMBOLDTFREDERICKNATIONAL JEWISH MEDICAL AND RESEARCH CENTERDENVERCONHLBIR01, HL068828Z-p.t@tn@ o2@12/1/200111/30/0512/1/2001 to 11/30/054/2005zMB88,"g@p@4Research"SMOKING RELAPSE PREVENTION STUDYWALL MICHAELOREGON HEALTH AND SCIENCE UNIVERSITYPORTLAND ORSFFNot Given@pT@t@ o@Not GivenNot GivenUncertain4/2005jaZZ,"n@`O@Research`@OWAKSCHLAGLAURENUNIVERSITY OF CHICAGOCHICAGOILNIDAK08, DA000330`Z-p.t@tDiscovery 1a Evaluation 1b@9/30/19978/31/20029/30/1997 to 8/31/20024/2005uokbKC88,"O@`@ResearchV@OVICKERSKRISTINMAYO CLINIC COLLEGE OF MEDICINEROCHESTERMNNCIR03, CA094760Z-p.T@tT@ o@9/1/20028/31/20059/1/2002 to 8/31/20054/2005zvkJA88,"G@@Researchv@OVAN WINKLELAURIEUNIVERSITY OF CALIFORNIA AT DAVISDAVISCACTRDRP11RT-0258,Z-p.@tl@oB@7/1/20026/30/20057/1/2002 to 6/30/20054/2005zvoLD88,"@ @Research`@OVAN WINKLELAURAUNIVERSITY OF CALIFORNIA AT DAVISDAVISCANIEHSR21, ES013066~Z-p.Biology and Cancerl@o@5/1/20043/31/20075/1/2004 to 3/31/20074/2005yunKD88,"O@3@Researchf@OUPADHAYAHIMANSHUMEDICAL UNIVERSITY OF SOUTH CAROLINACHARLESTONSCNIDAP50, DA016511}Z-p.Biology and Cancer AddictionP@o@9/1/20028/31/20079/1/2002 to 8/31/20074/2005~rLB88," @G@Researchp@OUNGERJENNIFERUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP7KT-0006{J-p.L@t@o@q7/1/19986/30/20027/1/1998 to 6/30/20024/2005}ylI?88," @@ResearchD@OTYCVIDAST. JUDE CHILDREN'S RESEARCH HOSPITALMEMPHISTNNCIR03, CA070267 xJ-p.T@t@o@q7/1/19986/30/20017/1/1998 to 6/30/20014/2005|wsjC=88,"LVALJ-p.|Tobacco use is the leading preventable cause of illness and mortality in the United States. The onset of tobacco use generally occurs before age 18; therefore, prevention of smoking initiation among children and adolescents is a powerful strategy for preventing much of the illness and mortality associated with tobacco use. To prevent children and adolescents from becoming smokers, it is important to understand the personal, social and environmental factors that cause them to become curious about smoking. Some children and adolescents are "susceptible" to smoking; that is, they have not expressed a firm commitment not to smoke, so they may be more vulnerable to social and media influences that encourage them to experiment with tobacco. Other children and adolescents are "non-susceptible'' they express a firm commitment not to smoke and may, therefore, be more resilient to pro-smoking messages from media and society. Previous research has shown that the susceptibility concept is useful for predicting which youth will become smokers in the future; susceptible youth are more likely to experiment with tobacco and to become regular smokers than are non-susceptible youth. However, it is not clear what differentiates susceptible youth from non-susceptible youth. The proposed study will examine susceptibility to smoking among adolescents who have not yet tried smoking. We will analyze questionnaire data collected from 8449 California nonsmoking adolescents in grades 5, 8, and 10, as part of an Independent Evaluation of the California Tobacco Control Program, to determine how susceptible and non-susceptible youth differ. This study will examine demographic and smoking-related variables (e.g., exposure to anti smoking programs, tobacco-related knowledge, attitudes and behaviors) to determine which of these factors differ between susceptible and non-susceptible youth. We will also examine characteristics of the school environment to determine which types of schools are likely to have large numbers of students sus LVALceptible to smoking, and which types of schools are likely to have few susceptible students. The results of this study can be used to develop effective smoking prevention programs that prevent children and adolescents becoming susceptible to smoking.LVALZ-p.~Cigarette smoking is common; approximately 25% of adults over 18 years of age are regular smokers. Craving is an important component of the symptoms experienced during smoking cessation and it considered a crucial factor in relapse. There is some evidence that menstrual cycle may impact smoking and relapse for women, but this has not been well explored. Hence, menstrual cycle phase may be an important modulator of craving and may contribute in relapse among women attempting smoking cessation. There is also data suggesting that there are different subjective and physiological responses to nicotine during different phases of the menstrual cycle, but little work has been done in exploring the effect of menstrual cycle phases on smoking cue-reactivity. Research on the effect of menstrual cycle phase on smoking cue-reactivity may be especially important for smoking cessation treatment as it is common practice in smoking cessation programs to set a quit date prior to the quit attempt. Knowledge about the menstrual cycle phase differences in cue-reactivity may help in setting an optimal quit date for women in order to maximize the chances of successful smoking cessation The specific aims of the proposed project are: 1. To examine the effect of menstrual cycle phase on reactivity to "in vivo" cigarette smoking cues and negative affect-inducing cues in nicotine-dependent women. 2. To examine gender differences in the reactivity to "in vivo" cigarette smoking cues and negative-affect inducing cues in nicotine-dependent men and women. The proposed project will use both in vivo smoking cues, as well as negative affect/stress cues to explore smoking cue-reactivity in female smokers during four biologically verified menstrual phases. Female cigarette smokers' reactivity will also be compared to the reactivity of male cigarette smokers who will be tested in a similar protocol. Both subjective craving and mood responses, as well as physiological responses (e.g., real-time heart rate, galvanic skin conductance) will bLVALe measured during the study. This information may help in designing specific smoking-cessation approaches for nicotine-dependent women.LVAL , \ADDICTION Relapse COMMUNITY Health Care Provider PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials TOBACCO Cigarette/Other Smoking WOMEN PostpartumAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Parent/MotherAGE Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Educational Materials Nicotine Replacement Therapy PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/ExerciseDISEASE/BIOLOGY Cardiovascular/Pulmonary RESEARCH1 Animal Studies TOBACCO Environmental Tobacco Smoke MISCELLANEOUS Sex/Gender DifferencesAGE Child Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms LOCATION Urban National RESEARCH1 Animal Studies TOBACCO Environmental Tobacco Smoke WOMEN PregnancyADDICTION Cessation Withdrawal Relapse LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Hormones MISCELLANEOUS Sex/Gender DifferencesLVALZ-p.Metabolism is a key step in eliminating xenobiotics from the body. Despite the fundamental importance of metabolism in determining the potency of contaminants and carcinogens, little is known about the influence of exposures early in life on the adult expression of these systems, particularly in females. Environmental tobacco smoke (ETS) is one of the most ubiquitous sources of pulmonary exposure to known human carcinogens. Widespread exposure of children to ETS is supported by the fact that as many as 85% of children have detectable levels of cotinine in their blood. Yet the effect of early life exposure on adult onset lung diseases such as cancer has received limited attention. We propose to investigate the effect of pre and post-natal ETS exposures on the expression of genes for metabolism and detoxification enzymes in the target organ for airborne carcinogens, the lung. ETS toxicity is of interest in the female population because women develop lung cancer earlier and after less cigarette exposure than men. We propose to investigate female specific alterations in gene expression in the airways. We will examine the effects of ETS exposures on the lung by comparing the gene expression profiles and histopathology of samples obtained from female mice exposed to well characterized aged and diluted side stream tobacco smoke with those from filtered air control mice. The proposed studies will use microarray approaches to define, at the cellular level, the occurrence and persistence of altered gene expression in mice exposed either prenatally or both pre and postnatally to side stream cigarette smoke. We will use an experimental approach that identifies changes in genes as well as pathobiology specific to conducting airways, the site of many changes associated with both smoke exposure and adult onset diseases such as asthma, chronic bronchitis and lung cancer. The central hypothesis is that adult onset lung diseases in females, such as lung cancer and asthma, are related to the ability of the lung to metabV LVALf olically activate compounds and this is profoundly influenced by the history of prior exposure to such compounds, particularly in utero. We will address the central hypothesis through 3 Specific Aims that will define: 1) the effect of pre and postnatal ETS exposure on gene expression in adult airways, 2) the effect of prenatal ETS exposure on gene expression in infant airways and 3) which changes in infant gene expression persist into adulthood. These studies will thus address the fetal basis of adult diseases of the lung caused by exposure in utero to environmental tobacco smoke.LVALZ-p.Environmental tobacco smoke (ETS) is a substantial public health hazard because of the large number of smokers and the widespread presence of ETS that can lead to involuntary exposure of nonsmokers. ETS exposure is causally associated with lung cancer in both adult men and women. However, important differences exist in susceptibility to lung cancer between men and women. The risk for all major lung cancer types is higher in women than in men at every level of exposure to tobacco smoke. Recent research has shown that women express certain genes at increased levels in response to tobacco smoke. These changes are not seen in men exposed to tobacco smoke. While these changes suggest that there are genetic reasons for the differences in lung cancer risk between men and women, there have been few studies that define the biologic basis for these differences. The proposed research will focus on the cellular changes that occur in mice exposed to tobacco smoke and will determine if these changes are different in female mice compared to male mice. Subtle effects such as cellular changes in response to ETS in males and females have not been thoroughly investigated. Furthermore, because these subtle changes may be very focal within the lung the experimental approach must use methods that are also site-specific and that can evaluate cellular changes in focal lung regions. Our laboratory frequently uses and develops new site-specific methods such as these and will apply them in the proposed studies. Preliminary data from our laboratory suggest that female mice are more sensitive to an air pollutant, naphthalene, that is found in both cigarette smoke and car exhaust. We feel that coexposure to tobacco smoke and excess naphthalene in air pollution may result in an accentuated effect (such as cell changes that lead to cancer or chronic bronchitis) in female animals. Our hypothesis in the proposed studies is that female mice will have increased lung injury compared to males. We will try to determine the mec LVAL hanism for the cellular changes. This research has potential impact for women who smoke or are exposed to ETS and who live in urban areas with high levels of air pollution. We expect these studies will benefit the general population by defining the mechanisms that make women more susceptible. Once this mechanism has been defined strategies can be devised that will afford sensitive populations some protection. These studies are highly relevant to TRDRP research priorities regarding tobacco smoke exposure in a sensitive population, women.LVALZ-p.This application will serve as the foundation on which the Principal Investigator will build a line of research dedicated to the area of nicotine dependence treatment for depressed smokers. Cigarette smoking is the single most important preventable cause of morbidity, mortality, and excess health costs in the United States. Depressive symptoms have been identified as a major barrier to smoking abstinence, and depressed women attempting smoking cessation may be particularly vulnerable to relapse related to negative affect. Consequently, researchers have identified the need for smoking interventions specifically targeting depressed women. Mood management interventions have been shown to increase the smoking abstinence rates for depressed smokers. Exercise is effective in the treatment of depression and is an aid for smoking cessation among women, but has not been studied in depressed smokers. Further, exercise interventions for smoking cessation have not included pharmacotherapy (e.g., nicotine patch). The proposed project addresses the current lack of effective smoking interventions specifically targeting depressed women. The specific aims of this pilot study are: 1) to evaluate the feasibility of an individually-tailored exercise intervention for depressed smokers, 2) to evaluate in a pilot randomized trial the effect of the exercise intervention compared to a health education intervention on the smoking abstinence rates at the end of treatment (week ten) and at week 24, 3) to examine the effect of the exercise intervention on depressive symptoms, and 4) to examine the relationship between baseline depressive symptoms, exercise adherence, and change in exercise levels among those assigned to the exercise intervention. We hypothesize that the exercise intervention will be feasible and associated with higher seven-day point-prevalence smoking abstinence rates than the health education intervention at weeks 10 and 24. Sixty women between the ages of 18 and 50 who are classified as depressed, based on a C: LVALJ enter for Epidemiologic Studies - Depression Scale (CES-D) score of greater than or equal too $16, will be randomly assigned to a ten week individual program of: 1) individually-tailored, moderate-intensity exercise or 2) health education. Participants in both conditions will receive nicotine patch therapy and nicotine dependence counseling. Data collected will provide feasibility and effect size estimates to be used for an R01 submission. The ultimate goal of this work is to develop effective interventions that will reduce future tobacco-related morbidity and mortality among depressed smokers.LVALZ-p.Research establishing links between mothers' smoking during pregnancy and children's behavior problems suggests a significant, potentially modifiable contributor to one of the most serious mental health disorders of childhood. To establish the etiologic significance of prenatal smoking for specific types of disruptive behavior disorders, however, further prospective research is needed. The proposed project aims to provide advanced training/mentorship to the candidate in the conduct of research examining the relation of prenatal exposure to cigarette smoke and young children's behavior problems. The candidate is a clinical-developmental psychologist who seeks this training towards her goal of studying the effects of prenatal substance exposure on the development of behavior problems. Her existing expertise in the study of parent-child relationships and the clinical assessment of young children will be supplemented by: a) ongoing mentorship in regard to design and implementation of longitudinal research examining effects of prenatal substance exposure; b) advanced training in biochemical measurement and neuropharmacological effects of smoking, and longitudinal data analysis and; c) conduct of independent research. The proposed research is a prospective examination of prenatal smoking and behavior problems in high-risk preschoolers, designed to identify pathways by which smoking may increase the risk of behavioral symptomatology. Participants in an ongoing study of low-income African-American families will be recruited for this preschool follow-up assessment. Prospective data include repeated measures of pre- and postnatal smoking, parenting and infant development. 105 mother-child pairs will be seen including prenatally, actively passively, and non-exposed children. Multi-method assessment of behavior problems will include parent/examiner ratings, structured psychiatric interviewing, laboratory assessment and behavioral ratings during parent-child interaction. Child developmental functioning, t LVAL parental psychopathology and parenting practices will also be assessed. Multivariate planned comparisons will be used to examine the relation of pre-and postnatal exposure to smoke and preschool behavior problems. Structural equation modeling will be used to identify direct and indirect effects of smoking with particular emphasis on causal pathways between smoking, parental psychopathology and the quality of the parent-child relationship.LVALZ-p.Children with asthma are particularly vulnerable to environmental tobacco smoke (ETS). However, despite this special vulnerability to ETS, children with asthma are at least as likely to live in smoking households, as are healthy children. Controversy exists, however, about whether or not the smoking members of households with children with asthma use specific strategies to reduce the harmful effects of their smoking on their children more than the smoking members of households of healthy children. The central aim of this case-control study is to examine whether or not primary school-aged children with asthma from low-income households have lower household ETS exposure than matched control children. Household ETS exposure will be measured by both objective monitoring, specifically passive nicotine dosimeters and child cotinine assays (the primary hypothesis), and maternal-report (the secondary hypothesis). Ninety children with physician diagnosed asthma and smoking mothers will be matched by age, gender, race/ethnicity, and other relevant variables to 90 healthy children. All children will be recruited from Metro Denver clinics providing services to low-income, underserved populations. The sample will contain equal numbers of African Americans, Hispanics, and Whites. Recruitment will target low-income populations due to their increased prevalence of, and associated morbidity from both asthma and tobacco smoking. We will also examine how specific household smoking behaviors, as reported by mothers, are associated with household nicotine and child cotinine levels. Finally, we have included a set of carefully chosen measures that will be examined in tertiary, exploratory analyses to help understand, clarify, and contextualize the observed results. This study has been carefully designed to correct the serious methodological problems of the prior work in this area. Accordingly, the proposed study will be able to resolve a number of extremely important child health questions of major theoretical and practicaL LVAL\ l importance: (1) do children with asthma have less household ETS exposure as measured by objective monitoring than healthy children; (2) do alterations in household smoking behavior account for this difference; and if so, (3) which specific strategies are effective in reducing children's ETS exposure and which are not? Knowing the answers to these questions, as well as whether there is significant racial/ethnic variability in the answers, will be invaluable to ongoing tobacco intervention and control efforts in families of children with asthma, as well as other vulnerable populations.LVAL \ "ECONOMICS Socio-Economic Status Medicaid/Medicare LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors RESEARCH Human Studies Clinical Research STUDY POPULATION African American TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Initiation Maintenance Cessation AGE Child Young Adult Adult EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Social Factors RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION Urban National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments RESEARCH Human Studies STUDY POPULATION African American TOBACCO Cigarette/Other Smoking WOMEN PregnancyAGE Child DISEASE/BIOLOGY Mechanisms Other Disease/Biology EDUCATION LEVEL Less than High School LOCATION National PSYCHOLOGICAL Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Parent/MotherAGE Child DISEASE/BIOLOGY Cardiovascular/Pulmonary Other Disease/Biology ECONOMICS Socio-Economic Status EDUCATION LEVEL Less than High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Biochemical Assessments RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian Hispanic TOBACCO Environmental Tobacco Smoke Nicotine WOMEN Parent/Mother MISCELLANEOUS Sex/Gender Differences|LVALTo assess the impact of the intervention described below on the reduction of exposure to tobacco smoke among patients receiving prenatal care in a City District Health District The proposed study aims to understand the relationship between prenatal smoke exposure and aggression in children. The study will expand on previous findings by also investigating the extent to which this relationship may be mediated by genetic factors; a mother's smoking behavior during pregnancy may be influenced by her own predisposition toward antisocial behavior. Aggression, along with other traits such as cognitive ability in 9 year old twins will be measured using in depth interviews and multiple informant behavior assessments. The mothers will be assessed for antisocial behavior in similar manner, including ascertainment of current and prenatal substance abuse. This study will be conducted in a genetically informative twin design, which will allow for the investigation of the smoking/aggression relationship while controlling for covariates. It is hypothesized that children exposed in utero to high levels of cigarette smoke will exhibit elevated aggression. Also hypothesized, however, is that the said relationship will be at least partially explained by other risk factors, such as genetic predisposition towards anti-social behavior in the mother. Birth complications will also be examined for possible exacerbation of the smoking/aggression relationship as evidenced in prior studies. The effects of smoke exposure are expected to be greatest in the presence of birth complications.LVALRisk and resiliency to tobacco smoking are examined in a US population-based, longitudinal survey to understand why racial and ethnic minorities are more resilient to smoking initiation in adolescence, and yet by midlife, they report higher risk to smoking and lower rates of cessation. The relationship between smoking and social roles is considered during the transition from adolescence into adulthood, and through the course of midlife, to determine whether this relationship is confounded by different timing and sequencing of adult socials. Past research documents that the age pattern of risk and resilience to smoking varies for people of different racial and ethnic backgrounds, as well as for men and women. Past research also documents that the timing and sequencing of social roles vary by race, ethnicity and gender. No known research has examined the relationship between the age patterns of social roles and the age patterns of smoking, or related these to racial/ethnic and gender differences. Over twenty years of data from the National Institutes on Drug Abuse sponsored supplements to the National Longitudinal Survey of Youth (1979) will be employed to model the interdependent processes of smoking and social role transitions with dynamic, random effects hazard regression. This study will contribute to the achievement of Healthy People 2010 by contextualizing the determinants and consequences of smoking and guiding public health practitioners to anticipate the needs of current and emerging vulnerable populations.pLVALPurpose: To assess the relationship between maternal depressive symptoms and other psychosocial factors with smoking cessation and smoking intensity early and later in pregnancy Research Design: A prospective (observational) study. All women presenting for prenatal care at one of three prenatal sites are administered a short screening questionnaire to assess smoking status. All women who are current smokers (having smoked at least one cigarette during the past week) or who quit within the past year are then administered a questionnaire to assess maternal depressive symptoms, exposure to stressors, intendedness of pregnancy and smoking behavior. This questionnaire will be administered again at 30 weak gestation. Study Population: Women are enrolled in the study at three care sites in the Greenville/Pitt County, North Carolina Area. These clinics all serve low-income women from the community of whom about 75 percent are Medicaid recipients and 70 percent are African American. The state of North Carolina has one of the highest rates in the state. Intervention (if appropriate): N/A Outcome Measures (If cessation or reduction, how defined): Relationships between maternal depressive symptoms and exposure to psychosocial stressors early and later (30 weeks #GA) in pregnancy with smoking behavior including cessation (defined as no smoking), relapse (defined as having smoked at least one cigarette in the week prior to the interview), and smoking intensity. LVALZ-p.Among women, the epidemic of smoking related cancers continues to grow and lung cancer recently surpassed breast cancer as the leading cause of cancer mortality. Smoking cessation is a cornerstone of cancer prevention and control because cancer risk declines following smoking cessation. Unfortunately, relapse is the "rule rather than the exception" among smokers attempting to quit and relapse remains the most refractory aspect of nicotine dependence. Women appear to have higher relapse rates than men and relapse prevention has been identified as a priority in reducing smoking prevalence among women. Basic and clinical research on the precipitants of smoking relapse have demonstrated that coping behaviors are powerful determinants of relapse. The most influential model of smoking relapse, "relapse prevention" (Marlatt & Gordon, 1985), proposes that self-efficacy and outcome expectations are causal determinants of coping behaviors, and in fact, these variables have been among the better predictors of relapse. Moreover, there is evidence that interventions based on relapse prevention theory are effective, that they instill coping skills, and that coping skill acquisition mediates intervention effects on abstinence. The specific aims of this proposal are to l) Develop and evaluate the efficacy of a unique, self-help smoking relapse prevention intervention among women. The intervention will be administered via a small hand-held computer. The general content of the intervention will be tailored specifically for women and each participant's intervention will be individualized prior to delivery based on state-of-the-art "ecological momentary assessment" techniques; and, 2) Examine the effects of the relapse prevention intervention on hypothesized treatment mechanisms (coping behaviors, self-efficacy, processes of change, negative affect, perceived stress) and the impact of those mechanisms on relapse, i.e. test for mediation effects. The proposal translates basic and clinical behavioral scien LVAL ce research into a novel, theoretically-based treatment that provides individualized, situation-specific coping strategies, motivational and supportive messages, and other relapse prevention information. Moreover, unlike conventional relapse prevention treatments, participants have access to the intervention at an time and in any place, i.e. the intervention occurs in real-time in naturally occurring settings. The intervention has the potential to produce significant advances in the prevention of smoking relapse.LVAL6 "dAGE Child EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco UseDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Rural RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Hormones Hormone Replacement Therapy MISCELLANEOUS Weight Gain/ExerciseAGE Adult Older Adult DISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Hormones Hormone Replacement Therapy MISCELLANEOUS Weight Gain/ExerciseDISEASE/BIOLOGY Cancer ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Small (< 100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Educational Materials Nicotine Replacement Therapy RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other SmokingADDICTION Cessation Relapse ECONOMICS Cost of Intervention/Prevention EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials PSYCHOLOGICAL Social Factors Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PostpartumADDICTION Relapse LOCATION National PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Depression/Mood/Anxeity RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking  | F bK=@p@4Researchn@ WOODTERESAOHIO STATE UNIVERSITYCOLUMBUSOHNINRF31, NR007460(-p.@t@o@11/15/2000Not Given11/15/2000 to ?4/2005qkg]F>88,"`~@b@ResearchL@WISEROBERTJOHNS HOPKINS UNIVERSITYBALTIMOREMDNHLBIU10, HL059274:@@t@o\@2/1/19981/31/20032/1/1998 to 1/31/20034/2005vok`F>88,"@@Research@WINICKOFFJONATHANGENERAL HOSPITAL CORPORATION--MASSACHUSETTS GENERAL HOSPITALBOSTONMARWJF51803|@T@t@o @9/1/20048/31/20069/1/2004 to 8/31/20064/2005MC88,"@@`8@Researchh@WINDHAMGAYLEIMPACT ASSESSMENT, INCLA JOLLACANICHDR03, HD036762>-p.t@t@o@3/1/20002/28/20023/1/2000 to 2/28/20024/2005unj`HA88,"G@@ResearchV@WINDHAMGAYLESEQUOIA FOUNDATIONBERKELEYCACTRDRP11RT-0173J-p.t@tR@o@7/1/20026/30/20047/1/2002 to 6/30/20044/2005}rjf\HA88," @@Researchv@WINDHAMGAYLESEQUOIA FOUNDATIONBERKELEYCACTRDRP7RT-0119-p.Biology and CancerR@o@7/1/19986/29/20017/1/1998 to 6/29/20014/2005|rjf\HA88,"`/@`8@Researchl@WILLETTWALTERHARVARD UNIVERSITY SCHOOL OF PUBLIC HEALTHBOSTON MANCIU01, CA067262i-p.t@tR@o@5/10/19962/28/20025/10/1996 to 2/28/20024/2005~uIA88,"@@@@ResearchSUBSTANCE ABUSE IN ADHD GIRLSWILENSTIMOTHYMASSACHUSETTS GENERAL HOSPITALBOSTONMANIDAR01, DA014419ti-p.@tR@o@5/5/200212/31/20065/5/2002 to 12/31/20064/2005h_WW,"g@p@4ResearchZ@WHITTEMOREALICENORTHERN CALIFORNIA CANCER CENTERUNION CITYCANCIU01, CA069417@t@tDiscovery 1b Evaluation 1bv@Not GivenNot GivenUncertain4/2005~znKD88,"@`@Researchl@WHITTEMOREALICESTANFORD UNIVERSITYPALO ALTOCANCIR01, CA097359i-p.t@tDiscovery 1b Evaluation 1b@9/20/20038/31/20059/20/2003 to 8/31/20054/2005tok`KD88," }@`@Researchn@WHITELEYJESSICAMIRIAM HOSPITALPROVIDENCERINCIR03, CA103499BZ-p.T@tT@o@9/1/20038/31/20059/1/2003 to 8/31/20054/2005qlh\KB88,"5@ @Researchb@$OWETTERDAVIDUNIVERSITY OF TEXAS MD ANDERSON CANCER CENTERHOUSTONTXNCIR01, CA089350p @j@ t@o4@2/1/20021/31/20072/1/2002 to 1/31/20074/2005vG@88,"@k@G@Researchj@#OWETTERDAVIDCENTER FOR HEALTH STUDIESSEATTLEWANCIR01, CA074517Z-p.j@ t@o@9/1/19976/30/20029/1/1997 to 6/30/20024/2005tokbG@88,"LVALPostpartum relapse rates among women who quit smoking during pregnancy are exceedingly high (i.e., approximately 45 percent at 2-3 months postpartum, 60-70 percent at 6 months, and up to 80 percent at one year). These high rates of postpartum relapse are surprising because they occur in a population where the majority of women have been abstinent for 7-9 months prior to giving birth. Thus, the tremendous public health opportunity to facilitate long-term abstinence from tobacco among mothers as well as reduce the detrimental effects on smoking on their children is not being fully realized. The overall aim of this project is to develop and evaluate a "Motivational Relapse Prevention" (MRP) treatment for reducing postpartum smoking relapse among women who quit during pregnancy. MRP will utilize a motivational enhancement approach that specifically targets increasing commitment and intrinsic motives for maintaining postpartum abstinence, relapse prevention theory constructs (i.e., self-efficacy, outcome expectancies, coping behavior), and issues of particular relevance to postpartum women (e.g., negative affect, stress, social support, weight concerns). Treatment will be telephone-based and is designed to be easily disseminated to population-based settings for tobacco control (e.g., state quitlines, health care systems). In addition, the project will assess the cost-effectiveness of MRP. Participants (N=400) will be randomly assigned to one of two groups: 1) Standard Relapse Prevention, or 2) MRP. MRP will consist of six telephone counseling calls, and relapse prevention self-help materials designed specifically for the postpartum period. Postpartum assessments will occur at weeks 8, 26, and 52.LVALZ-p.Cigarette smoking has been found to be associated with a two-fold increased risk of developing cervical neoplasia or squamous cell cancer. The constituents of smoke, in concert with human papillomavirus (HPV), may promote the development or progression of cervical neoplasia. Thus, women who are positive for HPV and who smoke are at increased risk for developing cervical cancer. Counseling regarding smoking cessation may be of particular benefit for women undergoing screening at a colposcopy clinic for the evaluation of an abnormal Papanicolaou (Pap) smear. This is considered to be a "teachable moment" for smoking cessation, in that the perceived risk of progression to cervical cancer is heightened. Smoking cessation can reduce this risk as well as other health risks. Additionally, women at the colposcopy clinic represent underserved female smokers in that they are young, of low socioeconomic status, and are more likely to be ethnic or racial minorities. In Phase I, three focus groups of 8 -10 women each will be conducted to adapt an efficacious group-based cognitive-behavioral smoking cessation intervention that is tailored to the needs of women. The adaptations will include modifying the intervention from a group to phone-based delivery format and addressing the unique smoking cessation barriers of the women at our study site colposcopy clinic. In Phase II, the refined materials will be used in a randomized pilot study. Thirty women will be randomized either to an AHRQ + Enhanced Smoking Cessation group (n = 15) or to an AHRQ + Contact Control group (n = 15). Both groups will receive the AHRQ guidelines for smoking cessation (self help materials, brief counseling, recommendation for nicotine replacement therapy) plus phone delivery of either the adapted smoking cessation intervention (AHRQ + Enhanced Cessation) or a health education intervention (AHRQ + Contact Control). Our primary hypothesis is that the women randomized to the AHRQ + Enhanced Cessation group will have higher quit rates then women i LVAL n the AHRQ + Contact Control group. Thus, we seek to: 1) conduct the formative work to adapt the cessation materials from a group to phone-based format and to address the needs of this population, 2) pilot the recruitment strategy, and 3) conduct a small randomized pilot trial to determine the preliminary efficacy of the materials for smoking cessation. This study, therefore, will serve as a pilot for a larger clinical trial.LVAL$&` , x , ` r  V N>N2fxInternational Network of Women Against CancerAnnual Investigator Meeting 2002. Women and Smoking: Smoking Has No Glass CeilingAfrican Women and Tobacco ConferenceWomen Statewide to Toss Their Tobacco ProductsThe National Partnership to Health Pregnant Smokers QuitEuropean Week against Cancer 2001: Women and TobaccoMETHYLATION RELATED GENES AND BREAST CANCER RISKTELEPHONE COUNSELING FOR PREGNANT SMOKERSCIGARETTE SMOKING OR PCBS EFFECTS ON ESTRADIOLPCBs, CYP1A1 POLYMORPHISM AND BREAST CANCER RISK IN CTNICOTINE AND ITS METABOLITES: APOPTOSIS IN DEVELOPING NEURONSCIGARETTE SMOKING AND RISK OF BREAST CANCER MORTALITY: EFFECT MODIFICATION OF ALCOHOLSMOKING, GENDER, HORMONES AND THE BRAINALPHA 1 AD CARRIERS AND LUNG CANCER RISKMEDIA AND SMOKING AMONG ADOLESCENT GIRLS ACROSS ETHNICITYGENETICS OF AIRWAY RESPONSIVENESS AND LUNG FUNCTIONNICOTINE/ NEUROENDOCRINE SIGNALING IN DEVELOPING LUNGNICOTINE AND NICOTINIC SIGNALING IN LUNG DEVELOPMENTMECHANISM OF NICOTINE ACTION IN DEVELOPING LUNGBREAST AND OTHER CANCER IN THE CALIFORNIA TEACHERS COHORTMULTI-LEVEL ANALYSIS OF URBAN CHILDHOOD ASTHMA RISKMESSAGE DEVELOPMENT USING AUDIENCE RESEARCHMASS MEDIA INTERVENTIONS TO REDUCE YOUTH SMOKINGVIRTUAL WORLD INTERNET CHAT ROOM FOR TEEN SMOKING CESSATIONTEST OF AN INTERNET VIRTUAL WORLD FOR TEEN SMOKING CESSATIONSMOKING CESSATION/REDUCTION IN PREGNANCY TRIAL BIOBEHAVIORAL ASPECTS OF ADOLESCENT NICOTINE DEPENDENCELUNG HEALTH STUDY--LONG TERM FOLLOW-UPTESTING THE FEASIBILITY AND EFFICACY OF A TOBACCO CONTROL STRATEGY FOR PARENTS OF NEWBORNSPRENATAL AND CHILDHOOD EXPOSURES AND AGE AT MENARCHEPRENATAL SMOKE EXPOSURE AND AGE AT MENARCHEEFFECTS OF TOBACCO SMOKE EXPOSURE ON HORMONES AND FERTILITYPREMENOPAUSAL HORMONE LEVELS AND RISK OF BREAST CANCERENVIRONMENTAL MODIFIERS OF BREAST CANCER RISKBREAST CANCER RISK MODIFIERS IN BRCA MUTATION CARRIERSSMOKING CESSATION FOR WOMEN AT RISK FOR CERVICAL CANCERhLVALi-p.xLifetime breast cancer risks among carriers of mutations of the genes BRCA1 and BRCA2 have been estimated at 40-80%. Thus some 20-60% of carriers live to advanced ages without developing the disease, which suggests that other genes or personal attributes may modify carriers' risks. At present however, title is known about such personal characteristics. There is urgent need to determine which, if any, modifiable lifestyle characteristics may alter a carrier's risk of developing breast cancer, to assist her in making rational, informed choices about such preventive options as prophylactic mastectomy. We propose to use uniformly collected data from young (aged < 50 years) case (N=425) and control (N=352) carriers of deleterious BRCA1 or BRCA2 mutations to evaluate associations between breast cancer risk and five modifiable characteristics. These are: history of oral contraceptive use, history of diagnostic or therapeutic chest irradiation prior to diagnosis, alcohol consumption, cigarette smoking, and physical activity patterns during puberty, young adulthood and middle age. We will focus on carriers under age 50 years at diagnosis (cases) or interview (controls) who have participated in an international Collaborative Family Registry for Breast Cancer Studies (CFRBCS) and in clinical studies in New York, Ontario and Australia. We will use unconditional logistic regression to estimate odds-ratios relating these attributes to breast cancer risk while controlling for potential confounders, and use robust variance estimators to account for any correlation present in attributes of related carriers. These data on modifiable characteristics from a large group of young carriers of BRCA1 or BRCA2 mutations represent a unique resource for advancing our knowledge about breast cancer prevention in premenopausal women at high risk for the disease. The proposed analysis will provide new information on alternatives to mastectomy as a preventive strategy for these women.dLVALtLifetime breast cancer risks among carriers of mutations of the genes BRCA1 and BRCA2 have been estimated at 40-80 percent. The fact that some 20-60 percent of carriers live to advanced ages without developing the disease suggests that other genes or environmental exposures may modify carriers? breast cancer risks. At present, however, little is known about how a carrier's risk varies with her reproductive and menstrual history, her diet and alcohol intake, her physical activity patterns, and her exogenous hormonal exposures. Many of these attributes are well-established risk factors for breast cancer in the general populations of noncarriers. There is urgent need to determine which, if an, modifiable lifestyles characteristics may alter a carrier?s risk of developing breast cancer, to assist her in making rational, informed choices about such preventive options as prophylactic mastectomy and the use of chemopreventive agents such as tamoxifen and raloxifene. The investigators propose to use the CFRBCS data to analyze the relation between breast cancer risk and specific environmental and hormonal attributes among an anticipated 800 female carriers of mutations of BRCA1 or BRCA2. Attributes include: 1) reproductive characteristics; 2) exogenous hormone use; 3) diet; 4) body size; 5) physical activity; 60 radiation exposure; 7) alcohol consumption; 8) cigarette smoking. The investigators will use a retrospective cohort design. Specifically, they will compare the attributes of each female carrier affected with breast cancer to those of all female carriers in her birth cohort who were free of breast cancer at the age when she was diagnosed. This large group of more than 800 carriers of BRCA1 or BRCA2 mutations represents a unique resource for advancing our knowledge about breast cancer management in women at high risk for the disease.LVALi-p.This is the first resubmission of an R01 application, 1 R01 DA14419-01, that is a response to a PA (97-043) encouraging research on the origins and pathways to substance abuse (SA). A mixed body of evidence suggests that SA is frequently preceded by childhood attention-deficit/hyperactivity disorder (ADHD) and associated comorbid disorders. The aim of this proposal is to test hypotheses about the co-occurrence of SA in ADHD adolescent girls growing up and their high-risk siblings. We are proposing to study a group of girls available from an NIMH funded five year, family-based, controlled follow-up study of girls with ADHD currently underway with a focus on SA. At baseline assessment, we ascertained 140 ADHD and 120 normal control girls from psychiatric and non-psychiatric settings with 464 and 402 first degree biological relatives, respectively. We now propose a five-year study that will re-examine the probands and families five years after their baseline assessment with a particular emphasis on SA, thus capturing these adolescents as they are beginning to pass through the risk for SA. We have two Main Aims: 1) To characterize SA in ADHD girls growing up, and 2) To determine predictors of SA in ADHD girls growing up. In our preliminary work, we have begun to address issues related to the overlap of SA and ADHD in boys and girls that are the focus of the proposed work. We view the proposed extension of our work as an essential step for several reasons: this work will be the first, prospective high risk family-based study of SA in ADHD girls; we will have extensive information on a well characterized group of children ascertained from medical and psychiatric settings spanning five years; and psychiatric comorbidity within ADHD was not excluded allowing analysis of its influence on later SA. Given the high prevalence of ADHD, its related comorbid disorders, and its frequent persistence into adulthood, the proposed study will shed light on ADHD adolescent and young adult females at highest risk for SA. Si` LVALp nce ADHD is treatable and identifiable in early years, these data will provide valuable information to formulate prevention interventions. Thus, the research, approach, and goals of this R01 application are consistent with those underscored in the PA and by the Institute of Medicine as being of the highest research priority.LVALi-p.The epidemiology of breast cancer suggests a central etiologic role for premenopausal endogenous sex hormones, yet current data do not indicate which specific endogenous hormones (or hormone fractions) are of greatest importance and at what levels risk is increased Similarly, current data suggest that urinary estrogen metabolites and plasma antioxidants may also be related to breast cancer risk yet these relations have not been assessed in a large prospective study The Nurses' Health Study Il (NHSII) is a large ongoing prospective cohort study of 116,678 female, U.S. registered nurses who were 25-42 years of age when the study began in 1989. We now propose to collect and archive blood and urine samples from approximately 40,000 premenopausal women participating in the NHSII who are at least 35 years of age, are free from cancer, have completed previous NHSII questionnaires, are not using exogenous hormones and are neither pregnant nor breastfeeding. Plasma drawn during both the follicular phase (days 3-5) and luteal phase (approx days 20-22), white and red blood cells, and a urine sample will be stored in liquid nitrogen freezers and later analyzed using a nested case-control design. We propose to assess the following specific hypotheses (1) higher levels of estrogens, androgens, prolactin and progesterone in both the follicular and luteal phase of the menstrual cycle each increase risk of breast cancer, (2) higher levels of plasma beta-carotene and other carotenoids, retinol, and alpha-tocopherol reduce the risk of breast cancer and (3) the ratio of 16-alpha to 2-hydroxylated urinary metabolites is positively associated with an increased risk of breast cancer. The ongoing NHSII will provide follow-up of the cohort and documentation of breast cancer (CA 50385) in addition to information on important covariates (such as body mass index, parity, age at menarche, smoking status and dietary intake, among others) for the proposed study. Overall, the large size of the cohort, the prospective design, LVAL"the high follow-up rate, the detailed covariate data, and the ability to collect blood specimens timed according to the menstrual cycle provide a unique opportunity to evaluate several important hypotheses related to breast cancer risk. fLVAL v AGE Adult Older Adult DISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Weight Gain/Exercise Sex/Gender DifferencesCOMMUNITY Health Care Provider LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Biochemical Assessments PSYCHOLOGICAL Social Factors RESEARCH Human Studies TOBACCO Cigarette/Other Smoking WOMEN Postpartum Parent/Mother Partner/Spouse MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy Menstral Cycle HormonesAGE Child Fetus/Prenatal DISEASE/BIOLOGY Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research STUDY POPULATION African American Caucasian TOBACCO Cigarette/Other Smoking WOMEN Pregnancy Menstral CycleDISEASE/BIOLOGY Mechanisms Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle HormonesDISEASE/BIOLOGY Cancer EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Menstral Cycle Menopause HormonesLVAL-p.Cigarette smoke is known to contain a large number of compounds, some of which are suspected to cause damage to the reproductive system. Smoking is one of the most preventable causes of low birth weight in exposed babies and has also been associated with pregnancy loss, infant death and infertility. Some evidence also suggests that smoking may affect hormone levels, which in turn could affect pregnancy and other hormone-dependent conditions. For example, women who smoke tend to reach menopause earlier than non-smokers. We previously conducted a study that looked at different aspects of the menstrual cycle. Women kept track of their periods and collected urine daily during several cycles. From the urine , the levels of two hormones which are secreted from the ovaries during each "normal" menstrual cycle, namely estrogen and progesterone, were measured. We found that menstrual cycles of heavy smokers tended to be shorter and more irregular than those of non-smokers. There also appeared to be some differences in hormone patterns by smoking status. Shorter cycles (in general) have been linked to earlier menopause and to higher risk of breast cancer. The timing of events in the menstrual cycle, including release of progesterone and estrogen, may affect the ability to get and stay pregnant, so these findings are important for reproductive fitness. This is one of the first studies to look at smoking and menstrual function in this way and the exact means by which smoke exposure may cause these changes is not clear. Therefore, we plan to pursue these findings further in this valuable database. The release of hormones by the ovary is under the control of messages from other organs, such as the pituitary and the brain. To learn more about how smoke exposure may act on this system, we will measure one of the pituitary hormones, called follicle stimulating hormone (FSH). FSH is important in preparing for ovulation (release of the egg in the middle of the cycle) and thus may be a marker of ovarian funLVALction. Two prior studies found some increase in FSH among smokers, but FSH was measured on only a few days. We will measure FSH on each day of a sample of menstrual cycles, so we can examine patterns throughout the cycle. FSH production will be compared by smoking status and to other menstrual cycle characteristics to determine whether it is involved in the changes in menstrual function we noted among smokers in this study. This study is directly relevant to the goals of the TRDRP to understand the biomedical effects of smoking. It is cost-effective because it uses information from a database of over 400 women and 2,000 menstrual cycles which was already collected at considerable cost and time. From this study, we expect to learn more about how smoking affects hormone systems and reproductive function. These hormone system, in turn, are critical for many other aspects of women's health.LVAL-p.This study will examine whether a mother's smoking during pregnancy affects puberty in her daughter. The marker of puberty that we will use is the age at which the daughter starts menstruating (e.g. age at menarche). Scientific evidence has been accumulating that events during pregnancy, when the baby is developing, can have later effects on health conditions that do not appear until childhood or even adulthood. Recently, there has been much concern that puberty is starting earlier than previously thought among American children, and that this might be due to modern day exposures. Cigarette smoke contains hundreds of chemicals, including some shown to harm reproduction in animals. Smoking is also known to have damaging effects on the development of a baby, causing problems such as low birth weight. Although there is little data addressing potential effects of smoke exposure on puberty, we have been conducting a study that suggests an earlier age at menarche among daughters of smokers. We found these associations to be stronger among children of a race other than White. In general, onset of menarche has been observed to occur at an earlier age among Blacks than Whites. The proposed investigation will make use of data already collected in a large-scale study with a 30-year follow-up, in order to quantify the effect of maternal smoking on early age at menarche, by race. The data to be analyzed are from the Collaborative Perinatal Project (CPP), a study of over 50,000 pregnant women and their children, conducted in 12 medical centers throughout the United States. Pregnant women were recruited from 1959-1965, their pregnancy outcomes were recorded, and their children were followed for up to 8 years for various health endpoints. Two investigators independently extended the follow-up of sub-sets of the children into adulthood, asking their age at menarche. By combining these two groups, we will have information on 1560 girls born into the CPP. Interviews with their mothers during pregnancy asked about a vaLVALriety of lifestyle factors, including smoking history. Factors that might bias an apparent effect of smoking on age at menarche are available from the pregnancy interviews and the later childhood exams and interviews. Age at menarche was asked of the daughters as part of the follow-up interview when they were young adults. The mean age at menarche will be calculated, as well as classifying it as "early" (<12) and "late" (>13) ages. These will be compared by amount smoked by the pregnant mother, controlling for related factors. The sub-sets followed include a high proportion of non-Whites (primarily Blacks) so we will be able to examine whether any associations found differ by race, as our earlier work indicated. We will also examine this question by combining this newer data with our previous data. Given the depth and quality of the data set to be examined, this analysis should yield valuable information about an area deserving further investigation, namely the effects of smoke exposure early in fetal development on later maturation, in a very cost-effective manner. This study will expand our knowledge of the reproductive process and of the effects of smoke exposure during pregnancy on the offspring and their later health. It will also provide guidance for designing future studies of this important issue. LVAL-p.Hazards posed to the developing fetus and child by exposure to chemical substances are receiving increasing attention. The developmental endpoints examined primarily have been adverse pregnancy outcomes, as well as some consideration of neurobehavioral development. Little is known about normal menstrual function and how it is initiated during adolescence. In this pilot study we propose to examine a measure of sexual development, namely, age at menarche, and its relationship to prenatal exposure to chemical substances including, tobacco smoke, alcohol and caffeine (TAC). Active smoking is a known reproductive hazard during pregnancy and has also been associated with infertility and alterations in hormone excretion levels. Prenatal alcohol exposure is associated with fetal growth retardation and neurologic impairment in offspring. Numerous studies have shown effects of alcohol on the endocrine system of adults and there is suggestive evidence it may effect sexual maturation. Known actions of caffeine present plausible mechanisms for alteration of hormonal profiles and an association with delayed time to conception has been reported. Thus all three exposures may possibly affect sexual development via actions on the prenatal hormonal milieu or the developing nervous system. The proposed pilot study would make use of a large data base of pregnancies ascertained in the early 1960's. Subjects of this study will be the 1000 daughters followed through childhood and adolescence, at which time age at menarche was ascertained. Extensive data was collected prospectively on prenatal exposures, as well as on potential confounders. A number of important exposures and conditions of childhood were also ascertained prospectively, including parental cigarette smoking, childhood behaviors, and growth. With these data we propose to examine whether in utero exposure to TAC or childhood exposure to parental smoking are related to perturbations in age at menarche. Early age at menarche has been associated with an LVAL increased risk of breast cancer, thus alteration in menarcheal age may serve as a sentinel of other adverse effects on children's and women's health. Such data will be valuable in designing further studies of the reproductive process and growth and development in relation to early life exposures.t LVAL Aim 1: To test the feasibility of implementing a systems-level tobacco control strategy for postpartum mothers and fathers initiated during the postpartum hospitalization. Aim 2: To pilot test the short-term efficacy of this theory-driven parental tobacco control strategy implemented within a major childbirth center.LVALThe Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long- term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airways reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participated, giving a potential sample size of 5600.LVAL-p.Adolescent smoking prevalence has continued to climb with 1997 estimates being the highest reported since 1979. The relationship between adolescent smoking and subsequent nicotine dependence in adulthood has been well established. While biological effects of smoking have been studied in adults, the biobehavioral aspects have not been examined in adolescents. In addition gender differences in smoking that have been reported for adolescents address sociobehavioral factors with limited emphasis on biological data which is essential for understanding adolescent nicotine dependence. The need to identify biomarkers of adolescent nicotine dependence is essential to the health of adolescent smokers. The first aim of this one-factor factorial design study is to characterize the biomarkers of smoke constituent exposure and smoking topography parameters in adolescent smokers. Smoke constituent exposure includes carbon monoxide and plasma nicotine increases post-cigarette and baseline cotinine levels. Smoking topography parameters include puff volume and duration, interpuff interval, and inhalation and exhalation duration. In the second aim smoking topography parameters, smoke constituent exposure, and level of nicotine dependence will be compared between adolescent male and female smokers. The third aim will compare smoke constituent exposure, smoking topography parameters and level of nicotine dependence of prepubescent and later teens. The final aim will contrast biological markers of smoke constituent exposure with accepted behavioral measures of nicotine dependence. Characterizing biological and behavioral aspects of smoking in adolescent boys and girls will provide a foundation to address the gap in this important research area. The proposed study represents the first phase of a program of research that includes analyzing differences in smoking behavior of adolescents from multiple ethnic groups, as well as increasing the scientific basis from which to design tailored smoking prevention and cessation intervLVALentions by gender and age group.LVAL J AGE Child LOCATION National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child EDUCATION LEVEL High School LOCATION National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Interview/Focus Group Quitline Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionAGE Child ECONOMICS Cost of Intervention/Prevention EDUCATION LEVEL High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Media-Websites/pamphlets/radio PREVENTION/TREATMENT Counseling/Behavior Therapy Interview/Focus Group Quitline Educational Materials RESEARCH Human Studies TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionCOMMUNITY Health Care Provider ECONOMICS Socio-Economic Status Medicaid/Medicare EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN PregnancyADDICTION Maintenance Cessation AGE Child DISEASE/BIOLOGY Mechanisms LOCATION National PSYCHOLOGICAL Depression/Mood/Anxeity Other Psychological RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Nicotine MISCELLANEOUS Knowledge/Attitudes/Risk Perception Sex/Gender DifferencesLVALSmoking among pregnant women, particularly public health maternity patients, is one of the most important risk factors in predicting infant and maternal morbidity and mortality. Smoking among pregnant women has been a national priority for our 1990 and Year 2000 health objectives. The objective of the proposed study-- Smoking Cessation and Reduction In Pregnancy Trial (SCRIPT) -- is to evaluate the EFFECTIVENESS of a smoking cessation intervention for pregnant smokers delivered as part of routine care by public health nurses in Alabama. Four aims will be completed 1) To randomly select a representative sample of public health maternity clinics and Medicaid-supported obstetrical care patients in Alabama; 2) To conduct, among patients and staff at Aim #1 sites, a three-phase formative evaluation of a multi component smoking cessation and reduction intervention, including a patient education, counseling, skills training program for nursing staff; 3) To evaluate the behavioral impact of the multi-component health education intervention program among at least 2000 pregnant smokers, 1000+ randomly assigned to an Experimental (E) Group and 1000+ randomly assigned to a Control (C) Group at their first prenatal visit; and, 4) To conduct a process evaluation to document the degree of patient exposure to the intervention methods and evaluation procedures specified in Aim #3. SCRIPT will confirm the EFFECTIVENESS RATES AND EXTERNAL VALIDITY of the intervention. Very limited insight is available in the Public Health Practice literature about these two outcomes.  u @ , .''`@`@ResearchP@YANGPINGMAYO CLINIC COLLEGE OF MEDICINEROCHESTERMNNCIR01, CA080127"-p.L@@@3/10/20002/28/20053/10/2000 to 2/28/20054/2005ytpeD>88,"&&@G@Researchr@YANGDONGYUNUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP8DT-0175-p.@t@@1/1/20006/30/20021/1/2000 to 6/30/20024/2005{wjG>88,"%%d@G@Researchf@XUXIPINGBRIGHAM AND WOMEN'S HOSPITALBOSTONMANHLBIR01, HL056371-p.Biology and CancerP@@7/10/19976/30/20027/10/1997 to 6/30/20024/2005unjbD<88,"$$ X@i@Researchj@WUENSCHELLCAROLUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANHLBIR29, HL054960-p.Biology and CancerDiscovery 1a Evaluation 1b@4/1/19973/31/20034/1/1997 to 3/31/20034/2005*"  {nKD88,"##@@u@Researchh@WUENSCHELLCAROLUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCANHLBIK02, HL003786p-p.Biology and CancerDiscovery 1a Evaluation 1b@7/5/19986/30/20037/5/1998 to 6/30/20034/2005*"  {nKD88,"""@@u@Research^@WUENSCHELLCAROLUNIVERSITY OF SOUTHERN CALIFORNIALOS ANGELESCACTRDRP9RT-0238D-p.Biology and CancerR@D@7/1/20006/30/20037/1/2000 to 6/30/20034/2005 {nKD88,"!!@@Researchr@WRIGHTWILLIAMPUBLIC HEALTH INSTITUTEOAKLANDCANCIR01, CA077398H-p.L@tT@<@9/25/19989/30/20039/25/1998 to 9/30/20034/2005tokbI@88,"  @@Researchf@WRIGHTROSALINDHARVARD UNIVERSITYBOSTONMANIEHSR01, ES010932-p.t@t@@9/30/20007/31/20059/30/2000 to 7/31/20054/2005qjf^J@88,"@@ResearchV@WORDENJOHNUNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGEBURLINGTON VTNCIP01, CA082708@@t@@9/30/20007/31/20059/30/2000 to 7/31/20054/2005|F@88,"@@Research`@ WORDENJOHNUNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGEBURLINGTON VTNCIP01, CA082708 @@t@D@9/30/20007/31/20059/30/2000 to 7/31/20054/2005|F@88,"@G@Researchv@ WOODRUFFSUSANSAN DIEGO STATE UNIVERSITYSAN DIEGOCACTRDRP9HT-3101-p.@t@o@7/1/20006/30/20027/1/2000 to 6/30/20024/2005|tpeIB88,"G@@Researchx@ WOODRUFFSUSANSAN DIEGO STATE UNIVERSITYSAN DIEGOCACTRDRP11HT-3301-p.@t@o@7/1/20026/30/20057/1/2002 to 6/30/20054/2005|tpeIB88,"L@^@Research^@ WOODBYLESAUNIVERSITY OF ALABAMA AT BIRMINGHAMBIRMINGHAMALNHLBIR01, HL056010R @T@t@o@1/1/199712/31/20021/1/1997 to 12/31/20024/2005{wkF@88,"LVAL-p.Smoking among children and adolescents has tremendous public health importance. Onset and development of smoking occurs primarily in adolescence, and because tobacco is highly addictive, regular use in adolescence develops into nicotine dependency. Smoking among adolescents is likely to continue into the adult years, increasing the risk of numerous long-term negative health consequences. However, after three decades of efforts to prevent smoking among children, large numbers of young people continue to smoke. Unfortunately, adolescent smokers are difficult to recruit and retain in smoking cessation studies. Even more discouraging, programs that have been effective with adults, when tried with adolescents in school clinics and classrooms, have not shown much promise. Many believe that advances in health promotion among young people, including motivating interest in smoking cessation, will focus on appropriate use of new technologies such as computers. The primary goal of this 3-year study is to test an innovative approach to smoking cessation that might be particularly attractive to teen smokers. The proposed intervention will take place in the context of a novel Internet technology--a virtual world chat room--while also using a state-of-the-art counseling approach, motivational interviewing conducted by a smoking cessation facilitator. The approach is likely to have a great deal of appeal to teens that typically enjoy using the Internet and may especially like the animated interaction available in a virtual world chat-room format. In addition, teens may find the motivational interviewing approach much less offensive than more traditional behavior-change counseling for  rebellious behaviors such as smoking. The chat room approach also circumvents the expense and logistical problems (e.g., classroom time, teacher training) involved in delivering a school-based classroom program. This innovative combination of virtual world chat room technology with motivational counseling for behavior change showed$LVAL4 promising results in our pilot study, but needs to be more strictly evaluated. Participants will be 330 teen smokers recruited from 12 high schools. Participants will use school computer resources to access the Internet chat room. Following an introduction to the chat room, participants will interact in seven 1-hour chat sessions over a 2-month period addressing topics shown to be effective and unique to the cessation experience of adolescents. The effectiveness of the chat room will be evaluated using responses to on-line tobacco use surveys. Participants survey responses will be compared to two other groups of participants: (1) those who access several smoking cessation educational web sites, and (2) those who only complete surveys. The three groups will be compared in terms of changes in their attitudes and quitting behavior. If the chat room approach is found to be effective, the academic and school partners will develop a plan to make the program available to more schools.LVAL-p.Smoking among children and adolescents has tremendous public health importance. Onset and development of smoking occurs primarily in adolescence, and because tobacco is highly addictive, regular use in adolescence develops into nicotine dependency. Smoking among adolescents is likely to continue into the adult years, increasing the risk of numerous long-term negative health consequences. Yet, even after three decades of efforts to prevent smoking among children, large numbers of young people continue to smoke. Further, although a large percent of adolescent smokers express an interest in quitting, few are successful. Unfortunately, adolescent smokers are difficult to recruit and retain in smoking cessation interventions, and even more discouraging, cognitive-behaviorally oriented cessation interventions that have been effective with adults, when tried with adolescents in school clinics and classrooms, have not shown much promise. Many believe that advances in health promotion among young people, including motivating interest in smoking cessation, will focus on innovative and appropriate use of emerging technologies such as computerized communication. Last year, a virtual reality chat room approach was pilot tested and evaluated in terms of feasibility (e.g., use and acceptability) and immediate effectiveness (e.g., changes in self-efficacy, intentions, and self-reported quit rates) with high-risk teen smokers recruited from six alternative high schools. A smoking cessation counselor trained in motivational interviewing techniques interacted with teen smokers in a real-time on-line virtual reality world. Results were very promising. In preparation for a proposal to test the chat room approach in a rigorous experimental design, over the next 18 months we are conducting efforts in four areas: (a) establishing strong connections with individual schools that would participate in further study, (b) developing an educational website-based intervention that would be an appropriate comparison with the vi LVAL& rtual chat room cessation intervention, (c) refining the virtual world chat room intervention, and (d) refining the evaluation measures. The virtual world chat room approach for teen smoking cessation has both public health potential and practical appeal. Virtual reality chat rooms can provide a technology appealing to adolescent boys and girls that is both convenient and  naturalistic in that it involves real-time communication. The computer-based cessation program can overcome many of the traditional barriers of school-based cessation programs, and offer a potentially effective intervention for a population that may be especially resistant to quitting smoking and for whom other strategies have not proven very effective or practical.*LVALz t $  j   & *LPrvzBdDevelopment 3 Development 4 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1aDiscovery 1a Discovery 1b Discovery 1c Discovery 2a Discovery 3 Development 1 Development 2 Development 3 Development 4 Development 5 Delivery 1 Delivery 2 Delivery 3 Delivery 4 Partnerships 1 Partnerships 2 Partnerships 3 Partnerships 4 Evaluation 1a Evaluation 1bDevelopment 3 Development 4 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1a Evaluation 1bDevelopment 3 Development 4 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1a Evaluation 1bDevelopment 3 Development 4 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1aDevelopment 3 Development 4 Development 5 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1aDevelopment 3 Development 4 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1aDevelopment 3 Development 4 Development 5 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1aDevelopment 3 Development 4 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1aDiscovery 1a Discovery 1c Discovery 2a Development 1 Development 3 Delivery 1 Evaluation 1aDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1a Discovery 2a Evaluation 1bDiscovery 1a Discovery 1b Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 2a Discovery 2b Development 5 Evaluation 1aDiscovery 1a Discovery 3 Evaluation 1bDiscovery 1a Discovery 1b Evaluation 1bDiscovery 1b Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 3 Evaluation 1a Evaluation 1bDiscovery 1c Discovery 2a Discovery 2b Discovery 3 Development 1 Development 3 Delivery 1 Delivery 2Discovery 1c Discovery 3 Development 3 Delivery 2 Evaluation 1aLVAL$Goals are to develop appealing and attractive mass media smoking prevention and cessation messages for youth in specific audience segments.Mass Media Interventions to Reduce Youth Smoking is a program project that will develop methods of design and delivery of comprehensive, theory-based media campaigns to reduce the prevalence of cigarette smoking among ethnically diverse adolescents, and to assess the effects of these methods on the prevention and cessation of tobacco use among these targeted population. This will be accomplished through the close integration of three research projects. Project 1, Message Development Using Audience Research, will apply diagnostic and formative research methods with ethnically/racially diverse populations of adolescents to inform the development of theory- based smoking prevention and cessation messages for media campaigns. Message content than will be tested with studies according to grade, gender, racial/ethnic identity, and smoking risk to help define audience segments for targeting smoking prevention and cessation interventions. Project 2, Reducing Youth Smoking Using Mass Media, will develop media messages in four-year campaigns designed to prevent smoking among adolescents and will evaluate their effectiveness in four intervention mass media markets versus four comparison areas. Project 3, Youth Smoking Cessation Using Mass Media, will develop mass media messages in a three-year campaign designed to help adolescents stop smoking and will evaluate their effectiveness with a cohort of weekly smokers established at baseline in four intervention mass media markets and in four comparison areas.LVAL r 6nDISEASE/BIOLOGY Cardiovascular/Pulmonary EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION International RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesAGE Child Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Nicotine WOMEN PregnancyAGE Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms RESEARCH1 Animal Studies RESEARCH In Vitro Studies TOBACCO Nicotine WOMEN PregnancyAGE Fetus/Prenatal DISEASE/BIOLOGY Cardiovascular/Pulmonary Mechanisms RESEARCH1 Animal Studies TOBACCO Nicotine WOMEN PregnancyAGE Young Adult Adult Older Adult DISEASE/BIOLOGY Cancer EDUCATION LEVEL College and Above EPIDEMIOLOGY/SURVEILLANCE Large (>=100) RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking Environmental Tobacco SmokeAGE Child ECONOMICS Socio-Economic Status EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION Urban National PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors RESEARCH Human Studies Clinical Research TOBACCO Environmental Tobacco Smoke WOMEN Parent/MotherAGE Child EDUCATION LEVEL Less than High School High School EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Counter-Marketing Media-Websites/pamphlets/radio PREVENTION/TREATMENT Educational Materials PSYCHOLOGICAL Social Factors Cultural Factors RESEARCH Human Studies STUDY POPULATION African American Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Sex/Gender DifferencesLVAL-p.The overall goal of this proposal is to elucidate the role of physical environmental determinants and psychosocial factors (in particular, life stress) in the rising asthma burden, particularly among socioeconomically disadvantaged children in inner city areas. The investigators' underlying concept is that stress experienced prenatally and during infancy and early childhood has significant potential to modify immune function and, hence, the development of asthma. They propose to examine the associations between various measures of life stress and asthma outcomes in a representative sample of urban children enrolled prenatally and followed prospectively for four years. Five hundred mother-infant pairs will be recruited from four participating community health centers serving ethnically diverse, inner city neighborhoods of Boston. They will complete a multilevel perspective survey, measuring both individual-level stress (i.e., negative life events, perceived stress, perceived threat of violence) and community-level stressors (neighborhood disadvantage (e.g., percent of subjects living in poverty, percent unemployed, diminished social capital and violent crime). In addition to examining associations between chronic early stress exposure and asthma onset, they will also assess the influence of stress on the infant hormonal stress response and on T-helper cell differentiation as reflected in cytokine profiles and IgE production (Th2 phenotype). Additional environmental and host factors to be assessed for their influence on the immune response and expression of asthma include parental asthma, acute lower respiratory illness, day care, environmental tobacco smoke, indoor allergens, gender, and race. The study will be conducted through a partnership involving researchers from Harvard's Longwood Medical Area, clinicians and care-providers from four community health centers serving the target population, and community advisors recruited through the health centers. A secondary, yet centrally important goal of th LVAL e project is to strengthen and build this partnership to facilitate future research. This will be achieved through a clinical database project. An additional feature of the proposal is the opportunity to involve under represented minority students (predoctoral and summer interns) from two NIH-funded grants whose principal investigator is a co-investigator on this proposal.LVAL-p.A cohort of 133,000 California school teachers has been established by a collaborative group of epidemiological investigators with the goals of evaluating unresolved issues related to breast cancer risk factors and studying other important issues related to women's health. The teachers were recruited with a detailed multiple choice, optically-scanned mail survey. Scanning of the questionnaires has been completed and data editing is ongoing. Planned follow-up includes routine linkage with the California Cancer Registry and California mortality files, annual re-contact of cohort members for follow-up, and biennial contact for collecting additional risk factor exposure data and information on other health outcomes. The Specific Aims for this project are to 1) test a series of unresolved and emerging hypotheses related to breast cancer aetiology (specifically associations with the lactation, hormone replacement therapy, abortion/miscarriage, dietary phytoestrogens, fibre, micronutrient consumption, alcohol intake, physical exercise and activities, family history of breast and other cancers, and active and passive cigarette smoke exposure); 2) conduct calibration/validation studies of the food-frequency questionnaire and self-reported information on family history of breast and other cancers reported in the baseline questionnaire; and 3) follow this cohort for five additional years, during which time, two or more questionnaires will be mailed to update initial exposure assessments, collect new exposure information, and assess additional disease outcomes for testing novel hypotheses of major importance to women's health, in a timely manner. During the next five years, 2,025 invasive incident and 390 in situ incident breast cancers are anticipated which will provide ample statistical power to address each of the proposed hypotheses in detail. The California Teachers Study presents a rare opportunity to study women's health, because of the size of the cohort, the uniformly high level of education among t LVAL eachers, their experience with survey instruments, their diversity of exposures and geographic residences, and the relative ease with which they can be followed in California. This research is intended to substantially increase knowledge of preventable risk factors for cancer and other health outcomes.LVAL-p.Evidence indicates that maternal smoking during pregnancy can lead to increased wheezing, decreased lung capacity, and increased respiratory infections in infants and children even in the absence of passive tobacco smoke exposure after birth. Further evidence suggests that it is the nicotine in tobacco smoke that is responsible for these effects. We have recently shown that nicotine can directly affect the development of embryonic mouse lungs isolated in a culture dish by interacting with some type of nicotine receptor similar to those found in the brain. We have also been able to detect the presence in embryonic, fetal, and adult lung tissue of a number of the subunit proteins that make up the various subtypes of nicotine receptor. It is not known, however, exactly where the receptors are located within the lung, or which subtype of nicotine receptor is responsible for the effects on lung development. The mechanism by which activation of nicotine receptors would bring about these effects is also unknown. The recent finding that the level the ?7 nicotine receptor subunit was increased in lungs exposed to maternally administered nicotine suggests involvement of the ?7 nicotine receptor subtype. A similar study showed increased levels in fetal lung of a hormone called gastrin releasing peptide (GRP). GRP has also been shown in other studies to affect lung development and many of the effects are similar to those of nicotine. This project will explore the mechanism underlying the developmental effects of nicotine in the lung by comparing four strains of mice that differ in nicotine response or in the presence or absence of a functional ?7 nicotine receptor. We will examine the hypothesis that nicotine acts through ?7 receptors located on the cells that line the developing airways causing these cells to make more GRP. The increased GRP would then cause the effects associated with nicotine exposure. Locations and levels of ?7 receptors and GRP in developing lungs will be compared in the four mouse strains.  LVAL Isolated embryonic mouse lungs grown in culture will be used to test whether blocking the action of GRP will also block the effect of nicotine. Elements of our proposed mechanism will also be examined in embryonic and fetal mouse lungs exposed to nicotine via the maternal drinking water. Insights gained from this study will contribute to our understanding of how nicotine exerts its adverse effects on fetal lung development. Since we know that nicotine receptors and GRP are also present in adult lungs, the information gained about mechanisms of nicotine action in developing lung may also contribute to our understanding of tobacco-related lung diseases in adult smokers. It is hoped that increased understanding of underlying disease mechanisms may help identify new treatments and new methods of prevention.LVAL-p.The candidate's goal is to pursue an independent research career in the field of lung developmental biology. The candidate was trained as a developmental biologist at UCLA. Her graduate and postdoctoral training involved the use of a variety of molecular and genetic approaches to the study of gene expression in developing neurobiological systems. Her entry into the area of lung biology is relatively recent and represents a new direction for her career. The candidate holds a faculty appointment at the Center for Craniofacial Molecular Biology of the University of Southern California. This highly interactive, state-of-the-art research center has provided full support for the candidate's independent research efforts for the past two and a half years and is committed to her continued pursuit of a research career. The candidate plans to develop her career by acquiring new research skills and increasing her knowledge of lung biology and lung diseases through course work, and through formation of new collaborations and new contacts with clinicians and researchers at USC and elsewhere. The candidate is interested in understanding the mechanisms by which prenatal exposure to maternal smoking affects embryonic and fetal lung development, leading to the observed short and long term effects on the respiratory health of the offspring. Her Research Plan addresses the following hypothesis: Nicotine alters the developmental program of the embryonic lung (including expression of surfactant protein genes) through a mechanism involving nicotinic acetylcholine receptors located on cells of the distal epithelium and stimulation of production of GRP by these same distal epithelial cells. The Specific aims are: 1) to characterize the effect of added nicotine on the development of embryonic mouse lungs grown in serumless culture with respect to specific gene expression, growth, branching morphogenesis and differentiation of epithelial cell types, 2) to determine the nature and location of nicotinic acetylcholine recdLVALteptors mediating the developmental effects of nicotine in the lung and 3) to test the role of the peptide growth factor GRP and its receptor in mediating the effects of nicotine in embryonic lung.LVAL-p.Prenatal exposure to maternal smoking adversely affects the respiratory health of children even in the absence of postnatal passive smoking. Transplacental nicotine exerts developments effects on fetal lung in animals, including lung hypoplasia and hyperplasia of pulmonary neuroendocrine cells. Paradoxically, the lungs of smoking-exposed infants appear to be more mature at birth than those of unexposed infants. The cellular and molecular mechanisms underlying these prenatal effects of maternal smoking are presently unknown. The study will use culture of whole embryonic mouse lungs in chemically defined medium as a model system to study the mechanism of nicotine action in development lung. Preliminary data show stimulation of branching and expression of the genes encoding the peptide growth factor GRP and surfactant proteins SP-C and SP-A in nicotine-treated lungs. The effect on SP-C gene expression is blocked by the nicotinic antagonist d-tubocurarine. Further, the increase in SP-C gene expression is blocked an antibody directed against the reactive region of GRP. Thus, the effects of nicotine in this system are mediated by nicotinic acetylcholine receptor (nAChR) subtype and GRP may be a mediator in the downstream pathway. The added observation that embryonic lung distal epithelial cells posses and partial neuroendocrine phenotype leads to this hypothesis; That nicotine alters the developmental program of the embryonic lung including expression of surfactant protein genes, through a mechanism involving nAChRs located on cells of the distal epithelium and stimulation of production of GRP by these name distal epithelial cells. The specific Aims are: 1) To characterize the effects of added nicotine on development of embryonic lung with respect to growth, branching morphogenesis, specific gene expression and differentiation of epithelial cells. 2) To determine the nature and location of the nAChRs mediating the developmental effects of nicotine in embryonic lung. 3) To test the role of GRP as, LVAL< a downstream mediator of nicotine effects by blocking strategies. The results of this study will provide insights into an aspect of normal lung development that has not previously been explored, as well as increasing our understanding of the mechanism of nicotine toxicity in developing lung and possible cancer risks from prenatal nicotine exposure.(LVAL-p.8Airway responsiveness and lung function, endpoints with a strong genetic basis, are central to the obstructive airway diseases (asthma and COPD). In contrast, the dissection of the underlying genes will require unique sample resources, accurate and comprehensive phenotyping, and an efficient study design. To address to this three-pronged challenge, a genomic screen is proposed that brings together a large, homogenous, mostly untreated sample from Anhui, China, a wealth of expertise in asthma phenotypes, and a potent study design based on extreme discordant sib pairs. Since this approach utilizes an extant asthmatic family population, no support for data collection will be required. The primary focus of the application will be two intermediate phenotypes related to asthma and COPD: airway responsiveness (characterized by increased responsiveness to histamine methacholine or other nonspecific agonists and measured by the slope of the dose response relationship) and FEV1. Since both traits are continuous, the appropriate study design is one that considers only siblings with extremely discordant phenotypes. For many studies, this strategy is not feasible due to the thousands of families that must be phenotyped to identify a sample of such siblings. The plan is to utilize the organization of a well-established network in China to collect 150 extreme discordant sib pairs of each intermediate phenotype. For airway responsiveness, the estimated power from this sample, equivalent to roughly 600 concordant sib pairs, is intended to surpass the power of all existing studies, including the U.S. Collaborative Study on Asthma. Further, with similar power, this will be the first study to test for linkage to FEV1. Moreover, to further augment power, potential phenotypic heterogeneity will be reduced by stratifying the analyses by total and specific serum IgE levels, skin test reactivity, peripheral blood eosinophilia, respiratory symptoms, age, gender, bronchodilator response, and cigarette smoking.LVAL-p.Smoking prevalence among adolescents has been increasing since the early 1990s in the United States and California. In California, more teenage girls reported smoking cigarettes in the past 30 days in 1996 than in 1990. More African-American, Hispanic and Asian female teenagers reported interest in trying a cigarette than their White counterparts. Tobacco advertising and promotion items appear to attract adolescents, especially girls who smoke to look "cool", to be mature, or to keep their weight down. Most current tobacco prevention programs are universal and do not consider the diverse cultural backgrounds of the targeted population. However, tobacco industry has employed ethnically specific marketing campaigns to attract young and/or female customers. More efforts are needed to improve the effectiveness of the current tobacco prevention programs by adding gender specific and culturally appropriate curricula. This project intends to study cigarette smoking behavior and media exposure among African-American, Asian, Hispanic, and White female teenagers. The proposed study also plans to investigate which ethnic groups are more vulnerable to tobacco advertising and promotion influences, and to determine whether the impact of tobacco marketing on female adolescent smoking differs across ethnicity among female teenagers. This study could provide better understanding of the relationship between media exposure and cigarette smoking among teenage girls. This study will use data already collected by the University of California, San Diego, and the California Department of Health Service. The two data sources were the California Tobacco Surveys (CTS) 1990-1991, 1992, 1993, and 1996, and the California Youth Tobacco Survey (CYTS) 1994-1997. The sample will be comprised of female adolescents with the following selfidentified ethnicities: African-American, Asian, Hispanic, and White (total N = 13,250). Both conventional and advanced statistical approaches will be employed to study ethnic differences BLVALRin media exposure and cigarette smoking. The findings in this study will enable the health professionals to design more successful tobacco use prevention programs to reduce media influences on female adolescents..LVAL  p (JDISEASE/BIOLOGY Cancer Mechanisms RESEARCH Human Studies In Vitro Studies Clinical Research TOBACCO Non-Specified Tobacco UseAGE Child Fetus/Prenatal COMMUNITY Health Care Provider EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National PREVENTION/TREATMENT Counseling/Behavior Therapy Quitline RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN Pregnancy PostpartumDISEASE/BIOLOGY Cancer Other Disease/Biology RESEARCH Human Studies In Vitro Studies Clinical Research TOBACCO Non-Specified Tobacco Use WOMEN Pregnancy HormonesDISEASE/BIOLOGY Cancer Other Disease/Biology EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco UseADDICTION Withdrawal DISEASE/BIOLOGY Other Disease/Biology LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Cigarette/Other Smoking WOMEN HormonesDISEASE/BIOLOGY Cancer Mechanisms EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National RESEARCH Human Studies Clinical Research TOBACCO Non-Specified Tobacco Use MISCELLANEOUS Sex/Gender DifferencesAGE Child EPIDEMIOLOGY/SURVEILLANCE Large (>=100) LOCATION National MARKETING Industry Media-Websites/pamphlets/radio RESEARCH Human Studies Clinical Research STUDY POPULATION African American Asian Pacific Islander Caucasian Hispanic TOBACCO Cigarette/Other Smoking MISCELLANEOUS Knowledge/Attitudes/Risk PerceptionLVAL-p.Lung cancer provides an ideal paradigm for investigating gene-environmental interactions. Although a majority of lung cancer victims are tobacco users, the unresolved paradox is that only a minority of long-term heavy smokers will develop the disease. Therefore, genetically determined susceptibility is likely an important component in lung cancer development. We plan to examine the role of the alpha1AD gene in lung cancer risk. This is a logical step because individuals who are either homozygous or heterozygous (carriers) for the alpha1AD allele are predisposed to the development of chronic obstructive pulmonary disease (COPD). COPD is a risk factor for lung cancer and shares common risk factors with lung cancer, such as cigarette smoking and familial aggregation. Thus, we hypothesize that alpha1AD allele carriers have an increased risk for lung cancer. The proposed case-control study is designed to test this hypothesis. As secondary hypotheses, we will test whether the association between lung cancer risk and alpha1AD carrier status varies by history of tobacco smoke exposure, COPD, histopathologic type of the tumor, and family history of cancer. Twelve hundred cases with primary lung cancer who are newly diagnosed (from April 1997 to September 2001) at Mayo Clinic will be recruited as the case group. Twelve hundred population-based controls (matched by age, gender, and race) will be assembled for testing the hypothesis that alpha1 AD carriers are at a higher lung cancer risk. Approximately twelve hundred full siblings from 600 lung cancer cases will be included as an ethnicity-matched control group to eliminate the bias due to population admixture (as observed in our pilot study). Data will be collected from medical records, patient interview, and self-administered questionnaires. Alpha1-antitrypsin (a protease inhibitor, Pi) allele type will be determined by isoelectric focusing assay. Statistical analyses include multiple logistic regression models for case-population control comparisons and a new LVAL ly developed multivariate score statistic will be used for case-sibling control comparisons. This study will allow us to evaluate the roles of 1) a common gene that is associated with lung tissue damage, 2) tobacco smoke (carcinogen) exposure, and 3) COPD that shares common risk factors with lung cancer and often occurs before the onset of lung cancer. Results from this study will lead to further understanding of the biologic basis of lung cancer development and progression, may uncover an additional marker for identifying high-risk individuals, and could provide additional impetus for targeted behavior modification, chemo-prevention, and gene therapy programs.XLVAL@ ( 0 (  f  \l Biology and Cancer Epidemiology and National Surveillance Interventions for Prevention and Treatment Awareness Risk Perception and Communications Community and Policy Interventions Global IssuesBiology and Cancer Addiction Epidemiology and National Surveillance Awareness Risk Perception and Communications Community and Policy Interventions Global IssuesAwareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Awareness Risk Perception and Communications Community and Policy InterventionsAwareness Risk Perception and Communications Community and Policy InterventionsInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsBiology and Cancer Addiction Epidemiology and National Surveillance Interventions for Prevention and Treatment Awareness Risk Perception and Communications Community and Policy Interventions Global IssuesInterventions for Prevention and Treatment Awareness Risk Perception and Communications Community and Policy InterventionsAwareness Risk Perception and Communications Community and Policy Interventions Global IssuesInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsInterventions for Prevention and Treatment Community and Policy InterventionsAwareness Risk Perception and Communications Global IssuesInterventions for Prevention and Treatment Awareness Risk Perception and CommunicationsAwareness Risk Perception and CommunicationsAwareness Risk Perception and Communications Community and Policy InterventionsAwareness Risk Perception and CommunicationsAddiction Interventions for Prevention and Treatment Community and Policy InterventionsInterventions for Prevention and Treatment Awareness Risk Perception and Communications Global IssuesCommunity and Policy InterventionsInterventions for Prevention and TreatmentBiology and Cancer Epidemiology and National SurveillanceEpidemiology and National SurveillanceLVAL-p.Despite steady progress in the fight against nicotine addiction over the past 25 years, the percentage of female smokers is increasing. The United States may soon become the first society in history in which more women than men smoke. In part, this is because women are less likely to be able to quit, whether they try on their own or with the help of smoking cessation programs. This appears to be especially true for nicotine replacement therapies (such as nicotine patches or gum), which have helped a greater percentage of men than women in almost every study. There is thus a clear need for new forms of treatment which are tailored especially for women. Nicotine is an addictive drug, and the primary reason people use cigarettes is to get nicotine. However, other aspects such as the taste of smoke also become pleasurable to the smoker. These other aspects may be more important for women, and this could be one reason that nicotine in the patch and gum may be less likely to help them give up cigarettes. To test this theory, we will study the differences in men and women's reaction to nicotine alone, or to smoking a cigarette which contains very little nicotine. Smokers often feel that cigarettes help them stay focused, and one of the symptoms of nicotine withdrawal is difficulty paying attention. In women, withdrawal symptoms and attentional ability may change at different points of the menstrual cycle. Our research will use a measure of attention to study the effect of smoking and withdrawal across the menstrual cycle. Our test is also able to determine differences between the right and left sides of the brain, and the effectiveness of the connections between the two sides. This is useful since gender, menstrual hormones, and withdrawal may be associated with changes in right/left balance. The brain controls smoking, as it does any other behavior. Knowledge of which brain areas are responsible will let new treatments to help smokers quit become more effective, by specifically targeting thoseZLVALj areas. Our research will help provide this knowledge, with special emphasis on factors (attention, menstrual cycle, and right/left brain function) that are believed to be important to female smokers. n :  JJJ^@@@MeetingH@!MeetingWHO@v@ 8@`@4/1/20034/1/20034/2005uuui]QEEEEE@@@7+"=II@1@Media Campaign\@ Media CampaignColorado Department of Public Health and Environment-p.@ @@5/13/20015/13/20014/2005NNN>2"=HH@1@Media CampaignWomen and SmokingMedia CampaignAmerican Legacy Foundationh@X@@@12/1/200112/1/20014/2005}}}}}aaaQ2"=GG 1@^@Media Campaignp@Media CampaignSFF&-p.@@v@4/25/20024/25/20024/2005wk_SSSSSNNN>2"=FF@`@Media CampaignLoud and ClearMedia CampaignThe National Coalition for Women Against Tobacco.-p.X@@@5/24/20005/24/20004/2005^^^N2"=EE@1@Media Campaign Great StartMedia CampaignAmerican Legacy Foundation0-p.@@8@12/4/200112/4/20014/2005wwwww[[[K2"=DD@1@Media Campaignj@Media CampaignAssociation of European Cancer Leagues-p.@@@9/5/20019/5/20014/2005vvvvvNNN>2"=CC 1@^@Listserv Girl-TalkListservCampaign for Tobacco Free KidsL @D@@ @10/1/200210/1/20024/2005ymmmmmMMMC,"=..@@Research`@ZHUYONGYALE UNIVERSITYNEW HAVENCTNCIR03, CA108369B-p.Biology and CancerDiscovery 1b Evaluation 1b:@3/1/20042/28/20063/1/2004 to 2/28/20064/2005 whc_TC=88,"--@G@ResearchR@ZHUSHU-HONGUNIVERSITY OF CALIFORNIA AT SAN DIEGOSAN DIEGOCACTRDRP8RT-0103-p.T@@ @7/1/19996/30/20027/1/1999 to 6/30/20024/2005}ynG=88,",,[@`@Research\@ZHUBAOUNIVERSITY OF SOUTH CAROLINA AT COLUMBIACOLUMBIASCNCIR01, CA074787-p.Biology and CancerR@ @5/1/19974/30/20015/1/1997 to 4/30/20014/2005zvlB=88,"++%@@Researchl@ZHENGTONGZHANGYALE UNIVERSITYNEW HAVENCTNCIR01, CA095788l@t@R@ @9/30/20018/31/20049/30/2001 to 8/31/20044/2005~ojf[J?88,"**@@u@Research|@ZHANGJUNHUMAN BIOMOLECULAR RESEARCH INSTITUTESAN DIEGOCACTRDRP9KT-0228-p.Biology and CancerR@ @j7/1/20006/30/20037/1/2000 to 6/30/20034/2005zvkD?88,"))g@p@4Research@ZHANGBOPUBLIC HEALTH SCIENCES, UNIVERSITY OF TORONTOTORONTOON, CANADACTCRINot GivenNot availableNot GivenNot GivenUncertain4/2005{rC?88,"?~((@@ResearchN@ZAIDELERANUNIVERSITY OF CALIFORNIA AT LOS ANGELESLOS ANGELESCACTRDRP8IT-0112z-p.Biology and Cancer AddictionR@@7/1/19996/30/20017/1/1999 to 6/30/20014/2005 |oF@88,"LVAL-p. Smoking is a chronic condition that affects more than 46 million Americans. People who smoke are at risk of heart disease, cancer, and other tobacco-related illnesses that cost more than $50 billion annually to treat, and an additional $47 billion in indirect costs from lost time at work and disability. Cigarette smoking during pregnancy not only damages the health of the smoker, increases the incidence of spontaneous abortion and low birth weight, but also causes long lasting effect such as learning disabilities and hyperactivity in the offspring. Even though the rate of smoking in pregnant women is much lower than the general population in the United States, there were still over 400,000 women who smoked during their pregnancy in 1996, endangering their own health and that of their children. This number will possibly increase in the years to come due to the increasing smoking rate among teenage girls and young women. This is also an important problem in the rapidly growing state of California. How nicotine affects the health of the fetus is a question that remains to be answered. We hypothesize that nicotine exposure during pregnancy can enhance a cell suicide program, called apoptosis, in developing neuronal cells of the fetus. The purpose of this proposal is to understand whether immature neurons in fetus are more sensitive to nicotine treatment as compare to mature neurons in adults; how the neurons commit to apoptosis after nicotine exposure; and whether we can use apoptosis inhibitors to stop this process. We will also study whether nicotine itself is the most potent reagent causing the neuron damage, or if nicotine metabolites, the products generated in human body from nicotine after its consumption, can also harm neurons. Finding from this study will provide information for the future scientific research on the long-term effect of maternal smoking on the offspring. The results can be also applied to educational efforts for the general public and pregnant women to stop smoking.LVALPolychlorinated biphenyls (PCBs) are potent environmental endocrine disruptors. They are also strong inducers of key genes involved in steroid metabolism and xenobiotic metabolism, such as human cytochrome CYP1A1. Recent epidemiological studies suggest that women are at increased risk of breast cancer if they have an elevated body burden of PCBs and a CYP1A1 m2 genotype. Toxicological studies support these findings by showing that PCBs induce CYP1A1 to metabolize environmental carcinogens into highly reactive intermediates resulting in DNA damage and ultimately carcinogenesis. Due to the widespread exposure to PCBs and the important role of CYP1A1 in carcinogen activation and steroid hormone metabolism, there exists an urgent need to study the relationship between PCBs, the CYP1A1 genotype and breast cancer risk. Against this background, a case-control study of body burden of PCBs, CYP1A1 genetic polymorphisms and breast cancer risk is proposed in Connecticut, one of the areas with the highest incidence rates of breast cancer in the United States. The primary aim of this study is to test the hypothesis that women with an elevated body burden of PCBs and with specific CYP1A1 genotypes have an increased risk of breast cancer. The blood samples used to determine CYP1A1 genotypes for the case-control study will come from a recently completed breast cancer case-control study in Connecticut, which has recruited 475 incident breast cancer cases and 502 controls. Information on environmental exposures and potential confounding factors has already been collected and blood serum samples were analyzed for PCBs and DDE through the aforementioned parent breast cancer case-control study. Use of existing blood samples and environmental exposure data collected by the parent breast cancer study provide cost efficiency to the study.LVAL-p.Earlier studies indicated that cigarette smokers have a decreased risk of uterine endometrial cancer and an increased risk of osteoporosis which are thought to be caused by an inhibitory effect of cigarette smoking on estrogen action. Some but not all studies have indicated that cigarette smokers have lower plasma levels of estradiol and enhanced systemic 2-hydroxylation of this estrogen. A major focus of this proposal is to characterize the effects of cigarette smoking on NADPH-dependent metabolism of estradiol to multiple hydroxylated and keto metabolites by human liver and, in particular, by extrahepatic estrogen target organs such as uterine endometrium and placenta. In addition, we will characterize the profile of multiple estradiol metabolites formed by placentas from women exposed accidentally to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans which are potent inducers of microsomal monooxygenases. Our proposed studies should not only enhance our understanding of the antiestrogenic effect of cigarette smoking in women, but they should also provide us with useful information on the inducibility of cytochrome P450 enzymes that catalyzed the formation of various estradiol metabolites (including hormonally- active and/or genotoxic metabolites) in human liver as well as in human target organs for estrogen action. We plan to: (l).Determine the profile of NADPH-dependent estradiol metabolites formed by uterine endometrial microsomes from cigarette smokers and matched nonsmokers. (2).Determine the profile of NADPH-dependent estradiol metabolites formed by placental microsomes from cigarette smokers and matched nonsmokers. (3).Determine the profile of NADPH-dependent estradiol metabolites formed by liver microsomes from cigarette smokers and matched nonsmokers. (4).Determine the profile of NADPH-dependent estradiol metabolites formed by placental microsomes from women exposed accidentally to polychlorinated biphenyls and polychlorinated dibenzofurans. (5).Determine the effects of sele LVAL ctive inhibitory antibodies to various cytochrome P450 isoforms on the pathways of estradiol metabolism observed in the studies described above. (6).Determine the effects of cigarette smoking on the concentration of unmetabolized estradiol in human uterine endometrium.LVAL-p.Maternal smoking during pregnancy or shortly after childbirth has serious health consequences for the fetus or the developing infant. It is associated with an increased risk for spontaneous abortion, pregnancy complications, premature delivery, low birth weight, and prenatal and neonatal death. The increased risk can be reversed or minimized if women stop smoking soon after they become pregnant. However, it is estimated that 15% of pregnant women in the United States smoke cigarettes. Furthermore, of those who successfully quit during their pregnancy, 70% relapse soon after their baby is born. Thus, there is a pressing need to develop programs that can help these women quit smoking during pregnancy and prevent them from relapsing after childbirth. Unfortunately, few pregnant women have access to a suitable program, one designed to account for their distinctive circumstances and needs. Quitting smoking is difficult at any point in time, but stresses unique to pregnancy and to the postpartum period make it even more challenging for the women. This study will test the effectiveness of a telephone counseling helpline specifically designed for pregnant women. The counseling will be provided over the phone so that the pregnant women need not leave home to receive the help. The counseling will be tailored to individual needs as each woman will be assigned to a specific counselor who will work with her individually to come up with a quitting plan that suits her personally. The counselor will provide counseling over the phone to assist her to stop smoking (or to stay quit) throughout the pregnancy, and offer counseling and support up to six months postpartum. This study will recruit participants through the Partnership for Smokefree Families (PSF), a collaboration of three large and integrated health care systems in San Diego, which provide health care for about 20,000 pregnant women each year. It is estimated that about 80% of these pregnant women see their doctor during the first trimester for pJLVALZrenatal care. This provides a prime opportunity to intervene with this population. Physicians can ask their pregnant patients if they smoke. If they do, physicians can advise them to quit, provide written self-help materials, and refer them to the telephone counseling helpline (known as the PSF Helpline). The referral consists of two elements: 1) The smokers will be encouraged to call the helpline; 2) permission to have a counselor call them at home will also be requested. This study will use a proactive calling procedure to enroll these pregnant smokers into counseling if they fail to call the helpline after their visit with the physicians. The physicians can also provide support and a degree of accountability for pregnant smokers by asking about their smoking status at subsequent prenatal visits. As physicians may not have the time or training to offer smoking cessation counseling, the prenatal visit will be used as a springboard to enroll smokers into more extensive assistance, in this case the telephone counseling helpline. This would allow pregnant women to get the attention they need and would minimize the time drain on physicians. This study is designed to: 1) Determine how often pregnant smokers will call a free helpline for counseling after they are advised to do so in their first prenatal visit. 2) Determine how many pregnant smokers will participate in counseling if contacted proactively. 3) Test if telephone counseling can help pregnant smokers quit smoking and stay abstinent after the baby is born. This will be accomplished with a randomized design. Determine if quitting as a result of doctors advice and/or telephone counseling increases birth weights of babies born to participating women.LVAL-p.Cancer has been recently recognized as a manifestation of both abnormal genetic and epigenetic events. Dysregulated epigenetic changes usually represented by abnormal DNA methylation patterns, such as global hypomethylation and region-specific hypermethylation, are a hallmark of most cancers, including breast cancer. Although the precise mechanisms underlying alterations of methylation patterns are far from complete, the overall methylation process is mainly regulated by a group of regulatory proteins including DNA methyltransferases (DNMTs) and methyl-cytosine guanine dinucleotide (CpG) binding proteins (MBDs). In this proposal, we hypothesize that adverse genotypes associated with methylation related genes may modulate their protein functions in epigenetic regulation, thereby influencing individual's susceptibility to human breast cancer. Our specific aims are: 1) To identify single nucleotide polymorphisms (SNPs) with potential functional impact on methylation related genes. SNPs will be collected from public SNP databases and screened by different bioinformatic tools. Prediction about functional impact will be made to both SNPs that alter an amino acid and SNPs located in the exonic splicing sites. 2) To determine the role that specific polymorphisms in these genes playin the modulation of breast cancer risk. Our hypothesis is that SNPs predicted to have functional significance in methylation process may be a panel of biomarkers to be associated with breast cancer risk. 3) To investigate the joint-effect between methylation related genes and environmental factors. Our hypothesis is that exposure to tobacco smoking, alcohol consumption and environmental estrogens may modify the risk of breast cancer for individuals with the putative high-risk genotypes in methylation related genes. Given the availability of DNA samples and exposure data, this proposal is both time and cost effective in terms of practical feasibility.fLVAL6 H |COMMUNITY Womens Group LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing POLICY Excise Tax TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Health Care Provider LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing PREVENTION/TREATMENT Counseling/Behavior Therapy Educational Materials TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy Postpartum MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Health Care Provider LOCATION Urban MARKETING Industry Media-Websites/pamphlets/radio Other Marketing PREVENTION/TREATMENT Counseling/Behavior Therapy Biochemical Assessments TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Womens Group Health Care Provider LOCATION Urban International MARKETING Industry Other Marketing STUDY POPULATION African American American Indian/Alaskan Native Asian Pacific Islander Caucasian Hispanic Lesbian Gay Bisexual Transgender TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseLVALGirl-Talk is a new listserv sponsored by the Campaign for Tobacco Free Kids (with support from the National Tobacco Control Training and Technical Assistance Consortium -- TTAC), which provides a forum to discuss issues surrounding women, girls and tobacco. The primary goal of the listserv is to provide a mechanism for organizations working on, or interested in working on, women, girls and smoking to communicate with each other and share ideas, resources and strategies with the aims of moving the issue higher on the agendas of the organizations involved and increasing the numbers of groups working on the issue. The listserv aims to facilitate an exchange of ideas between national and state groups and between tobacco control/public health groups and groups whose constituencies are women and girls. In developing the initial list of participants for the listserv, we were diligent to include representatives of both state and local organizations and from tobacco control, women's, girls, health, policy, education, nursing, medical and government groups. We worked to ensure include representatives of communities of color and the LGTB community. Girl-Talk was launched in October of 2002 and has over 50 members. We hope to carefully build the list of members to no more than 200 over the next year.LVAL-p.Smoking - an increasing threat to womens health and well-being in Europe The single most dangerous health habit among women in Europe is smoking. Tobacco use is one of the greatest burdens to the health and well-being of women around the world. At present it kills over half a million women each year, but this is expected to double by the year 2020. In some countries, lung cancer has already surpassed breast cancer as the main cause of cancer deaths among women. It is especially young women who smoke more than men. Since 1970's, the number of smokers have decreased more among men than women. World wide, the smoking habit is spreading especially among women in lower social classes, who quit smoking less often than other women. Finding ways to make lower class girls adopt a smoke-free lifestyle is a great challenge to schools and health care professionals. Lung cancer is rising more rapidly among women than among men in the European Union. Alarm bells are already ringing in some countries where lung cancer is currently more common among women under 45 years of age than men of the same age. Tobacco free - its a beautiful thing Women should not let themselves be fooled by the strong and persuasive messages of the tobacco industry, but realise that the best thing they can do themselves is to stop smoking. In addition to the indisputable and grave health effects, smoking has harmful effects on the appearance, skin, dental and oral hygiene. These effects appear relatively soon after smoking initiation. Most of them are fortunately reversible after stopping smoking. The damage on skin and the subsequent formation of wrinkles is irreversible, if smoking continues for decades. After 20 years of smoking the skin of a 40-year old woman has aged an additional 20 years. It is never too late to stop smoking. Tens of thousands of women succeed in smoking cessation every year in Europe alone. During the European Week Against Cancer on October 8 - 14 women are encouraged to stop smoking and provided with advicLVALe and support on how to succeed in this. The "Women and Tobacco" -campaign is targeted to women in the age of 20 - 35 years. During the week a variety of actions are taking place around Europe to promote reduction in womens smoking. The methods include conferences, advertising campaigns, media launches, press conferences, meetings and discussion groups, distribution of posters, leaflets and postcards, dissemination of cessation guidelines and advice on how to stop smoking. The campaign will be carried out in 20 European countries (Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Holland, Hungary, Iceland, Ireland, Italy, Luxembourg, Norway, Poland, Portugal, Slovakia, Slovenia, Spain and UK). The European Week Against Cancer is an annual health promotion campaign which has been organised since 1989. It is a joint effort of non-profit cancer fighting organisations and their partners. On the pan-European level the action is co-ordinated by the Association of European Cancer Leagues (ECL).LVAL-p.The American Legacy Foundation announced today the launch of its "Great Start" campaign to help the hundreds of thousands of women who smoke during their pregnancy to quit. Great Start is the first national campaign of its kind in the United States. The campaign includes: The first national telephone "Quitline" offering pregnant smokers free counseling sessions. Quitline operations, managed by the American Cancer Society, are available 24 hours a day, beginning today. The toll-free number to call is 1-866-66-START. A national television advertising campaign in all 50 states and the District of Columbia. Utah First Lady Jacalyn S. Leavitt and the wives of governors of 15 other states appear in ads that run in their home states. "About 426,000 women smoke during pregnancy each year in America," said Dr. Cheryl Healton, Legacy president and CEO. "That includes 13 percent of all pregnant women, and 18 percent of pregnant young women aged 15-19. We know that many of these expectant mothers want to stop smoking and would stop if they received assistance. We hope that Great Start will provide tens of thousands of women with the help they need to quit smoking during their pregnancy, and quit for good." American Cancer Society Chief Executive Officer John R. Seffrin, Ph.D., said, "The American Cancer Society takes care of more than a million telephone callers annually. We are the only organization in the nation with the capacity and the capably trained smoking cessation counseling resources to support Great Start. We are delighted to support our colleagues in the American Legacy Foundation in this important new campaign to positively influence the health of these expectant mothers and their babies." Healton said that smoking during or after pregnancy has been linked to one in 10 infant deaths. Smoking dramatically increases the risk for a wide range of reproductive health problems including miscarriage, stillbirth, and premature delivery. Women who smoke are also nearly 70 percent more likely to hLVALave a low birth weight baby. Smoking during pregnancy, or smoking by a mother or father around babies or young children (secondhand smoke exposure), can cause common children's health problems including asthma, pneumonia, bronchitis, hearing problems, and learning and behavioral problems. Smoking also causes about 1,000 cases of sudden infant death syndrome each year nationwide. "The U. S. ranks 26th in the world in infant mortality," Healton said. "Effective smoking cessation programs for pregnant women can help save many children." Starting today, pregnant smokers can call the toll-free Great Start Quitline to receive telephone counseling sessions with a counselor who is specially trained to help pregnant smokers quit. Spanish-language counseling is also available. Healton said, "The Quitline allows any expectant mother who smokes, anywhere in America, to get help quitting just by reaching for a telephone." Great Start has the support of a coalition of women state leaders organized and led by Utah First Lady Jacalyn S. Leavitt. The coalition includes representatives from the following states: Alaska, Arkansas, California, Florida, Idaho, Illinois, Indiana, Iowa, Kansas, Maine, Maryland, Michigan, Montana, Ohio, Oklahoma, Tennessee, Texas, and Washington. "The Great Start campaign is vitally important," Mrs. Leavitt said. "It will bring new visibility to a serious health problem that hasn't received the attention it deserves. We believe we can motivate pregnant women to take the first step toward a healthier family." The television ads deliver the inspiring message that smokers can make a difference in their health and the health of their babies if they quit smoking, and encourage pregnant women to call the toll-free Quitline for assistance. The national television campaign in all 50 states and the District of Columbia begins on Dec. 18. Ads begin running today in the states which are part of the coalition. LVAL-p.The Rise in Tobacco Ads in Magazines is a Call to Action! Alexandria, VA--The National Coalition FOR Women AGAINST Tobacco, a collective of 25 women's organizations founded by the American Medical Women's Association, declares that new information on the rise of tobacco magazine advertising is a call to action to join their efforts in countering the tobacco industry's latest attempts to recruit and addict women and girls. According to a new study released today by the American Legacy Foundation, the tobacco industry has actually stepped up its media bombardment of visual advertisements and images in the face of the Master Settlement Agreement to continually attract its most-promising new customers: our country's children and teenagers. No longer able to advertise by other visual means, the tobacco industry has turned to magazines, and magazines with a high readership of teens, to ensure that its brand recognition messaging is seen by young people. While this story is making news today because of its statistics, the truth is that statistics are only the beginning. Out of these statistics is a call to action to reduce the number of young people who become addicted smokers every year, and the thousands of those young people who will eventually die from cigarettes as the tobacco industry continues to relentlessly pursue them. The National Coalition FOR Women AGAINST Tobacco represents more than 11 million women in multiethnic, multigenerational groups across the country committed to countering the tobacco industry's targeted marketing of women and girls. As Philip Morris has released its latest Virginia Slims ad campaign, the Coalition has rallied to form a counter campaign, which will be launched next week at the National Press Club on Wednesday, May 24, 2000 at 10:00 a.m. Alvina Bey Bennett, Coalition Chair says, "This latest study confirms our suspicions about the true nature of the tobacco industry's response to the Master Settlement Agreement. What is even more disturbing, and is the focus of our LVALcounter campaign, is that the tobacco industry is now aggressively going after demographic subpopoulations. The latest Virginia Slims ads, placed in magazines whose readers are women and girls, target specific ethnic minority women. Tobacco magazine advertising is getting more intense - and more distinct." The Coalition's new counter campaign, titled "LOUD & CLEAR," is the largest to date national counter campaign against tobacco's targeted marketing to women and girls, and the only one poised to address the information found in the new studies. It responds to the Philip Morris Virginia Slims ads released under the theme "Find Your Voice." Implying that women should find their voices with cigarettes, the Coalition feels this message is an insulting attack on women. Joining the Coalition at next week's press conference to denounce this message will be Janet Sachman, former tobacco model and now national anti-tobacco advocate, and contemporary recording starts, the Indigo Girls. Says Joanne Koldare, Coalition Co-Chair, "The use of tobacco products continues to pose one of the greatest health threats to women. There are an estimated 23 million women smokers in this country, and we will not let the tobacco industry entice, fool, or seduce more young women with this newest attempt of recruitment."LVAL-p.In response to alarming rates of smoking during pregnancy, 40 groups are joining together to form The National Partnership to Help Pregnant Smokers Quit. The cornerstone of the National Partnerships efforts is a brief, easy-to-implement five-to-15-minute counseling approach which has been shown to dramatically affect quit rates, doubling, or even tripling them among pregnant smokers compared to simply advising them to quit. Making this counseling available to all pregnant women who smoke is one of the top aims of the National Partnership. "Quitting smoking is the most important thing a pregnant woman can do to improve both her health and the health of her unborn child," said Cathy Melvin, Ph.D., M.P.H., National Partnership chair and director of the Smoke-Free Families: National Dissemination Office. "Smoking cessation programs for pregnant women could prevent several thousand low-birth-weight births and save at least 1,000 lives each year," said James S. Marks, M.D., M.P.H., Director of the National Center for Chronic Disease Prevention and Health Promotion at the Centers for Disease Control and Prevention. "This could more than double the overall cost savings attributed to the rest of prenatal care." An estimated 20 percent of women smoke during pregnancy, causing 20 percent of all low-birth-weight births. This accounts for ten percent of all infant deaths in the United States each year -- approximately 1,000 babies. "This new intervention tells us what to say, what kinds of materials to offer, and how to use the time were already investing with our patients for best results. We can now intervene with more skill and confidence," said Sharon Phelan, M.D., of the American College of Obstetricians and Gynecologists. The National Partnership will develop a public service advertising and communications campaign to increase pregnant smokers' knowledge of cessation resources, and to illustrate how pregnant smokers' partners, family members, and friends can support and encourage them during tLVALheir quit attempts. As a first step, the National Partnership has developed a Mother's Day electronic card that friends and family members can send to show their support for someone they care about who is pregnant and trying to quit smoking. The card will be available at www.smokefreefamilies.org by April 30 "Changing behavior means that we need to help providers deliver effective services, and we also need to make sure people know they are available," noted C. Tracy Orleans, Ph.D., Senior Scientist at The Robert Wood Johnson Foundation. We plan to work with both national and local media to help pregnant smokers learn where to get the help they need. At the grassroots level, the National Partnership will work with communities and worksites to address the issue of smoking during pregnancy, support the development of local cessation resources and encourage employers to provide insurance coverage for smoking cessation services. In addition, the National Partnership will promote economic and other policy interventions that prevent and reduce maternal smoking, including improved coverage of cessation services. For example, only 13 states provide Medicaid coverage for cessation counseling for pregnant smokers, despite the fact that Medicaid is the primary health coverage for between one quarter and one half of all pregnant women. The success and impact of the National Partnership's work relies on up-to-date and accurate research, evaluation, and surveillance programs. Members of the National Partnership will coordinate research efforts to determine how to improve best-practice interventions, and to identify ways to strengthen surveillance of smoking during pregnancy to effectively track the problem and refine ways to treat it. "One of the questions we face is basic: how many pregnant smokers are there? Because some women may be reluctant to admit that they smoke, and because of disparities between state reporting processes, it's not a simple question to answer," said Dr. Melvin, "Developing a LVALstandard reporting process so that we gather better data is just one of the steps we need to take to increase our knowledge and develop better interventions." She continued, "The National Partnership believes that every pregnant smoker who wants to quit should have access to effective cessation services. Together, our actions will create a supportive network for pregnant women during their quit attempts, to help them quit successfully, and to create a smoke-free future for their babies and future generations." The National Partnership to Help Pregnant Smokers Quit is coordinated by Smoke-Free Families, based at the Cecil G. Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill, a program funded by The Robert Wood Johnson Foundation. For more information about the National Partnership, visit the Smoke-Free Families web site at www.smokefreefamilies.org.LVAL VAGE Child Young Adult COMMUNITY Health Care Provider LOCATION Urban MARKETING Industry POLICY Excise Tax Guidelines/Best Practices Regulatory Intervention Framework Convention on Tobacco Control TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke Nicotine WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Womens Group LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseDISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Health Care Provider ECONOMICS Socio-Economic Status LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing POLICY Excise Tax Guidelines/Best Practices Regulatory Intervention Framework Convention on Tobacco Control PREVENTION/TREATMENT Counseling/Behavior Therapy Support Group TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy Postpartum MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseLVALWe invite abstracts for 10-minute oral presentations on any aspects of women and tobacco in Africa. These may present findings of research, discuss interventions, evaluation of interventions or conceptual papers. We would particularly welcome contributions on: Gender issues in trading or farming tobacco, Youth and tobacco use  with a particular focus on girls/young women, Environmental tobacco smoke (second-hand smoke), Causes and consequences of tobacco use among women, Marketing tobacco to women, Tobacco control policy and legislation, and Litigation  an option for Africa?The women featured in this campaign are real women battling very real tobacco-related illnesses like emphysema, lung cancer and throat cancer. These are their real parting letters to their family and loved ones that they have generously allowed us to view. Through their honest words, they remind us that tobacco-related diseases not only kill women, but also devastate those left behind in the wake of sadness and emptiness. These women are brave. These women are ordinary. And unfortunately, these women are not alone. Every year tobacco-related diseases kill over 178,000 women in the U.S. With this national advertising campaign, we hope to raise awareness of the toll tobacco has taken upon women and encourage you or someone you love to seek help to quit smoking. Quitting may well be the most difficult thing you accomplish, but also the most rewarding and important. And when it comes to quitting smoking, there's no time like the present.LVAL-p.On Monday, May 13, the Colorado Women and Tobacco Coalition, which is comprised of 19 Colorado women's organizations, is kicking off National Women's Health Week with an invitation to women throughout the state to trade in their ashtrays, lighters and other tobacco paraphernalia for free cessation service information and t-shirts. Women's Health Week is being observed from Sunday, May 12, through Saturday, May 18. The t-shirts list the "Top 10 Reasons Colorado Women Quit." The top 10 reasons were created by the winners of a coalition contest conducted earlier this year in which women from throughout Colorado participated. Monday's trade-in events will be held at venues throughout the state, listed at the end of this page. The winning reasons for Colorado women to quit smoking are: 10. Ever try to accessorize with an oxygen tank? 9. Improved kissability. 8. High altitudes and low lung capacity don't mix. 7. Wrinkles, bad breath and yellow teeth are fine& for buffaloes. 6. Nicotine nixes the "Rocky Mountain High." 5. They've come a long way, baby. 4. They'd rather be skiing than dead. 3. Smoking around children = children smoking. 2. Because someone else needs them. 1. They CAN. Sara Miller, the program manager for the Comprehensive Cancer Prevention Control Program at the Colorado Department of Public Health and Environment, said, "The purpose of the tobacco trade-in project is twofold. It is an effort to both raise awareness about the special dangers tobacco use poses for women and, at the same time, to offer support to those who want to quit. "In Colorado, more women now die from lung cancer than those who die from breast cancer. In fact, tobacco use is the leading cause of preventable death for women in our state. In addition, smoking has damaging effects on women's reproductive health and is associated with pregnancy complications, reduced fertility and early menopause." Miller said that, according to the Office of the Surgeon General, smoking is one of the most important preventable  LVAL0cause of poor pregnancy outcomes among women in the United States. Smoking is associated with an increased risk of miscarriage, stillbirth, pre-term delivery, low birth weight and infant death. As many as 10 percent of all infant deaths could be prevented if pregnant women did not smoke. She said that smoking also can adversely affect children after they are born. For example, exposure to secondhand smoke increases the child's risk of pneumonia, bronchitis and fluid in the middle ear, Miller explained. Women, and men, who want to quit smoking are encouraged to use Colorado's new, free, tobacco cessation services, the Colorado Quitline and QuitNet. Since its launch in late October 2001, the Quitline (1-800-639-QUIT) has received 4,771 calls. Its online counterpart, QuitNet ( www.co.quitnet.com ), has logged 22,175 visitors since it became operational on December 21. Each is available 24 hours a day, seven days a week, and each offers personalized counseling services free of charge.8LVALR @NCOMMUNITY Womens Group Health Care Provider ECONOMICS Socio-Economic Status LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing POLICY Excise Tax PREVENTION/TREATMENT Counseling/Behavior Therapy TOBACCO Cigarette/Other Smoking Smokeless Non-Specified Tobacco Use Environmental Tobacco Smoke Nicotine MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Womens Group Health Care Provider LOCATION Urban International MARKETING Industry Other Marketing TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseDISEASE/BIOLOGY Cardiovascular/Pulmonary LOCATION Urban International MARKETING Industry Other Marketing PREVENTION/TREATMENT Counseling/Behavior Therapy TOBACCO Cigarette/Other Smoking Smokeless Nicotine MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Womens Group Health Care Provider Other Community DISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms ECONOMICS Socio-Economic Status LOCATION Urban International MARKETING Industry Counter-Marketing POLICY Excise Tax PREVENTION/TREATMENT Counseling/Behavior Therapy STUDY POPULATION African American TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke Nicotine WOMEN Pregnancy Postpartum MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/Exercise<LVAL x@ d X H`Development 3 Delivery 1 Delivery 2Discovery 1a Discovery 1c Discovery 2a Discovery 3 Development 1 Development 2 Development 3 Development 4 Delivery 1 Delivery 2 Delivery 3 Delivery 4 Partnerships 1 Partnerships 2 Partnerships 4 Evaluation 1a Evaluation 1bDiscovery 1a Discovery 1c Discovery 2a Discovery 3 Development 3 Development 4 Development 5 Delivery 1 Delivery 2 Delivery 3 Delivery 4 Partnerships 1 Partnerships 2 Partnerships 4 Evaluation 1a Evaluation 1bDevelopment 3 Development 5 Delivery 3Development 3 Development 5 Delivery 1 Delivery 2 Delivery 3 Partnerships 2 Partnerships 4Development 5 Delivery 3 Delivery 4 Partnerships 4Development 3 Delivery 2 Delivery 3 Delivery 4 Partnerships 1 Partnerships 4Discovery 1a Discovery 1b Discovery 1c Discovery 2a Discovery 2b Discovery 3 Development 1 Development 2 Development 3 Development 4 Development 5 Delivery 1 Delivery 2 Delivery 3 Delivery 4 Partnerships 1 Partnerships 2 Partnerships 3 Partnerships 4 Evaluation 1a Evaluation 1b Evaluation 1cDevelopment 5 Delivery 3 Delivery 4 Partnerships 2Development 1 Development 2 Development 3 Development 4 Development 5 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1aDiscovery 1a Discovery 1b Discovery 1c Discovery 3 Development 3 Development 4 Development 5 Delivery 2 Delivery 3 Delivery 4 Partnerships 2 Partnerships 4 Evaluation 1a Evaluation 1brLVALTRDRP focuses its 7th Annual Investigator Meeting on the theme of Women and Smoking to address what the U.S. Surgeon General describes as "an epidemic of tobacco-related diseases" for women. AIM's plenary session will examine: tobacco industry marketing aimed at women, health effects of tobacco use for women, sex and gender differences in tobacco-related disease mechanisms, and prevention and cessation strategies for women and girls. The conference will also include workshops on tobacco use and women's health and a Town Hall meeting exploring the issue of harm reduction. On Wednesday evening, a reception will be held at the nearby San Jose Art Museum. The conference will conclude with "TRDRP Listens"-an opportunity to tell us your views on TRDRP's research priorities and mission. Poster sessions included: Cardio, Pulmonary & Other Tobacco-Related Diseases; Environmental Tobacco Smoke; Youth Cigarette Smoking; Economics & Policy; Novel Cessation Approaches; Women & Smoking; Smoking in Multiethnic Populations; Nicotine Receptors & Addiction; Lung Cancer; and Genetic Epidemiology. Workshops included: Smoking and Breast Cancer, Cardiovascular Disease in Women, TCS Data on Women and Smoking in California, Tobacco Use Research Centers Panel Discussion, Cutting Edge Issues in COPD, and ETS and Adverse Pregnancy Outcomes   VV^@@@Smoking Cessation ServiceStop for LifeSmoking cessation servicePartnership Action on Tobacco and Health (PATH)/Scottish Executive@@J@ @200320034/2005sssX="=UU`@@ConferenceR@ConferenceScottish Tobacco Control Alliance@@@ @11/15/200411/15/20044/2005uiiiiiFFF:."=TT`@@Symposium@SymposiumInternational Network of Women Against Tobaccoj@L@@B@10/31/200410/31/20044/2005tttttDDD9-"=SS 1@^@Press Release Tobacco Touching Women's LivesPress releaseThe Colorado Women and Tobacco CoalitionN@X@P@d@11/14/200211/14/20024/2005lll]1"=RR@`@Media Campaign/WebsiteTruthMedia campaign/websiteAmerican Legacy Foundation@@@@2/1/20002/1/20004/2005eeeM:"=QQ^@@@Media Campaign/WebsiteSave Our DaughtersMedia campaign/websiteCampaign for Tobacco-Free Kids*@@j@d@200320034/2005rrrZ:"=PP 1@^@Media Campaign/WebsiteCircle of FriendsMedia campaign/websiteAmerican Legacy Foundation@@@P@6/1/20026/1/20024/2005qqqY:"=OO^@@@ConferenceZ@Conferencemultiple agenciesD@@r@R@12/10/2003-12/12/200312/10/2003 to 12/12/20034/2005}qeYYYYYFFF:."=NN@1@Media CampaignSmoking Stops HereMedia campaignMD Department of Health and Mental Hygiene@@j@@200120014/2005bbbR2"=MMg@p@4WebsiteZ@#WebsiteInternational Network of Women Against Tobacco|@@ 8@t@Not availableContinuing4/2005|ppppp@@@7+"=LL 1@^@WebsiteA Breath of Fresh AirWebsiteThe National Women s Health Information Center @@ @@8/1/20028/1/20024/2005WWWN+"=KK 1@^@Meeting@"MeetingCTDRP~ @@ @@12/4/2002-12/5/200212/4/2002 to 12/5/20024/2005wwwk_SGGGGG@@@7+"=LVALThis specialty section will help you and the people you love to breathe clean! Along with information on the health effects of smoking, we provide you with resources to help you quit if you are a smoker. We encourage you to learn as much as you can about smoking and to share this information with the ones you love. Remember, it's best to never start smoking and if you do smoke, don't give up on quitting. We know how hard quitting can be, but you'll be glad you did! Being smoke-free will help you to live longer with better health. We all need to be concerned about smoking. Today, about 1 out of every 5 women in America smokes, even though we know smoking is not good for our health. And, women are starting to smoke at younger and younger ages. Did you know that lung cancer kills more women every year than breast cancer? Did you also know that smoking could affect more than just your lungs? Smoking can increase your risk for heart disease, heart attack, stroke, osteoporosis (thinning or weakening of your bones), and cancers other than lung cancer. It can also affect your ability to get pregnant. Smoking when you are pregnant increases your chances of having problems with your pregnancy, including premature or early birth and having a baby with low birth weight.JLVAL^The purpose of the National Conference is to help improve and sustain the effectiveness and reach of tobacco control programs and activities in the United States.Maryland-Smoking Stops Here is a grassroots education movement that seeks to empower Marylanders in all 23 counties and Baltimore City to take action towards a tobacco-free lifestyle-whether it's at home, at work, at school, at college, at play or in the community. The movement is led by the Maryland Department of Health and Mental Hygiene, in conjunction with health departments, local coalitions, community groups, schools, colleges, businesses, health care facilities, sports leagues, the media and citizens of Maryland to educate the community about the dangers of tobacco use and secondhand smoke at the county level.The International Network of Women Against Tobacco (INWAT) was founded in 1990 by women tobacco control leaders to address the complex issues of tobacco use among women and young girls. INWAT: Provides contacts, primarily women, to individuals and organizations working in tobacco control. Collects and distributes information regarding global women and tobacco issues. Shares strategies to counter tobacco advertising and promotion. Supports the development of women-centered tobacco use prevention and cessation programs. Assists in the organization and planning of conferences on tobacco control. Collaborates on the development of publications regarding women and tobacco issues. Promotes female leadership. The website includes links to Women and Smoking: A Report of the Surgeon General 2001; the WHO Report on Women and Smoking; the INWAT Europe: Current Awareness Bulletin; Filtered Policy - Women and Tobacco in Canada; and Femmes and Tabac. Links to fact sheets on women and smoking from Australia, Canada, England, Scotland, Thailand, and the USA are also listed.LVALADDICTION Initiation Maintenance Cessation Withdrawal Relapse AGE Child Young Adult Adult Older Adult Fetus/Prenatal COMMUNITY Womens Group Health Care Provider Other Community DISEASE/BIOLOGY Cardiovascular/Pulmonary Cancer Mechanisms Other Disease/Biology ECONOMICS Socio-Economic Status Medicaid/Medicare Insurance Coverage Cost of Intervention/Prevention Cost of Smoking EDUCATION LEVEL Less than High School LOCATION Urban Rural National International MARKETING Industry Counter-Marketing Media-Websites/pamphlets/radio Other Marketing POLICY Excise Tax Guidelines/Best Practices Regulatory Intervention Framework Convention on Tobacco Control PREVENTION/TREATMENT Counseling/Behavior Therapy Support Group Interview/Focus Group Quitline Educational Materials Biochemical Assessments Buproprion Nicotine Replacement Therapy Other Pharmacological PSYCHOLOGICAL Depression/Mood/Anxeity Social Factors Cultural Factors Other Psychological RESEARCH1 Animal Studies RESEARCH Human Studies In Vitro Studies Clinical Research STUDY POPULATION African American American Indian/Alaskan Native Asian Pacific Islander Caucasian Hispanic Lesbian Gay Bisexual Transgender TOBACCO Cigarette/Other Smoking Smokeless Non-Specified Tobacco Use Nicotine WOMEN Pregnancy Postpartum Parent/Mother Partner/Spouse Menstral Cycle Menopause Hormones Hormone Replacement Therapy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/Exercise Sex/Gender DifferencesLVAL Smoking Cessation in Pregnancy ConferenceWomen, Tobacco, Lung Health and the Economic Consequences Symposium2003 National Conference on Tobacco or HealthLVAL L NDISEASE/BIOLOGY Cardiovascular/Pulmonary ECONOMICS Socio-Economic Status Medicaid/Medicare LOCATION Urban MARKETING Industry POLICY Excise Tax PSYCHOLOGICAL Depression/Mood/Anxeity Cultural Factors TOBACCO Cigarette/Other Smoking Environmental Tobacco Smoke WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Womens Group LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Health Care Provider LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing TOBACCO Cigarette/Other Smoking Smokeless Non-Specified Tobacco Use NicotineAGE Child Young Adult COMMUNITY Womens Group Health Care Provider LOCATION Urban International MARKETING Industry Media-Websites/pamphlets/radio Other Marketing POLICY Excise Tax Framework Convention on Tobacco Control TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Womens Group Health Care Provider LOCATION Urban International MARKETING Industry Other Marketing TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseLVAL Edgy. Hard-hitting. Unapologetic. That's truth, the foundation's advertising, grassroots, and online campaign to prevent youth smoking. By telling the truth about the tobacco industry and its products and exposing their marketing tactics, truth allows teens to make informed choices about tobacco use. It doesn't preach. It doesn't judge. It just works.Over 20% of high school girls are daily, regular smokers. Evidence shows that smoking in movies increases youth smoking. To make matters worse, in the PG-13 film Mona Lisa Smile and other movies, Sony Pictures shows smoking as a liberating and glamorous activity for young women! Send a letter to Sony Pictures CEO Michael Lynton asking him to stop producing movies that market cigarettes to young girls!The American Legacy Foundation began the national, grassroots social movement Circle of FriendsTM in 2002 with the goal to reduce the impact smoking has on women. The campaign focuses on women because of their special place in our society as positive change agents in their families and communities. By initially raising awareness of the impact of smoking and tobacco-related disease among women, the circle will ultimately expand to include everyone. Circle of FriendsTM aims to have all people - smokers and non-smokers alike - understand the impact of smoking on health and be empowered to quit smoking, or support friends and family who want to quit.PLVALHdThe conference will particularly benefit midwives, Practice Nurses, Health visitors, GPs, Health Promotion and Public Health professionals by providing an overview of the key developments and issues surrounding smoking cessation in pregnancy.The symposium titled Women, Tobacco, Lung Health and the Economic Consequenses will cover many aspects including addiction, health effects, social determinants, tobacco control policies, women's role in tobacco growing, poverty and human rights. The session will also recommend future actions and strategies. The Colorado Women and Tobacco Coalition Thursday invited the public to attend a free event to celebrate Colorado women choosing to live tobacco-free lifestyles and working to raise awareness about the free support and assistance that is available to women of all ages who want to pursue healthy, tobacco-free lifestyles. Part of the event will include the premiere showing of Tobacco Touching Women's Lives, a film created by community groups statewide, which depicts Colorado women's experiences with tobacco use. The women in the film represent a broad range, from teenagers in Denver and Custer counties to care center residents in Durango. Keynote speaker Deirdre Imershein will discuss the politics and insider tobacco practices of Hollywood and the effects of tobacco imaging in film. Imershein is a Hollywood producer whose work includes the award-winning documentary, Scene Smoking: Cigarettes, Cinema and the Myth of Cool. LVALl COMMUNITY Health Care Provider LOCATION Urban MARKETING Industry POLICY Excise Tax PREVENTION/TREATMENT Counseling/Behavior Therapy TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy Postpartum Menstral Cycle MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/ExerciseCOMMUNITY Health Care Provider Other Community LOCATION Urban MARKETING Industry PREVENTION/TREATMENT Counseling/Behavior Therapy TOBACCO Cigarette/Other Smoking Smokeless WOMEN Pregnancy Postpartum MISCELLANEOUS Knowledge/Attitudes/Risk Perception Weight Gain/Exercise"LVAL2Interventions for Prevention and Treatment Awareness Risk Perception and Communications Global Issuesd LVALt Stop for Life project, is a new smoking cessation service for pregnant women and their families. The Stop for Life project is funded by PATH, an initiative that aims to increase the number of people that successfully stop smoking in Scotland. Funded by the Scottish Executive, PATH was developed to support the implementation of policies outlined in the Government's 1998 White Paper Smoking Kills, and subsequent policy documents. PATH will, with key partners, develop and roll out best practice across key areas of training, data collection, evaluation, prevention and cessation. @iQkQJiMWj iQkQJiMWQiq`QOYJMJ`fJYUb`QOYJMJ`fJYUb `QOYJMJ`fJYUb `QOYJMJ`fJYUb `QOYJMJ`fJYUb `QOYJMJ`fJYUb `QOYJMJ`fJYUb`QOYJMJ`fJYUbsQLkYmQ`QOYJMJ`fJYUbsQLkYmQ`QOYJMJ`fJYUbsQLkYmQ`QQmYbU`QQmYbUfiQkkiQ^QJkQiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3 iQkQJiMW3 iQkQJiMW3 iQkQJiMW3 iQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJ iQkQJiMWJ iQkQJiMWJ iQkQJiMWJ iQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWc iQkQJiMWc iQkQJiMWc iQkQJiMWc iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW| iQkQJiMW| iQkQJiMW| iQkQJiMW| iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5 iQkQJiMW5 iQkQJiMW5 iQkQJiMW5 iQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWV iQkQJiMWV iQkQJiMWV iQkQJiMWV iQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWj iQkQJiMWj iQkQJiMWj iQkQJiMWj JiMWV  @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@MdbSQiQbMQMdbSQiQbMQ ^YkmkQiq`QOYJMJ`fJYUb`QOYJMJ`fJYUb `QOYJMJ`fJYUb `QOYJMJ`fJYUb `QOYJMJ`fJYUb `QOYJMJ`fJYUb `QOYJMJ`fJYUb`QOYJMJ`fJYUbsQLkYmQ`QOYJMJ`fJYUbsQLkYmQ`QOYJMJ`fJYUbsQLkYmQ`QQmYbU`QQmYbUfiQkkiQ^QJkQiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3iQkQJiMW3 iQkQJiMW3 iQkQJiMW3 iQkQJiMW3 iQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJiQkQJiMWJ iQkQJiMWJ iQkQJiMWJ iQkQJiMWJ iQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWciQkQJiMWc iQkQJiMWc iQkQJiMWc iQkQJiMWc iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW|iQkQJiMW| iQkQJiMW| iQkQJiMW| iQkQJiMW| iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMWiQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5iQkQJiMW5 iQkQJiMW5 iQkQJiMW5 iQkQJiMW5 iQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWViQkQJiMWV iQkQJiMWV iQkQJiMWV iQkQJiMWV iQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWjiQkQJiMWj iQkQJiMWj iQkQJiMWj iQkQJiMWj JiMWV K  $I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$I$iQkQJiMWj ~~~~~~~~~~ ~ ~ ~                          6666666666 6 6 6 FFFFFFFFFF F F F __________ _ _ _ uuuuuuuuuu u u u                              .......... . . . 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List], "")strictYYQ$ WG RecommendationsText@ |B@}strict@@8,  TitleTextnz([Title], "")none660  StateText@ |nz([State] , "")noneCC=  Review DateEquality@|nz([Review Date], "")strictTTL) Project TypeEquality@@|nz([Entry Type], "")strictTTL* Project IDTextV@|nz([Project ID], "")noneLLF$ PI Last NameText0@|nz([Last Name], "")noneMMG& Performance PeriodDatel@|"YYYY"44,,  KeywordsTextD@|nz([Keyword List], "")strictNNF" InstitutionText<@|nz([Institution] , "")noneOOI% FunderText@|nz([Funder], "")noneDD>  CityText@|nz([City] , "")noneAA;  AbstractTextnz([Abstract], "")none<<6TLVAL  R ` xzSELECT [tBreakout Sessions].[Breakout Session] FROM [tBreakout Sessions] ORDER BY [tBreakout Sessions].[Breakout Session No];SELECT [tWG Recommendations].[WG Recommendation] FROM [tWG Recommendations] ORDER BY [tWG Recommendations].[WG Recommendation No];SELECT DISTINCT [tProject Info].[State] FROM [tProject Info] WHERE ([tProject Info].[State]) Is Not Null ORDER BY [tProject Info].[State]SELECT DISTINCT [tProject Info].[Review Date] FROM [tProject Info];SELECT DISTINCT [tProject Info].[Entry Type] FROM [tProject Info] WHERE ((([tProject Info].[Entry Type]) Is Not Null)) ORDER BY [tProject Info].[Entry Type];SELECT [tIMPAC Activity Types Available].[IMPAC Activity Types] FROM [tIMPAC Activity Types Available] ORDER BY [tIMPAC Activity Types Available].[IMPAC Activity Types];SELECT DISTINCT [tProject Info].[Last Name] FROM [tProject Info] WHERE ([tProject Info].[Last Name]) Is Not Null ORDER BY [tProject Info].[Last Name]SELECT tYears.Year FROM tYears ORDER BY tYears.Year;SELECT tKeywords.Area AS ITEMS, tKeywords.[Keyword No] AS SortOrder FROM tKeywords WHERE (((tKeywords.Keyword) Is Null)) UNION SELECT " " & tKeywords.Keyword AS ITEMS, tKeywords.[Keyword No] AS SortOrder FROM tKeywords WHERE (((tKeywords.Keyword) Is Not Null)) ORDER BY SortOrder;SELECT DISTINCT [tProject Info].[Institution] FROM [tProject Info] WHERE ([tProject Info].[Institution]) Is Not Null ORDER BY [tProject Info].[Institution]SELECT DISTINCT [tProject Info].Funder FROM [tProject Info] WHERE ((([tProject Info].Funder) Is Not Null)) ORDER BY [tProject Info].Funder;SELECT DISTINCT [tProject Info].[City] FROM [tProject Info] WHERE ([tProject Info].[City]) Is Not Null ORDER BY [tProject Info].[City]LVALnz([WG Recommendation List] , "")4 w @JLkmiJMm{MYmv{SobOQi{YbkmYmomYdb{\QvsdiOk{fQiSdi`JbMQfQiYdO{fY^JkmbJ`Q{fid[QMmYO{fid[QMmmvfQ{iQqYQsOJmQ{ kmJmQ{ mYm^Q{ sUiQMd``QbOJmYdbk{ sdi\Uidof{ l Y N   Y d Y d Y  Y Y Y  Y  Y Y *Sort Field Descriptor4Sort Field Sent Descriptor*Sort Field Expression$Sort Field EnglishSort Order(Conditional PossibleBSort Field Conditional Expression Sort Combo Query Sort Combo LimitYYPrimaryKeySort OrderHv1b  m3> p I Work Group& Work Group[Breakout Session List]Breakout SessionsInstr(1,nz([Breakout Session List], ""),"$%^&")@~M:! WG Recommendation& WG Recommendation[WG Recommendation List]WG RecsInstr(1,nz([WG Recommendation List] , ""),"$@^$")@RI/ Title& Title[Title]TitleInstr(1,nz([Title],""),"$@^$")GG'  Start DateStart Date[Start Date Date]Start Date===1 Project ID& Project ID[Project ID]Project IDInstr(1,nz([Project ID], ""),"$@^$")@ma;/! PI Last NamePI Last Name[Last Name]PI Last Name===/" Keywords& Keywords[Keyword List]KeywordsInstr(1,nz([Keyword List], ""),"$@^$",0)$@ma7- Institution StateInstitution State[State]State<<<5, Institution NameInstitution Name[Institution]Institution NameKKK9* Institution CityInstitution City[City]City8882* FunderFunder[Funder]Funder(((  Entry TypeEntry Type[Entry Type]Project Type:::, End DateEnd Date[End Date Date]End Date555+ LVAL/ ( SELECT [tBreakout Sessions].[Breakout Session] FROM [tBreakoutSELECT [tBreakout Sessions].[Breakout Session] FROM [tBreakout Sessions] ORDER BY [tBreakout Sessions].[Breakout Session No];SELECT [tWG Recommendations].[WG Recommendation] FROM [tWG Recommendations] ORDER BY [tWG Recommendations].[WG Recommendation No];SELECT [tIMPAC Activity Types Available].[IMPAC Activity Types] FROM [tIMPAC Activity Types Available] ORDER BY [tIMPAC Activity Types Available].[IMPAC Activity Types];SELECT tKeywords.Area AS ITEMS, tKeywords.[Keyword No] AS SortOrder FROM tKeywords WHERE (((tKeywords.Keyword) Is Null)) UNION SELECT " " & tKeywords.Keyword AS ITEMS, tKeywords.[Keyword No] AS SortOrder FROM tKeywords WHERE (((tKeywords.Keyword) Is Not Null)) ORDER BY SortOrder;*  @QbOOJmQQbmivmvfQSobOQiYbkmYmomYdbMYmvYbkmYmomYdbbJ`QYbkmYmomYdbkmJmQ\QvsdiOk4fY^JkmbJ`Qfid[QMmYO4kmJimOJmQ mYm^Q4 sUiQMd``QbOJmYdb4 sdi\Uidof4   @           !YBNBBBBBBBY  Y d Y d Y 4Record IDProject IDTrial IDEditing4f4f4f44f4f4f44f4f4f44f4f4f44f4f4f4YYYYYEdited IDPrimaryKeyProject IDRecordIDTrial IDv1bx ?L` =܋{+hڇ#Xۅbh$n@1 )@tSearch and Sort Fields and Properties@zzznnnnnnnl @@n@zc@tKeywords@@@@44444442 @vMn@,n@tCurrent Sort Fields@VVVJJJJJJJH @Rn'Kb@PF_@qViewControlSizes @|@\PPDDDDDDDB @Mdn@Lj@qGet Startup Values&@|@`TTHHHHHHHF @I~s@~s@~sq_rrWTC Projects and Activities List4MR2KeepLocal Tnnnnnnnl @Eͷn@ͷn@~sq_cfTest Master~sq_cChild04MR2KeepLocal TZZZZZZZX @B2 -@q -@~sq_cfSearch Criteria~sq_ccboSearch54MR2KeepLocal Tjjjjjjjh @?f -@f -@~sq_cfSearch Criteria~sq_ccboSearch24MR2KeepLocal Tjjjjjjjh @<q -@q -@~sq_cfSearch Criteria~sq_ccboOper44MR2KeepLocal Tfffffffd @9+ -@+ -@~sq_cfSearch Criteria~sq_ccboOper14MR2KeepLocal Tfffffffd @6!v0@!v0@rWTC Projects and Activities List4 @pppdddddddb @'M@M@fWrap Error~@ DDD88888886 @$7~n@7~n@fTestRemote~@DDD88888886 @;V@;V@fShowClasses\@FFF:::::::8 @n@n@fPrint SelectionT@NNNBBBBBBB@ @};@};@Form1~@888,,,,,,,* @ ̓1o@!-@AccessLayout4MR2KeepLocal T@zz:::::::8 @)xn@)xn@Forms,,,,,,,,,,* 'n@Kup@tYearsW@:::......., @>A'n@3n@tWG Recommendations@TTTHHHHHHHF @|n@n@tTrial Project IDs Dup OK.@```TTTTTTTR @!DFon@co@tTrial Project IDs@RRRFFFFFFFD @W&c! j  5 Q o Qkj <Z_&R21CA098827R21, CA098827Comma inserted2"%1Z01ES046008-13Z01, ES046008Initial digit removed, Trailing number removed, Comma insertedf&$9RT-01429RT-0142None - non standard Project ID $$=#4067140671None - non standard Project ID $$7 "1R01DA017803-01R01, DA017803Initial digit removed, Trailing number removed, Comma insertedf&!5R01DA010887-04R01, DA010887Initial digit removed, Trailing number removed, Comma insertedf& 2R01DC000283-20R01, DC000283Initial digit removed, Trailing number removed, Comma insertedf&5R21DA013570-03R21, DA013570Initial digit removed, Trailing number removed, Comma insertedf&5U19DE13102-020003U19, DE13102Initial digit removed, Trailing number removed, Comma insertedh(7RT-0101A7RT-0101ANone - non standard Project ID $$?K07CA095666K07, CA095666Comma inserted2"9P50DA019706-06P50, DA019706Initial digit removed, Trailing number removed, Comma insertedf&1R01HL073108-01R01, HL073108Initial digit removed, Trailing number removed, Comma insertedf&1Z01ES049003-13Z01, ES049003Initial digit removed, Trailing number removed, Comma insertedf&5U10HL059291-05U10, HL059291Initial digit removed, Trailing number removed, Comma insertedf&5P50CA084735-050005P50, CA084735Initial digit removed, Trailing number removed, Comma insertedj*5U01HD042638-03U01, HD042638Initial digit removed, Trailing number removed, Comma insertedf&1R01DA018949-01R01, DA018949Initial digit removed, Trailing number removed, Comma insertedf&1RO1HD045763-01A11RO1HD045763-01A1None - non standard Project ID $$O,5R01HL023727-23R01, HL023727Initial digit removed, Trailing number removed, Comma insertedf&5U10HL059292-05U10, HL059292Initial digit removed, Trailing number removed, Comma insertedf&5K01DA000421-04K01, DA000421Initial digit removed, Trailing number removed, Comma insertedf&5F31NR008065-03F31, NR008065Initial digit removed, Trailing number removed, Comma insertedf&1R01CA106815-01R01, CA106815Initial digit removed, Trailing number removed, Comma insertedf&5U01HL059277-05U01, HL059277Initial digit removed, Trailing number removed, Comma insertedf& 3R01DA008075-07S1R01, DA008075Initial digit removed, Trailing number removed, Comma insertedh( 5R01DA008075-10R01, DA008075Initial digit removed, Trailing number removed, Comma insertedf& 5R01DA016351-02R01, DA016351Initial digit removed, Trailing number removed, Comma insertedf& 5R21CA088272-02R21, CA088272Initial digit removed, Trailing number removed, Comma insertedf& 1R03DA013435-01R03, DA013435Initial digit removed, Trailing number removed, Comma insertedf&5R29DA010809-05R29, DA010809Initial digit removed, Trailing number removed, Comma insertedf&5M01RR000034-400602M01, RR000034Initial digit removed, Trailing number removed, Comma insertedj*4707747077None - non standard Project ID $$7 5179751797None - non standard Project ID $$7 BC020201BC020201None - non standard Project ID $$=1R03CA093198-01R03, CA093198Initial digit removed, Trailing number removed, Comma insertedf&1R01CA104836-01A1R01, CA104836Initial digit removed, Trailing number removed, Comma insertedh(5R01HD035607-05R01, HD035607Initial digit removed, Trailing number removed, Comma insertedf&,)Y \ z V t  ! ?(u!;KNh3GONot GivenNot GivenNone - non standard Project ID $$?N5R01DA011301-05R01, DA011301Initial digit removed, Trailing number removed, Comma insertedf&M5R01AA011197-04R01, AA011197Initial digit removed, Trailing number removed, Comma insertedf&LPR033058PR033058None - no Project Type match $$;KR01, CA074386R01, CA074386None*$JZ01, CP010123Z01, CP010123None*$I5R01CA098763-02R01, CA098763Initial digit removed, Trailing number removed, Comma insertedf&H5P50CA084735-050003P50, CA084735Initial digit removed, Trailing number removed, Comma insertedj*G5R01NS039899-05R01, NS039899Initial digit removed, Trailing number removed, Comma insertedf&F3861138611None - non standard Project ID $$7 E10RT-004610RT-0046None - non standard Project ID $$?D11IT-008211IT-0082None - non standard Project ID $$?CZ01, CP005804Z01, CP005804None*$B5R44DA080460-03R44, DA080460Initial digit removed, Trailing number removed, Comma insertedf&A5M01RR002719-170239M01, RR002719Initial digit removed, Trailing number removed, Comma insertedj*@5R03CA103485-02R03, CA103485Initial digit removed, Trailing number removed, Comma insertedf&?5K32RR016293-045K32RR016293-04None - no Project Type match $$I(>5141551415None - non standard Project ID $$7 =5R01NR005313-04R01, NR005313Initial digit removed, Trailing number removed, Comma insertedf&<5U10HL059320-05U10, HL059320Initial digit removed, Trailing number removed, Comma insertedf&;Z01, CP010140Z01, CP010140None*$:5F31DA006052-02F31, DA006052Initial digit removed, Trailing number removed, Comma insertedf&95R21CA088297-02R21, CA088297Initial digit removed, Trailing number removed, Comma insertedf&81R03CA103478-01R03, CA103478Initial digit removed, Trailing number removed, Comma insertedf&75R01NS036695-04R01, NS036695Initial digit removed, Trailing number removed, Comma insertedf&65F31DA015570-03F31, DA015570Initial digit removed, Trailing number removed, Comma insertedf&55R29AA011164-05R29, AA011164Initial digit removed, Trailing number removed, Comma insertedf&45R01HL073366-02R01, HL073366Initial digit removed, Trailing number removed, Comma insertedf&35R01CA094256-03R01, CA094256Initial digit removed, Trailing number removed, Comma insertedf&25R01DA013712-03R01, DA013712Initial digit removed, Trailing number removed, Comma insertedf&15179951799None - non standard Project ID $$7 05R01CA075402-03R01, CA075402Initial digit removed, Trailing number removed, Comma insertedf&/5K23HD001307-04K23, HD001307Initial digit removed, Trailing number removed, Comma insertedf&.5R24MD000520-02R24, MD000520Initial digit removed, Trailing number removed, Comma insertedf&-Not GivenNot GivenNone - non standard Project ID $$?,5R01AG016592-05R01, AG016592Initial digit removed, Trailing number removed, Comma insertedf&+4396943969None - non standard Project ID $$7 *9DT-01309DT-0130None - non standard Project ID $$=)5R37DA002277-24R37, DA002277Initial digit removed, Trailing number removed, Comma insertedf&(3M01RR000083-40S10138M01, RR000083Initial digit removed, Trailing number removed, Comma insertedl,'3M01RR000083-40S10325M01, RR000083Initial digit removed, Trailing number removed, Comma insertedl, '6 { 3 O ' l  3MkPj"| Lfiv5R01CA017393-29R01, CA017393Initial digit removed, Trailing number removed, Comma insertedf&u4066440664None - non standard Project ID $$7 tNot GivenNot GivenNone - non standard Project ID $$?s1R01DA016903-01R01, DA016903Initial digit removed, Trailing number removed, Comma insertedf&r5P20CA091401-020001P20, CA091401Initial digit removed, Trailing number removed, Comma insertedj*q5P01CA068384-070002P01, CA068384Initial digit removed, Trailing number removed, Comma insertedj*pNot GivenNot GivenNone - non standard Project ID $$?o5R01DA014666-04R01, DA014666Initial digit removed, Trailing number removed, Comma insertedf&nZ01, CP010183Z01, CP010183None*$m1Z01CP010108-05Z01, CP010108Initial digit removed, Trailing number removed, Comma insertedf&l9HT-32019HT-3201None - non standard Project ID $$=k5R01DK064870-02R01, DK064870Initial digit removed, Trailing number removed, Comma insertedf&j5P50DA007074-130011P50, DA007074Initial digit removed, Trailing number removed, Comma insertedj*i2R01DA002812-22A2R01, DA002812Initial digit removed, Trailing number removed, Comma insertedh(hPF-04-100-01-CNBPF-04-100-01-CNBNone - non standard Project ID $$M*gRC-2004-0008RC-2004-0008None - non standard Project ID $$E"f5R01HD036890-05R01, HD036890Initial digit removed, Trailing number removed, Comma insertedf&e5R01HL062233-03R01, HL062233Initial digit removed, Trailing number removed, Comma insertedf&d5R03DA015373-02R03, DA015373Initial digit removed, Trailing number removed, Comma insertedf&c5P01CA042792-150004P01, CA042792Initial digit removed, Trailing number removed, Comma insertedj*b5R01HL056772-03R01, HL056772Initial digit removed, Trailing number removed, Comma insertedf&a5P50CA084735-030004P50, CA084735Initial digit removed, Trailing number removed, Comma insertedj*`5R01AG011099-10R01, AG011099Initial digit removed, Trailing number removed, Comma insertedf&_5K23DA015774-03K23, DA015774Initial digit removed, Trailing number removed, Comma insertedf&^5R01CA086311-03R01, CA086311Initial digit removed, Trailing number removed, Comma insertedf&]5R01HD032153-09R01, HD032153Initial digit removed, Trailing number removed, Comma insertedf&\7RT-0134H7RT-0134HNone - non standard Project ID $$?[1P20NR007812-010001P20, NR007812Initial digit removed, Trailing number removed, Comma insertedj*Z4067540675None - non standard Project ID $$7 Y5U10HL059275-05U10, HL059275Initial digit removed, Trailing number removed, Comma insertedf&X1R01CA105183-01A1R01, CA105183Initial digit removed, Trailing number removed, Comma insertedh(W5K07CA093756-03K07, CA093756Initial digit removed, Trailing number removed, Comma insertedf&V8DT-01708DT-0170None - non standard Project ID $$=U5R03CA093183-02R03, CA093183Initial digit removed, Trailing number removed, Comma insertedf&TNot GivenNot GivenNone - non standard Project ID $$?S5R01DA014301-02R01, DA014301Initial digit removed, Trailing number removed, Comma insertedf&R1R21CA081649-01R21, CA081649Initial digit removed, Trailing number removed, Comma insertedf&Q1P20CA090578-01A10001P20, CA090578Initial digit removed, Trailing number removed, Comma insertedl,P5R01DA013490-05R01, DA013490Initial digit removed, Trailing number removed, Comma insertedf&?'v! ; U s  G  b| NKidX5P01CA082708-030002P01, CA082708Initial digit removed, Trailing number removed, Comma insertedj*BC000437BC000437None - non standard Project ID $$=9RT-01129RT-0112None - non standard Project ID $$=5K22CA095555-02K22, CA095555Initial digit removed, Trailing number removed, Comma insertedf&5R01DA009453-06R01, DA009453Initial digit removed, Trailing number removed, Comma insertedf&5R03TW000886-03R03, TW000886Initial digit removed, Trailing number removed, Comma insertedf&5R21CA088307-02R21, CA088307Initial digit removed, Trailing number removed, Comma insertedf&BC980890BC980890None - non standard Project ID $$=Not GivenNot GivenNone - non standard Project ID $$?1R01HD036719-01A1R01, HD036719Initial digit removed, Trailing number removed, Comma insertedh(5K07CA093387-03K07, CA093387Initial digit removed, Trailing number removed, Comma insertedf&1F31AA015017-01F31, AA015017Initial digit removed, Trailing number removed, Comma insertedf&5R01CA073242-04R01, CA073242Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?8RT-00058RT-0005None - non standard Project ID $$=Not GivenNot GivenNone - non standard Project ID $$?5R01DA011748-05R01, DA011748Initial digit removed, Trailing number removed, Comma insertedf&3R01CA058858-04S1R01, CA058858Initial digit removed, Trailing number removed, Comma insertedh(5P50DA005274-170014P50, DA005274Initial digit removed, Trailing number removed, Comma insertedj*5R01DA011082-08R01, DA011082Initial digit removed, Trailing number removed, Comma insertedf&5U10HL059739-05U10, HL059739Initial digit removed, Trailing number removed, Comma insertedf&9IT-01779IT-0177None - non standard Project ID $$=5R01AA011510-07R01, AA011510Initial digit removed, Trailing number removed, Comma insertedf&5R01CA077081-04R01, CA077081Initial digit removed, Trailing number removed, Comma insertedf&10RT-032610RT-0326None - non standard Project ID $$?13RT-005013RT-0050None - non standard Project ID $$?5R01DA012503-05R01, DA012503Initial digit removed, Trailing number removed, Comma insertedf&1R01TW005955-01R01, TW005955Initial digit removed, Trailing number removed, Comma insertedf&5R01AG018239-03R01, AG018239Initial digit removed, Trailing number removed, Comma insertedf&5R01DA012165-05R01, DA012165Initial digit removed, Trailing number removed, Comma insertedf&5P50CA084718-050004P50, CA084718Initial digit removed, Trailing number removed, Comma insertedj*~5U01CA066572-07U01, CA066572Initial digit removed, Trailing number removed, Comma insertedf&}1Z01CP010105-07Z01, CP010105Initial digit removed, Trailing number removed, Comma insertedf&|1P20RR018787-010005P20, RR018787Initial digit removed, Trailing number removed, Comma insertedj*{5R01CA098889-02R01, CA098889Initial digit removed, Trailing number removed, Comma insertedf&z3U10HD021397-18S1U10, HD021397Initial digit removed, Trailing number removed, Comma insertedh(y5R21CA081638-02R21, CA081638Initial digit removed, Trailing number removed, Comma insertedf&x7RT-00907RT-0090None - non standard Project ID $$=w4066940669None - non standard Project ID $$7  +G J d > X v A O RO8RsOm5R01HL023727-24R01, HL023727Initial digit removed, Trailing number removed, Comma insertedf&1Z01CP010113-07Z01, CP010113Initial digit removed, Trailing number removed, Comma insertedf&4066840668None - non standard Project ID $$7 5U01HL066858-04U01, HL066858Initial digit removed, Trailing number removed, Comma insertedf&5R01DA012237-05R01, DA012237Initial digit removed, Trailing number removed, Comma insertedf&2S06GM008092-280003S06, GM008092Initial digit removed, Trailing number removed, Comma insertedj*R01, CA065725R01, CA065725None*$U01, CA098233U01, CA098233None*$5R01CA088891-02R01, CA088891Initial digit removed, Trailing number removed, Comma insertedf&1P60MD000270-010001P60, MD000270Initial digit removed, Trailing number removed, Comma insertedj*5K07CA087714-06K07, CA087714Initial digit removed, Trailing number removed, Comma insertedf&Z01, BC005480Z01, BC005480None*$5R01CA049449-14R01, CA049449Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?9KT-00729KT-0072None - non standard Project ID $$=5R01CA075455-05R01, CA075455Initial digit removed, Trailing number removed, Comma insertedf&5R01CA077318-05R01, CA077318Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?5141451414None - non standard Project ID $$7 4807948079None - non standard Project ID $$7 4572945729None - non standard Project ID $$7 4143041430None - non standard Project ID $$7 5R01AG020048-07R01, AG020048Initial digit removed, Trailing number removed, Comma insertedf&7RT-01057RT-0105None - non standard Project ID $$=1R43DA013305-01A1R43, DA013305Initial digit removed, Trailing number removed, Comma insertedh(R03, CA097752R03, CA097752None*$5R01DA013705-04R01, DA013705Initial digit removed, Trailing number removed, Comma insertedf&5R01HL056144-04R01, HL056144Initial digit removed, Trailing number removed, Comma insertedf&5M01RR000046-420989M01, RR000046Initial digit removed, Trailing number removed, Comma insertedj*5R01HD042256-03R01, HD042256Initial digit removed, Trailing number removed, Comma insertedf&5160451604None - non standard Project ID $$7 1R01DA014104-01A1R01, DA014104Initial digit removed, Trailing number removed, Comma insertedh(1R01DA017837-01R01, DA017837Initial digit removed, Trailing number removed, Comma insertedf&1Z01ES030108-06Z01, ES030108Initial digit removed, Trailing number removed, Comma insertedf&5P50DA013334-030008P50, DA013334Initial digit removed, Trailing number removed, Comma insertedj*5R01DE012085-05R01, DE012085Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?4066640666None - non standard Project ID $$7 3795837958None - non standard Project ID $$7 R01, CA086102R01, CA086102None*$RSGPB-04-009-01-CPPBRSGPB-04-009-01-CPPBNone - non standard Project ID $$U25K01DA015426-02K01, DA015426Initial digit removed, Trailing number removed, Comma insertedf&5R01DA011958-05R01, DA011958Initial digit removed, Trailing number removed, Comma insertedf&j)Ca 7 U + ] 3 z0N*i4RMg6PT-3003H6PT-3003HNone - non standard Project ID $$?5U01AA015035-02U01, AA015035Initial digit removed, Trailing number removed, Comma insertedf&5R01HD036514-04R01, HD036514Initial digit removed, Trailing number removed, Comma insertedf&1R01CA106316-01R01, CA106316Initial digit removed, Trailing number removed, Comma insertedf&5P50DA013334-050003P50, DA013334Initial digit removed, Trailing number removed, Comma insertedj*5R03CA097780-02R03, CA097780Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?5R01HD040398-03R01, HD040398Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?5K08DK064256-02K08, DK064256Initial digit removed, Trailing number removed, Comma insertedf&5R01DA014028-04R01, DA014028Initial digit removed, Trailing number removed, Comma insertedf&U01, CA062912U01, CA062912None*$5179851798None - non standard Project ID $$7 Not GivenNot GivenNone - non standard Project ID $$?U01, CA098758U01, CA098758None*$5R01CA034627-19R01, CA034627Initial digit removed, Trailing number removed, Comma insertedf&5180151801None - non standard Project ID $$7 1Z01HD008762-01Z01, HD008762Initial digit removed, Trailing number removed, Comma insertedf&5F31DA005980-02F31, DA005980Initial digit removed, Trailing number removed, Comma insertedf&1P50DA013333-01P50, DA013333Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?5K08HL067910-03K08, HL067910Initial digit removed, Trailing number removed, Comma insertedf&PR023104PR023104None - non standard Project ID $$=5R01CA087823-03R01, CA087823Initial digit removed, Trailing number removed, Comma insertedf&9IT-01929IT-0192None - non standard Project ID $$=1R03CA110928-01R03, CA110928Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?4067840678None - non standard Project ID $$7 4067440674None - non standard Project ID $$7 5R03CA096467-02R03, CA096467Initial digit removed, Trailing number removed, Comma insertedf&1R43DA016045-01R43, DA016045Initial digit removed, Trailing number removed, Comma insertedf&BC010602BC010602None - non standard Project ID $$=5R01ES009126-03R01, ES009126Initial digit removed, Trailing number removed, Comma insertedf&5R01HD036880-04R01, HD036880Initial digit removed, Trailing number removed, Comma insertedf&5K01AG019194-03K01, AG019194Initial digit removed, Trailing number removed, Comma insertedf&BC990882BC990882None - non standard Project ID $$=7R01DA013677-03R01, DA013677Initial digit removed, Trailing number removed, Comma insertedf&1R03CA105998-01R03, CA105998Initial digit removed, Trailing number removed, Comma insertedf&5R01HD043844-02R01, HD043844Initial digit removed, Trailing number removed, Comma insertedf&8RT-01318RT-0131None - non standard Project ID $$=5P60DE013059-030005P60, DE013059Initial digit removed, Trailing number removed, Comma insertedj*(t  ^ | % K N$>ZxLfa`7RT-00497RT-0049None - non standard Project ID $$=1Z01CP010134-07Z01, CP010134Initial digit removed, Trailing number removed, Comma insertedf&6RT-03606RT-0360None - non standard Project ID $$=1U01ES012801-010002U01, ES012801Initial digit removed, Trailing number removed, Comma insertedj*7RT-00257RT-0025None - non standard Project ID $$=9RT-00349RT-0034None - non standard Project ID $$=5P50DA013334-050002P50, DA013334Initial digit removed, Trailing number removed, Comma insertedj*5R01HD037688-04R01, HD037688Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?5R01DA012014-04R01, DA012014Initial digit removed, Trailing number removed, Comma insertedf&5R01AG015386-06R01, AG015386Initial digit removed, Trailing number removed, Comma insertedf&1F31DA017437-01F31, DA017437Initial digit removed, Trailing number removed, Comma insertedf& 5R18HL053478-06R18, HL053478Initial digit removed, Trailing number removed, Comma insertedf& 5R03HD037225-02R03, HD037225Initial digit removed, Trailing number removed, Comma insertedf& 3R03CA083352-02S1R03, CA083352Initial digit removed, Trailing number removed, Comma insertedh( 1Z01HD002520-09Z01, HD002520Initial digit removed, Trailing number removed, Comma insertedf& 5P50DA013334-050004P50, DA013334Initial digit removed, Trailing number removed, Comma insertedj*5R01CA090731-04R01, CA090731Initial digit removed, Trailing number removed, Comma insertedf&9DT-01159DT-0115None - non standard Project ID $$=5R01HL051319-04R01, HL051319Initial digit removed, Trailing number removed, Comma insertedf&5R03CA101527-02R03, CA101527Initial digit removed, Trailing number removed, Comma insertedf&10IT-026410IT-0264None - non standard Project ID $$?4811848118None - non standard Project ID $$7 6RT-03856RT-0385None - non standard Project ID $$=8RT-01158RT-0115None - non standard Project ID $$=11IT-002011IT-0020None - non standard Project ID $$?5P50DA007074-130010P50, DA007074Initial digit removed, Trailing number removed, Comma insertedj*5U10HL059290-05U10, HL059290Initial digit removed, Trailing number removed, Comma insertedf&5R01DA012697-04R01, DA012697Initial digit removed, Trailing number removed, Comma insertedf&5R01DA009110-10R01, DA009110Initial digit removed, Trailing number removed, Comma insertedf&5K05DA000081-24K05, DA000081Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?1R03DA018709-01R03, DA018709Initial digit removed, Trailing number removed, Comma insertedf&5P50CA084724-050004P50, CA084724Initial digit removed, Trailing number removed, Comma insertedj*2R01DA012403-06R01, DA012403Initial digit removed, Trailing number removed, Comma insertedf&5P01ES009581-050003P01, ES009581Initial digit removed, Trailing number removed, Comma insertedj*P20, CA090578P20, CA090578None*$5K01CA098753-02K01, CA098753Initial digit removed, Trailing number removed, Comma insertedf&5R01TW005991-03R01, TW005991Initial digit removed, Trailing number removed, Comma insertedf&5P50DA013332-040001P50, DA013332Initial digit removed, Trailing number removed, Comma insertedj* *1 G e  ` ~ k P$k{3Q:VUmC4713447134None - non standard Project ID $$7 BR21, CA092085R21, CA092085None*$A1R03DA016328-01R03, DA016328Initial digit removed, Trailing number removed, Comma insertedf&@5R01HL056177-09R01, HL056177Initial digit removed, Trailing number removed, Comma insertedf&?6RT-04076RT-0407None - non standard Project ID $$=>6PT-60016PT-6001None - non standard Project ID $$==5R01DA004174-17R01, DA004174Initial digit removed, Trailing number removed, Comma insertedf&<3R01CA077249-04S1R01, CA077249Initial digit removed, Trailing number removed, Comma insertedh(;5R01CA100680-02R01, CA100680Initial digit removed, Trailing number removed, Comma insertedf&:R03, CA108360R03, CA108360None*$95R01DA012854-05R01, DA012854Initial digit removed, Trailing number removed, Comma insertedf&85K21DA000272-05K21, DA000272Initial digit removed, Trailing number removed, Comma insertedf&75R01DA012540-05R01, DA012540Initial digit removed, Trailing number removed, Comma insertedf&66RT-03546RT-0354None - non standard Project ID $$=58RT-0107H8RT-0107HNone - non standard Project ID $$?4R29, CA078293R29, CA078293None*$35R01DA003994-18R01, DA003994Initial digit removed, Trailing number removed, Comma insertedf&25K05DA000343-05K05, DA000343Initial digit removed, Trailing number removed, Comma insertedf&18DT-01728DT-0172None - non standard Project ID $$=05F32NR008661-02F32, NR008661Initial digit removed, Trailing number removed, Comma insertedf&/5R03AA012764-02R03, AA012764Initial digit removed, Trailing number removed, Comma insertedf&.Not GivenNot GivenNone - non standard Project ID $$?-2R01DA013783-05A1R01, DA013783Initial digit removed, Trailing number removed, Comma insertedh(,R01, CA078564R01, CA078564None*$+1R01CA098380-01A2R01, CA098380Initial digit removed, Trailing number removed, Comma insertedh(*RSG-02-243-01-CCERSG-02-243-01-CCENone - non standard Project ID $$O,)9DT-01999DT-0199None - non standard Project ID $$=(5U01CA097450-03U01, CA097450Initial digit removed, Trailing number removed, Comma insertedf&'1Z01HD008745-02Z01, HD008745Initial digit removed, Trailing number removed, Comma insertedf&&5K01DA015396-03K01, DA015396Initial digit removed, Trailing number removed, Comma insertedf&%7RT-00687RT-0068None - non standard Project ID $$=$1R01DA015756-01A2R01, DA015756Initial digit removed, Trailing number removed, Comma insertedh(#Not GivenNot GivenNone - non standard Project ID $$?"1F31DA015268-01F31, DA015268Initial digit removed, Trailing number removed, Comma insertedf&!5R01DA010612-07R01, DA010612Initial digit removed, Trailing number removed, Comma insertedf& 1P0DA013332-0100031P0DA013332-010003None - non standard Project ID $$Q.1P50CA095856-01A10002P50, CA095856Initial digit removed, Trailing number removed, Comma insertedl,5R01CA063562-10R01, CA063562Initial digit removed, Trailing number removed, Comma insertedf&R03, CA091213R03, CA091213None*$5K07CA087724-05K07, CA087724Initial digit removed, Trailing number removed, Comma insertedf&7R01HL057457-06R01, HL057457Initial digit removed, Trailing number removed, Comma insertedf&TURSG-03-080-01-PBPTURSG-03-080-01-PBPNone - non standard Project ID $$S06*6 8  = w 5 S % } =W3M#hQ m5R01HL052449-06R01, HL052449Initial digit removed, Trailing number removed, Comma insertedf&l7RT-01357RT-0135None - non standard Project ID $$=kR01, CA089053R01, CA089053None*$j5R03CA086785-02R03, CA086785Initial digit removed, Trailing number removed, Comma insertedf&i5U01HD040561-04U01, HD040561Initial digit removed, Trailing number removed, Comma insertedf&h1F31DA006097-01F31, DA006097Initial digit removed, Trailing number removed, Comma insertedf&gNot GivenNot GivenNone - non standard Project ID $$?f5R03CA096434-02R03, CA096434Initial digit removed, Trailing number removed, Comma insertedf&e5U01HD032830-07U01, HD032830Initial digit removed, Trailing number removed, Comma insertedf&d7RT-01957RT-0195None - non standard Project ID $$=c5U54DE014257-020001U54, DE014257Initial digit removed, Trailing number removed, Comma insertedj*b5R01DA011386-05R01, DA011386Initial digit removed, Trailing number removed, Comma insertedf&a5U01CA097415-03U01, CA097415Initial digit removed, Trailing number removed, Comma insertedf&`5K23CA087558-04K23, CA087558Initial digit removed, Trailing number removed, Comma insertedf&_4800648006None - non standard Project ID $$7 ^2U01AI031834-11U01, AI031834Initial digit removed, Trailing number removed, Comma insertedf&]5P50CA058223-100013P50, CA058223Initial digit removed, Trailing number removed, Comma insertedj*\5R01CA076644-04R01, CA076644Initial digit removed, Trailing number removed, Comma insertedf&[TURSG-02-227-01-PBPTURSG-02-227-01-PBPNone - non standard Project ID $$S0Z5R01CA081330-05R01, CA081330Initial digit removed, Trailing number removed, Comma insertedf&Y1R21DA016581-01A1R21, DA016581Initial digit removed, Trailing number removed, Comma insertedh(XR21, CA089510R21, CA089510None*$W5R01CA098342-02R01, CA098342Initial digit removed, Trailing number removed, Comma insertedf&V5P50CA084735-059001P50, CA084735Initial digit removed, Trailing number removed, Comma insertedj*U8RT-00598RT-0059None - non standard Project ID $$=T5R01CA080266-04R01, CA080266Initial digit removed, Trailing number removed, Comma insertedf&S5R01DA015067-02R01, DA015067Initial digit removed, Trailing number removed, Comma insertedf&R5159251592None - non standard Project ID $$7 Q4867648676None - non standard Project ID $$7 P4667946679None - non standard Project ID $$7 O3860138601None - non standard Project ID $$7 N4525745257None - non standard Project ID $$7 M1R03CA110796-01R03, CA110796Initial digit removed, Trailing number removed, Comma insertedf&L9DT-00469DT-0046None - non standard Project ID $$=KNot GivenNot GivenNone - non standard Project ID $$?JK07, CA084603K07, CA084603None*$IK05, CA092633K05, CA092633None*$H10RT-033310RT-0333None - non standard Project ID $$?G1R01CA089053-01A1R01, CA089053Initial digit removed, Trailing number removed, Comma insertedh(F5R01CA076945-04R01, CA076945Initial digit removed, Trailing number removed, Comma insertedf&E5R01CA086295-04R01, CA086295Initial digit removed, Trailing number removed, Comma insertedf&D5P50DA013334-059005P50, DA013334Initial digit removed, Trailing number removed, Comma insertedj*))Vl D  m 8  7 ~ 't2y~ RpDNot GivenNot GivenNone - non standard Project ID $$?5R01CA081934-04R01, CA081934Initial digit removed, Trailing number removed, Comma insertedf&00-C-007900-C-0079None - non standard Project ID $$?5K07CA075159-04K07, CA075159Initial digit removed, Trailing number removed, Comma insertedf&5K23ES000354-05K23, ES000354Initial digit removed, Trailing number removed, Comma insertedf&5R01DA014662-03R01, DA014662Initial digit removed, Trailing number removed, Comma insertedf&5R21CA081645-02R21, CA081645Initial digit removed, Trailing number removed, Comma insertedf&5R01CA042730-14R01, CA042730Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?5R21DA014680-03R21, DA014680Initial digit removed, Trailing number removed, Comma insertedf&6IT-00716IT-0071None - non standard Project ID $$=5179651796None - non standard Project ID $$7 5R01ES011634-03R01, ES011634Initial digit removed, Trailing number removed, Comma insertedf&6RT-03276RT-0327None - non standard Project ID $$=1Z01DA000356-10Z01, DA000356Initial digit removed, Trailing number removed, Comma insertedf&5R03DA014334-02R03, DA014334Initial digit removed, Trailing number removed, Comma insertedf&5P50DA013334-050001P50, DA013334Initial digit removed, Trailing number removed, Comma insertedj*CRTG-03-074-01-PBPCRTG-03-074-01-PBPNone - non standard Project ID $$Q.4699346993None - non standard Project ID $$7 5R01DA012655-04R01, DA012655Initial digit removed, Trailing number removed, Comma insertedf&5M01RR000056-420680M01, RR000056Initial digit removed, Trailing number removed, Comma insertedj*5R01ES008977-07R01, ES008977Initial digit removed, Trailing number removed, Comma insertedf&5R01DA003976-15R01, DA003976Initial digit removed, Trailing number removed, Comma insertedf&6RT-01846RT-0184None - non standard Project ID $$=~5R01DA015668-03R01, DA015668Initial digit removed, Trailing number removed, Comma insertedf&}9RT-01039RT-0103None - non standard Project ID $$=|9RT-02189RT-0218None - non standard Project ID $$={5U01HL066852-04U01, HL066852Initial digit removed, Trailing number removed, Comma insertedf&zP50, CA105632P50, CA105632None*$y5180551805None - non standard Project ID $$7 x5R01CA098663-02R01, CA098663Initial digit removed, Trailing number removed, Comma insertedf&w5R01CA067594-08R01, CA067594Initial digit removed, Trailing number removed, Comma insertedf&v5R01CA080283-04R01, CA080283Initial digit removed, Trailing number removed, Comma insertedf&u4328143281None - non standard Project ID $$7 t5143651436None - non standard Project ID $$7 s5P50DA013334-050006P50, DA013334Initial digit removed, Trailing number removed, Comma insertedj*r5R01DA015167-03R01, DA015167Initial digit removed, Trailing number removed, Comma insertedf&q5M01RR006192-070161M01, RR006192Initial digit removed, Trailing number removed, Comma insertedj*p5M01RR006192-070193M01, RR006192Initial digit removed, Trailing number removed, Comma insertedj*o5M01RR006192-090156M01, RR006192Initial digit removed, Trailing number removed, Comma insertedj*nP50, DA013334P50, DA013334None*$l,GL C | ? ]  - r`Xlq<ZxC5R01DA008888-07R01, DA008888Initial digit removed, Trailing number removed, Comma insertedf&Z01, CP010124Z01, CP010124None*$5R01DA015337-02R01, DA015337Initial digit removed, Trailing number removed, Comma insertedf&1R15NR007735-01R15, NR007735Initial digit removed, Trailing number removed, Comma insertedf&5P50ES012359-03P50, ES012359Initial digit removed, Trailing number removed, Comma insertedf&5U10HL059294-05U10, HL059294Initial digit removed, Trailing number removed, Comma insertedf&R01, CA077378R01, CA077378None*$4105641056None - non standard Project ID $$7 9RT-01019RT-0101None - non standard Project ID $$=1Z01ES049034-07Z01, ES049034Initial digit removed, Trailing number removed, Comma insertedf&R03, CA094771R03, CA094771None*$4066540665None - non standard Project ID $$7 5P50DA013334-050005P50, DA013334Initial digit removed, Trailing number removed, Comma insertedj*3973139731None - non standard Project ID $$7 5180451804None - non standard Project ID $$7 4747247472None - non standard Project ID $$7 4067340673None - non standard Project ID $$7 Not GivenNot GivenNone - non standard Project ID $$?5R01CA071098-05R01, CA071098Initial digit removed, Trailing number removed, Comma insertedf&5R01CA078784-03R01, CA078784Initial digit removed, Trailing number removed, Comma insertedf&5P50AA011998-040003P50, AA011998Initial digit removed, Trailing number removed, Comma insertedj*5U10HL059276-05U10, HL059276Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?5R01NS033978-05R01, NS033978Initial digit removed, Trailing number removed, Comma insertedf&5R01HL050723-12R01, HL050723Initial digit removed, Trailing number removed, Comma insertedf&5M01RR000056-420762M01, RR000056Initial digit removed, Trailing number removed, Comma insertedj*10DT-016210DT-0162None - non standard Project ID $$?5R01CA098870-02R01, CA098870Initial digit removed, Trailing number removed, Comma insertedf&1R43HD038147-01R43, HD038147Initial digit removed, Trailing number removed, Comma insertedf&9RT-00129RT-0012None - non standard Project ID $$=4066740667None - non standard Project ID $$7 5179451794None - non standard Project ID $$7 5K01DA000450-05K01, DA000450Initial digit removed, Trailing number removed, Comma insertedf&U01, CA098216U01, CA098216None*$6RT-04266RT-0426None - non standard Project ID $$=13RT-001813RT-0018None - non standard Project ID $$?7RT-01427RT-0142None - non standard Project ID $$=5R01AA011986-03R01, AA011986Initial digit removed, Trailing number removed, Comma insertedf&RC-2004-0020RC-2004-0020None - non standard Project ID $$E"6KT-01176KT-0117None - non standard Project ID $$=5R01CA078828-03R01, CA078828Initial digit removed, Trailing number removed, Comma insertedf&4053940539None - non standard Project ID $$7 5R01HD036719-03R01, HD036719Initial digit removed, Trailing number removed, Comma insertedf&6KT-02066KT-0206None - non standard Project ID $$= &8 V t , Q k  .u+Ic So-Ie1R01DA016323-01A1R01, DA016323Initial digit removed, Trailing number removed, Comma insertedh(5P01HD013063-24P01, HD013063Initial digit removed, Trailing number removed, Comma insertedf&5F32CA088457-02F32, CA088457Initial digit removed, Trailing number removed, Comma insertedf&1K07CA095623-01A2K07, CA095623Initial digit removed, Trailing number removed, Comma insertedh(4067640676None - non standard Project ID $$7 1R01MH069229-01A1R01, MH069229Initial digit removed, Trailing number removed, Comma insertedh(5K01DK059293-03K01, DK059293Initial digit removed, Trailing number removed, Comma insertedf&9KT-01919KT-0191None - non standard Project ID $$=5R01CA106186-02R01, CA106186Initial digit removed, Trailing number removed, Comma insertedf&5P30ES007784-099004P30, ES007784Initial digit removed, Trailing number removed, Comma insertedj*2R01CA055769-14R01, CA055769Initial digit removed, Trailing number removed, Comma insertedf&5R01HD037131-05R01, HD037131Initial digit removed, Trailing number removed, Comma insertedf&5R01HL066118-03R01, HL066118Initial digit removed, Trailing number removed, Comma insertedf&5P51RR000163-430016P51, RR000163Initial digit removed, Trailing number removed, Comma insertedj*5R01DA014794-04R01, DA014794Initial digit removed, Trailing number removed, Comma insertedf&1G08LM008354-01G08, LM008354Initial digit removed, Trailing number removed, Comma insertedf&Not GivenNot GivenNone - non standard Project ID $$?BC001055BC001055None - non standard Project ID $$=5R01DA014537-02R01, DA014537Initial digit removed, Trailing number removed, Comma insertedf&5M01RR000400-360458M01, RR000400Initial digit removed, Trailing number removed, Comma insertedj*5S06GM008016-310098S06, GM008016Initial digit removed, Trailing number removed, Comma insertedj*5K07CA078548-05K07, CA078548Initial digit removed, Trailing number removed, Comma insertedf&5R01DA014247-03R01, DA014247Initial digit removed, Trailing number removed, Comma insertedf&1K07CA109361-01K07, CA109361Initial digit removed, Trailing number removed, Comma insertedf&5R01DA014374-04R01, DA014374Initial digit removed, Trailing number removed, Comma insertedf&5P50CA090440-020001P50, CA090440Initial digit removed, Trailing number removed, Comma insertedj*R03, CA089722R03, CA089722None*$R01, CA092705R01, CA092705None*$1Z01BC005761-06Z01, BC005761Initial digit removed, Trailing number removed, Comma insertedf&BC980583BC980583None - non standard Project ID $$=5R21DA011903-03R21, DA011903Initial digit removed, Trailing number removed, Comma insertedf&5R44DA013305-03R44, DA013305Initial digit removed, Trailing number removed, Comma insertedf&5R01DE012609-04R01, DE012609Initial digit removed, Trailing number removed, Comma insertedf&5R01HL056931-04R01, HL056931Initial digit removed, Trailing number removed, Comma insertedf&5R01CA087895-03R01, CA087895Initial digit removed, Trailing number removed, Comma insertedf&5R01DA010492-04R01, DA010492Initial digit removed, Trailing number removed, Comma insertedf&5R01CA042829-12R01, CA042829Initial digit removed, Trailing number removed, Comma insertedf&3R15HD039645-01A2S1R15, HD039645Initial digit removed, Trailing number removed, Comma insertedj*J)E \  [  V t   u-r*qA_36PR01, CA097359R01, CA097359None*$1R03CA103499-01R03, CA103499Initial digit removed, Trailing number removed, Comma insertedf&3R01CA089350-01A1S1R01, CA089350Initial digit removed, Trailing number removed, Comma insertedj*5R01CA074517-05R01, CA074517Initial digit removed, Trailing number removed, Comma insertedf& Not GivenNot GivenNone - 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UNot a research project $$! TNot a research project $$! SNot a research project $$! RNot a research project $$! QNot a research project $$! PNot a research project $$! ONot a research project $$! NNot a research project $$! MNot a research project $$! LNot a research project $$! KNot a research project $$! JNot a research project $$! INot a research project $$! HNot a research project $$! GNot a research project $$! FNot a research project $$! ENot a research project $$! DNot a research project $$! 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I)go{59ǺJL:אLast NameZ^rO9lr{59ǺJL:אFirst Namez E Qh{59ǺJL:אInstitution!¤D "HD9.{59ǺJL:אCity߷ospJ]3/{59ǺJL:אState1qހ@Zg{59ǺJL:אFundergӒIP'{59ǺJL:אProject IDM.yGQ {59ǺJL:אAbstract̃R9N0={59ǺJL:אBreakout Session ListӢq'G>{59ǺJL:אWG Recommendation Listo; C+Br=RU{59ǺJL:אKeyword List[9SRE{W[Y{59ǺJL:אStart Date TextxkMQQ&{59ǺJL:אStart Date Date] deD<>{59ǺJL:אStart Date Year<;UxvA99{59ǺJL:אEnd Date Text0N%8\FGÀ{59ǺJL:אEnd Date DateU0;F+uښv{59ǺJL:אEnd Date Year9IO@xC{59ǺJL:אActivity Date9x#F$PU{59ǺJL:אDisplay Date ͓K"i÷{59ǺJL:אDate Exception)kuM(7{59ǺJL:אReview Date+SA7[Display PI Nameܨ).r@EZ (Display State Xi!ˢ@ A4zDisplay FunderXRKY~!MԁDisplay Project ID KvcO<)   x e R > +  {  g T A -}jVC0 lYE2 n[H0 / //UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp / . ./UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp . - -/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp - , ,/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp , + +/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp + * */UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp * ) )/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp ) ( (/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp ( ' '/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp ' & &/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp & % %/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp % $ $/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp $ # #/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp # " "/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp " ! !/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp !    /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp    /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp  LVAL b f  24MR2 GUIDNameMap }~?GH&  Ua 9@X}2Yվ0n@XSo PtProject KeywordsVܠ0M3szc@XSo PtKeywords[/ǎNIyM!a 9@X}2YRecord IDsDѣ\E_Pr{\gVܠ0M3sArea߱1C0cVܠ0M3sKeywordW?pM>$;Ya 9@X}2YKeyword No[ڽw'C{59ǺJL:אWG Recommendation Listo; C+Br=RU{59ǺJL:אKeyword List}~?GH&xVܗ@%rSub Keywordsa 9@X}2Yվ0n@tProject KeywordsVܠ0M3szc@tKeywords[/ǎNIyM!a 9@X}2YRecord IDsDѣ\E_Pr{\gVܠ0M3sArea߱1C0cVܠ0M3sKeywordW?pM>$;Ya 9@X}2YKeyword No[ڽw'Cct}8[6 . U MR2 GUIDNameMapZ w/K6 . U MR2 GUIDNameMapZ h|>@Bࡘ6 . U MR2 GUIDNameMap  "EBv n U"{C( g @Ip9fTest Child MR2 GUIDNameMapJ "{C(&  U{59ǺJL:אڙU@tProject Info{BA3{59ǺJL:אRecord ID:^D. I)go{59ǺJL:אLast Name߷ospJ]3/{59ǺJL:אState MR2 GUIDNameMapZ 䕔obC.v/6 . U MR2 GUIDNameMapR lDfU. & UIЋ]C&Cĝ=D,n@\tCurrent Sort Fields Temp3rH!ҏBpwIЋ]C&Cĝ=Sort Order\OɩDI2d RIЋ]C&Cĝ=Compiled English Expression] AAikIЋ]C&Cĝ=Sort Field DescriptorcΜ_Ma hR@\tSort FieldscYUzD-fcΜ_MaSort Field DescriptorUg9E Qk cΜ_MaSort OrderP>vcO<)   x e R > +    z  yfeRQ>=*)xwdA A/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp A @ 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp @ @/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp @ ? 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp ? ?/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp ? > 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp > >/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp > = 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp = =/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp = < 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp < </UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp < ; 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp ; ;/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp ; : 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp : :/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp : 9 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp 9 9/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 9 8 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp 8 8/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 8 7 7/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 7 6 6/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 6 5 5/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 5 4 4/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 4 3 3/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 3 2 2/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 2 1 1/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp 1 0 0/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp HLVALXMR2 GUIDNameMap   GZ` X U^8D{ HĤ.|c~@qBrowseDB2BH .n@tPrint Recordsǥ*[*VMA 4<2BH Print Order{BA3^8D{ HĤ.Record IDD CwK|^8D{ HĤ.Project/Activity IDeEnDe@]ځ^8D{ HĤ.Entry TypetK!Eg&Ap^8D{ HĤ.Title:^D. 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ALZBj~^8D{ HĤ.Display PI Name5Ap^8D{ HĤ.Display PI ORGz E Qh^8D{ HĤ.Institution!¤D "HD9.^8D{ HĤ.City߷ospJ]3/^8D{ HĤ.State,&$Nl6^8D{ HĤ.Display State1qހ@Zg^8D{ HĤ.Funder"FZ7(CG c^8D{ HĤ.Display FundergӒIP'^8D{ HĤ.Project IDUCeOUts^8D{ HĤ.Display Project IDM.yGQ ^8D{ HĤ.AbstractP@G^8D{ HĤ.Display Abstract̃R9N0=^8D{ HĤ.Breakout Session ListӢq'G>^8D{ HĤ.WG Recommendation Listo; C+Br=RU^8D{ HĤ.Keyword List[9SRE{W[Y^8D{ HĤ.Start Date TextxkMQQ&^8D{ HĤ.Start Date Date] deD<>^8D{ HĤ.Start Date Year<;UxvA99^8D{ HĤ.End Date Text0N%8\FGÀ^8D{ HĤ.End Date DateU0;F+uښv^8D{ HĤ.End Date Year9IO@xC^8D{ HĤ.Activity Date9x#F$PU^8D{ HĤ.Display Date ͓K"i÷^8D{ HĤ.Date Exception)kuM(7^8D{ HĤ.Review DatepeEA2BH Record ID\RCgS_m.yy@{BrSub Detail Recs and Keys{59ǺJL:אڙU@tProject Info{BA3{59ǺJL:אRecord IDӢq'G>{59ǺJL:אWG Recommendation Listo; C+Br=RU{59ǺJL:אKeyword ListLI?NoUWhere1Q3E|ևQOrder14 wL.^2gMode1 LVALMR2 GUIDNameMap  "unEW6K.DA  U^8D{ HĤ.|c~@qBrowseDB2BH .n@tPrint Recordsǥ*[*VMA 4<2BH Print Order{BA3^8D{ HĤ.Record IDD CwK|^8D{ HĤ.Project/Activity IDeEnDe@]ځ^8D{ HĤ.Entry TypetK!Eg&Ap^8D{ HĤ.Title:^D. 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ALZBj~^8D{ HĤ.Display PI Name5Ap^8D{ HĤ.Display PI ORGz E Qh^8D{ HĤ.Institution!¤D "HD9.^8D{ HĤ.City߷ospJ]3/^8D{ HĤ.State,&$Nl6^8D{ HĤ.Display State1qހ@Zg^8D{ HĤ.Funder"FZ7(CG c^8D{ HĤ.Display FundergӒIP'^8D{ HĤ.Project IDUCeOUts^8D{ HĤ.Display Project IDM.yGQ ^8D{ HĤ.AbstractP@G^8D{ HĤ.Display Abstract̃R9N0=^8D{ HĤ.Breakout Session ListӢq'G>^8D{ HĤ.WG Recommendation Listo; C+Br=RU^8D{ HĤ.Keyword List[9SRE{W[Y^8D{ HĤ.Start Date TextxkMQQ&^8D{ HĤ.Start Date Date] deD<>^8D{ HĤ.Start Date Year<;UxvA99^8D{ HĤ.End Date Text0N%8\FGÀ^8D{ HĤ.End Date DateU0;F+uښv^8D{ HĤ.End Date Year9IO@xC^8D{ HĤ.Activity Date9x#F$PU^8D{ HĤ.Display Date ͓K"i÷^8D{ HĤ.Date Exception)kuM(7^8D{ HĤ.Review DatepeEA2BH Record IDFt@gCXšWhere1^jB2Order17#5 f#CZZw0bMode1 6Dvub a N M : &  v u b O ;(xwdQ=*zfS@,|iQ P P/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp P O O/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp O N N/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp N M M/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp M L L/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp L K K/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp K J J/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp J  /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   T/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp  T/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp   /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp  I I /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp I H H /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp H G 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp G G/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp G F F /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp F E E /UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp E D 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp D D/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp D C 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp C C/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp C B 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp B B/UYFoNQ|ܓv3)1PK]=ݳAC~FIO ma&B#RB;'aEyPlnp B A 1>3\FoNܞW4 HWK]=ݳAC~FI9Ru`H[Ł;'aEyPlnp )LVAL9MR2RecordLocksODBCTimeoutMaxRecordsRecordsetType FilterOrderByOrderByOnOrientationNameMapDefaultViewGUIDDOLK  <      ^8D{ HĤ.  U{59ǺJL:אڙU@vtProject Info{BA3{59ǺJL:אRecord ID6x$OZZ{59ǺJL:אMarkBoxD CwK|{59ǺJL:אProject/Activity IDeEnDe@]ځ{59ǺJL:אEntry TypetK!Eg&Ap{59ǺJL:אTitle:^D. I)go{59ǺJL:אLast NameZ^rO9lr{59ǺJL:אFirst Namez E Qh{59ǺJL:אInstitution!¤D "HD9.{59ǺJL:אCity߷ospJ]3/{59ǺJL:אState1qހ@Zg{59ǺJL:אFundergӒIP'{59ǺJL:אProject IDM.yGQ {59ǺJL:אAbstract̃R9N0={59ǺJL:אBreakout Session ListӢq'G>{59ǺJL:אWG Recommendation Listo; C+Br=RU{59ǺJL:אKeyword List[9SRE{W[Y{59ǺJL:אStart Date TextxkMQQ&{59ǺJL:אStart Date Date] deD<>{59ǺJL:אStart Date Year<;UxvA99{59ǺJL:אEnd Date Text0N%8\FGÀ{59ǺJL:אEnd Date DateU0;F+uښv{59ǺJL:אEnd Date Year9IO@xC{59ǺJL:אActivity Date9x#F$PU{59ǺJL:אDisplay Date ͓K"i÷{59ǺJL:אDate Exception)kuM(7{59ǺJL:אReview DateB$Display PI Name ? ALZBj~@"Display PI ORG 5Ap> Display State ,&$Nl6@"Display Funder "FZ7(CG cH*$Display Project ID UCeOUtsD& Display Abstract P@GLVAL 1MR2RecordLocksODBCTimeoutMaxRecords FilterOrderByOrderByOnOrientationDefaultViewGUIDDOLRecordsetTypeNameMap   <    *c*a!ESu̺  U{59ǺJL:אx8LN@tProject Info{BA3{59ǺJL:אRecord IDeEnDe@]ځ{59ǺJL:אEntry TypetK!Eg&Ap{59ǺJL:אTitlegӒIP'{59ǺJL:אProject ID1qހ@Zg{59ǺJL:אFunder:^D. 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URa X(3 h@tBlobsSa X(Ra X(Blob Filenameϩ_DD 1Ra X(Blob NicknameUa X(Ra X(Blob Content  Ra X(  Blob Filename        Sa X(  Blob Content        Ua X(  ~ Blob Nickname       m   MR2RecordLocksODBCTimeoutMaxRecordsRecordsetType FilterOrderByOrderByOnOrientationNameMapDefaultViewGUIDDOLColumnWidthColumnHidden  <      B-F`KK=| t UY– *@8:@tControl SizesY– *@Y– *@Form Name Y– *@Y– *@Control Named~E܁Y– *@Recenter On#A"0ѦY– *@Scale in Steps!Y– *@Y– *@Top"Y– *@Y– *@Left#Y– *@Y– *@Height$Y– *@Y– *@Width%Y– *@Y– *@Has Font&Y– *@Y– *@Font Base'Y– *@Y– *@Font Resize(Y– *@Y– *@Font Autosize)Y– *@Y– *@Font Min*Y– *@Y– *@Font Max+Y– *@Y– *@Font Group,Y– *@Y– *@Font Temp-Y– *@Y– *@Updated Control cHB[tControl Sizes].[Scale in Steps]    W<6[tControl Sizes].[Has Font]  d  Y>8[tControl Sizes].[Font Base]    aF@[tControl Sizes].[Font Autosize]    W<6[tControl Sizes].[Font Min]    [@:[tControl Sizes].[Font Group]    Y>8[tControl Sizes].[Font Temp]    eJD[tControl Sizes].[Updated Control]  H  ]B<[tControl Sizes].[Recenter On]    ]B<[tControl Sizes].[Font Resize]    W<6[tControl Sizes].[Font Max]  :  RLVAL/p.bMR2VOrientationOrderByOnNameMapDefaultViewRowHeightColumnWidthColumnOrderColumnHiddenRequiredAllowZeroLengthDisplayControlIMEModeIMESentenceMode$UnicodeCompressionDecimalPlacesDefaultValue FormatGUIDValidationRuleValidationText FilterOrderByDescriptionInputMaskCaptionSmartTags    Uw"hJ<6ܗ@5R@tBrowse Child Sort Fields~(­H3͹<w"hJ<6ܗSort Field DescriptorPȈBXZ w"hJ<6ܗSort Field ExpressionY$BvO0w"hJ<6ܗSort Field EnglishԆ`HEJ/w"hJ<6ܗSort Order朲Mw"hJ<6ܗConditional Possible|/u`BhvkTw"hJ<6ܗSort Field Conditional ExpressionFOF:!W}2 w"hJ<6ܗSort Combo Query|G"6Iw"hJ<6ܗSort Combo Limitw \AEYGΕw"hJ<6ܗAscendingLG:RqBs~w"hJ<6ܗConditional UsedS Wq^AbwՅw"hJ<6ܗValue~)dG~W8Xw"hJ<6ܗCompiled Sort ExpressionM:Kw"hJ<6ܗCompiled English Expression @#w"hJ<6ܗField Name    w"hJ<6ܗ0*Sort Field Descriptor        m       ~(­H3͹<}Ascending p     1   m w \AEYGΕSort Order |     0   m Ԇ`HEJ/͢60Compiled Sort Expression             ~)dG~W8X*$Sort Field English        m       Y$BvO0HBSort Field Conditional Expression        m       |/u`BhvkT.(Conditional Possible     Yes/No   j 朲M Value        m       S Wq^AbwՅ& Conditional Used      1   m LG:RqBs~& Sort Combo Query             FOF:!W}2 & Sort Combo Limit     Yes/No   j |G"6I0*Sort Field Expression        m       PȈBXZ <6Compiled English Expression             M:KxField Name        m      VLVAL/p.fMR2BOrientationOrderByOnNameMapColumnWidthColumnOrderColumnHiddenRequiredAllowZeroLengthDisplayControl$UnicodeCompression FormatDecimalPlacesDefaultValueGUID FilterOrderByValidationRuleValidationTextDescriptionInputMaskCaptionDefaultViewIMEModeIMESentenceModeSmartTags  | t UY– *@m8@tControl SizesY– *@Y– *@Form Name Y– *@Y– *@Control Name#A"0ѦY– *@Scale in Steps!Y– *@Y– *@Top"Y– *@Y– *@Left#Y– *@Y– *@Height$Y– *@Y– *@Width%Y– *@Y– *@Has Font&Y– *@Y– *@Font Base'Y– *@Y– *@Font Resize(Y– *@Y– *@Font Autosize)Y– *@Y– *@Font Min*Y– *@Y– *@Font Max+Y– *@Y– *@Font Group,Y– *@Y– *@Font Temp-Y– *@Y– *@Updated ControlT[&~J,uFY– *@Recenter On  Y– *@ Form Name      m   Y– *@  Control Name      m    Y– *@  |Has Font <   Yes/No  j %Y– *@Font Resize     Yes/No  j 'Y– *@}Font Base H      0  m &Y– *@{Font Min       0  m )Y– *@{Font Max       0  m *Y– *@$Updated Control 5   Yes/No  j -Y– *@q Top       0  m !Y– *@sLeft       0  m "Y– *@w Height       0  m #Y– *@u Width       0  m $Y– *@Font Group       0  m +Y– *@ Font Autosize    Yes/No  j (Y– *@}Font Temp       0  m ,Y– *@"Scale in Steps p   Yes/No  No  j #A"0ѦRecenter On      m     d~E܁LVAL/p.MR2BOrientationOrderByOnNameMapDefaultViewColumnWidthColumnOrderColumnHidden FormatRequiredDisplayControlDefaultValueAllowZeroLength$UnicodeCompressionIMEModeIMESentenceModeDecimalPlacesGUIDValidationRuleValidationText FilterOrderByDescriptionInputMaskCaptionSmartTagsC    UJ'|)U2@tCurrent Search(Īޫ# JqRJ/J'|Line No'%OɧJ'|ActiveG" L8m,kBJ'|Search Field<PEQNJ'|Search ExpressionJ{jyOޞ ؗJ'|Conditional Text\icI78nhJ'|Conditional Expression_Q~zCp"J'|Use Predicate61 1?Hi|J'|Value Ih=JF|J'|Value RestrictionƸALc 3J'|Log Optm{DPJ'|Where Stringp_lARJ'|Open Parenthesis=|\O @UwJ'|Close Parenthesis{b DO]AQJ'|And Or String/ @&$J'|Hierarchy OnbH M6(J'|Date Type   J'|Њ Active     Yes/No   j False '%OɧؔSearch Field        m      G" L8m,kB("Search Expression        m      <PEQN& Conditional Text        m      J{jyOޞ ؗ2,Conditional Expression        m      \icI78nh Use Predicate     Yes/No   j False _Q~zCp"yLine No      0   m (Īޫ# JqRJ/ Value        m      61 1?Hi|Where String            m{DP& Open Parenthesis        m      p_lAR("Close Parenthesis        m      =|\O @Uw And Or String        m      {b DO]AQHierarchy On     Yes/No   j / @&$0*Previous Hierarchy On     Yes/No   j bH M6.bE2@tCurrent Search Temp۴{ J▦t{qr9D.4>.bLine No^bI !HW X {qr9D.4>.bActivemEk-%C{qr9D.4>.bSearch Field L S{qr9D.4>.bSearch Expression87~FD 05{qr9D.4>.bConditional TextmgTHCjG{qr9D.4>.bConditional Expressionׂ ~ߡF.6IU{qr9D.4>.bUse Predicate]6LxCBL{qr9D.4>.bValuee8?FT2Fz{qr9D.4>.bValue Restriction#ɔA$o'Tc{qr9D.4>.bLog Opt,ke@WA|{qr9D.4>.bWhere String%I'"^i{qr9D.4>.bOpen Parenthesis56- Gj8mQ{qr9D.4>.bClose ParenthesisLTMX{qr9D.4>.bAnd Or StringlH=n%)9{qr9D.4>.bHierarchy Onl:I Gn#n{qr9D.4>.bPrevious Hierarchy OnqeEc{qr9D.4>.bDate Type   {qr9D.4>.b Active     Yes/No   j False ^bI !HW X Search Field        m      mEk-%C("Search Expression        m       L S& Conditional Text        m      87~FD 05¨2,Conditional Expression        m      mgTHCjG Use Predicate     Yes/No   j False ׂ ~ߡF.6IUyLine No      0   m ۴{ J▦t Value        m      ]6LxCBLWhere String            ,ke@WA|& Open Parenthesis        m      %I'"^i("Close Parenthesis        m      56- Gj8mQ And Or String        m      LTMXHierarchy On     Yes/No   j lH=n%)90*Previous Hierarchy On     Yes/No   j l:I Gn#n("Value Restriction   LVAL     m      e8?FT2FzyLog Opt      0   m #ɔA$o'TcvDate Type        m     LVAL&MR2VOrientationOrderByOnNameMapDefaultViewRowHeightColumnWidthColumnOrderColumnHiddenRequiredAllowZeroLengthDisplayControlIMEModeIMESentenceMode$UnicodeCompressionDecimalPlacesDefaultValue FormatGUIDValidationRuleValidationText FilterOrderByDescriptionInputMaskCaptionSmartTags   z UGwrC{.,n@tCurrent Sort Fieldsk~ _CRçGwrC{Sort Field DescriptorGtMαxa+GwrC{Sort Field ExpressionjfMWN.GwrC{Sort Field English3Gq0rGwrC{Sort OrderqUMoH=GwrC{Conditional Possible#C˱!F`B+&@qлT/IЋ]C&Cĝ=Sort Field Conditional Expressionp7kH&)FIЋ]C&Cĝ=Sort Combo Query`B8IЋ]C&Cĝ=Sort Combo LimitF+7I+IЋ]C&Cĝ=Ascending$<{nEpVV[^PIЋ]C&Cĝ=Conditional Usedpo&Fs=\(IЋ]C&Cĝ=ValueS~,Q@o?d,IЋ]C&Cĝ=Compiled Sort Expression\OɩDI2d RIЋ]C&Cĝ=Compiled English Expression    IЋ]C&Cĝ=0*Sort Field Descriptor        m       ] AAik}Ascending p     1   m F+7I+Sort Order |     0   m 3rH!ҏBpw60Compiled Sort Expression             S~,Q@o?d,*$Sort Field English        m       (&7$G.AHBSort Field Conditional Expression        m       Do>B+&@qлT/.(Conditional Possible     Yes/No   j cs KqYݦ%U Value        m       po&Fs=\(& Conditional Used      1   m $<{nEpVV[^P& Sort Combo Query             p7kH&)F& Sort Combo Limit     Yes/No   j `B80*Sort Field Expression        m        ڻԺBOoYɨ<6Compiled English Expression             \OɩDI2d RLVAL WMR2BOrientationOrderByOnNameMapDefaultViewColumnWidthColumnOrderColumnHiddenDecimalPlacesDefaultValueRequiredDisplayControlAllowZeroLengthIMEModeIMESentenceMode$UnicodeCompressionGUIDValidationRuleValidationText FilterOrderByDescription FormatInputMaskCaptionSmartTags3    Ui?~RJMopKR-n@tEntry Typesq@=_E di?~RJMopKSort Order+1;Ea%8+r6i?~RJMopKEntry Type   i?~RJMopKSort Order      0    m q@=_E dEntry Type         m      +1;Ea%8+r6MR2&OrientationOrderByOnNameMapDefaultViewColumnWidthColumnOrderColumnHiddenRequiredAllowZeroLengthDisplayControlIMEModeIMESentenceMode$UnicodeCompressionGUIDValidationRuleValidationText FilterOrderByDescription FormatInputMaskCaptionDefaultValueSmartTags+    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A,<6DdLVALtatasheet Row Height Resize     Yes/No  No   jSLVAL gMR2BOrientationOrderByOnNameMapDefaultViewColumnWidthColumnOrderColumnHiddenRequiredAllowZeroLengthDisplayControl$UnicodeCompressionIMEModeIMESentenceModeDecimalPlacesDefaultValueGUIDValidationRuleValidationText FilterOrderByDescription FormatInputMaskCaptionSmartTagsg  (   UVܠ0M3sv.n@tKeywords5KDVܠ0M3sArea NosDѣ\E_Pr{\gVܠ0M3sArea[ڽw'C)G,.n@tProject Breakout Sessions$I6EUZBw<>)G,Record IDB`)G,Breakout Session No   w<>)G,}Record ID      0    m $I6EUZBݑ,&Breakout Session No      0    m B`V3a{Gm\[yKBP_@8Modalhe`vG|^a{Gm\[yKBP_@8PopUp#HBX ja{Gm\[yKBP_@8BorderStyle   a{Gm\[yKBP_@8$Modal Form Name         m    X=H?R= Modal       Yes/No  False  j ;amXE>V3 PopUp       Yes/No  False  j he`vG|^BorderStyle         0  m #^u@WU A,LVAL/p.MR2&OrientationOrderByOnNameMapDefaultViewRowHeightColumnWidthColumnOrderColumnHiddenRequiredAllowZeroLength$UnicodeCompressionIMEModeIMESentenceModeDisplayControl 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