EFFECTS OF HYPOGLYCEMIA ON NEURONAL AND GLIAL CELL FUNCTION
 
Release Date:  August 7, 2001
 
RFA:  RFA-NS-02-008
 
National Institute of Neurological Disorders and Stroke
 (NINDS; http://www.ninds.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases
 (NIDDK; http://www.niddk.nih.gov/)
Juvenile Diabetes Research Foundation
 (http://www.jdrf.org)
 
Letter of Intent Receipt Date:  February 15, 2002
Application Receipt Date:       March 15, 2002

THIS RFA USES THE “MODULAR GRANT” AND “JUST-IN-TIME” CONCEPTS. IT 
INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS 
THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THS RFA.
 
PURPOSE
 
The National Institute of Neurological Disorders and Stroke (NINDS), 
the National Institute of Diabetes and Digestive and Kidney Diseases 
(NIDDK), and the Juvenile Diabetes Research Foundation (JDRF) solicit 
applications for studies designed to elucidate the effects of acute and 
recurrent episodes of hypoglycemia on glial and neuronal cells of the 
developing and mature central nervous system.  Recent therapeutic 
strategies aimed at closely controlling elevated glucose levels in 
diabetic individuals put them at risk for experiencing episodes of 
hypoglycemia.  Acute and recurrent hypoglycemia may cause transient or 
persistent alteration of cognitive function, and can result in seizures 
or coma.  Recent studies of ischemia have provided information about 
the effects of glucose deprivation coupled with hypoxia on cells of the 
central nervous system.  However, less is known about the effects of 
reduced glycemic levels on CNS cell function and survival in a normoxic 
environment. 
 
This RFA solicits basic studies 1) to define the effect of varying 
glycemic levels on cerebral metabolism, transport of glucose across the 
blood brain barrier, and astrocytic regulation of substrates for 
neuronal metabolism, and 2) to determine pathological consequences of 
acute and recurrent hypoglycemic insult on cells of the central nervous 
system.  
 
Two related RFAs solicit basic and clinical research specifically 
addressing the problems of hypoglycemia unawareness (DK-01-031) and 
prevention of hypoglycemia in patients with diabetes (DK-01-032).  In 
addition, although not formally participating in this RFA, the National 
Institute on Aging is interested in research on the effects of 
hypoglycemia on neuronal and glial cell function in the aging nervous 
system.  
 
RESEARCH OBJECTIVES
 
Background:
 
Large-scale clinical trials have established the importance of 
intensified diabetes control in reducing the complications that result 
from poorly controlled hyperglycemic levels.  However, therapeutic 
efforts to closely regulate glycemic levels may occasionally cause 
inadvertent and recurrent episodes of severe hypoglycemia.  Acute 
hypoglycemic episodes may result in transient or persistent alteration 
of brain function.  When plasma glucose levels fall below 3 mmol/L, 
cortical function deteriorates; confusion, abnormal behavior, seizures 
and coma can result.  The effects of acute or recurrent episodes of 
hypoglycemia on the cells of the central nervous system are potentially 
harmful, and may impose long-lasting damaging effects on the brain.  
This is of particular concern in the early childhood years when the 
nervous system is still developing and in fetuses exposed to maternal 
hypoglycemia.
 
The regulation of cerebral metabolism in settings of altered glycemia 
is poorly understood.  It is recognized that astrocytes can provide 
fuel substrates to neurons, and that the glial cells contain glycogen.  
However, the regulation of glial intracellular glycogen and patterns of 
glycogen breakdown in settings of varied glycemic states is unknown.  
In the context of altered glycemic levels, alternative fuel sources 
supplied by astrocytes could ameliorate the effects of hypoglycemia on 
other cells of the central nervous system.  However, recurrent 
hypoglycemic insults could potentially affect the ability of astrocytes 
to provide alternative fuel substrates, and this is an area that 
warrants investigation. In addition, the regulation of endothelial cell 
expression of glucose transporters may change in response to varied 
glycemic levels.

There is substantial evidence that hypoglycemia alters human behavior, 
and recurrent episodes of severe hypoglycemia may lead to memory loss 
or impaired cognitive function.  The pathogenesis of hypoglycemic-
induced nerve cell injury is largely unknown, but mechanisms that could 
result in damage to cells of the CNS include, but are not limited to, 
excitotoxicity related to a dysregulation of the glutamate-glutamine 
cycle or an impaired capacity of astrocytes to generate reducing 
equivalents in the presence of oxidative stress.  To understand the 
effects of acute or recurrent hypoglycemia on the cells of the central 
nervous system, it is essential to characterize the response of CNS 
cells to reduced glycemic levels, to determine the extent of CNS cell 
injury induced by hypoglycemia, and to identify the mechanisms involved 
in hypogylcemia-induced cell or tissue damage in brain.

To highlight the problem of hypoglycemia in individuals with diabetes, 
the JDRF, NIDDK, NINDS, National Institute of Child Health and 
Development (NICHD), and NASA cosponsored a workshop on Hypoglycemia 
and the Brain on Sept. 7-8, 2000.  Participants in the workshop 
identified a number of knowledge gaps requiring future research 
(http://www.jdf.org/research/workshop090800.pdf).  Research is needed 
to enhance understanding of the effects of hypoglycemia on neuronal and 
glial cell metabolism and hypoglycemia-induced CNS cell injury.  As a 
first step towards addressing this problem, the NINDS, NIDDK and JDRF 
have issued this RFA.  

Areas of interest
 
This RFA solicits basic studies 1) to define the effect of varying 
glycemic levels on cerebral metabolism, transport of glucose across the 
blood brain barrier, and astrocytic regulation of substrates for 
neuronal metabolism, and 2) to determine the pathological consequences 
of acute and recurrent hypoglycemic insult on cells of the central 
nervous system.  While an ischemic insult in the CNS subjects neurons 
and glia to glucose deprivation coupled with hypoxia, a hypoglycemic 
insult exposes the cells of the CNS to glucose deprivation in a 
normally oxygenated environment.  The state of tissue oxygenation 
directly impacts the ability of cells to maintain glycolysis.  Thus, 
this RFA seeks to solicit studies aimed at examining the effects of 
glucose reduction, which is physiologically relevant under normoxic 
conditions. 
 
Two related RFAs solicit basic and clinical research specifically 
addressing the problems of hypoglycemia unawareness (DK-01-031) and 
prevention of hypoglycemia in patients with diabetes (DK-01-032).  
  
Appropriate topics for investigation under this RFA would include but 
are not limited to: 
 
o Studies to determine the short and long-term effects of varying 
glycemic levels on glucose transport in the brain and how specific 
transporters may affect brain glucose metabolism
 
o Studies to evaluate the role of glial-derived alternative fuels in 
the maintenance of neuronal and glial function 
 
o Studies to examine cellular physiological alterations in response to 
hypoglycemia
 
o Studies to determine the role of astrocytic glycogen in maintaining 
neuronal function and survival during hypoglycemia
 
o Studies to elucidate the effects of hypoglycemia on mechanisms 
regulating astrocytic uptake of glutamate
 
o Studies to assess the extent and mechanism of CNS damage during 
acute or recurrent hypoglycemia, and to determine whether 
sensitivity to hypoglycemia varies with age (including in utero 
exposure)
 
o Studies on the relationship between the astrocyte pentose phosphate 
pathway, oxidative stress, and brain injury during glucose 
deprivation
 
o Studies on interactions between astrocytes and other cell types such 
as oligodendrocytes and their relationship to brain injury during 
hypoglycemia
 
o Studies to determine whether there is a therapeutic window during 
which hypoglycemia-induced CNS damage can be ameliorated or reversed
 
o Studies of potential agents (e.g. apoptosis inhibitors) that could 
be used to mitigate hypoglycemia-induced neuronal damage 
 

SPECIAL REQUIREMENTS 

Letter of Authorization 

Applicants should submit a brief letter to the NINDS indicating whether 
or not they wish their application to be considered for funding by the 
JDRF. While applicants may request that their applications be 
considered only by the NIH and not by the JDRF, it is necessary that 
the record indicate the applicant's consideration of this opportunity. 
For those applicants who wish to have the JDRF consider their 
application, all materials relating to the application will be promptly 
forwarded to that organization and the summary statements for such 
applications will be shared with the JDRF when available. This separate 
letter may be submitted with the Letter of Intent (see below) or as a 
cover letter with the application. 

MECHANISM OF SUPPORT
 
This RFA will use the National Institutes of Health (NIH) individual 
research project grant (R01) award mechanism and the 
Exploratory/Development (R21) mechanism.  The R21 awards are to 
demonstrate feasibility and to obtain preliminary data testing 
innovative ideas that represent clear departure from ongoing research 
interests. These grants are intended to 1) provide initial support for 
new investigators; 2) allow exploration of possible innovative new 
directions for established investigators; and 3) stimulate 
investigators from other areas to lend their expertise to research 
within the scope of this solicitation.
 
Applicants for the R21 must limit their requests to $125,000 direct 
costs per year and are limited to two years.  These R21 grants will not 
be renewable; continuation of projects developed under this program 
will be through the regular research grant (R01) program.  
Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  The total 
project period for an R01 application submitted in response to this RFA 
must not exceed four years and no more than $250,000 direct costs/year.  
This RFA is a one-time solicitation.  Future unsolicited competing 
continuation applications will compete with all investigator-initiated 
applications and be reviewed according to the customary peer review 
procedures.  The anticipated award date is September 30, 2002.
 
FUNDS AVAILABLE 
 
The NINDS and NIDDK intend to commit approximately $1,250,000 in FY 
2002 to fund four to five new grants in response to this RFA. The JDRF 
intends to commit up to $250,000 in additional funds to co-fund 
research project grants that are both scientifically meritorious and 
fit within the mission and research emphasis areas of the JDRF. (See 
http://www.jdfcure.org, for more information.). All awards will be 
issued by the NINDS and the NIDDK.  An applicant may request a project 
period of up to four years and a budget for direct costs of up to 
$250,000 per year (2 years and $125,000 for R21’s).  Because the nature 
and scope of the research proposed might vary, it is anticipated that 
the size of each award will also vary.  Although the financial plans of 
the IC(s) provide support for this program, awards pursuant to this RFA 
are contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications.  At this time, it is not 
known if this RFA will be reissued.
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for-profit and 
non-profit organizations, public and private, such as universities, 
colleges, hospitals, and laboratories, units of State and local 
governments, and eligible agencies of the Federal government. 
Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as Principal Investigators.
 
INQUIRIES
 
Inquiries concerning this RFA are encouraged.  The opportunity to 
clarify any issues or answer questions from potential applicants is 
welcome.
 
Direct inquiries regarding programmatic issues to:
 
Toby Behar, Ph.D.
Neural Environment Cluster
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2114A
Bethesda, MD  20892-9521
Telephone:  (301) 496-1431
FAX:  (301) 480-2424
Email:  tb72Z@nih.gov
 
Barbara Linder, M.D, Ph.D. 
Division of Diabetes, Endocrinology and Metabolic Diseases
NIDDK 
6707 Democracy Boulevard, Rm. 699 MSC 5460
Bethesda, MD  20892-5460
Telephone:  (301) 594-0021
FAX:  (301) 480-3503
E-mail:  linderb@extra.niddk.nih.gov
 
Direct inquiries regarding review issues to:
 
Lillian Pubols, Ph.D.
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 3208
Bethesda, MD  20892
Telephone:  (301) 496-9223
FAX:  (301) 402-0182
Email:  lp28e@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Mary Graham
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 3258
Bethesda, MD  20892
Telephone:  (301) 496-9231
FAX:  (301) 402-0219
Email:  grahamm@ninds.nih.gov
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that 
includes a descriptive title of the proposed research, the name, 
address, and telephone number of the Principal Investigator, the 
identities of other key personnel and participating institutions, and 
the number and title of the RFA in response to which the application 
may be submitted.  Although a letter of intent is not required, is not 
binding, and does not enter into the review of a subsequent 
application, the information that it contains allows IC staff to 
estimate the potential review workload and plan the review.
 
Prospective applicants are asked to submit, by February 15, 2002, a 
letter of Intent to be sent to: 
 
Toby Behar, Ph.D.
Neural Environment
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2114A
Bethesda, MD  20892-9521
Telephone:  (301) 496-1431
FAX:  (301) 480-2424
Email: tb72Z@nih.gov
 
 
SCHEDULE SUMMARY
 
Letter of Intent Receipt Date:    February 15, 2002
Application Receipt Date:         March 15, 2002
Peer Review Date:                 July, 2002
Council Review:                   September, 2002
Earliest Anticipated Start Date:  September 30, 2002
 
APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 
5/2001) available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used 
in applying for these grants. This version of the PHS 398 is available 
in an interactive, searchable PDF format. Although applicants are 
strongly encouraged to begin using the 5/2001 revision of the PHS 398 
as soon as possible, the NIH will continue to accept applications 
prepared using the 4/1998 revision until January 9, 2002. Beginning 
January 10, 2002, however, the NIH will return applications that are 
not submitted on the 5/2001 version.  For further assistance contact 
GrantsInfo, Telephone 301/435-0714, Email: GrantsInfo@nih.gov.

The RFA label available in the PHS 398 (rev. 5/2001) application form 
must be affixed to the bottom of the face page of the application.  
Type the RFA number on the label.  Failure to use this label could 
result in delayed processing of the application such that it may not 
reach the review committee in time for review.  In addition, the RFA 
title and number must be typed on line 2 of the face page of the 
application form and the YES box must be marked. The RFA label is also 
available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed, photocopies, in one package to:
 
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application 
must be sent to:
 
Lillian Pubols, Ph.D.
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 3208
Bethesda, MD  20892
Rockville, MD  20852(for express/courier service)
 
Applications must be received by the application receipt date listed in 
the heading of this RFA.  If an application is received after that 
date, it will be returned to the applicant without review.
  
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  The CSR will not accept any application that is 
essentially the same as one already reviewed. This does not preclude 
the submission of substantial revisions of applications already 
reviewed, but such applications must include an introduction addressing 
the previous critique.
 
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS

The modular grant concept establishes specific modules in which direct 
costs may be requested as well as a maximum level for requested 
budgets. Only limited budgetary information is required under this 
approach.  The just-in-time concept allows applicants to submit certain 
information only when there is a possibility for an award. It is 
anticipated that these changes will reduce the administrative burden 
for the applicants, reviewers and NIH staff.  The research grant 
application form PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used 
in applying for these grants, with modular budget instructions provided 
in Section C of the application instructions.  Applicants are 
permitted, however, to use the 4/1998 revision of the PHS 398 for 
scheduled application receipt dates until January 9, 2002.  If you are 
preparing an application using the 4/1998 version, please refer to the 
step-by-step instructions for Modular Grants available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.  Additional 
information about Modular Grants is also available on this site.

BUDGET INSTRUCTIONS
Modular Grant applications will request direct costs in $25,000 
modules, up to a total direct cost request of $250,000 per year (no 
more than $125,000 direct costs/year for R21’s). The total direct costs 
must be requested in accordance with the program guidelines and the 
modifications made to the standard PHS 398 application instructions 
described below
 
REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness by NINDS and NIDDK.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration.
 
Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NINDS in accordance with the review 
criteria stated below.  As part of the initial merit review, all 
applications will receive a written critique and undergo a process in 
which only those applications deemed to have the highest scientific 
merit, generally the top half of the applications under review, will be 
discussed, assigned a priority score, and receive a second level review 
by the NINDS and NIDDK National Advisory Councils. 
 
REVIEW CRITERIA
 
The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments reviewers will be asked to discuss the 
following aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals.  Each of these criteria will be addressed and 
considered in assigning the overall score, weighting them as 
appropriate for each application.  Note that the application does not 
need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.
 
(1) Significance:  Does this study address an important problem? If the 
aims of the application are achieved, how will scientific knowledge be 
advanced?  What will be the effect of these studies on the concepts or 
methods that drive this field?
 
(2) Approach:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Does the applicant acknowledge potential problem 
areas and consider alternative tactics?
 
(3) Innovation:  Does the project employ novel concepts, approaches or 
method? Are the aims original and innovative?  Does the project 
challenge existing paradigms or develop new methodologies or 
technologies?
 
(4) Investigator:  Is the investigator appropriately trained and well 
suited to carry out this work?  Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers 
(if any)?
 
(5) Environment:  Does the scientific environment in which the work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements?  Is there 
evidence of institutional support?
 
In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:
 
o The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will 
also be evaluated.
 
o The reasonableness of the proposed budget and duration in relation to 
the proposed research.
 
o The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the 
project proposed in the application.
 
o The adequacies of the proposed plan to share data, if appropriate.
 
AWARD CRITERIA
 
Award criteria that will be used to make award decisions include:
 
o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities, and program balance

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups 
and their sub-populations must be included in all NIH-supported 
biomedical and behavioral research projects involving human subjects, 
unless a clear and compelling rationale and justification are provided 
indicating that inclusion is inappropriate with respect to the health 
of the subjects or the purpose of  the research.  This policy results 
from the NIH Revitalization Act of 1993 (Section 492B of Public Law 
103-43). 

All investigators proposing research involving human subjects should 
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities 
as Subjects in Clinical Research," published in the NIH Guide for 
Grants and Contracts on August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a 
complete copy of the updated Guidelines are available at  
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm:  
The revisions relate to NIH defined Phase III clinical trials and 
require: a) all applications or proposals and/or protocols to provide a 
description of plans to conduct analyses, as appropriate, to address 
differences by sex/gender and/or racial/ethnic groups, including 
subgroups if applicable; and b) all investigators to report accrual, 
and to conduct and report analyses, as appropriate, by sex/gender 
and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age 
of 21) must be included in all human subjects research, conducted or 
supported by the NIH, unless there are scientific and ethical reasons 
not to include them.  This policy applies to all initial (Type 1) 
applications submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the Inclusion of Children as 
Participants in Research Involving Human Subjects that was published in 
the NIH Guide for Grants and Contracts, March 6, 1998, and is available 
at the following URL address: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators also may obtain copies of these policies from the program 
staff listed under INQUIRIES.  Program staff may also provide 
additional relevant information concerning the policy.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS

NIH policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  This policy announcement is found 
in the NIH Guide for Grants and Contracts Announcement dated June 5, 
2000, at the following website: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES
 
All applications and proposals for NIH funding must be self-contained 
within specified page limitations.  Unless otherwise specified in an 
NIH solicitation, Internet addresses (URLs) should not be used to 
provide information necessary to the review because reviewers are under 
no obligation to view the Internet sites.  Reviewers are cautioned that 
their anonymity may be compromised when they directly access an 
Internet site.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom 
of Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at:
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.
 
HEALTHY PEOPLE 2010
 
The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a 
PHS-led national activity for setting priority areas.  This Request for 
Applications (RFA), “Effect of hypoglycemia on glial and neuronal cell 
function”, is related to one or more of the priority areas.  Potential 
applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople/.
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic Assistance 
No. 93.847 (NIDDK) and 93.853 (NINDS).  Awards are made under 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284) and administered under NIH grants 
policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  
This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.
 
The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children.  This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.

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