PAR07-231 Abstracts
PAR07-231 Abstracts
1 R36 CK000113-01 - Hantavirus Transmission in Natural Populations of Deer Mice in Outdoor Enclosures
BAGAMIAN, KAROUN HEIDI
DESCRIPTION (provided by applicant): Hantavirus pulmonary syndrome (HPS) is a severe (case fatality = 35%) rodent-borne viral disease of the Americas. Sin Nombre hantavirus (SNV) hosted by the widespread deer mouse (Peromyscus maniculatus) is responsible for the majority of hantavirus pulmonary syndrome (HPS) cases in the United States. The design and implementation of effective disease prevention interventions for HPS and the targeting of these interventions depends upon a detailed knowledge of the factors controlling SNV propagation in host populations. Field studies have identified the primary routes of transmission between mice and humans and among deer mice. However, because of difficulties in achieving natural virus transmission in the laboratory environment, laboratory studies have contributed little to clarifying the dynamics of SNV infection and transmission in deer mouse populations. The main objective of this project is to study the SNV infection cycle and transmission dynamics within enclosed, outdoor deer mouse populations. These controlled field experiments will elucidate the temporal pattern of virus transmission in mice, patterns of viral shedding, and social, demographic, and ecological factors that contribute to the transmission and maintenance of SNV in deer mouse populations. This information is critical to understanding changes in human risk and developing models to predict times and places of increased human disease risk.
1 R36 CI000607-01 - Mathematically modeling the transmission and control of extensively drug resistant (XDR) tuberculosis
BASU, SANJAY
DESCRIPTION (provided by applicant): Extensively drug-resistant (XDR) tuberculosis has emerged as a significant international public health threat. Little is known about the transmission dynamics of XDR tuberculosis. The optimal set of interventions to prevent the further spread of XDR tuberculosis also remains controversial. The proposed project will offer insights into the transmission and control of XDR tuberculosis, using mathematical modeling techniques designed to achieve three research objectives: 1. To characterize the dynamics of XDR tuberculosis transmission using back-calculation techniques applied to data from Tugela Ferry, South Africa, where the largest cluster of XDR tuberculosis cases to date has been reported; 2. To apply these calculations to projections of the geographical spread of XDR tuberculosis; and 3. To use the resulting epidemic model to simulate the potential impact of hospital-based and community-level interventions to prevent the development and transmission of XDR tuberculosis. This research proposal provides detailed descriptions of the datasets and novel modeling techniques that will be used to achieve these research objectives. Relevance The emergence of extensively drug-resistant (XDR) tuberculosis is of major public health concern. Because this form of TB is nearly untreatable, it is of vital importance to determine where it will spread and how to best reduce its transmission. The goal of this project is to determine how to reduce XDR tuberculosis incidence, using mathematical models of its transmission.
1 R36 DP001324-01 - Population Disparities in Breastfeeding in the United States
BELANOFF, CANDICE MIRIAM
DESCRIPTION (provided by applicant): The purpose of this project is to document and describe the extent to which breastfeeding rates, as well as social disparities in breastfeeding, vary across the United States, and to examine whether certain state-level policy factors and social conditions are associated with these rates and disparities. This project addresses the CDC's Health Protection Goal, "Healthy People in Every Stage of Life: Infants and Toddlers, ages 0-3: Start Strong" and specifically, starter objective #2: "Promote social and physical environments that support the health, safety, and development of infants and toddlers;" and starter objective #3: "Promote optimal development among infants and toddlers." Furthermore, the project supports Healthy People 2010 objective 16-19, to increase the proportion of mothers who breastfeed their babies, and the overarching goal of eliminating health disparities. The project involves three overarching aims: 1) To describe the extent to which rates of breastfeeding vary across the United States, controlling for population composition, and to describe the extent to which social disparities in breastfeeding rates (by race and social class) are variable across the states; 2) To identify whether differences in state-level Temporary Aid to Needy Families (TANF) policy are associated with disparate breastfeeding rates by family income; and 3) To identify associations of state-level measures of the "status of women" with state breastfeeding rates, and to identify whether state-level disparities in the women's status by race are associated with state-level racial disparities in breastfeeding rates. For all three analyses, multi-level logistic regression analyses modeling the probability of breastfeeding and the probability of breastfeeding at 6-months, will be conducted using data from the National Survey of Children's Health of 2003, (NSCH). NSCH data will be linked to state-level variables, including TANF policy and "status of women" composite measures obtained from the Institute for Women's Policy Research. The results of this study will help to fill critical gaps in knowledge around factors potentially driving long- standing, and to date, unexplained population disparities in breastfeeding. Examining the effects of state-level conditions provides an opportunity to identify determinants of breastfeeding disparities which may be modified by changes in policy. This project addresses Healthy People 2010 objective 16-19, to increase the proportion of mothers who breastfeed their babies, and the goal of eliminating health disparities, and also aligns with the CDC's new health protection goal, "Healthy People in Every Stage of Life: Start Strong." The study will be informative around policy and social conditions affecting breastfeeding disparities in the United States.
1 R36 EH000380 - Do active communities support activity or support active people?
Boone, Janne
DESCRIPTION (provided by applicant): Existing research shows promising results regarding the association between the built environment and physical activity. However, little is known about how built environment features are interrelated over time, and the predominant literature is cross-sectional and thus vulnerable to residential selection bias due to lack of control for individual choice of environments on the basis of their activity-related amenities. Objectives include (1) Description of built environmental features patterning across key life stages, and (2) Estimation of the longitudinal effects of the built environment on physical activity using several methods to control for and quantify residential selection bias due to: (2a) observed characteristics, (2b) time invariant unobserved characteristics, and (2c) time invariant unobserved characteristics. We will use data from a unique large scale Geographic Information System (GIS) that links community- and individual-level data in both space and time in two large ethnically diverse samples. The National Longitudinal Study of Adolescent Health (Add Health), a prospective cohort followed from adolescence to young adulthood, and the Coronary Artery Risk Development in young Adults (CARDIA), a prospective cohort followed from young adulthood, provide extensive health and behavioral data. A wide range of community-level factors include land use, street connectivity, recreation facilities, economic, climate, crime data, and others. Analyses will include: (1) Using descriptive methods and confirmatory factor analysis, we will describe patterning of built environment characteristics and how this patterning differs from adolescence to young and middle adulthood. Based on these findings, we will construct built environment summary variables to be used to estimate built environment effects on physical activity in subsequent aims. (2) By comparing estimates of the longitudinal effects of the built environment on physical activity using several methods for controlling for residential selection bias, we will quantify residential selection bias due to different types of factors: (2a) observed characteristics: compare random effects models (na_ve estimate) vs. propensity score weighting (control for observed characteristics), (2b) time invariant observed and unobserved characteristics: compare 2a estimates versus fixed effects models, and (2c) time invariant and variant, observed and unobserved characteristics: compare 2a-b estimates versus instrumental variables estimates. This study will improve the ability to make causal conclusions regarding the effects of the built environment on physical activity. Findings will improve the scientific knowledge base regarding "built environments that promote physical...health by encouraging healthy behaviors...," one objective of CDC's "Healthy People in Healthy Places" health impact goal. It also contributes to the "Healthy People in Every Stage of Life" goal by investigating health-promoting environments throughout several critical life stages.
1 R36 IP000187-01 - Contribution of PB1-F2 to transmission in the guinea pig model
CONENELLO, GINA
DESCRIPTION (provided by applicant): The PB1-F2 protein is the most recently discovered influenza A virus protein. The protein is translated from the +1 reading frame of the PB1 gene of the influenza A virus genome. This small protein of 87 amino acids has been shown to cause apoptosis in infected cells. PB1-F2 interacts with the mitochondrial membrane proteins adenine nucleotide translocator 3 (ANT3) and voltage dependent anion channel (VDAC1) and this interaction induces apoptosis via the mitochondrial pathway as shown by Zamarin et al. It has also been shown in the mouse model that viruses knocked out for PB1-F2 expression have reduced pathogenicity. Previous studies show that PB1-F2 contributes to pathogenesis and that amino acid change N66S in the C-terminus can increase pathogenicity in the mouse model. In this study we will examine the effects of PB1-F2 on transmission in the guinea pig model. We hypothesize that increased virus replication and pathogenesis caused by PB1-F2 in animal models may lead to more efficient transmission. Our study will focus on the use of the recombinant A/Texas/91 virus. This virus model has been used in previous transmission experiments in ferrets to examine the contribution of H5N1 and 1918 pandemic virus genes to pathogenesis. A/Texas/91 is a good model to study transmission because preliminary experiments have shown that this virus has a 17% transmission rate without expressing a full-length PB1-F2. PB1-F2 can be expressed without changing any other proteins or genes of the virus, by fixing a stop codon to a tryptophan in the coding sequence of PB1-F2. This is ideal because we know that there is not an inherent block in transmission coming from other genes of the virus, but we will also be able to observe changes, either increases or decreases in transmission. The experiments outlined in this proposal are designed to examine the effects of PB1-F2 on transmission in the guinea pig model using the recombinant A/Texas/91 virus. Contribution of PB1-F2 to transmission in the guinea pig model.
1 R36 EH000308-01 - You are what you eat: Longitudinal associations between the neighborhood food environment, away from home eating patterns, obesity and diabetes
DUFFEY, KIYAH
DESCRIPTION (provided by applicant): The physical food environment is hypothesized to play a critical role in influencing dietary patterns, obesity, and diabetes; however research on this topic has been largely cross-sectional. Consequently, little is known about the long-term associations between access to away-from-home food (restaurants and fast food places), patterns of away-from-home eating, and health outcomes. Objectives: This study seeks to examine longitudinal changes in the physical food environment and determine their effect on diet and health outcomes. Specifically, we hope to (1) determine factors in the built environment that are associated with the number of away-from-home food places in an individual's residential neighborhood; (2) determine the relationship between the number of away-from-home eating places in an individual's residential neighborhood and frequency of away-from-home food consumption; and (3) determine the longitudinal associations between the frequency of away-from-home eating with 13-year changes in weight and glucose status. Methods: Data collected from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal cohort of 5,115 young adults, will be used in these analyses. Individual-level health and diet data have been linked by residential location to a Geographic Information Systems (GIS)-derived database which includes measures of the food environment (i.e. location of restaurants), environmental features (i.e. road networks), and census measures (i.e. block-group average household income), resulting in a complex database of both individual and environmental factors. We will use a combination of multivariate, hierarchical linear regression ([HLM] a form of multilevel modeling), and longitudinal fixed-effect models. HLM allows us to examine the independent contribution of both individual and environmental factors to the frequency of away-from-home eating. Fixed effect models, used to examine inter-individual changes in behaviors and health outcomes over time, have the additional benefit of providing inherent control for endogeneity (unobserved, time-invariant heterogeneity within individuals). Implications: Weight loss and weight gain prevention efforts focused solely on individual-level factors have been met with limited success. Understanding influences of the community food environment on dietary choice and health-related outcomes may be necessary for promoting healthy lifestyles. Results from this study will identify factors that could be targeted for the design and development of community environments that improve individuals' diets and support healthy behaviors.
1 R36 EH000379-01 - Spatial Modeling of Air Pollution Exposure and Uncertainty with Application to Adverse Birth Outcomes
GRAY, SIMONE
DESCRIPTION (provided by applicant): Although several studies suggest that air pollution exposure may be associated with adverse birth outcomes, it is challenging to assess pollution exposure during pregnancy. There are numerous factors that need to be taken into account when modeling the relationship between air pollution and any health outcome, including model choice, selection of appropriate covariates as well as the method used to measure exposure. This project attempts to better understand the relationship between maternal exposure to air pollution and birth outcomes by using statistical models that incorporate both spatial modeling techniques and methods for evaluating the associated measurement error. We believe that understanding and addressing these environmental health issues on this vulnerable subgroup of pregnant women is of critical importance to the overall health of the nation. The goals of this project include: 1. Quantifying the uncertainty related to measuring local air pollution exposure, based upon monitoring station data, in order to understand the associated measurement error. 2. Determining how ambient exposure measures from monitoring stations connect to pregnancy outcomes in order to understand how to incorporate the different estimates of exposure and determine how these estimates affect the exposure-response relationship. 3. Using hierarchical modeling techniques to model the relationship between adverse pregnancy outcomes and maternal exposure to air pollution while accounting for the effects of measurement error. The statistical analyses presented in this project will utilize spatial techniques and hierarchical modeling from a Bayesian perspective. We propose model fitting within a Bayesian framework as spatial modeling of multilevel specifications are handled naturally through Bayesian modeling. In the Bayesian context we avoid the need to rely on possibly inappropriate asymptotic inference. The first stage of our hierarchical model will focus on the measurement error associated with measuring exposure. The second stage measures long-term air pollution exposure using observed measurements from monitoring stations. The final stage of the model measures the exposure-response relationship while introducing personal covariate information into the model. Project Summary Although several studies suggest that air pollution exposure may be associated with adverse birth outcomes, it is challenging to assess pollution exposure during pregnancy. There are numerous factors that need to be taken into account when modeling the relationship between air pollution and any health outcome, including model choice, selection of appropriate covariates as well as the method used to measure exposure. This project attempts to better understand the relationship between maternal exposure to air pollution and birth outcomes by using statistical models that incorporate both spatial modeling techniques and methods for evaluating the associated measurement error. We believe that understanding and addressing these environmental health issues on this vulnerable subgroup of pregnant women is of critical importance to the overall health of the nation. The goals of this project include: 1. Quantifying the uncertainty related to measuring local air pollution exposure, based upon monitoring station data, in order to understand the associated measurement error. 2. Determining how ambient exposure measures from monitoring stations connect to pregnancy outcomes in order to understand how to incorporate the different estimates of exposure and determine how these estimates affect the exposure-response relationship. 3. Using hierarchical modeling techniques to model the relationship between adverse pregnancy outcomes and maternal exposure to air pollution while accounting for the effects of measurement error. Research Design and Methods The statistical analyses presented in this project will utilize spatial techniques and hierarchical modeling from a Bayesian perspective. We propose model fitting within a Bayesian framework as spatial modeling of multilevel specifications are handled naturally through Bayesian modeling. In the Bayesian context we avoid the need to rely on possibly inappropriate asymptotic inference. The first stage of our hierarchical model will focus on the measurement error associated with measuring exposure. The second stage measures long-term air pollution exposure using observed measurements from monitoring stations. The final stage of the model measures the exposure-response relationship while introducing personal covariate information into the model.
1 R36 IP000288-01 - The Role of Airway Surface Tethered Mucin 1 in Influenza Virus Infection
HENNESSEY, MARGARET ADELE
DESCRIPTION (provided by the investigator): The long-term goal of this research is to understand the viral and host determinants that allow for efficient infection of the human respiratory tract by influenza viruses. Influenza virus is a major respiratory pathogen affecting people of all ages and a perpetually re-emerging public health threat causing both annual epidemics and sporadic pandemics in the human population. Despite the prevalence of influenza, little is known about how this virus interacts with its target tissue for infection, the human ciliated airway epithelium. Human influenza viruses bind to glycoconjugates containing terminal a2,6-linked sialic acids on target ciliated and non- ciliated cells in the airway epithelium to facilitate infection, yet the relevant underlying molecules in the airway that present these sialic acids have not been defined. Our preliminary data indicate that human influenza viruses interact with sialic acid on MUC1, a mucin protein that is tethered to the apical surface of airway epithelial cells and abundant throughout the respiratory tract. Mucin glycoproteins are a major constituent of mucus and are critical for normal lung function, as well as lung defense by trapping particulate matter and pathogens for removal from the airway. The consequences of MUC1 interaction with influenza virus with respect to the pathogenesis of this virus are currently unknown. We hypothesize that influenza virus interactions with MUC1 on the human airway surface impacts the ability of influenza virus to infect target epithelial cells. MUC1 may be facilitative for infection (i.e., act as a receptor molecule), or restrictive (i.e., act as a physically block). MUC1 may also initiate signal transduction pathways leading to anti-viral or pro-inflammatory cytokine responses that may influence the ability of influenza virus to replicate and spread. We propose to determine the role of MUC1 in influenza virus infection using both in vitro and in vivo model systems. Specific Aim 1 will characterize influenza virus binding, entry, replication and spread as well as the host cytokine response in both cell lines stably expressing human MUC1 and models of differentiated pseudo- stratified airway epithelium in which MUC1 expression is reduced or absent. Because the role of MUC1 in influenza virus infection is likely multi-factoral, Specific Aim 2 will investigate correlates of infection and host response in wild type mice compared to mice genetically deleted for Muc1 (the mouse homolog) to determine the overall contribution of this mucin to influenza virus pathogenesis. This research will provide a comprehensive analysis of a major mucin protein of the human respiratory tract in influenza virus infection and provides the basis for future studies investigating influenza virus infection in models, such as chronic lung disease models, where mucin expression is altered.
1 R36 DP001325-01 - Understanding childhood obesity in a diverse population of low income children living in rural America
HENNESSY, ERIN
DESCRIPTION (provided by applicant): US Children living in impoverished rural communities have limited opportunities for physical activity and accessibility to healthy foods. Research in this area is limited as much of the work has been done in urban and suburban areas. Given the increasing obesity rates it is necessary to identify the factors that are driving this epidemic in rural areas. Specific Aims and Hypotheses: 1. To describe the feeding and parenting styles of low income, rural parents living in four distinct areas of the US (Appalachia, Central Valley, Mississippi River Delta, and the Southeast) and to examine the agreement among feeding style instruments (CFSQ/CFQ) and between feeding style and parenting style instruments (CFSQ/PDI-S). Hypothesis 1a: There are associations between the feeding style dimensions of demandingness and responsiveness (CFSQ) and the feeding style dimensions (CFQ) of pressure to eat, restriction, and level of monitoring. Hypothesis 1b: There are associations between the feeding style dimensions of demandingness and responsiveness (CFSQ) and the parenting style subscales (PDI-S) of nurturance, inconsistency, follow thru, organization, letting go, punishment, reasoning, reminding, and control. 2. To determine the relationship between parent feeding styles and child's dietary quality, energy intake, and weight status in a low income, rural population. Hypothesis 2a: There are associations between child diet quality and parent level of demandingness (+) and responsiveness (+) toward feeding, as measured by the CFSQ, and pressure to eat (+), restriction (-), and level of monitoring (+), as measured by the CFQ. Hypothesis 2b: There are associations between child energy intake and parent level of demandingness (-) and responsiveness (-) toward feeding as measured by the CFSQ and pressure to eat (-), restriction (+), and level of monitoring (-) as measured by the CFQ. Hypothesis 2c: The pressure to eat score reported by parents, as measured by the CFQ, will be different between children who have a high vs. average BMI z-score. 3. To determine the relationship between physical activity-related parenting practices and parenting styles of low income rural parents and their child's physical activity level. Hypothesis 3a: There is a positive association between a child's PA level and their parents activity-related practices score. Hypothesis 3b: Levels of physical activity will be different in children with an authoritative parent, as measured by the PDI-S, compared to children with a nonauthoritative parent. Methods: a. Study/evaluation design: Quantitative, cross-sectional assessment of parenting style, feeding styles, body composition, and physical activity and dietary habits among 99 parent-child dyads. b. Setting and population: The target population is rural American elementary school children between the ages of 6-11 years living in poor areas within the Central Valley (CA), Mississippi Delta (MS, AR), Appalachia (KY), and Southeast (GA, SC) regions of the US. We will randomly select 1 school from each region (N=4 schools). c. Measures: Parents will complete the Caregiver's Feeding Styles Questionnaire, Child Feeding Questionnaire, Parenting Dimensions Inventory as measures of feeding style and global parenting style. Parents will also report their family demographics, seasonal activities, and questions about their own habits, attitudes, and perceptions toward physical activity. Children will self-report their food and activity preferences as well as participate in a parent-assisted 24-hour recall and wear a physical activity monitor. Both parents and children will have their height and weight measured to determine BMI. d. Analysis: Descriptive, exploratory, and correlation analyses will be performed using SPSS for the quantitative data. The 24-hour recalls will be analyzed using NDS-R. Activity monitor data will be downloaded and computed using SAS. Multivariate regression models will test for the effect of feeding style and parenting style on child health outcomes.
1 R36 CD000704-01 - Employing Narrative Forms of Communication for Cervical Cancer Prevention Message
HOPFER, SUELLEN
DESCRIPTION (provided by applicant): Cervical cancer remains a significant public health burden with an estimated 10,370 women diagnosed and 3,710 dying in 2007. A human papillomavirus (HPV) vaccine, Gardasil. approved in June 2006, has shown promise in reducing the incidence of high-risk HPV types 16 and 18, which are necessary though not sufficient causes of cervical cancer. Communication will play a key role in realizing the preventive potential of this vaccine. Health care providers have limited guidelines for how to effectively communicate about the HPV vaccine because research is just beginning to address this concern. The proposed study will address this need through a tri-phased process guided by a theoretical framework based on narrative theory of cancer communication (Kreuter et al., 2007), the theory of normative social behavior (Rimal & Real, 2005) and the story model (Pennington & Hastie, 1986). Formative research (in-depth interviews) will be conducted to identify determinants of vaccine acceptability and develop narratives (phase 1). Formative research findings and theory will inform health message design about the HPV vaccine and cervical cancer prevention (phase 2). Health messages will be piloted and subsequently tested in a clinical trial (phase 3). Specific aims of the proposed study include identifying determinants (attitudes, beliefs, and practices) of HPV vaccine acceptability among college women and developing an online narrative intervention for effective delivery of HPV vaccine information. These specific aims address the CDC mission to (a) reduce cervical cancer incidence and sexually transmitted infections (STIs) such as HPV, and (b) improve health literacy. Cervical cancer remains a significant public health burden with annual newly diagnosed case estimates at 10,370 and annual mortality rates at 3710. The human papillomavirus (HPV) vaccine Gardasil , released in June 2006, has the preventive potential to reduce cervical cancer incidence up to 70 percent, HPV, and costs related to cervical disease. The overall goal of the proposed research is to (a) identify effective, evidence-based communication strategies to increase utilization of the HPV vaccine among college age women and, (b) test a theory-based online narrative intervention that shows promise to improve health literacy.
1 R36 GD000075-01 - Microbial Genome Informatics Platform: a computational resource for comparative genomics and multi-locus sequencing typing of Neisseria
KATZ, LEE SCOTT
DESCRIPTION (provided by applicant): We propose to create an online computational tool called the Microbial Genome Informatics Platform (MGIP), which will analyze multi-locus sequence typing (MLST) and have comparative genomics functionality. MGIP will be able to categorize strains of Neisseria meningitidis using MLST and will facilitate epidemiological studies worldwide. MGIP will be able to compare all complete genomes of Neisseria meningitidis and N. gonorrhoeae, including four as-of-yet unpublished N. meningitidis strains that we are assembling. Therefore, it is imperative to develop computational support to match the load of incoming data. Bacterial meningitis has about a 10% fatality rate plus another 15% with long-term sequelae. In sub-Saharan Africa, there can be up to 400,000 reported cases per year. MGIP falls in line with the CDC's goals of "People Prepared for Emerging Health Threats" because it will facilitate worldwide epidemiological studies of meningococcus and accelerate crucial genetic studies of hypervirulent strains.
1 R36 CD000695-01 - Exercise: A Novel Treatment for Obstructive Sleep Apnea
KLINE, CHRISTOPHER EDWARD
DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is a common sleep disorder, affecting approximately 10% of adults. The disorder is a public health threat, as OSA has been linked to cognitive impairment, impaired sleep quality, cardiovascular disease, diabetes and mortality. However, despite its harmful impact on numerous health outcomes, successful treatment options for OSA remain elusive. Surgery and nasal continuous positive airway pressure (nCPAP) therapy are the most common treatments, but these options are plagued by dismal success rates and low compliance rates, respectively. Exercise has been considered as a potential supplemental treatment option for OSA, primarily because of its weight loss effects. Surprisingly little investigation into this area has been undertaken, though. Consistent with the CDC Health Protection Goal of "Healthy People in Every Stage of Life," this proposal is designed with the objective of "preventing chronic diseases [i.e., the sequelae of OSA] and their consequences among adults." Specifically, the proposed study will investigate the efficacy of exercise as a complementary or alternative treatment for the treatment of OSA and its consequences. The study will utilize a randomized experimental design to assess the effect of a 8-week resistance and aerobic exercise program on the severity and complications of OSA. Specific Aim 1 is to evaluate the effect of exercise on the apnea-hypopnea index (AHI), the primary measure of OSA severity. Additionally, mediators of the effect of exercise on AHI will be evaluated. Because the effects of OSA on health outcomes are wide- ranging, Specific Aim 2 will evaluate the effect of exercise on a variety of OSA complications, including metabolic function, cognitive performance, daytime sleepiness, sleep quality, psychological health, systemic inflammation, and cardiovascular health. The results of this study will provide important and much needed information on whether exercise is an efficacious supplemental or alternative treatment option for individuals with OSA. Obstructive sleep apnea is a prevalent sleep disorder and emerging public health threat, with harmful consequences on cardiovascular health, metabolic functioning, cognition, and psychological health. Exercise has been understudied as a treatment option for attenuating the severity and complications of this disorder, especially since available treatment options are suboptimal. The proposed study will provide the first controlled evidence of the efficacy of exercise for the management of obstructive sleep apnea, and will shed light on whether exercise therapy can be advanced as an alternative or supplemental treatment option.
1 R36 DD000486-01 - Preventing Kernicterus: Serum Albumin-Bilirubin Binding
KRENZEL, EILEEN S
DESCRIPTION (provided by applicant): Unconjugated bilirubin (UCB) is the normal, but toxic end product of red blood cell catabolism and circulates in the plasma. However, because of its very low aqueous solubility of <70 nM, it is transported primarily by human serum albumin (HSA). UCB is conjugated in the liver into a water-soluble compound, conjugated bilirubin, for excretion into the bile. In near term and full term infants the enzyme responsible for conjugating bilirubin is not yet fully functional and UCB levels can exceed 175 ?M, though never exceeding the binding capacity of HSA, with more UCB being presumably pushed into the lower affinity binding sites. Since the circulating HSA now contains a high amount of bound UCB, UCB can more easily diffuses through plasma membranes, allowing UCB to accumulate in tissues, causing jaundice. Similarly, these high circulating levels of TSB (>428 ?M) also diffuse across the blood brain barrier where it causes severe neurological deficits in untreated infants. This disease is Kernicterus, or bilirubin-induced encephalopathy, and causes athetoid cerebral palsy, deafness, upgaze abnormalities, and hypoplasia of baby teeth enamel. Since this devastating disease is preventable and reversible with the proper treatment, the American Academy of Pediatrics has developed treatment guidelines. In order to have healthy birth outcomes and to prevent these children from becoming dependent on the healthcare system, it is imperative to efficiently and quickly identify those infants in need of treatment. For this, measures of the total serum bilirubin in the body are performed to determine the potential for bilirubin toxicity. However, this measurement has been deemed a poor determinant of bilirubin toxicity. In order to rectify this, a more complete understanding of the mechanisms of transport of bilirubin throughout the body is needed. We propose to determine the primary and secondary binding sites on HSA for UCB. The exact binding site(s) of UCB have evaded years of research, and these sites and their relationships to fatty acid (FA) and drug binding sires needs to be known at the molecular level. We will use novel applications of 1D and 2D Nuclear Magnetic Resonance (NMR) Spectroscopy, to study aqueous complexes of UCB with HSA and with/without FAs at their physiological concentrations. For direct studies of binding and identification of the primary bilirubin binding site, we will use 13C-labeled bilirubin synthetic analogs together with our methods established for identifying FA sites, namely drug displacement techniques and HSA mutants. Additionally, for clinical applications, it is critical to identify the lower affinity sites and determine in a site specific manner how FA and drug binding forces UCB into the lower affinity sites. These additional studies will utilize unlabeled bilirubin and displacement by 13C-labeled FA. Not only does this proposal identify the primary and secondary bilirubin binding sites on HSA, but will also study how drug binding affects bilirubin binding, for example, predicting whether binding of therapeutic drugs may have an unintended effect of displacing bilirubin into lower affinity sites, and thus increasing the chances for accumulation of UCB in the tissues and brain.
1 R36 DP001849-01 - Residential Segregation, Neighborhood Social Environment, and Preterm Birth among 14 Ethnic Groups in New York City
MARSHALL, SUSAN S
DESCRIPTION (provided by applicant): Because it is a leading contributor to racial and ethnic disparities in infant mortality, the Centers for Disease Control and Prevention has identified preterm birth as a vital subject for public health research. While the causes of preterm birth and preterm birth disparities are not well understood, a growing body of literature implicates neighborhood social and material environments as determinants of poor birth outcomes. Residential segregation organizes racial and ethnic groups into different neighborhoods, and as such it may contribute to preterm birth disparities by influencing the distribution of risk factors and resources across population groups. Thus, building a nation of Healthy People in Healthy Places may depend on addressing residential segregation as a social determinant of health in minority communities. Previous research has documented detrimental social, economic, and health effects of residential segregation on the US black population. Some theoretical literature and a few epidemiologic studies have suggested that neighborhood-level racial/ethnic homogeneity resulting from segregation may be beneficial for certain health outcomes, however. Segregation may, in fact, have both positive and negative effects on health, the balance of which may differ across ethnic groups and contexts; for example, positive birth outcomes among Hispanics are often attributed to beneficial health behaviors and social support that may be promoted in Hispanic neighborhoods. Thus, appropriately addressing residential segregation as a social determinant of preterm birth requires an understanding of the potentially complex relationship between segregation and health. Because most studies of segregation and health have included only US-born non-Hispanic black and white populations, however, this complexity remains largely unexplored. Moreover, previous studies have used aspatial measures of segregation that ignore potentially important spatial relationships between neighborhoods. The proposed study will use a spatial measure of segregation and New York City birth records (1995-2003) linked to 2000 Census data in order to (1) assess the effects of segregation, defined as own-ethnic-group density in the residential area, on preterm birth risk in 14 groups including US- and foreign-born whites, blacks, Hispanics, and Asians; (2) examine whether preterm birth risk among black women residing in non-black neighborhoods is affected by the specific ethnic groups that are present; and (3) among foreign-born black women, explore the extent to which preterm birth risk is influenced by the density of individuals in a woman's neighborhood who share her region-of-origin ("cultural") group.
1 R36 DP001850-01 - Mediation and moderation of the effects of obesity on coronary heart disease in a bi-ethnic cohort: the Atherosclerosis Risk in Communities (ARIC) Study
MCCLAIN, JILL
DESCRIPTION (provided by applicant): Excess adiposity is associated with coronary heart disease (CHD), high blood pressure, elevated glucose and dyslipidemia. Racial and gender differences have been found in the prevalences of obesity, CHD risk factors and CHD outcomes, as well as in the associations among these variables. Few studies have examined mediation of the obesity-CHD event relationship by CHD risk factors or compared mediation across risk factors, and it is unknown whether risk factors mediate the obesity-CHD relationship to the same degree in African Americans and Whites or in men and women. The lack of such studies is due in part to the scarcity of appropriate data and in part to limitations of traditional epidemiologic methods. Mediation is commonly analyzed in other fields using structural equation modeling (SEM). SEM has several advantages over standard regression for mediation, including specification of each path (and non-path) among variables and modeling of measurement error. SEM also permits significance-testing of mediated effects. Aim 1. Examine risk factors as mediators of the relationship between obesity (body mass index (BMI) and waist circumference) and time to CHD. SEM will be used with Cox proportional hazards regression to assess mediation by systolic and diastolic blood pressure, glucose, LDL and HDL cholesterol and triglycerides. 1.a. Examine and compare metabolic risk factors individually as mediators of the effect of obesity on CHD 1.b. Examine and compare metabolic risk factors in combination as mediators of the effect of obesity on CHD 1.c. Determine if mediation of the obesity-CHD relationship differs by race and/or gender A comparison of effects of obesity on CHD through blood pressure, glucose and lipids must consider how to incorporate medication use in the analysis. This issue is especially important for blood pressure medication because of the high prevalence of antihypertensive medication use among middle-aged Americans. Aim 2. Investigate the effect of medication use on relationships of BMI and waist circumference with blood pressure and CHD. This secondary aim will be used to inform the analyses for the primary aim, above. 2.a. Determine if antihypertensive medications modify the cross-sectional associations between obesity and blood pressure 2.b. Explore how antihypertensive, lipid-lowering and diabetes medications affect mediation of the relationship between obesity and time to CHD These analyses will use data from the Atherosclerosis Risk in Communities (ARIC) Study, a cohort of 15,689 African American and White adults aged 45-64 at baseline (1987-1989). Follow-up data on fatal and non-fatal CHD events through 2004 will be available. To our knowledge, this will be the first study to use SEM to examine and compare metabolic risk factors as mediators of the adiposity-CHD relationship, as well as the first to systematically examine differences in mediation across race-gender groups.
1 R36 DD000365-01 - Social Determinants for Early Intervention Participation and Efficacy
MCMANUS, BETH MARIE
DESCRIPTION (provided by applicant): The 2001 Survey of Children with Special Health Care Needs (CSHCN) shows that, among children less than 3 years of age, the prevalence of health and developmental impairments significant enough to warrant increased medical or therapeutic services or to impact daily living is 6.5% (Data Resource Center, CSHCN). However, this data underestimates children at risk for developmental difficulties. In a similar nationally representative survey, the National Survey of Children's Health, 40% of parents of children less than 5 reported concern that their child was at risk for neurodevelopmental difficulties including delayed language acquisition, poor social skills, and limited mobility (The Health and Well-Being of Children: A Portrait of States and the Nation, 2005). Early childhood social policy, the Individuals with Disabilities Education Act Part C, was promulgated to create state Early Intervention (EI) programs in order to ameliorate neurodevelopmental risk among infants and toddlers. Qualitative studies reveal that there exists extreme variation across states in many facets of Part C programming including eligibility requirements (Spiker, 2001), models of service coordination (Scarborough, 2004) while quantitative studies suggest mixed effect of EI in small samples (Shonkoff, 1986; Hebbeler, 2007). What is unknown are the social determinants of variability of EI participation, the degree to which health and developmental services are coordinated and seamless, and whether EI is associated with improved neurodevelopmental outcomes at the population level. The purpose of this research is to examine, among a cohort of young children at risk for neurodevelopmental difficulties, 1) the social determinants in participation In Early Intervention services and the extent to which these might be explained by relevant sociopolitical, contextual factors (Paper 1), 2) the social determinants in satisfaction with care coordination and the extent to which these might be explained by relevant sociopolitical, contextual factors (Paper 2), and 3) the relationship between changes in neurodevelopment over time and participation in Early Intervention (Paper 3). This research will be completed to fulfill my doctoral dissertation requirement of three publishable quality manuscripts. It will entail secondary data analyses using two nationally representative surveys, the 2005 National Survey of Children with Special Healthcare Needs and the Early Childhood Longitudinal Study Birth Cohort. For the first two papers, multi-level modeling will be used, which allows for investigation of individual and contextual level variables simultaneously while appropriately addressing the clustering of individuals within states. The third paper will entail a longitudinal analysis which will allow for an investigation of the relationship between EI participation and neurodevelopmental outcomes over time. This research will contribute to the field of public health as it directly relates to not only social policy and programmatic initiatives aimed at addressing social disparities in access to health and developmental services for vulnerable populations, but also is consonant with the CDC's objective of promoting "Healthy People at Every Stage of Life." Early Intervention (EI) is a federally mandated, state-based program to reduce developmental risk in infants and toddlers. This study will explore social determinants of access to, satisfaction with, and effectiveness of EI programming among a nationally representative sample of children at risk for developmental difficulties.
1 R36 OH009486-01 - Association between musculoskeletal disorders and physical exposures
MEYERS, ALYSHA ROSE
DESCRIPTION (provided by applicant): The CDC has identified musculoskeletal disorders (MSDs) as a Research Theme within the Health Protection goal of Healthy People in Healthy Places. After decades of epidemiologic research, consensus is emerging that 1) forceful exertions, 2) awkward postures, and 3) repetitive motions of the hand and wrist are risk factors for upper extremity MSDs [3, 4]. Recent efforts have been made to pool these three risk factors into a single metric or scale to estimate UEMSD risk. The Strain Index (SI) is a highly reliable, widely used tool that was developed for this purpose [5-13]. The SI outcome value is an ordinal numerical score. Higher SI scores are associated with greater UEMSD health outcomes, although no published studies have compared SI scores to incident UEMSDs. Despite its wide acceptance, there is also considerable evidence that the current SI cut-off scores overestimate risk. Our expectations are that more appropriate risk categories can be established. The long-term of the investigators is to prevent UEMSDs among manufacturing workers by implementing ergonomic interventions. The main rationale for conducting this study is to better assess the SI as an exposure assessment tool by using more powerful epidemiological methods and more precise alternate estimates of exposure to physical risk factors. The specific aims of this study are: 1) For UEMSD outcomes among manufacturing workers, separately model a) associations between the SI using the original job risk categories and incident UEMSD outcomes and b) associations between the SI using the empirically derived quartile job risk categories and incident UEMSD outcomes; and 2) Compare the adequacy of fit of a) models that regress UEMSD outcomes on exposure estimated with the SI to b) models that regress UEMSD outcomes on exposure estimated with separate highly reliable and precise measures of force, repetition and posture. This project requires additional analyses of existing video exposure and health outcome data from a three year prospective cohort study of manufacturing workers in Iowa (n=387). All SI evaluations will be conducted independently by two investigators and then the final SI score will be determined by consensus. Multinomial logistic regression will be used to test both specific aims. For Specific Aim 1, incidence data for upper extremity musculoskeletal outcomes (symptom free, symptom positive, or disorder positive) in the dominant arm will be regressed on exposure estimated by 1) the original SI job risk categories, and 2) the proposed empirically derived SI risk categories. For specific aim 2, the Akaike Information Criterion (AIC) will be used to test the adequacy of fit of the aforementioned multinomial logit model will be compared to an alternate multinomial logit model that will estimate exposure using separate measures of force (surface electromyography), repetition (Hand Activity Level), and posture (% time spent in awkward wrist postures).
1 R36 DP001322-011 - Physical Activity during Pregnancy, Fetal Growth, and Toddler Body Size
MUDD, LANAY MARIE
DESCRIPTION (provided by applicant): Both increased and decreased rates of fetal growth are associated with adverse infant and maternal health outcomes. While the causes and health risks of restricted fetal growth have been studied extensively, the etiology of excess fetal growth has received less attention. Fetal overgrowth is associated with increased risk of birth trauma and cesarean delivery. Furthermore, excess fetal growth appears to predispose infants towards developing into overweight children. Thus, examining factors that could modify fetal overgrowth may uncover new pathways for preventing childhood overweight status. Our research team has found that maternal physical activity during pregnancy may control fetal overgrowth. However, the independent effects of pre-pregnancy exercise training status, pregnancy physical activity habits, and maternal body size on fetal growth are not clearly delineated. The proposed study seeks to evaluate the effects of pre-pregnancy and trimester-specific physical activity on fetal growth and toddler body size while controlling for maternal body size and pregnancy-related weight gain. We will investigate these relationships using a cohort of 298 women who recently participated in a study that recorded their physical activity at the time of their first prenatal care visits. Women will be contacted ~1.5-2.5 years after their pregnancies. Pre-pregnancy and trimester specific physical activity histories will be recorded and validated using previously collected data. Infant birth weight and other pertinent perinatal information will be gathered from birth records and medical records with the mother's consent. Toddler height and weight at ~18-28 months old will be reported by the mother. We hypothesize that pregnancy physical activity will help control fetal overgrowth and will alter relationships between fetal growth and toddler body size. If proven true, pregnancy physical activity may decrease risk of birth trauma associated with having a large infant and may also provide a new strategy for addressing the major public health concern of childhood overweight. This project has the potential to help improve the health of women, infants, and children and addresses the Centers for Disease Control and Prevention Health Impact Goal of Healthy People in Every Stage of Life to "Start Strong" by promoting healthy pregnancy and birth outcomes. Identifying the role of pregnancy physical activity participation on fetal growth could inform future research concerning physical activity recommendations for child-bearing women and improve maternal health. Gaining insight into potentially modifiable determinants of fetal growth could also have downstream effects on infant and child health, since birth size has been related to several future health conditions, including childhood overweight status.
1 R36 SH000008-01 - Migration and Diabetes Risk among the U.S. Foreign-Born
OZA-FRANK, REENA
DESCRIPTION (provided by applicant): In 2005, the US foreign-born population at 36 million accounted for 12% of the total population. This is the largest proportion since the early 1900s, reflecting a 57% increase between 1999 and 2000. As the foreign born population continues to grow in numbers (projected to be 42 million in 2025) and diversity, it is important to understand their health status, because factors related to migration may influence their health. Although the growing number of people with diabetes in the US is well documented (20.8 million people in 2005), there is little data on diabetes in the US foreign-born population. Migrants exhibit increasing rates of overweight and obesity as their duration of residence in the US increases, increasing their risk of diabetes. Thus, the primary objective of this proposal is to determine the magnitude of diabetes in the US foreign-born population, and to assess if diabetes is associated with any factor(s) specific to the dynamics of migration. Data from the National Health Interview Survey (NHIS) will be the primary source of data for the proposed study. Gaining a better understanding of the dynamics of migration and how they may influence diabetes can aid in promoting health and reducing chronic disease. Specifically, this project will fill a major gap in public health research in the area of diabetes in a diverse, large and growing segment of the US population, and will enable policy development toward prevention of diabetes and reduction of disparities. Results of this study will reveal how diabetes prevention efforts can be tailored to optimize the health of the US foreign-born population by taking migrant specific characteristics (age at migration, duration of residence, region of origin) into consideration. The unique factors the US foreign-born may have related to migration dynamics may also help tease out gene environment interactions and the contributions of ethnicity, over and above migration-specific factors, to the disease process.
1 R36 IP000289-01 - Attitudes toward influenza vaccination and vaccine uptake among rural adolescents
PAINTER, JULIA E
DESCRIPTION (provided by investigator): This study proposes collection of survey data from students investigating adolescent attitudes and beliefs toward influenza vaccinations as an ancillary supplement to an existing study, "Influenza Vaccine Delivery to Adolescents: Two Multicomponent Interventions." This study will complement the Parent Study by examining whether the relationship between a school-based influenza vaccination intervention and receipt of influenza vaccination is mediated by adolescent attitudes and beliefs toward influenza vaccination. The aims of this study follow a traditional four step mediation analysis, delineated by Barron and Kenny [33]. Steps 1-4 include determining: 1) the relationship between intervention condition and receipt of influenza vaccination; 2) the relationship between intervention condition and change in adolescent attitudes and beliefs toward influenza vaccination; 3) the relationship between change in adolescent attitudes and beliefs toward influenza vaccination and receipt of influenza vaccination; and 4) whether the relationship between intervention condition and receipt of influenza vaccination is mediated by adolescent attitudes and beliefs toward influenza vaccination. Step 1 will be determined by the Parent Study and Steps 2 - 4 will be conducted by this study. The proposed study will recruit 1290 rural adolescents who attend middle- or high school in Warren County, GA or Wilkes County, GA. Prior to receiving the school-based intervention, eligible participants will complete surveys regarding their attitudes and beliefs toward influenza vaccination. At 6 months post intervention, participants will again complete the survey. This study aims to provide valuable information which can be used inform future influenza vaccination interventions among rural adolescents.
1 R36 PS001304-01 - Genetic Susceptibility to Mother-To-Child Transmission of HIV
PEDERSEN, BONNIE
DESCRIPTION (provided by the investigator): Mother-To-Child transmission (MTCT) of HIV is a worldwide public health problem but is of particular importance in Sub-Saharan Africa, where over 13.3 million women are living with HIV and over 600,000 infants are infected with HIV each year. Despite the reduction in transmission by the use of antiretrovirals such as single-dose nevirapine, transmission rates remain up to 30%, and the mechanisms of transmission are not completely understood. Identification of genetic variants associated with viral transmission will more adequately describe the mechanisms of MTCT of HIV and aid the development of pharmaceutical interventions, including a vaccine to protect infants from infection. The objective of this application is to evaluate the association between expression of two key genes and the risk of MTCT of HIV. Specifically, we wish to describe the placental expression of the gene HS3ST3A1 and CCR5 in a population of mother-infant pairs from Malawi. Preliminary work involved a genome wide association scan for variants of infant genomes to determine susceptibility to maternal HIV infection. Analyses revealed a variant in the gene, HS3ST3A1, associated with the risk of MTCT. This gene is highly expressed in human placenta and produces a rate-limiting enzyme for the biosynthesis of the 3-O-sulfated subtype of heparan sulfate (HS). This HS subtype is used by herpes simplex virus 1 for viral entry, but its application to MTCT of HIV is unclear. Another gene, CCR5, plays a known role in the risk of HIV infection and progression to AIDS. Neither HS3ST3A1 nor CCR5 have been evaluated in the context of placental expression and risk of MTCT. We aim to perform this work as well as to evaluate gene-gene interactions. The implications of this study are a clearer understanding of the mechanisms of MTCT, most notably the mechanisms with genetic underpinnings. Ultimately, this work may contribute to pharmaceutical advancements for HIV/AIDS.
1 R36 DP001847-01 - Tobacco Free for Recovery: Reducing Smoking among People with Mental Illness
SOLWAY, ERICA SINGER
DESCRIPTION (provided by applicant): While the rates of smoking in the general population have declined substantially over the last decades, the prevalence of smoking among people with mental illness is still extremely high. For example, various estimates suggest that 50-90% of people with serious mental illness smoke, and nearly half of tobacco-related deaths each year occur among people with mental illness. This research project is an attempt to understand the development and emergence of a partnership based on collaborative efforts between the mental health and smoking cessation communities to address the high rates of smoking among people with mental illness and the resulting health disparities that exist for this group. In this dissertation research, the following questions will be explored: To what extent does the partnership between the mental health and smoking cessation communities fit the definition of a social movement? Who are the key actors in bringing together the mental health and smoking cessation communities and what strategies are utilized by these actors? Why did the mental health community historically overlook the high rates of smoking among people with mental illness and what are the implications for current public health efforts? What are the health policy and public health implications of the partnership's efforts? These questions will be explored through qualitative mixed methods approaches including (1) individual in-person and telephone interviews with 25 smoking cessation and mental health experts nationally, (2) 5 focus group interviews with mental health consumers, (3) participant observation and fieldwork, and (4) textual analysis of recently published articles on this topic in 6 leading U.S. newspapers, and data will be analyzed using grounded theory. These sources of data will be understood within the context of three sociological theoretical perspectives: (1) the social construction of social problems literature to highlight the ways in which the social problem of smoking among people with mental illness is recognized, identified, and framed, (2) social movements theories to examine whether the partnership's efforts constitute a social movement and in what ways this body of literature can help to understand the partnership's progress so far and the potential outcomes of its efforts, and (3) political economy theories to study the ways in which political and economic structures shape the experiences of people with mental illness and the strengths and challenges the partnership may encounter in working to achieve its ultimate aims. The long-term goal of this research is to understand how collaborative efforts between the mental health and smoking cessation communities can effectively and sensitively lower the rates of smoking among people with mental illness to reduce tobacco-related diseases and increase the quality of life, number of years of life, and possibilities for recovery. This project aims to meet the Centers for Disease Control and Prevention's Health Protection Goal of Healthy People in Every Stage of Life in that it focuses on smoking cessation efforts for a people with mental illness as this population experiences significant health disparities resulting from high rates of tobacco use.
1 R36 PS001104-01 - The Natural History of Bacterial Vaginosis and Modes of Transmission among Women
THOMA, MARIE
DESCRIPTION (provided by applicant): Bacterial vaginosis (BV) is the most prevalent gynecologic syndrome among women of reproductive age and has been associated with adverse pregnancy and reproductive health outcomes, including low birthweight, preterm birth, pelvic inflammatory disease and increased risk of HIV and other sexually transmitted infections (STIs). In keeping with CDC Health Protection Goal of Healthy People in Every Stage of Life, the long-term goals of this research proposal are to further existing knowledge on the natural history and etiology of bacterial vaginosis in order to promote healthy pregnancy and birth outcomes (Start Strong), improve reproductive and sexual health, and prevent infectious diseases and their consequences among adults (Live a Healthy, Productive, and Satisfying Life). The specific aims of the proposed research are to provide comprehensive epidemiologic information on patterns of BV, determine potentially modifiable risk factors and identify sexual and non-sexual modes of transmission in rural Ugandan women. To address these issues, two complimentary longitudinal studies of vaginal flora changes were conducted in Rakai, Uganda. The first study followed women ages 13-39 for two years and obtained self-collected vaginal swabs at weekly intervals to assess changes in vaginal flora over time. The second study followed polygamous household units (husbands, wives, and other co-resident women aged 13- 49 in the household) at 6 month intervals to assess clustering of BV among co-resident women with a common sex partner (husband) compared to other co-resident women without a common sex partner. Different analytic strategies will be employed to assess changes in vaginal flora and risk factors associated with these changes. Nonparametric regression techniques, summary measures, and transition matrices will be used to describe vaginal flora patterns within individuals over time. Longitudinal regression techniques, such as random-effects models and transition models, that appropriately account for the correlation within women over time and within households will be used to identify risk factors associated with changes in vaginal flora. Finally, random-intercept models will be used to assess (intra-class) correlation of vaginal flora status between women within polygamous households and to determine whether sharing the same sex partner (polygamous husband) or sharing of other (non-sexual) household items (bathing items, towels, etc.) accounts for this correlation.
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Page last modified: October 20, 2008
Content source: Office of the Chief Science Officer (OCSO)
