Search

Background: Applying latent class analysis (LCA) to accelerometry can help elucidated underlying patterns. This study described the patterns of accelerometer-determined sedentary behavior and physical activity among youth by applying LCA to a nationally representative United States (US) sample., Methods: Using 2003-2006 National Health and Nutrition Examination Survey data, 3998 youths 6-17 years wore an ActiGraph 7164 accelerometer for one week, providing > =3 days of wear for > =8 h/day from 6:00 am-midnight. Cutpoints defined sedentary behavior (<100 counts/minute), light activity (100-2295 counts/minute), moderate to vigorous physical activity (MVPA; > = 2296 counts/minute), and vigorous activity (> = 4012 counts/minute). To account for wear time differences, outcomes were expressed as percent of day in a given intensity. LCA was used to classify daily (Monday through Sunday) patterns of average counts/minute, sedentary behavior, light activity, MVPA, and vigorous activity separately. The latent classes were explored overall and by age (6-11, 12-14, 15-17 years), gender, and whether or not youth attended school during measurement. Estimates were weighted to account for the sampling frame., Results: For average counts/minute/day, four classes emerged from least to most active: 40.9% of population (mean 323.5 counts/minute/day), 40.3% (559.6 counts/minute/day), 16.5% (810.0 counts/minute/day), and 2.3% (1132.9 counts/minute/day). For percent of sedentary behavior, four classes emerged: 13.5% of population (mean 544.6 min/day), 30.1% (455.1 min/day), 38.5% (357.7 min/day), and 18.0% (259.2 min/day). For percent of light activity, four classes emerged: 12.3% of population (mean 222.6 min/day), 29.3% (301.7 min/day), 41.8% (384.0 min/day), and 16.6% (455.5 min/day). For percent of MVPA, four classes emerged: 59.9% of population (mean 25.0 min/day), 33.3% (60.9 min/day), 3.1% (89.0 min/day), and 3.6% (109.3 min/day). For percent of vigorous activity, three classes emerged: 76.8% of population (mean 7.1 min/day), 18.5% (23.9 min/day), and 4.7% (47.4 min/day). Classes were developed by age, gender, and school attendance since some patterns differed when stratifying by these factors., Conclusion: The models supported patterns for average intensity, sedentary behavior, light activity, MVPA, and vigorous activity. These latent class derived patterns can be used in other youth studies to explore correlates or outcomes and to target sedentary behavior or physical activity interventions.

Early life exposure to endocrine disrupting chemicals may alter adipogenesis and energy balance leading to changes in obesity risk. Several studies have evaluated the association of prenatal bisphenol A exposure with childhood body size but only one study of male infants has examined other environmental phenols. Therefore, we assessed associations between prenatal exposure to environmental phenols and fat mass in a prospective birth cohort. We quantified four phenol biomarkers in third trimester maternal spot urine samples in a cohort of women enrolled in New York City between 1998 and 2002 and evaluated fat mass in their children using a Tanita scale between ages 4 and 9years (173 children with 351 total observations). We estimated associations of standard deviation differences in natural log creatinine-standardized phenol biomarker concentrations with percent fat mass using linear mixed effects regression models. We did not observe associations of bisphenol A or triclosan with childhood percent fat mass. In unadjusted models, maternal urinary concentrations of 2,5-dichlorophenol were associated with greater percent fat mass and benzophenone-3 was associated with lower percent fat mass among children. After adjustment, phenol biomarkers were not associated with percent fat mass. However, the association between benzophenone-3 and percent fat mass was modified by child's sex: benzophenone-3 concentrations were inversely associated with percent fat mass in girls (beta=-1.51, 95% CI=-3.06, 0.01) but not boys (beta=-0.20, 95% CI=-1.69, 1.26). Although we did not observe strong evidence that prenatal environmental phenols exposures influence the development of childhood adiposity, the potential antiadipogenic effect of benzophenone-3 in girls may warrant further investigation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the impact of an episode of intermenstrual bleeding on the probability of conception in a menstrual cycle (fecundability)., Design: Prospective, time-to-pregnancy cohort study., Setting: Community-based cohort., Patient(s): Women trying to conceive, ages 30 to 44 years, without known infertility., Intervention(s): Not applicable., Main Outcome Measure(s): Current cycle and subsequent cycle fecundability., Result(s): A total of 549 women provided 1,552 complete cycles for analysis. Intermenstrual and luteal bleeding were reported in 36% and 34% of cycles, respectively. Ninety-three percent of all intermenstrual bleeding was luteal. Cycles in which women had intermenstrual bleeding or luteal bleeding were statistically significantly less likely to result in conception (fecundability ratio [FR] 0.23; 95% confidence interval [CI], 0.16-0.34; and FR 0.22; 95% CI, 0.14-0.33). Women with an episode of intermenstrual and luteal bleeding had a statistically significant increase in the probability of pregnancy in the subsequent cycle (FR 1.61; 95% CI, 1.15-2.25; and FR 2.01; 95% CI, 1.52-2.87, respectively)., Conclusion(s): Intermenstrual bleeding statistically significantly decreases the odds of conceiving in that cycle but does not appear to negatively impact a woman's immediate future reproductive potential., Clinical Trial Registration Number: NCT01028365., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Phthalates are hypothesized to cause obesity, but few studies have assessed whether prenatal phthalate exposures are related to childhood body mass index (BMI)., Methods: We included 707 children from three prospective cohort studies enrolled in the US between 1998 and 2006 who had maternal urinary phthalate metabolite concentrations measured during pregnancy, and measures of weight and height at ages 4 to 7 years. We calculated age- and sex-standardized BMI z scores and classified children with BMI percentiles ≥85 as overweight/obese. We used mixed effects regression models to estimate associations between a 1 standard deviation increase in natural log phthalate metabolite concentrations and BMI z scores and overweight/obesity. We estimated associations in multiple metabolite models adjusted for confounders, and evaluated heterogeneity of associations by child's sex, race/ethnicity, and cohort., Results: Mono-3-carboxypropyl phthalate concentrations were positively associated with overweight/obese status in children (odds ratio [95% credible interval] = 2.1 [1.2, 4.0]) but not with BMI z scores (β = -0.02 [-0.15, 0.11]). We did not observe evidence of obesogenic effects for other metabolites. However, monoethyl phthalate and summed di-(2-ethylhexyl) phthalate metabolites (∑DEHP) concentrations were inversely associated with BMI z scores among girls (monoethyl phthalate beta = -0.14 [-0.28, 0.00]; ∑DEHP beta = -0.12 [-0.27, 0.02])., Conclusions: Maternal urinary mono-3-carboxypropyl phthalate, a nonspecific metabolite of several phthalates, was positively associated with childhood overweight/obesity. Metabolites of diethyl phthalate and DEHP were associated with lower BMI in girls but not in boys, suggesting that prenatal exposures may have sexually dimorphic effects on physical development.

Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neurotoxicity. Although welding-related airborne Fe levels are about 10-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose-response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain magnetic resonance imaging (MRI) were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole-blood Fe levels compared with controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole-blood Fe concentration. This study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects., Methods: We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status., Results: We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14])., Conclusion: Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240-249, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Experimental animal studies and limited epidemiologic evidence suggest that prenatal exposure to phthalates may be obesogenic, with potential sex-specific effects of phthalates having anti-androgenic activity., Objectives: We aimed to assess associations between prenatal phthalate exposures and childhood fat mass in a prospective cohort study., Methods: We measured phthalate metabolite concentrations in third-trimester maternal urine in a cohort of women enrolled in New York City between 1998 and 2002 (n = 404). Among 180 children (82 girls and 98 boys), we evaluated body composition using a Tanita scale at multiple follow-up visits between ages 4 and 9 years (363 total visits). We estimated associations of standard deviation differences or tertiles of natural log phthalate metabolite concentrations with percent fat mass using linear mixed-effects regression models with random intercepts for repeated outcome measurements. We assessed associations in multiple metabolite models and adjusted for covariates including prepregnancy body mass index, gestational weight gain, maternal smoking during pregnancy, and breastfeeding., Results: We did not observe associations between maternal urinary phthalate concentrations and percent body fat in models examining continuous exposures. Fat mass was 3.06% (95% CI: -5.99, -0.09%) lower among children in the highest tertile of maternal urinary concentrations of summed di(2-ethylhexyl) phthalate (ΣDEHP) metabolites than in children in the lowest tertile. Though estimates were imprecise, there was little evidence that associations between maternal urinary phthalate concentrations and percent fat mass were modified by child's sex., Conclusions: Prenatal phthalate exposures were not associated with increased body fat among children 4-9 years of age, though high prenatal DEHP exposure may be associated with lower fat mass in childhood., Citation: Buckley JP, Engel SM, Mendez MA, Richardson DB, Daniels JL, Calafat AM, Wolff MS, Herring AH. 2016. Prenatal phthalate exposures and childhood fat mass in a New York City cohort. Environ Health Perspect 124:507-513; http://dx.doi.org/10.1289/ehp.1509788.

Background: Despite studies having consistently linked exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to breast cancer, it is unclear whether single sources or specific groups of PAH sources should be targeted for breast cancer risk reduction., Objectives: This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures., Methods: In a population-based case-control study conducted on Long Island, New York (N=1508 breast cancer cases/1556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake., Results: Most women were exposed to PAHs from multiple sources, and the most common included active/passive smoking and grilled/smoked food intake. In multiple-PAH source models, breast cancer incidence was associated with residential ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.40) and synthetic firelog burning (OR=1.29, 95%CrI=1.06, 1.57); these estimates are similar, but slightly attenuated, to those from single-source models. Additionally when we considered PAH exposure groups, the most pronounced significant associations included total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.45, 95%CrI=1.02, 2.04)., Conclusions: Groups of PAH sources, particularly indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

It is common in biomedical research to run case-control studies involving high-dimensional predictors, with the main goal being detection of the sparse subset of predictors having a significant association with disease. Usual analyses rely on independent screening, considering each predictor one at a time, or in some cases on logistic regression assuming no interactions. We propose a fundamentally different approach based on a nonparametric Bayesian low rank tensor factorization model for the retrospective likelihood. Our model allows a very flexible structure in characterizing the distribution of multivariate variables as unknown and without any linear assumptions as in logistic regression. Predictors are excluded only if they have no impact on disease risk, either directly or through interactions with other predictors. Hence, we obtain an omnibus approach for screening for important predictors. Computation relies on an efficient Gibbs sampler. The methods are shown to have high power and low false discovery rates in simulation studies, and we consider an application to an epidemiology study of birth defects., (© 2015, The International Biometric Society.)

Background: Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure., Objectives: Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence., Methods: Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996-1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960-1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH-DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression., Results: The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960-1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic-breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants]., Conclusions: In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise., Citation: Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic-related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30-38; http://dx.doi.org/10.1289/ehp.1307736.

Numerous studies have investigated the relationship between the built environment and physical activity. However these studies assume that these relationships are invariant over space. In this study, we introduce a novel method to analyze the association between access to recreational facilities and exercise allowing for spatial heterogeneity. In addition, this association is studied before and after controlling for crime, a variable that could explain spatial heterogeneity of associations. We use data from the Chicago site of the Multi-Ethnic Study of Atherosclerosis of 781 adults aged 46 years and over. A spatially varying coefficient Tobit regression model is implemented in the Bayesian setting to allow for the association of interest to vary over space. The relationship is shown to vary over Chicago, being positive in the south but negative or null in the north. Controlling for crime weakens the association in the south with little change observed in northern Chicago. The results of this study indicate that spatial heterogeneity in associations of environmental factors with health may vary over space and deserve further exploration.

Background: High urbanicity and income are risk factors for cardiovascular-related chronic diseases in low- and middle-income countries, perhaps due to low physical activity (PA) in urban, high income areas. Few studies have examined differences in PA over time according to income and urbanicity in a country experiencing rapid urbanization., Methods: We used data from the China Health and Nutrition Survey, a population-based cohort of Chinese adults (n = 20,083; ages 18-75y) seen a maximum of 7 times from 1991-2009. We used sex-stratified, zero-inflated negative binomial regression models to examine occupational, domestic, leisure, travel, and total PA in Chinese adults according to year, urbanicity, income, and the interactions among urbanicity, income, and year, controlling for age and region of China., Results: We showed larger mean temporal PA declines for individuals living in relatively low urbanicity areas (1991: 500 MET-hours/week; 2009: 300 MET-hours/week) compared to high urbanicity areas (1991: 200 MET-hours/week; 2009: 125 MET-hours/week). In low urbanicity areas, the association between income and total PA went from negative in 1991 (p < 0.05) to positive by 2000 (p < 0.05). In relatively high urbanicity areas, the income-PA relationship was positive at all time points and was statistically significant at most time points after 1997 (p < 0.05). Leisure PA was the only domain of PA that increased over time, but >95% of individuals in low urbanicity areas reported zero leisure PA at each time point., Conclusions: Our findings show changing associations for income and urbanicity with PA over 18 years of urbanization. Total PA was lower for individuals living in more versus less urban areas at all time points. However, these differences narrowed over time, which may relate to increases in individual-level income in less urban areas of China with urbanization. Low-income individuals in higher urbanicity areas are a particularly critical group to target to increase PA in China.

The purpose of this study was to reduce the dimensionality of a set of neighborhood-level variables collected on participants in the Multi-Ethnic Study of Atherosclerosis (MESA) while appropriately accounting for the spatial structure of the data. A common spatial factor analysis model in the Bayesian setting was utilized in order to properly characterize dependencies in the data. Results suggest that use of the spatial factor model can result in more precise estimation of factor scores, improved insight into the spatial patterns in the data, and the ability to more accurately assess associations between the neighborhood environment and health outcomes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To determine which combination of risk factors from Community Care of North Carolina's (CCNC) Pregnancy Medical Home (PMH) risk screening form was most predictive of preterm birth (PTB) by parity and race/ethnicity., Methods: This retrospective cohort included pregnant Medicaid patients screened by the PMH program before 24 weeks gestation who delivered a live birth in North Carolina between September 2011-September 2012 (N = 15,428). Data came from CCNC's Case Management Information System, Medicaid claims, and birth certificates. Logistic regression with backward stepwise elimination was used to arrive at the final models. To internally validate the predictive model, we used bootstrapping techniques., Results: The prevalence of PTB was 11 %. Multifetal gestation, a previous PTB, cervical insufficiency, diabetes, renal disease, and hypertension were the strongest risk factors with odds ratios ranging from 2.34 to 10.78. Non-Hispanic black race, underweight, smoking during pregnancy, asthma, other chronic conditions, nulliparity, and a history of a low birth weight infant or fetal death/second trimester loss were additional predictors in the final predictive model. About half of the risk factors prioritized by the PMH program remained in our final model (ROC = 0.66). The odds of PTB associated with food insecurity and obesity differed by parity. The influence of unsafe or unstable housing and short interpregnancy interval on PTB differed by race/ethnicity., Conclusions: Evaluation of the PMH risk screen provides insight to ensure women at highest risk are prioritized for care management. Using multiple data sources, salient risk factors for PTB were identified, allowing for better-targeted approaches for PTB prevention.

Public health research often concerns relationships between exposures and correlated count outcomes. When counts exhibit more zeros than expected under Poisson sampling, the zero-inflated Poisson (ZIP) model with random effects may be used. However, the latent class formulation of the ZIP model can make marginal inference on the sampled population challenging. This article presents a marginalized ZIP model with random effects to directly model the mean of the mixture distribution consisting of 'susceptible' individuals and excess zeroes, providing straightforward inference for overall exposure effects. Simulations evaluate finite sample properties, and the new methods are applied to a motivational interviewing-based safer sex intervention trial, designed to reduce the number of unprotected sexual acts.

Although the essential element manganese (Mn) is neurotoxic at high doses, the effects of lower exposure are unclear. MRI T1-weighted (TIW) imaging has been used to estimate brain Mn exposure via the pallidal index (PI), defined as the T1W intensity ratio in the globus pallidus (GP) versus frontal white matter (FWM). PI may not, however, be sensitive to Mn in GP because Mn also may accumulate in FWM. This study explored: (1) whether T1 relaxation rate (R1) could quantify brain Mn accumulation more sensitively; and (2) the dose-response relationship between estimated Mn exposure and T1 relaxation rate (R1). Thirty-five active welders and 30 controls were studied. Occupational questionnaires were used to estimate hours welding in the past 90 days (HrsW) and lifetime measures of Mn exposure. T1W imaging and T1-measurement were utilized to generate PI and R1 values in brain regions of interest (ROIs). PI did not show a significant association with any measure of Mn and/or welding-related exposure. Conversely, in several ROIs, R1 showed a nonlinear relationship to HrsW, with R1 signal increasing only after a critical exposure was reached. The GP had the greatest rate of Mn accumulation. Welders with higher exposure showed significantly higher R1 compared either with controls or with welders with lower exposure. Our data are additional evidence that Mn accumulation can be assessed more sensitively by R1 than by PI. Moreover, the nonlinear relationship between welding exposure and Mn brain accumulation should be considered in future studies and policies., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background/objectives: Nonglycemic factors like iron deficiency (ID) or anemia may interfere with classification of diabetes and prediabetes using hemoglobin A1c (HbA1c). However, few population-based studies of diabetes in areas with endemic ID/anemia have been conducted. We aimed to determine how mutually exclusive categories of ID alone, anemia alone and iron-deficiency anemia (IDA) were each associated with prediabetes and diabetes prevalence using fasting blood glucose (FBG) versus HbA1c in a population-based study of adults with endemic ID/anemia., Subjects/methods: We used data from the China Health and Nutrition Survey, a longitudinal, population-based study across 228 communities within nine provinces of China. This analysis included 7308 adults seen in the 2009 survey aged 18-75 years. We used descriptive and covariate-adjusted models to examine relative risk of prediabetes and diabetes using FBG alone, HbA1c alone, HbA1c and FBG, or neither (normoglycemia) by anemia alone, ID alone, IDA or normal iron/hemoglobin., Results: Approximately 65% of individuals with diabetes in our sample were concordantly classified with diabetes using both FBG and HbA1c, while 35% had a discordant diabetes classification: they were classified using either FBG or HbA1c, but not both. Fewer participants with ID alone versus normal iron/hemoglobin were classified with diabetes using HbA1c only. From covariate-adjusted, multinomial regression analyses, the adjusted prevalence of prediabetes using HbA1c only was 22% for men with anemia alone, but 13% for men with normal iron/hemoglobin. In contrast, the predicted prevalence of prediabetes using HbA1c only was 8% for women with ID alone, compared with 13% for women with normal iron/hemoglobin., Conclusions: These findings suggest potential misclassification of diabetes using HbA1c in areas of endemic ID/anemia. Estimating diabetes prevalence using HbA1c may result in under-diagnosis in women with ID and over-diagnosis in men with anemia.

Infants born preterm or small for gestational age have elevated rates of morbidity and mortality. Using birth certificate records in Texas from 2002 to 2004 and Environmental Protection Agency air pollution estimates, we relate the quantile functions of birth weight and gestational age to ozone exposure and multiple predictors, including parental age, race, and education level. We introduce a semi-parametric Bayesian quantile approach that models the full quantile function rather than just a few quantile levels. Our multilevel quantile function model establishes relationships between birth weight and the predictors separately for each week of gestational age and between gestational age and the predictors separately across Texas Public Health Regions. We permit these relationships to vary nonlinearly across gestational age, spatial domain and quantile level and we unite them in a hierarchical model via a basis expansion on the regression coefficients that preserves interpretability. Very low birth weight is a primary concern, so we leverage extreme value theory to supplement our model in the tail of the distribution. Gestational ages are recorded in completed weeks of gestation (integer-valued), so we present methodology for modeling quantile functions of discrete response data. In a simulation study we show that pooling information across gestational age and quantile level substantially reduces MSE of predictor effects. We find that ozone is negatively associated with the lower tail of gestational age in south Texas and across the distribution of birth weight for high gestational ages. Our methods are available in the R package BSquare., (© 2015, The International Biometric Society.)

Background: Postpartum women are encouraged to participate in ≥ 150 min/week of moderate-intensity aerobic activity, but few women achieve this recommendation. This study sought to identify factors associated with participation in physical activity after pregnancy., Methods: We examined correlates of any self-reported moderate-to-vigorous physical activity (MVPA) (≥ 10 min/week across all modes) and any recreational MVPA (≥ 10 min/week) among women enrolled in the Pregnancy, Infection, and Nutrition Postpartum study at 3 months postpartum (n = 667) and at 12 months postpartum (n = 530). Potential correlates were identified according to the socioecological framework., Results: At 3 and 12 months postpartum, lower odds of participation in any MVPA were associated with lower education, breastfeeding, and minimal emotional support. Low exercise self-efficacy, receipt of advice about physical activity, and warmer seasons were associated with higher odds of any MVPA. For recreational MVPA, lower odds of participation were associated with unmarried status, lower education, employment, low income, preeclampsia, and minimal emotional support. Involvement in child/adult care activities, transportation MVPA, and warmer seasons were associated with higher odds of recreational MVPA., Conclusion: These findings suggest that several modifiable intrapersonal and interpersonal factors are associated with postpartum MVPA and should be considered when developing interventions to help women maintain or increase MVPA after pregnancy.

Background: A positive association between smoking and increased risk of tuberculosis disease is well documented for populations outside the USA. However, it is unclear whether smoking increases risk of tuberculosis in the USA, where both smoking prevalence and disease rates are much lower than in the countries where previous studies have been conducted., Methods: To explore the tuberculosis-smoking association in a more generalisable US population-based sample, we conducted a nested case-control study among members of Kaiser Permanente Northern California (KPNC). We identified all newly diagnosed cases of active pulmonary tuberculosis (PTB) disease between 1996 and 2010. Each of the 2380 cases were individually matched to two controls by age, gender and race/ethnicity. ORs and 95% CIs for the association between smoking status and PTB were calculated using conditional logistic regression adjusted for all matching factors., Results: Increased PTB risk was observed among ever-smokers (OR=1.35; 95% CI 1.19 to 1.53), as well as current (OR=1.26; 95% CI 1.08 to 1.48) and past (OR=1.43; 95% CI 1.23 to 1.67) smokers, compared with never-smokers. Increased intensity and duration of smoking were also positively associated with PTB risk., Conclusions: Our findings among a more generalisable US population support the hypothesis that smoking increases risk of PTB, underscoring the importance of tobacco cessation and prevention programmes in eliminating tuberculosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Little is known about whether large-scale environmental changes, such as those seen with urbanization, are differentially associated with SBP versus DBP, and whether those changes vary by birth cohort., Methods: We used data from the China Health and Nutrition Survey, a population-based cohort study of Chinese adults (n = 18 754 aged 18-70 years), seen a maximum of seven times from 1991 to 2009. We used hierarchical multivariable linear models to simultaneously estimate SBP and DBP as correlated outcomes over time, accounting for their physiologic, time-varying correlation. Main exposure variables were urbanicity, age, and birth cohort. Over 18 years of modernization, median SBP and DBP increased by 10 and 7 mmHg, respectively., Results: Our hierarchical model results suggest greater temporal increases in SBP and particularly DBP at lower versus higher urbanicity. At the same chronological age, for a 10-year difference in birth cohort (i.e. born in 1980s versus 1970s), the adjusted mean DBP was approximately 3 mmHg higher for the later birth cohort (P < 0.001). Pulse pressure (calculated as model-predicted SBP minus DBP) was also higher at low versus high urbanicity., Conclusions: These results suggest increased susceptibility of DBP (and thus peripheral vascular resistance) to environmental change, particularly in younger Chinese adults. Because DBP more strongly predicts cardiovascular disease risk in younger adulthood, hypertension-related health burden in China may increase over time.

Background: Over the past three decades, obesity-related diseases have increased tremendously in China, and are now the leading causes of morbidity and mortality. Patterns of weight change can be used to predict risk of obesity-related diseases, increase understanding of etiology of disease risk, identify groups at particularly high risk, and shape prevention strategies., Methods: Latent class trajectory modeling was used to compute weight change trajectories for adults aged 18 to 66 using the China Health and Nutrition Survey (CHNS) data (n = 12,611). Weight change trajectories were computed separately for males and females by age group at baseline due to differential age-related patterns of weight gain in China with urbanization. Generalized linear mixed effects models examined the association between weight change trajectories and baseline characteristics including urbanicity, BMI category, age, and year of study entry., Results: Trajectory classes were identified for each of six age-sex subgroups corresponding to various degrees of weight loss, maintenance and weight gain. Baseline BMI status was a significant predictor of trajectory membership for all age-sex subgroups. Baseline overweight/obesity increased odds of following 'initial loss with maintenance' trajectories. We found no significant association between baseline urbanization and trajectory membership after controlling for other covariates., Conclusion: Trajectory analysis identified patterns of weight change for age by gender groups. Lack of association between baseline urbanization status and trajectory membership suggests that living in a rural environment at baseline was not protective. Analyses identified age-specific nuances in weight change patterns, pointing to the importance of subgroup analyses in future research.

Background: This study described the patterns of accelerometer-determined physical activity and sedentary behavior among adults using a nationally representative sample from the United States., Methods: Using 2003-2006 National Health and Nutrition Examination Survey (NHANES) data, 7931 adults at least 18 years old wore an ActiGraph accelerometer for one week, providing at least 3 days of wear for >=8 hours/day. Cutpoints defined moderate to vigorous physical activity (MVPA; >= 2020 and >=760 counts/minute), vigorous physical activity (> = 5999 counts/minute), and sedentary behavior (<100 counts/minute). Latent class analysis (LCA) was used to estimate patterns of physical activity and sedentary behavior. All estimates were weighted to reflect the United States population., Results: For weighted percent of MVPA out of total wearing time, 5 classes were identified from least to most active: 65.3% of population (weighted mean 9.3 minutes/day), 24.9% (32.1 minutes/day), 3.2% that was low on the weekdays but much higher on the weekends (52.0 minutes/day), 5.9% (59.9 minutes/day), and 0.7% in the highest class (113.6 minutes/day). Using the lower MVPA threshold, 6 classes emerged with each class ranging in population from 1.2% to 43.6%. A vigorous activity class could not be derived due to low prevalence. For weighted percent of sedentary behavior out of total wearing time, 5 classes were identified from most to least sedentary: 6.3% of population (weighted mean 660.2 minutes/day), 25.1% (546.8 minutes/day), 37.7% (453.9 minutes/day), 24.0% (354.8 minutes/day), and 7.0% (256.3 minutes/day). Four of the classes showed generally similar results across every day of the week, with the absolute percents differing across classes. In contrast, the least sedentary class showing a marked rise in percent of time spent in sedentary behavior on the weekend (weighted mean 336.7-346.5 minutes/day) compared to weekdays (weighted mean 255.2-292.4 minutes/day)., Conclusion: The LCA models provided a data reduction process to identify patterns using minute-by-minute accelerometry data in order to explore meaningful contrasts. The models supported 5 or 6 distinct patterns for MVPA and sedentary behavior. These physical activity and sedentary behavior patterns can be used as intervention targets and as independent or dependent variables in future studies of correlates, determinants, or outcomes.

Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations., Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children., Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals., Results: DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization's recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length., Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations.

Objective: We conducted a laboratory-based calibration study to determine relevant cutpoints for a hip-worn accelerometer among women ≥60 years, considering both type and filtering of counts., Methods: Two hundred women wore an ActiGraph GT3X+ accelerometer on their hip while performing eight laboratory-based activities. Oxygen uptake was measured using an Oxycon portable calorimeter. Accelerometer data were analyzed in 15-second epochs for both normal and low frequency extension (LFE) filters. Receiver operating characteristic (ROC) curve analyses were used to calculate cutpoints for sedentary, light (low and high), and moderate to vigorous physical activity (MVPA) using the vertical axis and vector magnitude (VM) counts., Results: Mean age was 75.5 years (standard deviation 7.7). The Spearman correlation between oxygen uptake and accelerometry ranged from 0.77 to 0.85 for the normal and LFE filters and for both the vertical axis and VM. The area under the ROC curve was generally higher for VM compared to the vertical axis, and higher for cutpoints distinguishing MVPA compared to sedentary and light low activities. The VM better discriminated sedentary from light low activities compared to the vertical axis. The area under the ROC curves were better for the LFE filter compared to the normal filter for the vertical axis counts, but no meaningful differences were found by filter type for VM counts., Conclusion: The cutpoints derived for this study among women ≥60 years can be applied to ongoing epidemiologic studies to define a range of physical activity intensities.

Background: Emerging research suggests that young adult sexual minorities (identifying as lesbian, gay, or bisexual or engaging in same-sex attractions or behaviors) experience poorer health than their majority counterparts, but many measures of health inequity remain unexamined in population-based research., Purpose: To describe a wide range of health status and healthcare access characteristics of sexual minorities in comparison with those of the majority population in a national sample of U.S. young adults., Methods: Binary and multinomial logistic regression analyses of Wave IV data (2008) from the National Longitudinal Study of Adolescent Health (participants aged 24-32 years, n=13,088) were conducted. Health measures were self-rated health; diagnosis of any of several physical or mental illnesses or sexually transmitted infections; measured BMI; depression classified from self-reported symptoms; use of antidepressant and anxiolytic medication; uninsured; forgone care; and receipt of physical, dental, and psychological services. Analyses were conducted in 2012-2013., Results: Sexual minority women had elevated odds of most adverse health conditions and lower odds of receiving a physical or dental examination. Sexual minority men had elevated odds of fewer adverse health conditions., Conclusions: Young adult sexual minorities are at higher risk of poor physical and mental health. The results highlight the multidimensionality of sexual minority status and respond to calls for greater understanding of the health of this population., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background/aims: There are inconsistent associations between white rice consumption and diabetes and dyslipidemia, perhaps due to the nature of samples studied and quality of diet data., Methods: Using regionally diverse data from adults enrolled in the China Health and Nutrition Survey (n = 7,878) with diet data from three repeated 24-hour recalls and fasting blood to derive diabetes and dyslipidemia, we examined the odds of diabetes and dyslipidemia in participants across region-specific tertiles of percent energy from white rice consumption., Results: The prevalence of undiagnosed diabetes, high triglycerides, high low-density lipoprotein (LDL), low high-density lipoprotein (HDL), and atherogenic dyslipidemia (AD) was 4.7%, 31.8%, 31.3%, 25.9%, and 14.6%, respectively. We found an inverse association between the highest (versus lowest) tertile of rice intake and diabetes in Central China (odds ratio (OR): 0.59, 95% confidence interval (CI): 0.36-0.99). The highest rice consumption was also associated with high triglycerides (OR: 1.46, 95% CI: 1.09-1.95), low HDL (OR: 1.38, 95% CI: 1.03-1.85), and AD (OR: 1.63, 95% CI: 1.15-2.31) in North China, and low LDL (OR: 0.54, 95% CI: 0.42-0.69) in Central China., Conclusions: The association between white rice consumption and diabetes and dyslipidemia markers varied across regions of China, suggesting a role of other dietary and health-related exposures, beyond rice., (2015 S. Karger AG, Basel.)

Objective: Diuretics are often prescribed off-label to premature infants, particularly to prevent or treat bronchopulmonary dysplasia. We examined their use and safety in this group., Study Design: Retrospective cohort study of infants < 32 weeks gestation and < 1,500 g birth weight exposed to diuretics in 333 neonatal intensive care units from 1997 to 2011. We examined use of acetazolamide, amiloride, bumetanide, chlorothiazide, diazoxide, ethacrynic acid, furosemide, hydrochlorothiazide, mannitol, metolazone, or spironolactone combination. Respiratory support and fraction of inspired oxygen on the first day of each course of diuretic use were identified., Results: About 37% (39,357/107,542) infants were exposed to at least one diuretic; furosemide was the most commonly used (93% with ≥ 1 recorded dose), followed by spironolactone, chlorothiazide, hydrochlorothiazide, bumetanide, and acetazolamide. About 74% patients were exposed to one diuretic at a time, 19% to two diuretics simultaneously, and 6% to three diuretics simultaneously. The most common combination was furosemide/spironolactone, followed by furosemide/chlorothiazide and chlorothiazide/spironolactone. Many infants were not receiving mechanical ventilation on the first day of each new course of furosemide (47%), spironolactone (69%), chlorothiazide (61%), and hydrochlorothiazide (68%). Any adverse event occurred on 42 per 1,000 infant-days for any diuretic and 35 per 1,000 infant-days for furosemide. Any serious adverse event occurred in 3.8 for any diuretic and 3.2 per 1,000 infant-days for furosemide. The most common laboratory abnormality associated with diuretic exposure was thrombocytopenia., Conclusion: Despite no Food and Drug Administration (FDA) indication and little safety data, over one-third of premature infants in our population were exposed to a diuretic, many with minimal respiratory support., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The zero-inflated Poisson (ZIP) regression model is often employed in public health research to examine the relationships between exposures of interest and a count outcome exhibiting many zeros, in excess of the amount expected under sampling from a Poisson distribution. The regression coefficients of the ZIP model have latent class interpretations, which correspond to a susceptible subpopulation at risk for the condition with counts generated from a Poisson distribution and a non-susceptible subpopulation that provides the extra or excess zeros. The ZIP model parameters, however, are not well suited for inference targeted at marginal means, specifically, in quantifying the effect of an explanatory variable in the overall mixture population. We develop a marginalized ZIP model approach for independent responses to model the population mean count directly, allowing straightforward inference for overall exposure effects and empirical robust variance estimation for overall log-incidence density ratios. Through simulation studies, the performance of maximum likelihood estimation of the marginalized ZIP model is assessed and compared with other methods of estimating overall exposure effects. The marginalized ZIP model is applied to a recent study of a motivational interviewing-based safer sex counseling intervention, designed to reduce unprotected sexual act counts., (Copyright © 2014 John Wiley & Sons, Ltd.)

Context: Identifying adolescent characteristics associated with different patterns of sexual initiation is critical to promoting healthy sexual development., Methods: Patterns of sexual initiation were examined among 12,378 respondents to Waves 1 (1994-1995) and 4 (2008) of the National Longitudinal Study of Adolescent Health. Multinomial logistic regression explored associations between adolescent characteristics and membership in five latent classes capturing the timing, sequence, pace and variety of sexual initiation patterns., Results: Age and indicators of greater psychosocial conventionality were associated with membership in the atypical "postponers" class (characterized by postponement of oral, vaginal and anal sexual activity until early adulthood), although patterns of associations varied by gender. For example, compared with males who attended religious services at least once a week, males who never attended religious services were more likely to appear in the vaginal initiators/multiple behaviors class (characterized by initiation of vaginal sex first and then initiation of another behavior after at least one year), rather than in the postponers class (relative risk ratio, 2.5). Compared with women who prayed at least once a day, those who never prayed were more likely to be in the vaginal initiators/single behavior class (whose members typically engaged in only one type of behavior), rather than in the postponers class (2.0)., Conclusions: Individuals who are more adherent, and presumably more committed, to the attitudes, values and expectations of conventional society are more likely than others to delay multiple types of sexual activity until well beyond the norm for their peers., (Copyright © 2014 by the Guttmacher Institute.)

Background: Toxic metals including arsenic, cadmium, manganese, and lead are known human developmental toxicants that are able to cross the placental barrier from mother to fetus. In this population-based study, we assess the association between metal concentrations in private well water and birth defect prevalence in North Carolina., Methods: A semi-ecologic study was conducted including 20,151 infants born between 2003 and 2008 with selected birth defects (cases) identified by the North Carolina Birth Defects Monitoring Program, and 668,381 non-malformed infants (controls). Maternal residences at delivery and over 10,000 well locations measured for metals by the North Carolina Division of Public Health were geocoded. The average level of each metal was calculated among wells sampled within North Carolina census tracts. Individual exposure was assigned as the average metal level of the census tract that contained the geocoded maternal residence. Prevalence ratios (PR) with 95% confidence intervals (CI) were calculated to estimate the association between the prevalence of birth defects in the highest category (≥90th percentile) of average census tract metal levels and compared to the lowest category (≤50th percentile)., Results: Statewide, private well metal levels exceeded the EPA Maximum Contaminant Level (MCL) or secondary MCL for arsenic, cadmium, manganese, and lead in 2.4, 0.1, 20.5, and 3.1 percent of wells tested. Elevated manganese levels were statistically significantly associated with a higher prevalence of conotruncal heart defects (PR: 1.6 95% CI: 1.1-2.5)., Conclusions: These findings suggest an ecologic association between higher manganese concentrations in drinking water and the prevalence of conotruncal heart defects.

We evaluate the use of three different exposure metrics to estimate maternal agricultural pesticide exposure during pregnancy. Using a geographic information system-based method of pesticide exposure estimation, we combine data on crop density and specific pesticide application amounts/dates to create the three exposure metrics. For illustration purposes, we create each metric for a North Carolina cohort of pregnant women, 2003-2005, and analyze the risk of congenital anomaly development with a focus on metric comparisons. Based on the results, and the need to balance data collection efforts/computational efficiency with accuracy, the metric which estimates total chemical exposure using application dates based on crop-specific earliest planting and latest harvesting information is preferred. Benefits and drawbacks of each metric are discussed and recommendations for extending the analysis to other states are provided.

Aims/hypothesis: Although obesity is a major risk factor for diabetes, little is known about weight gain trajectories across adulthood, and whether they are differentially associated with metabolic markers of diabetes., Methods: We used fasting blood samples and longitudinal weight data for 5,436 adults (5,734 observations, aged 18-66 years) from the China Health and Nutrition Survey (1991-2009). Using latent class trajectory analysis, we identified different weight gain trajectories in six age and sex strata, and used multivariable general linear mixed effects models to assess elevated metabolic markers of diabetes (fasting glucose, HbA1c, HOMA-IR, insulin) across weight trajectory classes. Models were fitted within age and sex strata, and controlled for baseline weight (or baseline weight by weight trajectory interaction terms), height, and smoking habit, with random intercepts to control for community-level correlations., Results: Compared with weight gain, classes with weight maintenance, weight loss, or a switch from weight gain to loss had lower values for metabolic markers of diabetes. These associations were stronger among younger women (aged 18-29 and 30-39 years) and men (18-29 years) than in older (40-66 years) men and women. An exception was HOMA-IR, which showed class differences across all ages (at least p < 0.004)., Conclusion: Trajectory analysis identified heterogeneity in adult weight gain associated with diabetes-related metabolic markers, independent of baseline weight. Our findings suggest that variation in metabolic markers of diabetes across patterns of weight gain is masked by a homogeneous classification of weight gain.

Background: Epidemiologic literature suggests that exposure to air pollutants is associated with fetal development., Objectives: We investigated maternal exposures to air pollutants during weeks 2-8 of pregnancy and their associations with congenital heart defects., Methods: Mothers from the National Birth Defects Prevention Study, a nine-state case-control study, were assigned 1-week and 7-week averages of daily maximum concentrations of carbon monoxide, nitrogen dioxide, ozone, and sulfur dioxide and 24-hr measurements of fine and coarse particulate matter using the closest air monitor within 50 km to their residence during early pregnancy. Depending on the pollutant, a maximum of 4,632 live-birth controls and 3,328 live-birth, fetal-death, or electively terminated cases had exposure data. Hierarchical regression models, adjusted for maternal demographics and tobacco and alcohol use, were constructed. Principal component analysis was used to assess these relationships in a multipollutant context., Results: Positive associations were observed between exposure to nitrogen dioxide and coarctation of the aorta and pulmonary valve stenosis. Exposure to fine particulate matter was positively associated with hypoplastic left heart syndrome but inversely associated with atrial septal defects. Examining individual exposure-weeks suggested associations between pollutants and defects that were not observed using the 7-week average. Associations between left ventricular outflow tract obstructions and nitrogen dioxide and between hypoplastic left heart syndrome and particulate matter were supported by findings from the multipollutant analyses, although estimates were attenuated at the highest exposure levels., Conclusions: Using daily maximum pollutant levels and exploring individual exposure-weeks revealed some positive associations between certain pollutants and defects and suggested potential windows of susceptibility during pregnancy.

Objective: To determine the impact of sexual intercourse around the time of implantation on the probability of achieving a pregnancy., Design: Time-to-pregnancy cohort using day-specific probability of pregnancy modeling to account for intercourse during the fertile window., Setting: Community cohort., Patient(s): Women trying to conceive naturally, ages 30-44, without known infertility., Intervention(s): None., Main Outcome Measure(s): Positive pregnancy test., Result(s): A total of 564 women provided 1,332 complete cycles for analysis. Intercourse frequency during the fertile window and during the peri-implantation window were significantly correlated. Cycles in which couples had 2 or more days with intercourse during the implantation window were significantly less likely to result in a positive pregnancy test compared with cycles in which couples did not have intercourse in this window, after adjusting for age, race, history of regular menstrual cycles, previous pregnancy, and body mass index (fecundability ratio, 0.62; 95% confidence interval, 0.42-0.91)., Conclusion(s): Intercourse during the peri-implantation window may be detrimental to natural fertility. Methods that allow couples to time intercourse to the fertile window may decrease time to pregnancy by not only increasing the probability of fertilization but also decreasing the probability of failed implantation., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The statistics literature on functional data analysis focuses primarily on flexible black-box approaches, which are designed to allow individual curves to have essentially any shape while characterizing variability. Such methods typically cannot incorporate mechanistic information, which is commonly expressed in terms of differential equations. Motivated by studies of muscle activation, we propose a nonparametric Bayesian approach that takes into account mechanistic understanding of muscle physiology. A novel class of hierarchical Gaussian processes is defined that favors curves consistent with differential equations defined on motor, damper, spring systems. A Gibbs sampler is proposed to sample from the posterior distribution and applied to a study of rats exposed to non-injurious muscle activation protocols. Although motivated by muscle force data, a parallel approach can be used to include mechanistic information in broad functional data analysis applications.

Objective: Reduced maternal plasma levels of the peptide vasodilator adrenomedullin have been associated with adverse pregnancy outcomes. We measured the extent to which genetic polymorphisms in the adrenomedullin signaling pathway are associated with birth weight, glycemic regulation, and preeclampsia risk., Study Design: We genotyped 1,353 women in the Pregnancy, Infection, and Nutrition Postpartum Study for 37 ancestry-informative markers and for single-nucleotide polymorphisms in adrenomedullin (ADM), complement factor H variant (CFH), and calcitonin receptor-like receptor (CALCRL). We used linear and logistic regression to model the association between genotype and birth weight, glucose loading test (GLT) results, preeclampsia, and gestational diabetes (GDM). All models were adjusted for pregravid body mass index, maternal age, and probability of Yoruban ancestry. p values of < 0.05 were considered statistically significant., Results: Among Caucasian women, ADM rs57153895, a proxy for rs11042725, was associated with reduced birth weight z-score. Among African-American women, ADM rs57153895 was associated with increased birth weight z-score. Two CALCRL variants were associated with GDM risk. CFH rs1061170 was associated with higher GLT results and increased preeclampsia risk., Conclusion: Consistent with studies of plasma adrenomedullin and adverse pregnancy outcomes, we found associations between variants in the adrenomedullin signaling pathway and birth weight, glycemic regulation, and preeclampsia., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: Head and neck cancers (HNC) are commonly treated with radiation and platinum-based chemotherapy, which produce bulky DNA adducts to eradicate cancerous cells. Because nucleotide excision repair (NER) enzymes remove adducts, variants in NER genes may be associated with survival among HNC cases both independently and jointly with treatment., Methods: Cox proportional hazards models were used to estimate race-stratified (White, African American) hazard ratios (HRs) and 95 % confidence intervals for overall (OS) and disease-specific (DS) survival based on treatment (combinations of surgery, radiation, and chemotherapy) and 84 single nucleotide polymorphisms (SNPs) in 15 NER genes among 1,227 HNC cases from the Carolina Head and Neck Cancer Epidemiology Study., Results: None of the NER variants evaluated were associated with survival at a Bonferroni-corrected alpha of 0.0006. However, rs3136038 [OS HR = 0.79 (0.65, 0.97), DS HR = 0.69 (0.51, 0.93)] and rs3136130 [OS HR = 0.78 (0.64, 0.96), DS HR = 0.68 (0.50, 0.92)] of ERCC4 and rs50871 [OS HR = 0.80 (0.64, 1.00), DS HR = 0.67 (0.48, 0.92)] of ERCC2 among Whites, and rs2607755 [OS HR = 0.62 (0.45, 0.86), DS HR = 0.51 (0.30, 0.86)] of XPC among African Americans were suggestively associated with survival at an uncorrected alpha of 0.05. Three SNP-treatment joint effects showed possible departures from additivity among Whites., Conclusions: Our study, a large and extensive evaluation of SNPs in NER genes and HNC survival, identified mostly null associations, though a few variants were suggestively associated with survival and potentially interacted additively with treatment.

Objective: To estimate the association of physical activity on in vitro fertilization (IVF)., Design: Prospective cohort study., Setting: Academic infertility clinic., Patient(s): Women (n = 121) undergoing nondonor IVF embryo transfer (fresh or frozen)., Intervention(s): The women completed a questionnaire on past year physical activity and wore an accelerometer from embryo transfer to serum pregnancy testing., Main Outcome Measure(s): Implantation, intrauterine gestation, and live birth., Result(s): Based on self-reported past year physical activity, the adjusted odds of intrauterine gestation was higher among those that had higher continuous active living (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.09-3.50), sports/exercise (OR 1.48, CI 1.02-2.15), and total activity (OR 1.52, 95%CI 1.15-2.01) indices. After embryo transfer, women did almost no vigorous activity (median 0 min/d) as measured by the accelerometer. More of their time was spent in light activity (median 3.0 h/d) and sedentary behaviors (median 9.3 h/d). Accelerometer-measured physical activity and sedentary behavior after embryo transfer were not associated with any IVF outcome., Conclusion(s): An active lifestyle in the preceding year favorably impacted the IVF outcome. After embryo transfer, women engaged in mostly light physical activity and sedentary behaviors; therefore, the impact of vigorous physical activity on implantation could not be determined., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Genome-wide association studies (GWAS) and candidate gene analyses have led to the discovery of several dozen genetic polymorphisms associated with breast cancer susceptibility, many of which are considered well-established risk factors for the disease. Despite attempts to replicate these same variant-disease associations in African Americans, the evaluable populations are often too small to produce precise or consistent results. We estimated the associations between 83 previously identified single nucleotide polymorphisms (SNPs) and breast cancer among Carolina Breast Cancer Study (1993-2001) participants using maximum likelihood, Bayesian, and hierarchical methods. The selected SNPs were previous GWAS hits (n = 22), near-hits (n = 19), otherwise well-established risk loci (n = 5), or located in the same genes as selected variants (n = 37). We successfully replicated 18 GWAS-identified SNPs in whites (n = 2,352) and 10 in African Americans (n = 1,447). SNPs in the fibroblast growth factor receptor 2 gene (FGFR2) and the TOC high mobility group box family member 3 gene (TOX3) were strongly associated with breast cancer in both races. SNPs in the mitochondrial ribosomal protein S30 gene (MRPS30), mitogen-activated protein kinase kinase kinase 1 gene (MAP3K1), zinc finger, MIZ-type containing 1 gene (ZMIZ1), and H19, imprinted maternally expressed transcript gene (H19) were associated with breast cancer in whites, and SNPs in the estrogen receptor 1 gene (ESR1) and H19 gene were associated with breast cancer in African Americans. We provide precise and well-informed race-stratified odds ratios for key breast cancer-related SNPs. Our results demonstrate the utility of Bayesian methods in genetic epidemiology and provide support for their application in small, etiologically driven investigations.

The emergence of partnered sexual behavior represents an important developmental transition. However, little is known about individuals who remain sexually inexperienced well into adulthood. We used data from 2,857 individuals who participated in Waves I-IV of the National Longitudinal Study of Adolescent Health (Add Health) and reported no sexual activity (i.e., oral-genital, vaginal, or anal sex) by age 18 to identify, using discrete-time survival models, adolescent sociodemographic, biosocial, and behavioral characteristics that predicted adult sexual inexperience. The mean age of participants at Wave IV was 28.5 years (SD = 1.92). Over one out of eight participants who did not initiate sexual activity during adolescence remained abstinent as young adults. Sexual non-attraction significantly predicted sexual inexperience among both males (aOR = 0.5) and females (aOR = 0.6). Males also had lower odds of initiating sexual activity after age 18 if they were non-Hispanic Asian, reported later than average pubertal development, or were rated as physically unattractive (aORs = 0.6-0.7). Females who were overweight, had lower cognitive performance, or reported frequent religious attendance had lower odds of sexual experience (aORs = 0.7-0.8) while those who were rated by the interviewers as very attractive or whose parents had lower educational attainment had higher odds of sexual experience (aORs = 1.4-1.8). Our findings underscore the heterogeneity of this unique population and suggest that there are a number of different pathways that may lead to either voluntary or involuntary adult sexual inexperience. Understanding the meaning of sexual inexperience in young adulthood may have important implications for the study of sexuality development across the life course.

This article presents a multiple imputation method for sensitivity analyses of time-to-event data with possibly informative censoring. The imputed time for censored values is drawn from the failure time distribution conditional on the time of follow-up discontinuation. A variety of specifications regarding the post-discontinuation tendency of having events can be incorporated in the imputation through a hazard ratio parameter for discontinuation versus continuation of follow-up. Multiple-imputed data sets are analyzed with the primary analysis method, and the results are then combined using the methods of Rubin. An illustrative example is provided.

We examined consistency in self-reports of age at first vaginal sex among 9,399 male and female respondents who participated in Waves III and IV (separated by approximately seven years) of the National Longitudinal Study of Adolescent Health (Add Health). Respondents were coded as consistent if they reported an age at first vaginal intercourse at Wave IV that was within one year of the age they reported at Wave III. Sociodemographic, behavioral, and cognitive predictors of consistency were examined using bivariate and multivariate logistic regression. Overall, 85.43% of respondents were able to provide consistent reports. Among both males and females, consistency was associated with age, years since first vaginal intercourse, race/ethnicity, and lifetime number of other-sex partners in final multivariate models. Respondents who were older and had more recently had their first sexual experience were more likely to be consistent. For females only, those who reported a history of nonparental, physically forced sex were less likely to be consistent. Most young adults consistently report age at first vaginal intercourse, supporting the credibility of retrospective self-reports about salient sexual events such as timing of first vaginal intercourse.

Background: Gene expression analyses indicate that breast cancer is a heterogeneous disease with at least five immunohistologic subtypes. Despite growing evidence that these subtypes are etiologically and prognostically distinct, few studies have investigated whether they have divergent genetic risk factors. To help fill in this gap in our understanding, we examined associations between breast cancer subtypes and previously established susceptibility loci among white and African-American women in the Carolina Breast Cancer Study., Methods: We used Bayesian polytomous logistic regression to estimate ORs and 95% posterior intervals for the association between each of 78 single nucleotide polymorphisms (SNP) and five breast cancer subtypes. Subtypes were defined using five immunohistochemical markers: estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptors 1 and 2 (HER1/2), and cytokeratin (CK) 5/6., Results: Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2-) or basal-like breast cancer (ER-, PR-, HER2-, HER1, or CK 5/6+), and one SNP (rs3104746) was associated with both. SNPs in FGFR2 were associated with luminal A, luminal B (ER/PR+, HER2+), or HER2+/ER- disease, but none were associated with basal-like disease. We also observed subtype differences in the effects of SNPs in 2q35, 4p, TLR1, MAP3K1, ESR1, CDKN2A/B, ANKRD16, and ZM1Z1., Conclusion and Impact: We found evidence that genetic risk factors for breast cancer vary by subtype and further clarified the role of several key susceptibility genes. .

Objective: In adulthood, excess BMI is associated with cardiovascular disease (CVD); it is unknown whether risk differs by BMI trajectories from adolescence to adulthood., Design and Methods: The National Longitudinal Study of Adolescent Health, a nationally representative, longitudinal adolescent cohort (mean age: 16.9 years) followed into adulthood (mean age: 28.8 years) [n = 13,984 individuals (41,982 observations)] was examined. Separate logistic regression models for diabetes, hypertension, and inflammation were used to examine odds of risk factors at given adult BMI according to varying BMI trajectories from adolescence to adulthood., Results: CVD risk factor prevalence at follow-up ranged from 5.5% (diabetes) to 26.4% (hypertension) and 31.3% (inflammation); risk differed across BMI trajectories. For example, relative to men aged 27 years (BMI = 23 kg/m(2) maintained over full study period), odds for diabetes were comparatively higher for men of the same age and BMI ≈ 30 kg/m(2) with ≈8 BMI unit gain between 15 and 20 years (OR = 2.35; 95% CI, 1.51, 3.66) or in those who maintained BMI ≈ 30 kg/m(2) across the study period (OR = 2.33; 1.92, 2.83) relative to the same ≈8 BMI unit gain, but between 20 and 27 years (OR = 1.44; 1.10, 1.87)., Conclusions: Specific periods and patterns of weight gain in the transition from adolescence to adulthood might be critical for CVD preventive efforts., (Copyright © 2013 The Obesity Society.)

Objective: To assess the use of cervical mucus monitoring (CMM) in women trying to conceive and determine whether monitoring is associated with increased cycle-specific probability of conception (fecundability)., Design: Time-to-pregnancy cohort study., Setting: Population-based cohort., Patient(s): Three hundred thirty-one women trying to conceive, ages 30 to 44 years, without known infertility., Intervention(s): None., Main Outcome Measure(s): CMM prevalence and fecundability., Result(s): During the first cycle of the study, CMM was performed consistently (checked on >66% of pertinent cycle days) by 20 women (6%), inconsistently (34% to 66% of days) by 60 women (18%), infrequently (≤33% of days) by 73 women (22%), and not performed by 178 women (54%). Cycles in which CMM was consistently performed were statistically significantly more likely to result in conception after adjusting for age, race, previous pregnancy, body mass index, intercourse frequency, and urinary luteinizing hormone (LH) monitoring. Fecundability also increased with increasing consistency of CMM., Conclusion(s): Among women trying to conceive, CMM is uncommon, but our study suggests that CMM-a free, self-directed method to determine the fertile window-is associated with increased fecundability independent of intercourse frequency or use of urinary LH monitoring., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Heavy alcohol consumption increases risk of developing squamous cell carcinoma of the head and neck (SCCHN). Alcohol metabolism to cytotoxic and mutagenic intermediates acetaldehyde and reactive oxygen species is critical for alcohol-drinking-associated carcinogenesis. We hypothesized that polymorphisms in alcohol metabolism-related and antioxidant genes influence SCCHN survival., Methods: Interview and genotyping data (64 polymorphisms in 12 genes) were obtained from 1227 white and African-American cases from the Carolina Head and Neck Cancer Epidemiology study, a population-based case-control study of SCCHN conducted in North Carolina from 2002 to 2006. Vital status, date and cause of death through 2009 were obtained from the National Death Index. Kaplan-Meier log-rank tests and adjusted hazard ratios were calculated to identify alleles associated with survival., Results: Most tested SNPs were not associated with survival, with the exception of the minor alleles of rs3813865 and rs8192772 in CYP2E1. These were associated with poorer cancer-specific survival (HRrs3813865, 95% CI=2.00, 1.33-3.01; HRrs8192772, 95% CI=1.62, 1.17-2.23). Hazard ratios for 8 additional SNPs in CYP2E1, GPx2, SOD1, and SOD2, though not statistically significant, were suggestive of differences in allele hazards for all-cause and/or cancer death. No consistent associations with survival were found for SNPs in ADH1B, ADH1C, ADH4, ADH7, ALDH2, GPx2, GPx4, and CAT., Conclusions: We identified some polymorphisms in alcohol and oxidative stress metabolism genes that influence survival in subjects with SCCHN. Previously unreported associations of SNPs in CYP2E1 warrant further investigation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Cigarette smoking is associated with increased head and neck cancer (HNC) risk. Tobacco-related carcinogens are known to cause bulky DNA adducts. Nucleotide excision repair (NER) genes encode enzymes that remove adducts and may be independently associated with HNC, as well as modifiers of the association between smoking and HNC., Methods: Using population-based case-control data from the Carolina Head and Neck Cancer Epidemiology (CHANCE) Study (1,227 cases and 1,325 controls), race-stratified (White, African American), conventional, and hierarchical logistic regression models were used to estimate ORs with 95% intervals (I) for the independent and joint effects of cigarette smoking and 84 single-nucleotide polymorphisms (SNP) from 15 NER genes on HNC risk., Results: The odds of HNC were elevated among ever cigarette smokers and increased with smoking duration and frequency. Among Whites, rs4150403 on ERCC3 was associated with increased HNC odds (AA+AG vs. GG; OR, 1.28; 95% CI, 1.01-1.61). Among African Americans, rs4253132 on ERCC6 was associated with decreased HNC odds (CC+CT vs. TT; OR, 0.62; 95% CI, 0.45-0.86). Interactions between ever cigarette smoking and three SNPs (rs4253132 on ERCC6, rs2291120 on DDB2, and rs744154 on ERCC4) suggested possible departures from additivity among Whites., Conclusions: We did not find associations between some previously studied NER variants and HNC. We did identify new associations between two SNPs and HNC and three suggestive cigarette-SNP interactions to consider in future studies., Impact: We conducted one of the most comprehensive evaluations of NER variants, identifying a few SNPs from biologically plausible candidate genes associated with HNC and possibly interacting with cigarette smoking., (©2013 AACR)

Objective: Many of the individuals with serious mental illness involved in the criminal justice system have experienced interpersonal victimization, such as sexual abuse, and have high rates of alcohol and drug use disorders. Little attention has been paid to the prevalence of posttraumatic stress disorder (PTSD) and its potential role in the substance misuse of offenders with mental illness., Methods: The study used a path analytic framework to test the hypothesis that PTSD mediates the relationship between sexual abuse and level of alcohol and drug use among individuals (N=386) with mental illness enrolled in a multisite (N=7) jail diversion project., Results: Sexual abuse was strongly associated with PTSD, which was in turn associated with both heavy drug use and heavy drinking., Conclusions: These findings suggest that PTSD may be an important target for jail diversion programs.