mpower: An R Package for Power Analysis via Simulation for Correlated Data

Estimating sample size and statistical power is an essential part of a good study design. This R package allows users to conduct power analysis based on Monte Carlo simulations in settings in which consideration of the correlations between predictors is important. It runs power analyses given a data generative model and an inference model. It can set up a data generative model that preserves dependence structures among variables given existing data (continuous, binary, or ordinal) or high-level descriptions of the associations. Users can generate power curves to assess the trade-offs between sample size, effect size, and power of a design. This paper presents tutorials and examples focusing on applications for environmental mixture studies when predictors tend to be moderately to highly correlated. It easily interfaces with several existing and newly developed analysis strategies for assessing associations between exposures and health outcomes. However, the package is sufficiently general to facilitate power simulations in a wide variety of settings

Alpha-defensins 1-3 Release by Dendritic Cells is Reduced by Estrogen

During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response. We compare culture-generated monocyte derived DCs (MDDCs) with directly isolated myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG) treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy

Causal Inference Considerations for Endocrine Disruptor Research in Children's Health

Substantial population exposure to endocrine disrupting chemicals, combined with available biomarkers and public concern, has resulted in an explosion of human health effects research. At the same time, remarkable shifts in the regulations governing the composition of some consumer products that contain endocrine disruptors (EDs) has occurred. However, important questions remain as to the weight of evidence linking EDs to human health end points. In this review, we critically examine the literature linking ED exposures to child neurodevelopment, focusing in particular on two model exposures to demonstrate issues related to bioaccumulative [e.g., polychlorinated biphenyls (PCBs)] and rapidly metabolized (e.g., phthalates) compounds, respectively. Issues of study design, confounding, and exposure measurement are considered. Given widespread exposure to these compounds, the potential public health consequences of even small effects on human health are substantial. Therefore, advancing our understanding of any impact calls for careful attention to the principles of causal inference

Prenatal exposure to environmental phenols and childhood fat mass in the Mount Sinai Children's Environmental Health Study

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 9 years (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

Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

<p>Abstract</p> <p>Background</p> <p>During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response.</p> <p>Methods</p> <p>We compare culture-generated monocyte derived DCs (MDDCs) with directly isolated myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG) treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy.</p> <p>Results</p> <p>We show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients.</p> <p>Conclusions</p> <p>Here, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.</p

Emerging exposures of developmental toxicants

PURPOSE OF REVIEW: The purpose of this review is to identify emerging developmental toxicants that are understudied in children's health. Exposures may arise from new products designed to improve utility, to reduce toxicity, or to replace undesirable chemicals. Exposures to less-toxic chemicals may also be significant if they are very commonly used, thereby generating widespread exposure. Sources of exposure include the workplace, personal, home, and office products; food, water, and air. RECENT FINDINGS: We describe eight exposure categories that contain numerous potential developmental toxicants. References are discussed if reported in PubMed during the past decade at least 10 times more frequently than in 1990-2000. Examples included phthalates, phenols, sunscreens, pesticides, halogenated flame retardants, perfluoroalkyl coatings, nanoparticles, e-cigarettes, and dietary polyphenols. Replacements are often close structural homologs of their precursors. We suggest biomonitoring as preferred means of exposure assessment to emerging chemicals. Some existing analytic methods would require minimal modification to measure these exposures, but others require toxicokinetic and analytic investigation. SUMMARY: A deliberate strategy for biomonitoring of emerging replacement chemicals is warranted, especially in view of concerns regarding developmental toxicity. To prevent adverse health effects, it is important to characterize such exposures before they become widely disseminated

Prenatal phthalate biomarker concentrations and performance on the Bayley Scales of Infant Development-II in a population of young urban children

Evidence suggests prenatal phthalate exposures may have neurodevelopmental consequences. Our objective was to investigate prenatal exposure to phthalates and cognitive development in a cohort of young urban children

County-level hurricane exposure and birth rates: application of difference-in-differences analysis for confounding control

Abstract Background Epidemiological analyses of aggregated data are often used to evaluate theoretical health effects of natural disasters. Such analyses are susceptible to confounding by unmeasured differences between the exposed and unexposed populations. To demonstrate the difference-in-difference method our population included all recorded Florida live births that reached 20 weeks gestation and conceived after the first hurricane of 2004 or in 2003 (when no hurricanes made landfall). Hurricane exposure was categorized using ≥74 mile per hour hurricane wind speed as well as a 60 km spatial buffer based on weather data from the National Oceanic and Atmospheric Administration. The effect of exposure was quantified as live birth rate differences and 95 % confidence intervals [RD (95 % CI)]. To illustrate sensitivity of the results, the difference-in-differences estimates were compared to general linear models adjusted for census-level covariates. This analysis demonstrates difference-in-differences as a method to control for time-invariant confounders investigating hurricane exposure on live birth rates. Results Difference-in-differences analysis yielded consistently null associations across exposure metrics and hurricanes for the post hurricane rate difference between exposed and unexposed areas (e.g., Hurricane Ivan for 60 km spatial buffer [−0.02 births/1000 individuals (−0.51, 0.47)]. In contrast, general linear models suggested a positive association between hurricane exposure and birth rate [Hurricane Ivan for 60 km spatial buffer (2.80 births/1000 individuals (1.94, 3.67)] but not all models. Conclusions Ecological studies of associations between environmental exposures and health are susceptible to confounding due to unmeasured population attributes. Here we demonstrate an accessible method of control for time-invariant confounders for future research

Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood

Background: Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates