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Stephanie M. Engel

Publications and source records attributed to Stephanie M. Engel.

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Prenatal phthalate exposures and adiposity outcomes trajectories: a multivariate Bayesian factor regression approach

Experimental animal evidence and a growing body of observational studies suggest that prenatal exposure to phthalates may be a risk factor for childhood obesity. Using data from the Mount Sinai Children's Environmental Health Study (MSCEHS), which measured urinary phthalate metabolites (including MEP, MnBP, MiBP, MCPP, MBzP, MEHP, MEHHP, MEOHP, and MECPP) during the third trimester of pregnancy (between 25 and 40 weeks) of 382 mothers, we examined adiposity outcomes: body mass index (BMI), fat mass percentage, waist-to-hip ratio, and waist circumference, of 180 children between ages 4 and 9. We aimed to assess the effects of prenatal exposure to phthalates on these adiposity outcomes, with potential time-varying and sex-specific effects. We applied a novel Bayesian multivariate factor regression (BMFR) that (1) represents phthalate mixtures as latent factors, a DEHP and a non-DEHP factor, (2) borrows information across highly correlated adiposity outcomes to improve estimation precision, (3) models potentially non-linear time-varying effects of the latent factors on adiposity outcomes, and (4) fully quantifies uncertainty using state-of-the-art prior specifications. The results show that in boys, at younger ages (4-6), all phthalate components are associated with lower adiposity outcomes; however, after age 7, they are associated with higher outcomes. In girls, there is no evidence of associations between phthalate factors and adiposity outcomes.

stat.ME

Inferring Synergistic and Antagonistic Interactions in Mixtures of Exposures

There is abundant interest in assessing the joint effects of multiple exposures on human health. This is often referred to as the mixtures problem in environmental epidemiology and toxicology. Classically, studies have examined the adverse health effects of different chemicals one at a time, but there is concern that certain chemicals may act together to amplify each other's effects. Such amplification is referred to as synergistic interaction, while chemicals that inhibit each other's effects have antagonistic interactions. Current approaches for assessing the health effects of chemical mixtures do not explicitly consider synergy or antagonism in the modeling, instead focusing on either parametric or unconstrained nonparametric dose response surface modeling. The parametric case can be too inflexible, while nonparametric methods face a curse of dimensionality that leads to overly wiggly and uninterpretable surface estimates. We propose a Bayesian approach that decomposes the response surface into additive main effects and pairwise interaction effects, and then detects synergistic and antagonistic interactions. Variable selection decisions for each interaction component are also provided. This Synergistic Antagonistic Interaction Detection (SAID) framework is evaluated relative to existing approaches using simulation experiments and an application to data from NHANES.

stat.AP

mpower: An R Package for Power Analysis of Exposure Mixture Studies via Monte Carlo Simulations

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.

stat.ME

Bayesian Matrix Completion for Hypothesis Testing

We aim to infer bioactivity of each chemical by assay endpoint combination, addressing sparsity of toxicology data. We propose a Bayesian hierarchical framework which borrows information across different chemicals and assay endpoints, facilitates out-of-sample prediction of activity for chemicals not yet assayed, quantifies uncertainty of predicted activity, and adjusts for multiplicity in hypothesis testing. Furthermore, this paper makes a novel attempt in toxicology to simultaneously model heteroscedastic errors and a nonparametric mean function, leading to a broader definition of activity whose need has been suggested by toxicologists. Real application identifies chemicals most likely active for neurodevelopmental disorders and obesity.

stat.AP

A Bayesian approach to the g-formula

Epidemiologists often wish to estimate quantities that are easy to communicate and correspond to the results of realistic public health scenarios. Methods from causal inference can answer these questions. We adopt the language of potential outcomes under Rubin's original Bayesian framework and show that the parametric g-formula is easily amenable to a Bayesian approach. We show that the frequentist properties of the Bayesian g-formula suggest it improves the accuracy of estimates of causal effects in small samples or when data may be sparse. We demonstrate our approach to estimate the effect of environmental tobacco smoke on body mass index z-scores among children aged 4-9 years who were enrolled in a longitudinal birth cohort in New York, USA. We give a general algorithm and supply SAS and Stan code that can be adopted to implement our computational approach in both time-fixed and longitudinal data.

stat.ME