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William Bekerman

Publications and source records attributed to William Bekerman.

7 recordsLinked to original sources

Powerful Multivariate Sensitivity Analysis via Sample Splitting in an Observational Study of the Effects of Poverty on Cardiovascular Disease Risk Factors

When assessing the causal effect of an exposure on two or more outcomes in an observational study, a linear combination of outcomes may lessen the sensitivity of a test of the global null hypothesis to potential unmeasured biases. While all linear combinations of scored outcomes can be considered using Scheffe projections or constrained variants thereof, finding the combination that minimizes sensitivity to unmeasured biases requires corrections for multiple testing, which can erode power, especially when many outcomes are of interest. To mitigate this issue, we propose splitting the sample into a planning sample to identify an optimal linear combination and an analysis sample to conduct inference. We provide a novel characterization of the set of linear combinations for which this approach is guaranteed to achieve the same asymptotic power as full-sample alternatives and conduct extensive simulation studies that demonstrate enhanced power in finite samples. Finally, we apply our method to investigate the effects of poverty on the emergence of cardiovascular disease risk factors in children and adolescents. We discover adverse consequences on outcomes related to body composition, physical activity, and tobacco exposure. Although the impact of poverty on elevated tobacco exposure shows some robustness to unmeasured confounding, the other findings remain sensitive to potential biases.

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Beyond the ACE Score: Replicable Combinations of Adverse Childhood Experiences That Worsen Depression Risk

Adverse childhood experiences (ACEs) are categories of childhood abuse, neglect, and household dysfunction. Screening by a single additive ACE score (e.g., a $\ge 4$ cutoff) has poor individual-level discrimination. We instead identify replicable combinations of ACEs that elevate adult depression risk. Our data turnover framework enables a single research team to explore, confirm, and replicate within one observational dataset while controlling the family-wise error rate. We integrate isotonic subgroup selection (ISS) to estimate a higher-risk subgroup under a monotonicity assumption -- additional ACE exposure or higher intensity cannot reduce depression risk. We pre-specify a risk threshold $\tau$ corresponding to roughly a two-fold increase in the odds of depression relative to the no-ACE baseline. Within data turnover, the prespecified component improves power while maintaining FWER control, as demonstrated in simulations. Guided by EDA, we adopt frequency coding for ACE items, retaining intensity information that reduces false positives relative to binary or score codings. The result is a replicable, pattern-based higher-risk subgroup. On held-out BRFSS 2022, we show that, at the same level of specificity (0.95), using our replicable subgroup as the screening rule increases sensitivity by 26\% compared with an ACE-score cutoff, yielding concrete triggers that are straightforward to implement and help target scarce clinical screening resources toward truly higher-risk profiles.

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Protocol For An Observational Study On The Effects Of Combinations Of Adverse Childhood Experiences On Adult Depression

Adverse childhood experiences (ACEs) have been linked to a wide range of negative health outcomes in adulthood. However, few studies have investigated what specific combinations of ACEs most substantially impact mental health. In this article, we provide the protocol for our observational study of the effects of combinations of ACEs on adult depression. We use data from the 2023 Behavioral Risk Factor Surveillance System (BRFSS) to assess these effects. We will evaluate the replicability of our findings by splitting the sample into two discrete subpopulations of individuals. We employ data turnover for this analysis, enabling a single team of statisticians and domain experts to collaboratively evaluate the strength of evidence, and also integrating both qualitative and quantitative insights from exploratory data analysis. We outline our analysis plan using this method and conclude with a brief discussion of several specifics for our study.

stat.AP

Protocol for an Observational Study on the Effects of Paternal Alcohol Use Disorder on Children's Later Life Outcomes

The harmful effects of growing up with a parent with an alcohol use disorder have been closely examined in children and adolescents, and are reported to include mental and physical health problems, interpersonal difficulties, and a worsened risk of future substance use disorders. However, few studies have investigated how these impacts evolve into later life adulthood, leaving the ensuing long-term effects of interest. In this article, we provide the protocol for our observational study of the long-term consequences of growing up with a father who had an alcohol use disorder. We will use data from the Wisconsin Longitudinal Study to examine impacts on long-term economic success, interpersonal relationships, physical, and mental health. To reinforce our findings, we will conduct this investigation on two discrete subpopulations of individuals in our study, allowing us to analyze the replicability of our conclusions. We introduce a novel statistical design, called data turnover, to carry out this analysis. Data turnover allows a single group of statisticians and domain experts to work together to assess the strength of evidence gathered across multiple data splits, while incorporating both qualitative and quantitative findings from data exploration. We delineate our analysis plan using this new method and conclude with a brief discussion of some additional considerations for our study.

stat.AP

Planning for gold: Hypothesis screening with split samples for valid powerful testing in matched observational studies

Observational studies are valuable tools for inferring causal effects in the absence of controlled experiments. However, these studies may be biased due to the presence of some relevant, unmeasured set of covariates. One approach to mitigate this concern is to identify hypotheses likely to be more resilient to hidden biases by splitting the data into a planning sample for designing the study and an analysis sample for making inferences. We devise a powerful and flexible method for selecting hypotheses in the planning sample when an unknown number of outcomes are affected by the treatment, allowing researchers to gain the benefits of exploratory analysis and still conduct powerful inference under concerns of unmeasured confounding. We investigate the theoretical properties of our method and conduct extensive simulations that demonstrate pronounced benefits, especially at higher levels of allowance for unmeasured confounding. Finally, we demonstrate our method in an observational study of the multi-dimensional impacts of a devastating flood in Bangladesh.

stat.ME

Comparison of CYGNSS and Jason-3 Wind Speed Measurements via Gaussian Processes

Wind is a critical component of the Earth system and has unmistakable impacts on everyday life. The CYGNSS satellite mission improves observational coverage of ocean winds via a fleet of eight micro-satellites that use reflected GNSS signals to infer surface wind speed. We present analyses characterizing variability in wind speed measurements among the eight CYGNSS satellites and between antennas. In particular, we use a carefully constructed Gaussian process model that leverages comparisons between CYGNSS and Jason-3 during a one-year period from September 2019 to September 2020. The CYGNSS sensors exhibit a range of biases, most of them between -1.0 m/s and +0.2 m/s with respect to Jason-3, indicating that some CYGNSS sensors are biased with respect to one another and with respect to Jason-3. The biases between the starboard and port antennas within a CYGNSS satellite are smaller. Our results are consistent with, yet sharper than, a more traditional paired comparison analysis. We also explore the possibility that the bias depends on wind speed, finding some evidence that CYGNSS satellites have positive biases with respect to Jason-3 at low wind speeds. However, we argue that there are subtle issues associated with estimating wind speed-dependent biases, so additional careful statistical modeling and analysis is warranted.

stat.AP

RZiMM-scRNA: A regularized zero-inflated mixture model framework for single-cell RNA-seq data

Applications of single-cell RNA sequencing in various biomedical research areas have been blooming. This new technology provides unprecedented opportunities to study disease heterogeneity at the cellular level. However, unique characteristics of scRNA-seq data, including large dimensionality, high dropout rates, and possibly batch effects, bring great difficulty into the analysis of such data. Not appropriately addressing these issues obstructs true scientific discovery. Herein, we propose a unified Regularized Zero-inflated Mixture Model framework designed for scRNA-seq data (RZiMM-scRNA) to simultaneously detect cell subgroups and identify gene differential expression based on a developed importance score, accounting for both dropouts and batch effects. We conduct extensive simulation studies in which we evaluate the performance of RZiMM-scRNA and compare it with several popular methods, including Seurat, SC3, K-Means, and Hierarchical Clustering. Simulation results show that RZiMM-scRNA demonstrates superior clustering performance and enhanced biomarker detection accuracy compared to alternative methods, especially when cell subgroups are less distinct, verifying the robustness of our method. Our empirical investigations focus on two brain tumor studies dealing with astrocytoma of various grades, including the most malignant of all brain tumors, glioblastoma multiforme (GBM). Our goal is to delineate cell heterogeneity and identify driving biomarkers associated with these tumors. Notably, RZiMM-scNRA successfully identifies a small group of oligodendrocyte cells which has drawn much attention in biomedical literature on brain cancers.

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