Statistical Theory Commons^™

A Predictive Coding Account Of Spatial Working Memory Following Prophylactic Levetiracetam Administration Prior To Traumatic Brain Injury, Omeima Mutwali

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) symptom prevention and remediation is an important area of research that would benefit vulnerable groups, including active-duty and veteran soldiers. These patients can sustain penetrative forces in fields of combat or in training, which result in focal lesions that trigger inflammatory and degenerative processes in the brain. Both primary and secondary injuries are associated with changes to cognition, behavior and affective state. This disease poses increased risk of epileptogenesis, as well. Given these outcomes, prior research has evaluated levetiracetam (LEV) as a prophylactic treatment for seizures, cognitive deficits and negative emotionality. LEV acts as a presynaptic …

Theoretical Foundations And Applied Performance Of Periodicity-Aware Imputation: Variable Bandpass Block Bootstrap Methods For Incomplete Time Series, Asmaa Ahmad

Electronic Theses & Dissertations (2024 - present)

Time series data are prevalent across a wide range of disciplines, including health surveillance, public policy, and environmental monitoring. In the presence of underlying cyclical patterns, the integrity of time series analysis depends critically on the ability to detect, model, and impute structured missing data without compromising the temporal structure. This dissertation introduces and validates a novel imputation framework that integrates the Variable Bandpass Periodic Block Bootstrap (VBPBB) into multiple imputation procedures, improving the accuracy, robustness, and interpretability of time series models under high rates of missingness and noise. The overarching goal of this dissertation was to develop and evaluate …

Latent Classification Of Multi-Model Non-Homogeneous Continuous-Time Markov Chains, Joonha Chang

Dissertations and Theses (Open Access)

The continuous-time Markov chain (CTMC) model and latent clustering models are commonly used to study longitudinal measures of categorical outcomes. Because of its simple but powerful Markovian property, CTMC models have been widely used in medical and public health researches. Due to limitations in the standard CTMC model, there have been some studies on non-homogeneous continuous-time Markov chain (NH-CTMC) that utilized time-dependent rates, but the progresses have been limited. NH-CTMC can be more powerful than CTMC by its default nature of time-dependent rate that can be fitted to a wider range of applications in medical studies. In this study, we …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

Accounting For The Uncertainty Due To Chemicals Below The Detection Limit In Mixture Analysis, Paul M. Hargarten

Theses and Dissertations

Humans are exposed to multiple chemicals every day. Epidemiological studies have shown that chemical mixtures are associated with cancers, allergies, neurodevelopmental disorders, and other adverse health effects. To assess these associations, investigators are increasingly using chemical mixture approaches like weighted quantile sum (WQS) regression. In these studies, the research objectives are to determine whether a mixture of correlated chemicals is associated with an adverse health outcome and to identify the important chemicals. However, as experimental equipment measures each exposure to a chemical-specific detection limit, the exposures are unknown between zero and the detection limit. Indeed, the number of exposures below …

Evaluation Of Progress Towards The Unaids 90-90-90 Hiv Care Cascade: A Description Of Statistical Methods Used In An Interim Analysis Of The Intervention Communities In The Search Study, Laura Balzer, Joshua Schwab, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

WHO guidelines call for universal antiretroviral treatment, and UNAIDS has set a global target to virally suppress most HIV-positive individuals. Accurate estimates of population-level coverage at each step of the HIV care cascade (testing, treatment, and viral suppression) are needed to assess the effectiveness of "test and treat" strategies implemented to achieve this goal. The data available to inform such estimates, however, are susceptible to informative missingness: the number of HIV-positive individuals in a population is unknown; individuals tested for HIV may not be representative of those whom a testing intervention fails to reach, and HIV-positive individuals with a viral …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Adaptive Pair-Matching In The Search Trial And Estimation Of The Intervention Effect, Laura Balzer, Maya L. Petersen, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In randomized trials, pair-matching is an intuitive design strategy to protect study validity and to potentially increase study power. In a common design, candidate units are identified, and their baseline characteristics used to create the best n/2 matched pairs. Within the resulting pairs, the intervention is randomized, and the outcomes measured at the end of follow-up. We consider this design to be adaptive, because the construction of the matched pairs depends on the baseline covariates of all candidate units. As consequence, the observed data cannot be considered as n/2 independent, identically distributed (i.i.d.) pairs of units, as current practice assumes. …

Estimating Effects On Rare Outcomes: Knowledge Is Power, Laura B. Balzer, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Many of the secondary outcomes in observational studies and randomized trials are rare. Methods for estimating causal effects and associations with rare outcomes, however, are limited, and this represents a missed opportunity for investigation. In this article, we construct a new targeted minimum loss-based estimator (TMLE) for the effect of an exposure or treatment on a rare outcome. We focus on the causal risk difference and statistical models incorporating bounds on the conditional risk of the outcome, given the exposure and covariates. By construction, the proposed estimator constrains the predicted outcomes to respect this model knowledge. Theoretically, this bounding provides …

Assessing Association For Bivariate Survival Data With Interval Sampling: A Copula Model Approach With Application To Aids Study, Hong Zhu, Mei-Cheng Wang

Johns Hopkins University, Dept. of Biostatistics Working Papers

In disease surveillance systems or registries, bivariate survival data are typically collected under interval sampling. It refers to a situation when entry into a registry is at the time of the first failure event (e.g., HIV infection) within a calendar time interval, the time of the initiating event (e.g., birth) is retrospectively identified for all the cases in the registry, and subsequently the second failure event (e.g., death) is observed during the follow-up. Sampling bias is induced due to the selection process that the data are collected conditioning on the first failure event occurs within a time interval. Consequently, the …

A Regularization Corrected Score Method For Nonlinear Regression Models With Covariate Error, David M. Zucker, Malka Gorfine, Yi Li, Donna Spiegelman

Harvard University Biostatistics Working Paper Series

No abstract provided.

Variable Importance Analysis With The Multipim R Package, Stephan J. Ritter, Nicholas P. Jewell, Alan E. Hubbard

U.C. Berkeley Division of Biostatistics Working Paper Series

We describe the R package multiPIM, including statistical background, functionality and user options. The package is for variable importance analysis, and is meant primarily for analyzing data from exploratory epidemiological studies, though it could certainly be applied in other areas as well. The approach taken to variable importance comes from the causal inference field, and is different from approaches taken in other R packages. By default, multiPIM uses a double robust targeted maximum likelihood estimator (TMLE) of a parameter akin to the attributable risk. Several regression methods/machine learning algorithms are available for estimating the nuisance parameters of the models, including …

Minimum Description Length And Empirical Bayes Methods Of Identifying Snps Associated With Disease, Ye Yang, David R. Bickel

COBRA Preprint Series

The goal of determining which of hundreds of thousands of SNPs are associated with disease poses one of the most challenging multiple testing problems. Using the empirical Bayes approach, the local false discovery rate (LFDR) estimated using popular semiparametric models has enjoyed success in simultaneous inference. However, the estimated LFDR can be biased because the semiparametric approach tends to overestimate the proportion of the non-associated single nucleotide polymorphisms (SNPs). One of the negative consequences is that, like conventional p-values, such LFDR estimates cannot quantify the amount of information in the data that favors the null hypothesis of no disease-association.

We …

Landmark Prediction Of Survival, Layla Parast, Tianxi Cai

Harvard University Biostatistics Working Paper Series

No abstract provided.

Nonparametric Regression With Missing Outcomes Using Weighted Kernel Estimating Equations, Lu Wang, Andrea Rotnitzky, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Survival Analysis With Error-Prone Time-Varying Covariates: A Risk Set Calibration Approach, Xiaomei Liao, David M. Zucker, Yi Li, Donna Spiegelman

Harvard University Biostatistics Working Paper Series

No abstract provided.

Causal Inference For Nested Case-Control Studies Using Targeted Maximum Likelihood Estimation, Sherri Rose, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

A nested case-control study is conducted within a well-defined cohort arising out of a population of interest. This design is often used in epidemiology to reduce the costs associated with collecting data on the full cohort; however, the case control sample within the cohort is a biased sample. Methods for analyzing case-control studies have largely focused on logistic regression models that provide conditional and not marginal causal estimates of the odds ratio. We previously developed a Case-Control Weighted Targeted Maximum Likelihood Estimation (TMLE) procedure for case-control study designs, which relies on the prevalence probability q0. We propose the use of …

Spatial Cluster Detection For Repeatedly Measured Outcomes While Accounting For Residential History, Andrea J. Cook, Diane Gold, Yi Li

Harvard University Biostatistics Working Paper Series

No abstract provided.

Spatial Cluster Detection For Weighted Outcomes Using Cumulative Geographic Residuals, Andrea J. Cook, Yi Li, David Arterburn, Ram C. Tiwari

Harvard University Biostatistics Working Paper Series

No abstract provided.

The Importance Of Scale For Spatial-Confounding Bias And Precision Of Spatial Regression Estimators, Christopher J. Paciorek

Harvard University Biostatistics Working Paper Series

Increasingly, regression models are used when residuals are spatially correlated. Prominent examples include studies in environmental epidemiology to understand the chronic health effects of pollutants. I consider the effects of residual spatial structure on the bias and precision of regression coefficients, developing a simple framework in which to understand the key issues and derive informative analytic results. When the spatial residual is induced by an unmeasured confounder, regression models with spatial random effects and closely-related models such as kriging and penalized splines are biased, even when the residual variance components are known. Analytic and simulation results show how the bias …

Analysis Of Randomized Comparative Clinical Trial Data For Personalized Treatment Selections, Tianxi Cai, Lu Tian, Peggy H. Wong, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Small Sample Correction For Estimating Attributable Risk In Case-Control Studies, Daniel B. Rubin

U.C. Berkeley Division of Biostatistics Working Paper Series

The attributable risk, often called the population attributable risk, is in many epidemiological contexts a more relevant measure of exposure-disease association than the excess risk, relative risk, or odds ratio. When estimating attributable risk with case-control data and a rare disease, we present a simple correction to the standard approach making it essentially unbiased, and also less noisy. As with analogous corrections given in Jewell (1986) for other measures of association, the adjustment often won't make a substantial difference unless the sample size is very small or point estimates are desired within fine strata, but we discuss the possible utility …

Calibrating Parametric Subject-Specific Risk Estimation, Tianxi Cai, Lu Tian, Hajime Uno, Scott D. Solomon, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Evaluating Subject-Level Incremental Values Of New Markers For Risk Classification Rule, Tianxi Cai, Lu Tian, Donald M. Lloyd-Jones, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Nonparametric Regression Using Local Kernel Estimating Equations For Correlated Failure Time Data, Zhangsheng Yu, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Comparison Of Methods For Estimating The Causal Effect Of A Treatment In Randomized Clinical Trials Subject To Noncompliance, Rod Little, Qi Long, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Semiparametric Maximum Likelihood Estimation In Normal Transformation Models For Bivariate Survival Data, Yi Li, Ross L. Prentice, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Doubly Robust Ecological Inference, Daniel B. Rubin, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

The ecological inference problem is a famous longstanding puzzle that arises in many disciplines. The usual formulation in epidemiology is that we would like to quantify an exposure-disease association by obtaining disease rates among the exposed and unexposed, but only have access to exposure rates and disease rates for several regions. The problem is generally intractable, but can be attacked under the assumptions of King's (1997) extended technique if we can correctly specify a model for a certain conditional distribution. We introduce a procedure that it is a valid approach if either this original model is correct or if we …

Marginal Structural Models For Partial Exposure Regimes, Stijn Vansteelandt, Karl Mertens, Carl Suetens, Els Goetghebeur

Harvard University Biostatistics Working Paper Series

Intensive care unit (ICU) patients are ell known to be highly susceptible for nosocomial (i.e. hospital-acquired) infections due to their poor health and many invasive therapeutic treatments. The effects of acquiring such infections in ICU on mortality are however ill understood. Our goal is to quantify these effects using data from the National Surveillance Study of Nosocomial Infections in Intensive Care

Units (Belgium). This is a challenging problem because of the presence of time-dependent confounders (such as exposure to mechanical ventilation)which lie on the causal path from infection to mortality. Standard statistical analyses may be severely misleading in such settings …

Estimation Of Controlled Direct Effects, Sylvie Goetgeluk, Stijn Vansteelandt, Els Goetghebeur

Harvard University Biostatistics Working Paper Series

No abstract provided.