Statistics and Probability Commons^™

Natural Lead-In Approaches To Response-Adaptive Allocation In Clinical Trials, Erin E. Donahue

Theses and Dissertations

Response-adaptive (RA) allocation designs can be implemented in clinical trials to skew the allocation of incoming subjects toward the better performing treatment group based on the previously accrued subjects' responses. These designs alleviate potential ethical concerns of equally allocating subjects in a trial when one treatment arm is inferior. The RA design can be generalized to include covariate information in the covariate-adjusted response-adaptive (CARA) design, which aims to maximize treatment successes conditional on a set of patient characteristics. While RA and CARA designs can improve the treatment of patients, they have unstable estimators and increased variability in early stages of …

Phenotype Extraction: Estimation And Biometrical Genetic Analysis Of Individual Dynamics, Kevin L. Mckee

Theses and Dissertations

Within-person data can exhibit a virtually limitless variety of statistical patterns, but it can be difficult to distinguish meaningful features from statistical artifacts. Studies of complex traits have previously used genetic signals like twin-based heritability to distinguish between the two. This dissertation is a collection of studies applying state-space modeling to conceptualize and estimate novel phenotypic constructs for use in psychiatric research and further biometrical genetic analysis. The aims are to: (1) relate control theoretic concepts to health-related phenotypes; (2) design statistical models that formally define those phenotypes; (3) estimate individual phenotypic values from time series data; (4) consider hierarchical …

Estimating Response Status In Sequential Multiple Assignment (Smar)-Like Trials, Keighly Bradbrook

Theses and Dissertations

Sequential, multiple assignment, randomized trials (SMARTs) allow investigators to develop and compare experimental treatment regimens in which individuals are successively randomized to different treatments based on some set of predetermined rules. The rules used to make decisions on when and how to switch treatments are based on a chosen set of tailoring variables. Although not always true, intermediate response is commonly used as the primary tailoring variable as it is often predictive of future treatment success. As such, successful implementation depends on identifying patients who respond to treatment, though in some situations such mechanisms may not exist. Further, patient-level covariates …

The Analysis Of Neural Heterogeneity Through Mathematical And Statistical Methods, Kyle Wendling

Theses and Dissertations

Diversity of intrinsic neural attributes and network connections is known to exist in many areas of the brain and is thought to significantly affect neural coding. Recent theoretical and experimental work has argued that in uncoupled networks, coding is most accurate at intermediate levels of heterogeneity. I explore this phenomenon through two distinct approaches: a theoretical mathematical modeling approach and a data-driven statistical modeling approach.

Through the mathematical approach, I examine firing rate heterogeneity in a feedforward network of stochastic neural oscillators utilizing a high-dimensional model. The firing rate heterogeneity stems from two sources: intrinsic (different individual cells) and network …

Characterizing The Permanence And Stationary Distribution For A Family Of Malaria Stochastic Models, Divine Wanduku

Biology and Medicine Through Mathematics Conference

No abstract provided.

Quantifying Sleep Architecture For Pediatric Hypersomnia Conditions, Alicia K. Colclasure

Biology and Medicine Through Mathematics Conference

No abstract provided.

Bayesian Nonparametric Analysis Of Longitudinal Data With Non-Ignorable Non-Monotone Missingness, Yu Cao

Theses and Dissertations

In longitudinal studies, outcomes are measured repeatedly over time, but in reality clinical studies are full of missing data points of monotone and non-monotone nature. Often this missingness is related to the unobserved data so that it is non-ignorable. In such context, pattern-mixture model (PMM) is one popular tool to analyze the joint distribution of outcome and missingness patterns. Then the unobserved outcomes are imputed using the distribution of observed outcomes, conditioned on missing patterns. However, the existing methods suffer from model identification issues if data is sparse in specific missing patterns, which is very likely to happen with a …

Site- And Location-Adjusted Approaches To Adaptive Allocation Clinical Trial Designs, Brian S. Di Pace

Theses and Dissertations

Response-Adaptive (RA) designs are used to adaptively allocate patients in clinical trials. These methods have been generalized to include Covariate-Adjusted Response-Adaptive (CARA) designs, which adjust treatment assignments for a set of covariates while maintaining features of the RA designs. Challenges may arise in multi-center trials if differential treatment responses and/or effects among sites exist. We propose Site-Adjusted Response-Adaptive (SARA) approaches to account for inter-center variability in treatment response and/or effectiveness, including either a fixed site effect or both random site and treatment-by-site interaction effects to calculate conditional probabilities. These success probabilities are used to update assignment probabilities for allocating patients …

Methods For Evaluating Dropout Attrition In Survey Data, Camille J. Hochheimer

Theses and Dissertations

As researchers increasingly use web-based surveys, the ease of dropping out in the online setting is a growing issue in ensuring data quality. One theory is that dropout or attrition occurs in phases that can be generalized to phases of high dropout and phases of stable use. In order to detect these phases, several methods are explored. First, existing methods and user-specified thresholds are applied to survey data where significant changes in the dropout rate between two questions is interpreted as the start or end of a high dropout phase. Next, survey dropout is considered as a time-to-event outcome and …

Assessing The Impact Of Incorporating Residential Histories Into The Spatial Analysis Of Cancer Risk, Anny-Claude Joseph

Theses and Dissertations

In many spatial epidemiologic studies, investigators use residential location at diagnosis as a surrogate for unknown environmental exposures or as a geographic basis for assigning measured exposures. Inherently, they make assumptions about the timing and location of pertinent exposures which may prove problematic when studying long latency diseases such as cancer.

In this work we explored how the association between environmental exposures and disease risk for long-latency health outcomes like cancer is affected by residential mobility. We used simulation studies conditioned on real data to evaluate the extent to which the commonly held assumption of no residential mobility 1) affected …

Methods For Joint Normalization And Comparison Of Hi-C Data, John C. Stansfield

Theses and Dissertations

The development of chromatin conformation capture technology has opened new avenues of study into the 3D structure and function of the genome. Chromatin structure is known to influence gene regulation, and differences in structure are now emerging as a mechanism of regulation between, e.g., cell differentiation and disease vs. normal states. Hi-C sequencing technology now provides a way to study the 3D interactions of the chromatin over the whole genome. However, like all sequencing technologies, Hi-C suffers from several forms of bias stemming from both the technology and the DNA sequence itself. Several normalization methods have been developed for normalizing …

Latent Growth Model Approach To Characterize Maternal Prenatal Dna Methylation Trajectories, Dana Lapato

Theses and Dissertations

Background. DNA methylation (DNAm) is a removable chemical modification to the DNA sequence intimately associated with genomic stability, cellular identity, and gene expression. DNAm patterning reflects joint contributions from genetic, environmental, and behavioral factors. As such, differences in DNAm patterns may explain interindividual variability in risk liability for complex traits like major depression (MD). Hundreds of significant DNAm loci have been identified using cross-sectional association studies. This dissertation builds on that foundational work to explore novel statistical approaches for longitudinal DNAm analyses. Methods. Repeated measures of genome-wide DNAm and social and environmental determinants of health were collected up to six …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Spectral Methods For The Detection And Characterization Of Topologically Associated Domains, Kellen Garrison Cresswell

Theses and Dissertations

The three-dimensional (3D) structure of the genome plays a crucial role in gene expression regulation. Chromatin conformation capture technologies (Hi-C) have revealed that the genome is organized in a hierarchy of topologically associated domains (TADs), sub-TADs, and chromatin loops which is relatively stable across cell-lines and even across species. These TADs dynamically reorganize during development of disease, and exhibit cell- and conditionspecific differences. Identifying such hierarchical structures and how they change between conditions is a critical step in understanding genome regulation and disease development. Despite their importance, there are relatively few tools for identification of TADs and even fewer for …

Statistical Designs For Network A/B Testing, Victoria V. Pokhilko

Theses and Dissertations

A/B testing refers to the statistical procedure of experimental design and analysis to compare two treatments, A and B, applied to different testing subjects. It is widely used by technology companies such as Facebook, LinkedIn, and Netflix, to compare different algorithms, web-designs, and other online products and services. The subjects participating in these online A/B testing experiments are users who are connected in different scales of social networks. Two connected subjects are similar in terms of their social behaviors, education and financial background, and other demographic aspects. Hence, it is only natural to assume that their reactions to online products …

Stochastic Averaging For Multiple Cooperative And Antagonistic Molecular Motors, Joe Klobusicky

Biology and Medicine Through Mathematics Conference

No abstract provided.

Quantitative Electroencephalography For Detecting Concussions, Sara Krehbiel, Kathy Hoke, Joanna Wares

Biology and Medicine Through Mathematics Conference

No abstract provided.

Penalized Mixed-Effects Ordinal Response Models For High-Dimensional Genomic Data In Twins And Families, Amanda E. Gentry

Theses and Dissertations

The Brisbane Longitudinal Twin Study (BLTS) was being conducted in Australia and was funded by the US National Institute on Drug Abuse (NIDA). Adolescent twins were sampled as a part of this study and surveyed about their substance use as part of the Pathways to Cannabis Use, Abuse and Dependence project. The methods developed in this dissertation were designed for the purpose of analyzing a subset of the Pathways data that includes demographics, cannabis use metrics, personality measures, and imputed genotypes (SNPs) for 493 complete twin pairs (986 subjects.) The primary goal was to determine what combination of SNPs and …

Examining The Confirmatory Tetrad Analysis (Cta) As A Solution Of The Inadequacy Of Traditional Structural Equation Modeling (Sem) Fit Indices, Hangcheng Liu

Theses and Dissertations

Structural Equation Modeling (SEM) is a framework of statistical methods that allows us to represent complex relationships between variables. SEM is widely used in economics, genetics and the behavioral sciences (e.g. psychology, psychobiology, sociology and medicine). Model complexity is defined as a model’s ability to fit different data patterns and it plays an important role in model selection when applying SEM. As in linear regression, the number of free model parameters is typically used in traditional SEM model fit indices as a measure of the model complexity. However, only using number of free model parameters to indicate SEM model complexity …

Estimating The Respiratory Lung Motion Model Using Tensor Decomposition On Displacement Vector Field, Kingston Kang

Theses and Dissertations

Modern big data often emerge as tensors. Standard statistical methods are inadequate to deal with datasets of large volume, high dimensionality, and complex structure. Therefore, it is important to develop algorithms such as low-rank tensor decomposition for data compression, dimensionality reduction, and approximation.

With the advancement in technology, high-dimensional images are becoming ubiquitous in the medical field. In lung radiation therapy, the respiratory motion of the lung introduces variabilities during treatment as the tumor inside the lung is moving, which brings challenges to the precise delivery of radiation to the tumor. Several approaches to quantifying this uncertainty propose using a …

Uncovering Functional Relationships In Leukemia, Reginald Mcgee

Biology and Medicine Through Mathematics Conference

No abstract provided.

Firing Rate Heterogeneity And Consequences For Coding In Feedforward Circuits, Cheng Ly, Gary Marsat

Biology and Medicine Through Mathematics Conference

No abstract provided.

On The Analysis Of The Sir Epidemic Model For Small Networks: An Application In Hospital Settings, Martin Lopez-Garcia

Biology and Medicine Through Mathematics Conference

No abstract provided.

Methods For Parameter Estimation Of A Stochastic Seir Model, Kaitlyn Martinez

Biology and Medicine Through Mathematics Conference

No abstract provided.

Using Mathematical Models Of Biological Processes In Genome-Wide Association Studies Of Psychiatric Disorders, Amy Cochran

Biology and Medicine Through Mathematics Conference

No abstract provided.

Parametric, Nonparametric And Semiparametric Approaches In Profile Monitoring Of Poisson Data, Sepehr Piri

Theses and Dissertations

Profile monitoring is a relatively new approach in quality control best used when the process data follow a profile (or curve). The majority of previous studies in profile monitoring focused on the parametric modeling of either linear or nonlinear profiles under the assumption of the correct model specification. Our work considers those cases where the parametric model for the family of profiles is unknown or, at least uncertain. Consequently, we consider monitoring Poisson profiles via three methods, a nonparametric (NP) method using penalized splines, a nonparametric (NP) method using wavelets and a semi parametric (SP) procedure that combines both parametric …

Tuning Optimization Software Parameters For Mixed Integer Programming Problems, Toni P. Sorrell

Theses and Dissertations

The tuning of optimization software is of key interest to researchers solving mixed integer programming (MIP) problems. The efficiency of the optimization software can be greatly impacted by the solver’s parameter settings and the structure of the MIP. A designed experiment approach is used to fit a statistical model that would suggest settings of the parameters that provided the largest reduction in the primal integral metric. Tuning exemplars of six and 59 factors (parameters) of optimization software, experimentation takes place on three classes of MIPs: survivable fixed telecommunication network design, a formulation of the support vector machine with the ramp …

The Generalized Monotone Incremental Forward Stagewise Method For Modeling Longitudinal, Clustered, And Overdispersed Count Data: Application Predicting Nuclear Bud And Micronuclei Frequencies, Rebecca Lehman

Theses and Dissertations

With the influx of high-dimensional data there is an immediate need for statistical methods that are able to handle situations when the number of predictors greatly exceeds the number of samples. One such area of growth is in examining how environmental exposures to toxins impact the body long term. The cytokinesis-block micronucleus assay can measure the genotoxic effect of exposure as a count outcome. To investigate potential biomarkers, high-throughput assays that assess gene expression and methylation have been developed. It is of interest to identify biomarkers or molecular features that are associated with elevated micronuclei (MN) or nuclear bud (Nbud) …

Adversarial Decision Making In Counterterrorism Applications, Dogucan Mazicioglu

Theses and Dissertations

Our main objective is to improve decision making in counterterrorism applications by implementing expected utility for prescriptive decision making and prospect theory for descriptive modeling. The areas that we aim to improve are behavioral modeling of adversaries with multi objectives in counterterrorism applications and incorporating risk attitudes of decision makers to risk matrices in assessing risk within an adversarial counterterrorism framework. Traditionally, counterterrorism applications have been approached on a single attribute basis. We utilize a multi-attribute prospect theory approach to more realistically model the attacker’s behavior, while using expected utility theory to prescribe the appropriate actions to the defender. We …

Comparing The Structural Components Variance Estimator And U-Statistics Variance Estimator When Assessing The Difference Between Correlated Aucs With Finite Samples, Anna L. Bosse

Theses and Dissertations

Introduction: The structural components variance estimator proposed by DeLong et al. (1988) is a popular approach used when comparing two correlated AUCs. However, this variance estimator is biased and could be problematic with small sample sizes.

Methods: A U-statistics based variance estimator approach is presented and compared with the structural components variance estimator through a large-scale simulation study under different finite-sample size configurations.

Results: The U-statistics variance estimator was unbiased for the true variance of the difference between correlated AUCs regardless of the sample size and had lower RMSE than the structural components variance estimator, providing better type 1 error …