Biostatistics Commons^™

Expectile Neural Networks For Genetic Data Analysis Of Complex Diseases, Jinghang Lin, Xiaoran Tong, Chenxi Li, Qing Lu

Biostatistics Faculty Publications

The genetic etiologies of common diseases are highly complex and heterogeneous. Classic methods, such as linear regression, have successfully identified numerous variants associated with complex diseases. Nonetheless, for most diseases, the identified variants only account for a small proportion of heritability. Challenges remain to discover additional variants contributing to complex diseases. Expectile regression is a generalization of linear regression and provides complete information on the conditional distribution of a phenotype of interest. While expectile regression has many nice properties, it has rarely been used in genetic research. In this paper, we develop an expectile neural network (ENN) method for genetic …

Deep Learning-Based Technique For The Perception Of The Cervical Cancer, Aya Haraz, Hossam El-Din Moustafa, Abeer Twakol Khaleel, Ahmed H. Eltanboly

Mansoura Engineering Journal

In third-world countries, cervical cancer is the most prevalent and leading cause of death. It is affected by a variety of factors, including smoking, poor nutritional status, immunological inadequacy, and prolonged use of contraception. The Pap smear test, which is intended to prevent cervical cancer, finds preneoplastic changes in cervical epithelial cells. This study framework classified cervical cancer cells from Pap smears into five specified cell types using machine learning-based classification algorithms. The SIPaKMeD database is used in this investigation. This public dataset, which was manually cropped from 966 cluster cell images taken from Pap smear slides, has 4045 isolated …

Novel Feature Evaluation In Ultra-High Dimensional Right-Censored Data, With Applications To Head And Neck Cancer, Atika Farzana Urmi

Graduate Research Posters

Background: Head and neck cancer is the 6th most common cancer worldwide with an expected 1.08 million new cases each year. Such cancer data are ultra-high dimensional with thousands of clinical features and gene expressions, making it challenging for the traditional analytical tools to extract the potential biomarker for the cancer survival and control false discoveries. In addition, presence of heavy censoring can affect the screening procedures based on Kaplan-Meier (K-M) survival estimates.

Aim: To propose a model free, ultra-high dimensional feature screening method with two-dimensional survival outcome allowing false discovery rate (FDR) control.

Method: 516 primary tumor patients with …

Utilizing Markov Chains To Estimate Allele Progression Through Generations, Ronit Gandhi

Honors Program: Senior Projects (Public)

All populations display patterns in allele frequencies over time. Some alleles cease to exist, while some grow to become the norm. These frequencies can shift or stay constant based on the conditions the population lives in. If in Hardy-Weinberg equilibrium, the allele frequencies stay constant. Most populations, however, have bias from environmental factors, sexual preferences, other organisms, etc. We propose a stochastic Markov chain model to study allele progression across generations. In such a model, the allele frequencies in the next generation depend only on the frequencies in the current one.

We use this model to track a recessive allele …

Modeling The Bidirectional Relationship Between Shared-Patient Physician Networks And Patient Longitudinal Treatment Patterns: Application To Physician Risky-Prescribing, Xin Ran

Dartmouth College Ph.D Dissertations

Risky-prescribing is a pressing public health concern in the United States. Opioids, benzodiazepines, and non-benzodiazepine sedative-hypnotics (sedative-hypnotics) are three commonly-prescribed but potentially risky drug groups, prescribed alone or in combination. Physician shared-patient networks provide a unique perspective in studying physician network characteristics and structures, as well as their association with the delivery of health care. Understanding how physician shared-patient networks are related to their prescribing may inform network-based interventions targeting risky-prescribing, which is yet to be fully studied.

We investigated patient receipt of risky prescriptions and physician risky-prescribing intensity through the scope of shared-patient networks. We used retrospective Medicare insurance …

Variability In Causal Effects On A Binary Outcome And Noncompliance In A Multisite Randomized Trial, Xinxin Sun

Theses and Dissertations

Noncompliance to treatment assignment is widespread in randomized trials and presents challenges in causal inference. In the presence of noncompliance, the most commonly estimated effect of treatment assignment, also known as intent-to-treat (ITT) effect, is biased. Of interest in this setting is the complier average causal effect (CACE), the ITT effect among compliers. Further complication arises when the outcome variable is partially observed.

My research focuses on estimating the distribution of a site-specific CACE in a multisite randomized controlled trial (MRCT) by maximum likelihood (ML). Assuming compliance missing at random (MAR). We express the likelihood as an integral with respect …

Reassessing Replication: Addressing The Replication Crisis From A Statistical Perspective, Alicia Richards Phd

Theses and Dissertations

In 2015, Open Science Framework directly replicated 100 psychology studies and found astonishingly low replication rates. Since, researchers have suggested factors that may have influenced the low rates, including the metrics used to assess replications. The definitions used to decide whether a replication study was successful all suffer from flaws. Therefore, we propose a new metric for assessing replication that can estimate the likelihood a study successfully replicated rather than forcing a binary choice and accounts for study design limitations.

Using equivalence study techniques, we first propose a new metric to assess replication, defining a successful replication as one where …

Model-Based Imputation Of Below Detection Limit Missing Data And Group Selection In Bayesian Group Index Regression, Matthew Carli

Theses and Dissertations

Investigations into the association between chemical exposure and health outcomes are increasingly focused on the role of chemical mixtures, as opposed to individual chemicals. The analysis of chemical mixture data required the development of novel statistical methods, one of these being Bayesian group index regression. A statistical challenge common to all chemical mixture analyses is the ubiquitous presence of below detection limit (BDL) data. We propose an extension of Bayesian group index regression that treats both regression effects and missing BDL observations as parameters in a model estimated through a Markov Chain Monte Carlo algorithm that we refer to as …

Integrative Post-Gwas Analyses Of Psychiatric Disorders: Identifying Putative Risk Genes And Gene Sets Using Transcriptome, Proteome And Methylome Information, Huseyin Gedik

Theses and Dissertations

Genome-wide association studies (GWAS) of psychiatric disorders (PD) yield numerous loci with significant signals, but often they do not implicate specific protein coding genes. Because GWAS risk loci are enriched in expression/protein/methylation quantitative loci (e/p/mQTL, hereafter xQTL), transcriptome/proteome/methylome-wide association studies (T/P/MWAS, hereafter XWAS), which integrate information from GWAS and x-level (mRNA, protein or DNA methylation levels) coming from largest xQTL studies, can link GWAS signals to effects on specific genes. For gene level analyses, researchers use mendelian randomization (MR) methods to fine-map the association between x-levels and trait. However, none of the previous studies ever jointly analyzed XWAS of multiple …

The Birds And The Trees: Quantifying The Drivers Of Whitebark Pine Decline And Clark's Nutcracker Habitat Use In Glacier National Park, Vladimir Kovalenko

Graduate Student Theses, Dissertations, & Professional Papers

Whitebark pine (Pinus albicaulis), recently listed as threatened under the Endangered Species Act, is in steep decline in Glacier National Park, Montana, USA due to the non-native pathogen Cronartium ribicola, causal agent of the fatal disease white pine blister rust. A sample of the park’s population suggests that approximately 70 percent of whitebark pines have died, while 65 percent of the remaining trees are infected. Using landscape and climate variables, we show how geographic location, elevation, aspect, solar radiation, relative humidity, and snowpack interact with tree diameter to affect mortality, disease incidence, cone production, and regeneration. We also examine how …

Laboratory Practices And Antimicrobial Resistance In A Florida Hospital, Crispina Marie Sy-Trias

Walden Dissertations and Doctoral Studies

Antibiotic resistance is a health threat affecting millions of Americans. Microorganisms develop resistance to antibiotics, rendering them useless for treating infections. The purpose of this quantitative study was to assess the associations between sample processing time and antibiotic resistance and is based on the health belief model. A retrospective specimen tracking activity of data from November 2019 to November 2020 was obtained by random sampling of 246 bacterial cultures. One hundred ninety-six (80%) samples were processed on time, and 50 (20%) were delayed; 167 (68%) samples were determined to have the presence of antimicrobial resistance (AMR), and 79 (32%) with …

Transformations Between Rotational And Translational Invariants Formulated In Reciprocal Spaces, Philip R Baldwin

Faculty, Staff and Students Publications

Correlation functions play an important role in the theoretical underpinnings of many disparate areas of the physical sciences: in particular, scattering theory. More recently, they have become useful in the classification of objects in areas such as computer vision and our area of cryoEM. Our primary classification scheme in the cryoEM image processing system, EMAN2, is now based on third order invariants formulated in Fourier space. This allows a factor of 8 speed up in the two classification procedures inherent in our software pipeline, because it allows for classification without the need for computationally costly alignment procedures. In this work, …

Knowledge Discovery On The Integrative Analysis Of Electrical And Mechanical Dyssynchrony To Improve Cardiac Resynchronization Therapy, Zhuo He

Dissertations, Master's Theses and Master's Reports

Cardiac resynchronization therapy (CRT) is a standard method of treating heart failure by coordinating the function of the left and right ventricles. However, up to 40% of CRT recipients do not experience clinical symptoms or cardiac function improvements. The main reasons for CRT non-response include: (1) suboptimal patient selection based on electrical dyssynchrony measured by electrocardiogram (ECG) in current guidelines; (2) mechanical dyssynchrony has been shown to be effective but has not been fully explored; and (3) inappropriate placement of the CRT left ventricular (LV) lead in a significant number of patients.

In terms of mechanical dyssynchrony, we utilize an …

Statistical Methods For Gene Selection And Genetic Association Studies, Xuewei Cao

Dissertations, Master's Theses and Master's Reports

This dissertation includes five Chapters. A brief description of each chapter is organized as follows.

In Chapter One, we propose a signed bipartite genotype and phenotype network (GPN) by linking phenotypes and genotypes based on the statistical associations. It provides a new insight to investigate the genetic architecture among multiple correlated phenotypes and explore where phenotypes might be related at a higher level of cellular and organismal organization. We show that multiple phenotypes association studies by considering the proposed network are improved by incorporating the genetic information into the phenotype clustering.

In Chapter Two, we first illustrate the proposed GPN …

On Kernel-Based Estimator Of Odds Ratio Using Different Stratified Sampling Schemes, Abbas Eftekharian, Hani Samawi, Haresh Rochani

Biostatistics, Epidemiology & Environmental Health Sciences: Faculty Publications

The kernel-based estimator of Cochran Mantel-Haenszel odds ratio based on stratified simple and ranked set sampling is proposed. The expectation and variance of the estimator are analytically obtained. Using a simulation study, the estimator based on stratified ranked set sampling is more efficient than its counterpart based on stratified simple random sampling. Finally, the estimator's performance is investigated by using base deficit data.

Association Of Chlorhexidine Use And Scaling And Root Planing With Birth Outcomes In Pregnant Individuals With Periodontitis: A Systematic Review And Meta-Analysis, Maxwell Akonde, Rajat Das Gupta, Maxwell Akonde, Mark Reynolds, Stephanie Smith-Warner, Jihong Liu Sc.D., Fouzia Tarannum, James Beck, Donald Mattison

Faculty Publications

Importance Chlorhexidine mouthwash enhances treatment effects of conventional periodontal treatment, but data on chlorhexidine as a source of heterogeneity in meta-analyses assessing the treatment of maternal periodontitis in association with birth outcomes are lacking.

Objective To assess possible heterogeneity by chlorhexidine use in randomized clinical trials (RCTs) evaluating the effect of periodontal treatment (ie, scaling and root planing [SRP]) vs no treatment on birth outcomes.

Data Sources Cochrane Oral Health’s Trials Register, Cochrane Pregnancy and Childbirth’s Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science …

Association Of Chlorhexidine Use And Scaling And Root Planing With Birth Outcomes In Pregnant Individuals With Periodontitis: A Systematic Review And Meta-Analysis, Anwar T. Nerchant, Rajat Das Gupta, Maxwell Akonde, Mark Reynolds, Stephanie Smith-Warner, Jihong Liu, Fouzia Tarannum, James Beck, Donald Mattison

Faculty Publications

Importance Chlorhexidine mouthwash enhances treatment effects of conventional periodontal treatment, but data on chlorhexidine as a source of heterogeneity in meta-analyses assessing the treatment of maternal periodontitis in association with birth outcomes are lacking.

Objective To assess possible heterogeneity by chlorhexidine use in randomized clinical trials (RCTs) evaluating the effect of periodontal treatment (ie, scaling and root planing [SRP]) vs no treatment on birth outcomes.

Data Sources Cochrane Oral Health’s Trials Register, Cochrane Pregnancy and Childbirth’s Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science …

Regression Modeling Of Complex Survival Data Based On Pseudo-Observations, Rong Rong

Statistical Science Theses and Dissertations

The restricted mean survival time (RMST) is a clinically meaningful summary measure in studies with survival outcomes. Statistical methods have been developed for regression analysis of RMST to investigate impacts of covariates on RMST, which is a useful alternative to the Cox regression analysis. However, existing methods for regression modeling of RMST are not applicable to left-truncated right-censored data that arise frequently in prevalent cohort studies, for which the sampling bias due to left truncation and informative censoring induced by the prevalent sampling scheme must be properly addressed. Meanwhile, statistical methods have been developed for regression modeling of the cumulative …

A Bayesian Susceptible-Infectious-Hospitalized-Ventilated-Recovered Model To Predict Demand For Covid-19 Inpatient Care In A Large Healthcare System, Stella Coker Watson Self Ph.D., Ms, Rongjie Huang, Shrujan Amin, Joseph Ewing, Carolina Rudisill, Alexander C. Mclain Ph.D.

Faculty Publications

The COVID-19 pandemic has strained healthcare systems in many parts of the United States. During the early months of the pandemic, there was substantial uncertainty about whether the large number of COVID-19 patients requiring hospitalization would exceed healthcare system capacity. This uncertainty created an urgent need to accurately predict the number of COVID-19 patients that would require inpatient and ventilator care at the local level. As the pandemic progressed, many healthcare systems relied on such predictions to prepare for COVID-19 surges and to make decisions regarding staffing, the discontinuation of elective procedures, and the amount of personal protective equipment (PPE) …

A Bayesian Susceptible-Infectious-Hospitalized-Ventilated-Recovered Model To Predict Demand For Covid-19 Inpatient Care In A Large Healthcare System, Stella Coker Watson Self Ph.D., Ms, Rongjie Huang, Shrujan Amin, Joseph Ewing, Caroline Rudisill, Alexander C. Mclain

Faculty Publications

The COVID-19 pandemic has strained healthcare systems in many parts of the United States. During the early months of the pandemic, there was substantial uncertainty about whether the large number of COVID-19 patients requiring hospitalization would exceed healthcare system capacity. This uncertainty created an urgent need to accurately predict the number of COVID-19 patients that would require inpatient and ventilator care at the local level. As the pandemic progressed, many healthcare systems relied on such predictions to prepare for COVID-19 surges and to make decisions regarding staffing, the discontinuation of elective procedures, and the amount of personal protective equipment (PPE) …

Survival Of Epithelial Ovarian Cancer In Black Women: A Society To Cell Approach In The African American Cancer Epidemiology Study (Aaces), Joellen M. Schildkraut, Courtney Johnson, Lauren F. Dempsey, Bo Qin, Paul Terry, Maxwell Akonde, Edward S. Peters, Hannah Mandle, Michele L. Cote, Lauren Peres, Patricia Moorman, Ann G. Schwartz, Micheal Epstein, Jeffrey Marks, Melissa Bondy, Andrew B. Lawson, Anthony Alberg, Elisa V. Bandera

Faculty Publications

Purpose

The causes for the survival disparity among Black women with epithelial ovarian cancer (EOC) are likely multi-factorial. Here we describe the African American Cancer Epidemiology Study (AACES), the largest cohort of Black women with EOC.

Methods

AACES phase 2 (enrolled 2020 onward) is a multi-site, population-based study focused on overall survival (OS) of EOC. Rapid case ascertainment is used in ongoing patient recruitment in eight U.S. states, both northern and southern. Data collection is composed of a survey, biospecimens, and medical record abstraction. Results characterizing the survival experience of the phase 1 study population (enrolled 2010–2015) are presented.

Results …

Effects Of A Behavioral Intervention On Physical Activity, Diet, And Health-Related Quality Of Life In Pregnant Women With Elevated Weight: Results Of The Hipp Randomized Controlled Trial, Sarah Wilcox Phd, Jihong Liu, Gabrielle Turner-Mcgrievy Ph.D., Rd, Alycia K. Boutte, Ellen Wingard Msph, Rd, Ld

Faculty Publications

Background

Physical activity (PA), diet, and health-related quality of life (HRQOL) are related to maternal and infant health, but interventions to improve these outcomes are needed in diverse pregnant women with elevated weight.

Methods

Health In Pregnancy and Postpartum (HIPP) was a randomized controlled trial. Women who were pregnant (N=219, 44% African American, 56% white) with overweight or obesity but otherwise healthy were randomized to a behavioral intervention grounded in Social Cognitive Theory (n=112) or to standard care (n=107). The intervention group received an in-depth counseling session, a private Facebook group, and 10 content-based …

Dynamics Of Redox-Driven Molecular Processes In Local And Systemic Plant Immunity, Philip Berg

Theses and Dissertations

The work here presents two main parts. In the first part, chapters 1 – 3 focus on dynamical systems modeling in plant immunity, whereas chapters 4 – 6 describe contributions to computational modeling and analysis of proteomics and genomics data. Chapter 1 investigates dynamical and biochemical patterns of reversibly oxidized cysteines (RevOxCys) during effector-triggered immunity (ETI) in Arabidopsis, examines the regulatory patterns associated with Arabidopsis thimet oligopeptidase 1 and 2’s (TOP1 and TOP2), roles in the RevOxCys events during ETI, and analyzes the redox phenotype of the top1top2 mutant. The second chapter investigates the peptidome dynamics during ETI …

Towards Structured Planning And Learning At The State Fisheries Agency Scale, Caleb A. Aldridge

Theses and Dissertations

Inland recreational fisheries has grown philosophically and scientifically to consider economic and sociopolitical aspects (non-biological) in addition to the biological. However, integrating biological and non-biological aspects of inland fisheries has been challenging. Thus, an opportunity exists to develop approaches and tools which operationalize planning and decision-making processes which include biological and non-biological aspects of a fishery. This dissertation expands the idea that a core set of goals and objectives is shared among and within inland fisheries agencies; that many routine operations of inland fisheries managers can be regimented or standardized; and the novel concept that current information and operations can …

Larval Ecology Of Atlantic Bluefin Tuna (Thunnus Thynnus): New Insights From Otolith Microstructure, Biotic, And Abiotic Analyses From The Gulf Of Mexico And Mediterranean Sea, Estrella Malca

All HCAS Student Capstones, Theses, and Dissertations

Atlantic bluefin tuna (ABT), Thunnus thynnus, spawn in the Gulf of Mexico (GoM) and the Mediterranean Sea (MED). Spawning occurs within narrow temporal and environmental parameters. Efforts to characterize growth of ABT in wild conditions revealed a wide range of growth variability during the early life stages. This series of studies examined potential biotic and abiotic influences of larval growth from seven ABT cohorts, and identified several key drivers of growth for this commercially valuable species. A detailed investigation of larval dynamics using otolith microstructure was conducted as follows. First, companion growth curves and stable isotope analysis from the same …

Metabolic Alterations And Cardiovascular Risk After Hepatitis C Cure In Subjects With Or At Risk For Hiv, Christophe Maxime Fokoua Dongmo

Legacy Theses & Dissertations (2009 - 2024)

Background. Hepatitis C virus (HCV) infection engenders substantial metabolic changes. These changes are altered when the virus is cleared after successful treatment. We measured these metabolic alterations that occur after HCV cure; further, we assessed whether these alterations differed in subgroups defined by patients’ characteristics.

Evaluating The Health Impacts Of Fruit And Vegetable Intake At The Individual Level And Food Pantry Level Among Food Pantry Users, Jiacheng Chen

Legacy Theses & Dissertations (2009 - 2024)

Background: Chronic diseases impose heavy burdens on individuals and the healthcare system in the US. Many factors were found to be associated with chronic diseases, including demographics, family history, social environmental factors, and individual behavioral factors such as diet and physical activity. Among those factors, fruit and vegetable intake can have substantial health impacts via a variety of causal pathways. Fruit and vegetable (F&V) consumption is generally lower among individuals living in households experiencing food insecurity and rely on food assistance programs. Decreased F&V intake among food pantry users may negatively impact health. However, conducting quantitative analysis on this population …

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 …

Bayesian Adaptive Clinical Trial Design, Mengyi Lu

Dissertations and Theses (Open Access)

The landscape of drug development in oncology has changed from conventional chemotherapies to molecular targeted therapies and immunotherapies, which provide innovative therapeutic modalities for treating cancers. These novel therapeutic agents work through mechanisms that fundamentally differ from standard chemotherapeutic agents, making the conventional trial design paradigm inefficient and dysfunctional. Specifically, the focus of dose-finding trials has shifted from finding the maximum tolerated dose (MTD) to the optimal biological dose (OBD), defined as the dose that optimizes the risk–benefit tradeoff. How to accurately identify the OBD and its dosing schedule is of great importance to maximize efficacy and safety of targeted …

Infrastructure Development For Personalized Risk Prediction To Reduce Cardiovascular Disease In Childhood Cancer Survivors, Suman Shrestha

Dissertations and Theses (Open Access)

Although childhood cancer survivors have lengthy life expectancies, they run the risk of experiencing long-term health issues as a result of their treatment. The most frequent non-cancerous cause of morbidity and mortality for these survivors is cardiac disease. Radiation therapy (RT) has been linked in numerous cohort studies to a higher chance of developing a late cardiac disease in these survivors, and this risk rises with higher mean heart doses and increased RT exposure to larger cardiac volumes. Since, the heart is a heterogeneous organ made up of several distinct substructures, RT dose received by the entire heart does not …