Biostatistics Commons^™

New Bayesian Methods For Longitudinal Data Analysis With Complex Dependence Structures., Anish Mukherjee

Electronic Theses and Dissertations

Longitudinal data in real-world settings are frequently found to be heterogeneous and exhibit intricate spatio-temporal dependence structures. Analyzing such complex data to obtain reliable estimation while quantifying uncertainty necessitates using sophisticated Bayesian methodology. In this work, we present novel Bayesian methods developed to address these challenges. We often observe heterogeneity in longitudinal data, where the mean and variance for certain profiles meaningfully differs from the rest. Some profiles may also exhibit outliers at a limited number of measurements. Using a standard mixed effects model, which assumes homogeneity, can lead to overestimating the residual variance and inefficient estimation. In this work, …

Innovative Methods For The Design And Analysis Of Phase Ii Clinical Trials, Feng Tian

Dissertations and Theses (Open Access)

Drug development has become increasingly time-consuming, costly, and risky in recent years. There is significant potential for improving clinical trial designs, particularly for phase II trials, which play a critical role in the drug development process. Innovative methods are especially necessary for addressing key challenges in phase II trials in terms of dose-ranging study, patient population selection, and decentralized clinical trials (DCTs). This dissertation presents a comprehensive set of methodologies that address these critical issues with three projects. The first project introduces a Bayesian adaptive dose-ranging design that integrates both efficacy and toxicity data to evaluate each dose comprehensively. The …

Dual-Criterion Dose Finding Designs For Phase I Clinical Trials, Yunlong Yang

Dissertations and Theses (Open Access)

The primary objective of Phase I oncology trials is to assess the safety and tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However, as cancer therapies have evolved from chemotherapy to targeted therapies, these traditional methods have become problematic. Many targeted therapies rarely produce DLT and are administered over multiple cycles, potentially resulting in the accumulation of lower-grade toxicities, which can lead to intolerance, such as dose reduction or interruption. To address this issue, we proposed dual-criterion designs that find the MTD based on both DLT and non-DLT-caused intolerance. …

Novel Statistical Methods For Mediation Analysis With High-Dimensional Omics Mediators, Zhichao Xu

Dissertations and Theses (Open Access)

Mediation analysis is a widely used statistical method for examining how molecular traits, such as gene or protein expression, act as intermediaries linking an exposure to a health outcome. For example, it can help explain how smoking affects disease risk through molecular changes. The rapid progress in high-throughput omics profiling technologies and large-scale epidemiology consortia, such as the Trans-Omics for Precision Medicine (TOPMed) program from the National Heart, Lung and Blood Institute (NHLBI) and UK Biobank, now has resulted in an extensive accumulation of genomic data for biomedical research and analysis. At the same time, it poses significant methodological challenges, …

Identifying And Characterizing Transition Cells In Developmental Processes From Scrna-Seq Data, Yuanxin Wang

Dissertations and Theses (Open Access)

During the development of multicellular organisms, individual cells make distinct decisions about their cell types and states. Understanding the molecular mechanisms underlying cellular state transitions at different developmental stages provides deep insights into physiology, morphology and the etiology of diseases. Single-cell RNA-sequencing (scRNA-seq), which is widely used to study complex cell states and dynamic gene expression patterns, enables us to investigate molecular mechanisms of cellular state transitions. Currently, however, computational tools available for identifying cellular states and state transitions remain limited.

Although trajectory-based methods such as Monocle and Slingshot assume that state transitions generate continuous expression profiles, they cannot distinguish …

Sexually Transmitted Infection (Sti) Incidence And Risk Factors Among People With Hiv (Pwh): Insights From A 13-Year Cohort Study In South Carolina, Salome-Joelle Gass, Shujie Chen, Jiajia Zhang Ph.D., Bankole Olatosi

Faculty Publications

The Ending the HIV Epidemic (EHE) initiative aims to reduce new HIV infections by 90% by 2030 in the United States (US). However, rising sexually transmitted infection (STI) rates exacerbate the bidirectional infection risk between HIV and STIs. Most research on STIs among people with HIV (PWH) has focused on high-risk groups, resulting in limited data on broader populations. This study addresses that gap by examining the incidence and risk factors for gonorrhea, chlamydia, and syphilis in a statewide cohort of PWH in South Carolina. Data from South Carolina’s HIV and STI surveillance systems were linked, and all PWH aged …

Environmental Risk And Alpha-Gal Syndrome (Ags) In The Mid-Atlantic United States, Brandon D. Hollingsworth Ph.D., Margaret Wiener, Dana A. Giandimenico, Scott P. Commins, Ross M. Boyce

Faculty Publications

Alpha-gal syndrome (AGS), commonly referred to as the tick bite red meat allergy, has been reported worldwide with the number of suspected cases in the United States increasing from 24 in 2009 to over 34,000 in 2019. Within the US, AGS is associated with the bite of two tick species, Amblyomma americanum and Ixodes scapularis, and has particularly high incidence rates in the mid-Atlantic region. Because AGS is associated with tick bites, the risk of developing AGS is affected by the environment individuals visit. Despite this, as well as the numerous studies associating the environment with Am. americanum, …

Diabetes: Non-Invasive Blood Glucose Monitoring Using Federated Learning With Biosensor Signals, Narmatha Chellamani, Saleh Ali Albelwi, Manimurugan Shanmuganathan, Palanisamy Amirthalingam, Anand Paul

School of Public Health Faculty Publications

Diabetes is a growing global health concern, affecting millions and leading to severe complications if not properly managed. The primary challenge in diabetes management is maintaining blood glucose levels (BGLs) within a safe range to prevent complications such as renal failure, cardiovascular disease, and neuropathy. Traditional methods, such as finger-prick testing, often result in low patient adherence due to discomfort, invasiveness, and inconvenience. Consequently, there is an increasing need for non-invasive techniques that provide accurate BGL measurements. Photoplethysmography (PPG), a photosensitive method that detects blood volume variations, has shown promise for non-invasive glucose monitoring. Deep neural networks (DNNs) applied to …

Human Capital And Lifetime Income Gains Of Scaling-Up Small-Quantity Lipid Nutrient Supplements Among Children Under 2 Years: A Modelling Analysis, Nandita Perumal Phd, Goodrarz Danaei, Günther Fink, Mark Lambiris, Christopher R. Sudfeld

Faculty Publications

Undernutrition in early childhood is associated with adverse health and developmental outcomes later in life and remains a persistent global public health problem. Providing small-quantity lipid nutrient supplements (SQ-LNS) to children aged 6-24 months improves child growth and neurodevelopmental outcomes, but the potential long-term benefits to human capital have not been previously estimated. We estimated the potential returns to schooling and lifetime income attributable to increasing coverage of SQ-LNS for children < 2 years of age from 0% to 50% or 90% per five-year birth cohort in five countries (Bangladesh, Burkina Faso, Ethiopia, Pakistan, and Uganda) with a high burden of undernutrition. Random-effects meta-analyses were used to estimate the effect of SQ-LNS on child development using evidence from randomized controlled trials, and to estimate the returns to lifetime income as a function of change in development based on a de novo meta-analysis of observational economic studies. Gains in school years attributable to scaling-up SQ-LNS to 90% coverage ranged from 0.14 million school years (95% uncertainty interval [UI]: 0.064, …

Ahr Activation At The Air-Blood Barrier Alters Systemic Microrna Release After Inhalation Of Particulate Matter Containing Environmentally Persistent Free Radicals, Ankit Aryal, Ashlyn C. Harmon, Alexandra Noël, Qingzhao Yu, Kurt J. Varner, Tammy R. Dugas

School of Public Health Faculty Publications

Particulate matter containing environmentally persistent free radicals (EPFRs) is formed when organic pollutants are incompletely burned and adsorb to the surface of particles containing redox-active metals. Our prior studies showed that in mice, EPFR inhalation impaired vascular relaxation in a dose- and endothelium-dependent manner. We also observed that activation of the aryl hydrocarbon receptor (AhR) in the alveolar type-II (AT-II) cells that form the air-blood interface stimulates the release of systemic factors that promote endothelial dysfunction in vessels peripheral to the lung. AhR is a recognized regulator of microRNA (miRNA) biogenesis, and miRNA control diverse signaling pathways. We thus hypothesized …

Predicting Capture And Survival Probabilities Of The Arizona Tiger Salamander: A Comparison Of Capture-Recapture Models, Brittney Nelson

Scholars Week

Capture-recapture models are essential tools for estimating population dynamics in ecological studies. A fundamental component of these models is the capture history matrix, which records individual detection over time and serves as the basis for estimating survival and capture probabilities. This presentation explores three statistical approaches to these estimations: the Cormack-Jolly-Seber (CJS) model, the Hidden Markov Model (HMM) for CJS, and the Bayesian CJS model. The CJS model provides a likelihood-based framework for estimation, and the HMM CJS incorporates latent states into the model to account for uncertainty in detection. The Bayesian CJS extends this same analysis by integrating prior …

Opioid Vs. Money Choice Preference Patterns In Regular Heroin Users, Amolak S. Jhand, Mark Greenwald

Medical Student Research Symposium

About two-thirds of people treated for opioid use disorder (OUD) return to opioid use within the first-year post-treatment, and about 10% report use while on agonist therapy. Understanding determinants of opioid-seeking is vital to reducing recurrence and its risks. We assessed individual differences in effortful choices between opioid and money amounts, modeling real-world choices.

Our lab conducted studies in which regular heroin-users were stabilized on buprenorphine to suppress withdrawal. Within experimental sessions, the participant could choose repeatedly across 12 trials between units of hydromorphone (HYD, 1 or 2 mg IM) vs. money ($2 or $4); HYD and money amounts differed …

Surgical Versus Nonsurgical Management Of Civilian Craniocerebral Gunshot Injuries, Wesley Shoap, George Austin Crabill, Roboan Guillen, Kaleb Derouen, Jack Leoni, Zhide Fang, Berje Shammassian

School of Medicine Faculty Publications

Introduction: Craniocerebral gunshot wounds in the civilian population constitute a devastating subset of traumatic brain injuries (TBI). The aim of this study was to determine the association of mortality, intensive care unit length of stay (ICU LOS), and the Glasgow Outcome Scale Extended (GOS-E) among craniocerebral gunshot patients based on timing and type of intervention. Methods: The trauma database was queried for GSWH patients ages 15 and older who received neurosurgical intervention from January 1st 2016 to June 1st 2023. Operative notes were reviewed and patients were then divided into three groups; intracranial pressure monitor only with medical treatment (ICP), …

Liver Tet1 Promotes Metabolic Dysfunction-Associated Steatotic Liver Disease, Hongze Chen, Muhammad Azhar Nisar, Joud Mulla, Xinjian Li, Kevin Cao, Shaolei Lu, Katsuya Nagaoka, Shang Wu, Peng Sheng Ting, Tung Sung Tseng, Hui Yi Lin, Xiao Ming Yin, Wenke Feng, Zhijin Wu, Zhixiang Cheng, William Mueller, Amalia Bay, Layla Schechner, Xuewei Bai, Chiung Kuei Huang

School of Public Health Faculty Publications

Global hepatic DNA methylation change has been linked to human patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DNA demethylation is regulated by the TET family proteins, whose enzymatic activities require 2-oxoglutarate (2-OG) and iron that both are elevated in human MASLD patients. We aimed to investigate liver TET1 in MASLD progression. Depleting TET1 using two different strategies substantially alleviated MASLD progression. Knockout (KO) of TET1 slightly improved diet induced obesity and glucose homeostasis. Intriguingly, hepatic cholesterols, triglycerides, and CD36 were significantly decreased upon TET1 depletion. Consistently, liver specific TET1 KO led to improvement of MASLD progression. Mechanistically, TET1 promoted …

Differences In Covid-19 Deaths Amongst Cancer Patients And Possible Mediators For This Relationship, Leah Vaidya, Nubaira Rizvi, Xiao Cheng Wu, Lauren S. Maniscalco, Yong Yi, Augusto Ochoa, Qingzhao Yu

School of Public Health Faculty Publications

Previous research demonstrated Non-Hispanic Black populations experience higher COVID-19 mortality rates than Non-Hispanic White individuals. Additionally, cancer status is a known risk factor for COVID-19 death. While prior studies investigated comorbidities as exploratory variables in differences in COVID-19 hospitalization, none have explored their role in COVID-19-related deaths. This study aimed to evaluate whether Charlson Comorbidity Index (CCI) and subsequently, individual diseases are potential explanatory variables for this relationship. The analysis focused on Non-Hispanic Black and Non-Hispanic White cancer patients aged 20 or older, diagnosed between 2011 and 2019, who tested positive for COVID-19 from the start of pandemic through June …

Unlocking Precision Using K-Means++- Improved Genetic Algorithm-Radial Basis Function Neural Network: Data-Driven Evolution Of Smart Gloves For Gesture Recognition, Liang Xiao Ding, Kuan Way Chee, Hong Lü, Anand Paul, Jeonghong Kim, Jang Myung Lee

School of Public Health Faculty Publications

Human-computer interaction technologies have been used since the 1970s but have only gained growing popularity in recent years with new design paradigms. Ongoing research and development in gesture recognition systems with broad application prospects have focused on improving accuracy and real-time performance as well as the robustness of specific machine learning algorithms against environmental conditions. This paper addresses the accuracy enhancement of a novel Fifth Dimension Technologies data-glove-based gesture recognition system using a genetic-algorithm (GA)-trained k-means++-improved radial basis function (RBF) or GK-RBF neural network. First, we analyzed and modeled the sensor distribution in the data glove and proposed joint constraints …

Racial And Ethnic Inequalities In Actual Vs Nearest Delivery Hospitals, Nansi S. Boghossian, Lucy T. Greenberg, Jeffrey S. Buzas, Joshua Radack, Molly Passarella, Jeannette Rogowski, George R. Saade, Ciaran S. Phibbs, Scott A. Lorch

Faculty Publications

IMPORTANCE Minoritized racial and ethnic groups, such as American Indian and Black individuals, often receive lower quality health care compared with White individuals. There is limited understanding of how these disparities extend to obstetric care, particularly when comparing the quality of care at the actual delivery hospital vs the nearest obstetric hospital based on the birthing individual’s residence. OBJECTIVE To examine inequality in care based on the actual delivery hospital and the closest delivery hospital to the birthing individual’s residential zip code centroid. DESIGN, SETTING, AND PARTICIPANTS This population-based retrospective cohort study used data from 5 states (2008 to 2020 …

Linking Water Quality And Climate Change To Long-Term Trends In Species Abundance In Norwalk Harbor, Viktoria Savatorova, Aidan Kieft, Nicole C. Spiller, Kasey Burns

Spora: A Journal of Biomathematics

This study examines the effects of environmental changes on fish populations in Norwalk Harbor, focusing on winter flounder (Pseudopleuronectes americanus), cunner (Tautogolabrus adspersus), northern pipefish (Syngnathus fuscus), and naked goby (Gobiosoma bosci) as examples of species responding to climate-related shifts. We analyze how water temperature, salinity, and dissolved oxygen correlate with fish abundance. To assess statistically significant differences in catch per unit effort (CPUE) across harbor regions, we applied the Kruskal-Wallis test followed by Dunn's post-hoc test. Seasonal variations in CPUE were examined by comparing monthly catch data for each species. K-means …

A Deep Sparse Capsule Network For Non-Invasive Blood Glucose Level Estimation Using A Ppg Sensor, Narmatha Chellamani, Saleh Ali Albelwi, Manimurugan Shanmuganathan, Palanisamy Amirthalingam, Emad Muteb Alharbi, Hibah Qasem Salman Alatawi, Kousalya Prabahar, Jawhara Bader Aljabri, Anand Paul

School of Public Health Faculty Publications

Diabetes, a chronic medical condition, affects millions of people worldwide and requires consistent monitoring of blood glucose levels (BGLs). Traditional invasive methods for BGL monitoring can be challenging and painful for patients. This study introduces a non-invasive, deep learning (DL)-based approach to estimate BGL using photoplethysmography (PPG) signals. Specifically, a Deep Sparse Capsule Network (DSCNet) model is proposed to provide accurate and robust BGL monitoring. The proposed model’s workflow includes data collection, preprocessing, feature extraction, and predictions. A hardware module was designed using a PPG sensor and Raspberry Pi to collect patient data. In preprocessing, a Savitzky–Golay filter and moving …

Discounting Effect Size When Borrowing External Data In Clinical Studies, Zhuanzhuan Ma, Chul Ahn, Bin Wang, Xuefeng Li

Research Symposium

Background: When borrowing information from external data to augment a current trial, many available methods discount the sample size but retain the effect size from previous studies. Discounting the sample size is just one way to discount the prior information. It may not be appropriate if the underlying assumption of unbiased treatment effect does not hold, for example, when the treatment effect in the historical study is likely higher than the one expected in the current trial.

Methods: To tackle this potential issue, we study some methods to shrink the effect size from previous studies assuming that the prior effect …