Physical Sciences and Mathematics Commons^™

A Deep Learning U-Net For Detecting And Segmenting Liver Tumors, Vidhya Cardozo

Theses and Dissertations

Visualization of liver tumors on simulation CT scans is challenging even with contrast-enhancement, due to the sensitivity of the contrast enhancement to the timing of the CT acquisition. Image registration to magnetic resonance imaging (MRI) can be helpful for delineation, but differences in patient position, liver shape and volume, and the lack of anatomical landmarks between the two image sets makes the task difficult. This study develops a U-Net based neural network for automated liver and tumor segmentation for purposes of radiotherapy treatment planning. Non-contrast simulation based abdominal CT axial scans of 52 patients with primary liver tumors were utilized. …

Live Cell Biomass Tracking For Basic, Translational, And Clinical Research, Graeme Murray

Theses and Dissertations

Single cell mass is tightly regulated throughout generations and the cell cycle, making it an important marker of cell health. Abnormal changes in cell size can be the first indication of dysfunction in response to environmental stimuli such as cytotoxic drugs. Described here is the further development of high-speed live cell interferometry (HSLCI) to concurrently measure the changes in single cell mass of thousands of cells over time. Critically, the high-throughput nature of HSLCI provides realistic pictures of tumor heterogeneity. This throughput enabled HSLCI to correctly predict in vivo carboplatin sensitivity of three triple negative breast cancer patient derived xenografts, …

Bisphosohoglycertae Mutase: A Potential Target For Sickle Cell Disease, Anfal S. Aljahdali

Theses and Dissertations

Bisphosphoglycerate mutase (BPGM) is a part of the erythrocyte glycolysis system. Specifically, it is a central enzyme in the Rapoport-Leubering pathway, a side glycolytic pathway involved in the regulation of the concentration of the natural allosteric effector of hemoglobin (Hb), 2,3-bisphosphoglycerate (2,3-BPG). BPGM catalyses the synthesis and hydrolysis of 2,3-BPG through its synthase and phosphatase activities. The synthase activity is the main role of BPGM, while the phosphatase activity is low and is activated by the physiological effector, 2-phosphoglycolate (2-PG) with the latter mechanism poorly understood.

BPGM activity and 2,3-BPG levels in red blood cells (RBCs) have a significant role …

Bivariate Markov Chain Model Of Irritable Bowel Syndrome (Ibs) Subtypes And Abdominal Pain, Ricardo Reyna Jr.

Theses and Dissertations

Researchers use stochastic models like continuous-time Markov chains (CTMC) to model progression of morbidities of public health impact, like HIV and Hepatitis C. Most of the research in that area is done for a single disease. In this research, we use a bivariate continuous-time Markov chain (CTMC) to model progression of co-morbidities. In particular, we use a bivariate CTMC to model the joint progression of Irritable Bowel Syndrome (IBS) and abdominal pain. Symptoms of IBS are known to change throughout the duration of the disorder. Hence, patients are normally asked to make a journal of the stool type, symptoms, and …

Machine-Learning-Based Prediction Of Sepsis Events From Vertical Clinical Trial Data: A Naïve Approach, Tyler Michael Gaddis

Theses and Dissertations

Sepsis is a potentially life-threatening condition characterized by a dysregulated, disproportionate immune response to infection by which the afflicted body attacks its own tissues, sometimes to the point of organ failure, and in the worst cases, death. According to the Centers for Disease Control and Prevention (CDC) Sepsis is reported to kill upwards of 270,000 Americans annually, though this figure may be greater given certain ambiguities in the current accepted diagnostic framework of the disease.

This study attempted to first establish an understanding of past definitions of sepsis, and to then recommend use of machine learning as integral in an …

Prediction Of Drug-Drug Interaction Potential Using Machine Learning Approaches, Joseph Scavetta

Theses and Dissertations

Drug discovery is a long, expensive, and complex, yet crucial process for the benefit of society. Selecting potential drug candidates requires an understanding of how well a compound will perform at its task, and more importantly, how safe the compound will act in patients. A key safety insight is understanding a molecule's potential for drug-drug interactions. The metabolism of many drugs is mediated by members of the cytochrome P450 superfamily, notably, the CYP3A4 enzyme. Inhibition of these enzymes can alter the bioavailability of other drugs, potentially increasing their levels to toxic amounts. Four models were developed to predict CYP3A4 inhibition: …

Infant Mortality In The United States: Socioeconomic Factors Predicting Infant Survival In Late Neo-Natal And Post Neo-Natal Infants From Birth Certificate Data, Mark Brunk-Grady

Theses and Dissertations

According to the Centers for Disease Control and Prevention, the infant mortality rate in the United States in 2018 was 5.6 deaths per 1000 live births. Infant mortality is defined as a child being born alive but dying before their first birthday. This study aimed to determine if adding socioeconomic factors to traditional predictive survival models improved the predictive power in terms of survival for late and post neonatal infants. Secondly, this study looked to develop a risk score to and predict which mothers would be classified as “High” or “Low” risk for infant death.

Data were analyzed from a …

Mathematical Modeling Of Nonlinear Dynamics Of Blood Hormones On The Regulatory System, Gabriela Urbina

Theses and Dissertations

We study a mathematical modeling of nonlinear dynamics of blood hormones, which includes glucose and insulin. On Chapter I, II, III and IV, we introduce this work, analyze an effect of the secreted insulin by the pancreatic beta cells and glucagon hormones and state concluding remarks, respectively. This model considers the time evolution of nonlinear dynamics of the equations for glucose, glucagon and insulin concentrations plus insulin and glucagon actions and the secreted insulin as a result of elevation of glucose in the blood plasma. Using both analytical and numerical procedures, we determine such quantities using different parameters for different …

Electronic Image Detectability Under Varying Illumination Conditions, Jeremy J. Miller

Theses and Dissertations

Light in the built environment plays an essential role in the vision and the health of humans through non-visual receptors in the eyes. Unfortunately, image analysts and other Air Force personnel who engage in the detection of objects on softcopy displays are often required to work in very dimly-lit or dark environments as higher illumination reduces the contrast of displayed information. Literature has shown that increases in light exposure improves circadian rhythm entrainment and reduces the negative health consequences of insufficient lighting. This research examines the effects of indoor lighting to determine if increases in ambient illumination or changes to …

Stability Analysis For The Equilibria Of A Monkeypox Model, Rachel Elizabeth Tewinkel

Theses and Dissertations

Monkeypox virus was first identified in 1958 and has since been an ongoing problem in Central and Western Africa. Although the smallpox vaccine provides partial immunity against monkeypox, the number of cases has greatly increased since the eradication of smallpox made its vaccination unnecessary. Although studied by epidemiologists, monkeypox has not been thoroughly studied by mathematicians to the extent of other serious diseases. Currently, to our knowledge, only three mathematical models of monkeypox have been proposed and studied. We present the first of these models, which is related to the second, and discuss the global and local asymptotic stability of …

The Assessment Of Technology Adoption Interventions And Outcome Achievement Related To The Use Of A Clinical Research Data Warehouse, Katie A. Mccarthy

Theses and Dissertations

Introduction: While funding for research has declined since 2004, the need for rapid, innovative, and lifesaving clinical and translational research has never been greater due to the rise in chronic health conditions, which have resulted in lower life expectancy and higher rates of mortality and adverse outcomes. Finding effective diagnostic and treatment methods to address the complex challenges in individual and population health will require a team science approach, creating the need for multidisciplinary collaboration among practitioners and researchers.

To address this need, the National Institutes of Health (NIH) created the Clinical and Translational Science Awards (CTSA) program. The CTSA …

2nd Tier Assay For The Detection Of Congenital Adrenal Hyperplasia By Virginia’S Newborn Screening Laboratory: Steroid Profile By Hplc-Ms/Ms, Christopher E. Nixon

Theses and Dissertations

Congenital Adrenal Hyperplasia (CAH) encompasses several disorders related to disruptions in the adrenal steroid production pathway. These disruptions may cause virilization of the external female sex organs, incorrect gender assignment, precocious puberty, and in the most severe form, may cause life-threatening salt wasting and adrenal crisis if not detected and treated early in the newborn period.

17α-Hydroxyprogesterone (17-OHP) is the primary target for immunofluorescence detection of CAH from dried blood spots in newborn screening (NBS). Unfortunately, current immunoassay techniques for the detection of CAH suffer from high false positive rates. The primary factors contributing to false positive determinations can include …

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 …

Network Analysis Of Scientific Collaboration And Co-Authorship Of The Trifecta Of Malaria, Tuberculosis And Hiv/Aids In Benin., Gbedegnon Roseric Azondekon

Theses and Dissertations

Despite the international mobilization and increase in research funding, Malaria, Tuberculosis and HIV/AIDS are three infectious diseases that have claimed more lives in sub Saharan Africa than any other place in the World. Consortia, research network and research centers both in Africa and around the world team up in a multidisciplinary and transdisciplinary approach to boost efforts to curb these diseases. Despite the progress in research, very little is known about the dynamics of research collaboration in the fight of these Infectious Diseases in Africa resulting in a lack of information on the relationship between African research collaborators. This dissertation …

Quantitative Phenotype Analysis To Identify, Validate And Compare Rat Disease Models, Yiqing Zhao

Theses and Dissertations

Introduction

The laboratory rat has been widely used as an animal model in biomedical research. There are many strains exhibiting a wide variety of phenotypes. Capturing these phenotypes in a centralized database provides researchers with an easy method for choosing the appropriate strains for their studies. Current resources such as NBRP and PhysGen provided some preliminary work in rat phenotype databases. However, there are drawbacks in both projects: (1) small number of animals (6 rats) used by NBRP; (2) NBRP project is a one-time effort for each strain; (3) PhysGen web interface only enables queries within a single study – …

Radiological Decontamination In The Urban Environment Utilizing An Irreversible Wash-Aid Recovery System, Keith A. Sanders

Theses and Dissertations

The radioactive fallout from the Fukushima Daiichi nuclear reactors accident and the ongoing threat of nuclear or radioactive terrorism have forced the need for urban radiological decontamination into the forefront. Many of the established decontamination techniques are not ideally suited for the urban milieu. One of the keys to maximize the effectiveness of long-term remediation and recovery in the urban environment is immediate mitigation within a few days of the incident and before a rain event. The Integrated Wash-Aid, Treatment, and Emergency Reuse System (IWATERS) provides a potentially safe and effective method for early responders and remediation teams to perform …

Semi-Synthesis Of A Novel Library Of Alkaloids As Potential Selective Analgesics, Brittany M. Gallagher

Theses and Dissertations

Semi-synthetic compounds are an important part of the therapeutic drug discovery process. The goals of the project were to synthesize different generations of matrine analogues in order to gain many opportunities to manipulate the core structure. The long-term goal was, by manipulating the structure, the possibility to increase the biological activity of the original compound while also decreasing the toxicity. The first-generation matrine analogue allows for a synthesis similar to the Striker reaction producing aminonitriles. An alkyne coupling reaction was also possible with the modification, producing propargyl-amines. Both of the reactions resulted in the addition of a triple bond substituent …

Motion-Induced Artifact Mitigation And Image Enhancement Strategies For Four-Dimensional Fan-Beam And Cone-Beam Computed Tomography, Matthew J. Riblett

Theses and Dissertations

Four dimensional imaging has become part of the standard of care for diagnosing and treating non-small cell lung cancer. In radiotherapy applications 4D fan-beam computed tomography (4D-CT) and 4D cone-beam computed tomography (4D-CBCT) are two advanced imaging modalities that afford clinical practitioners knowledge of the underlying kinematics and structural dynamics of diseased tissues and provide insight into the effects of regular organ motion and the nature of tissue deformation over time. While these imaging techniques can facilitate the use of more targeted radiotherapies, issues surrounding image quality and accuracy currently limit the utility of these images clinically.

The purpose of …

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 …

Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie

Theses and Dissertations

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …

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 …

5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala

Theses and Dissertations

5-HT_2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens …

Utilizing Consumer Health Posts For Pharmacovigilance: Identifying Underlying Factors Associated With Patients’ Attitudes Towards Antidepressants, Maryam Zolnoori

Theses and Dissertations

Non-adherence to antidepressants is a major obstacle to antidepressants therapeutic benefits, resulting in increased risk of relapse, emergency visits, and significant burden on individuals and the healthcare system. Several studies showed that non-adherence is weakly associated with personal and clinical variables, but strongly associated with patients’ beliefs and attitudes towards medications. The traditional methods for identifying the key dimensions of patients’ attitudes towards antidepressants are associated with some methodological limitations, such as concern about confidentiality of personal information. In this study, attempts have been made to address the limitations by utilizing patients’ self report experiences in online healthcare forums to …

Modeling Of Anticancer Drug Delivery By Temperature-Sensitive Liposomes, Vera Franziska Loeser

Theses and Dissertations

Cytotoxic anticancer drugs are used to treat cancer, particularly tumors. These drugs themselves do not distinguish between healthy and tumor cells and attack all of them. Consequently physicians and chemists investigate safer ways of delivery that minimize damage to healthy cells. One of these ways are liposomal formulations of the anticancer drugs. Liposomes are vesicles that encapsulate the drug to shield the healthy parts of the body from the toxicity of the drugs. Due to the abnormal structure of tumors, especially their leaky vasculature, these macromolecules are able to diffuse into the tumor tissue whereas the normal vasculature prevents them …

Computational Fluid Dynamics In A Terminal Alveolated Bronchiole Duct With Expanding Walls: Proof-Of-Concept In Openfoam, Jeremy Myers

Theses and Dissertations

Mathematical Biology has found recent success applying Computational Fluid Dynamics (CFD) to model airflow in the human lung. Detailed modeling of flow patterns in the alveoli, where the oxygen-carbon dioxide gas exchange occurs, has provided data that is useful in treating illnesses and designing drug-delivery systems. Unfortunately, many CFD software packages have high licensing fees that are out of reach for independent researchers. This thesis uses three open-source software packages, Gmsh, OpenFOAM, and ParaView, to design a mesh, create a simulation, and visualize the results of an idealized terminal alveolar sac model. This model successfully demonstrates that OpenFOAM can be …

Mathematical Models Of The Inflammatory Response In The Lungs, Sarah B. Minucci

Theses and Dissertations

Inflammation in the lungs can occur for many reasons, from bacterial infections to stretch by mechanical ventilation. In this work we compare and contrast various mathematical models for lung injuries in the categories of acute infection, latent versus active infection, and particulate inhalation. We focus on systems of ordinary differential equations (ODEs), agent-based models (ABMs), and Boolean networks. Each type of model provides different insight into the immune response to damage in the lungs. This knowledge includes a better understanding of the complex dynamics of immune cells, proteins, and cytokines, recommendations for treatment with antibiotics, and a foundation for more …

Marginal Structural Cox Model For Survival Data With Treatment-Confounder Feedback, Yanan Zhang

Theses and Dissertations

In an observational longitudinal study, there can be time-varying exposure/treatment and time-varying confounders. When the confounders affect the exposure and prior exposure also has an impact on levels of confounders, there is treatment confounder feedback. To admit estimation of unbiased causal effects, these conditions need to be hold, exchangeability, positivity, consistency. The traditional method of conditioning on potential confounders does not meet these 3 conditions. Therefore, parameter estimates from traditional Cox model are biased casual effect estimates when the treatment confounder feedback exists. The marginal structural Cox model can be used to address this issue. By calculating and including inverse …

Weighted Quantile Sum Regression For Analyzing Correlated Predictors Acting Through A Mediation Pathway On A Biological Outcome, Bhanu M. Evani

Theses and Dissertations

Abstract

Weighted Quantile Sum Regression for Analyzing Correlated Predictors Acting Through a Mediation Pathway on a Biological Outcome

By

Bhanu M. Evani, Ph.D.

A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2017.

Major Director: Robert A. Perera, Asst. Professor, Department of Biostatistics

This work examines mediated effects of a set of correlated predictors using the recently developed Weighted Quantile Sum (WQS) regression method. Traditionally, mediation analysis has been conducted using the multiple regression method, first proposed by Baron and Kenny (1986), which has since …

Comparison Of Atypical Bacteriophages That Infect Caulobacter Crescentus, Doreen Nguyen

Theses and Dissertations

Several Caulobacter bacterial genomes have been recently sequenced, and all of the genomes contained one or more clusters of genes with phage origins. This observation indicates that bacteriophages contribute to the Caulobacter gene pool, so in order to understand bacteria genomes we will need to understand phage genomes as well. As part of understanding the phage genomes, we want to isolate novel bacteriophages and study their genomics. This study resulted in the isolation of 12 new phages, including four that differ from the well-studied CbKlike phages. Two of these novel phages are Podoviruses with icosahedral heads and small tails, and …

The Utility Of Mobile Phones For Health Among Women Living With Hiv In Urban Malawi, Linda Marie Dietrich

Theses and Dissertations

The use of mobile phones are becoming ubiquitous with growing interest by healthcare providers to utilize mobile phone technology for various health-related applications, called mHealth. This is especially true in low-income countries such as those in sub-Saharan Africa. When implementing mHealth applications, it is important to understand the dynamic social, cultural and environmental factors where mHealth will be implemented to ensure that interventions developed are effective. A qualitative study to explore the sociotechnical factors experienced by women participating in an HIV support group in urban Malawi was conducted to enhance our understanding of women’s experience with mobile phone use and …