Medicine and Health Sciences Commons^™

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations and Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

The Role Of Daam1 In Kidney Development, Vanja Krneta-Stankic

Dissertations and Theses (Open Access)

Kidneys, like most organs in our bodies, consist of a network of epithelial tubules. Kidney tubules are called nephrons, and their morphology is important for kidney function. Nephrons develop from mesodermally derived aggregates of progenitor cells. The nephric progenitors organize into nephric tubules lined with hair-like sensory projections called cilia. Many diseases of the kidney are characterized by abnormal nephron morphology with current treatment aimed at symptom control. To understand the mechanisms underlying kidney diseases and achieve the development of novel therapies, a better understanding of how nephrons develop is needed. Although the actin cytoskeleton is critical for cell behaviors …

Packaging And Secretion Of Airway Mucins, Oanh Ngoc Hoang

Dissertations and Theses (Open Access)

In the conducting airways of the lungs, the mobile mucus gel layer sits on top of the airway epithelium, and through ciliary beating it is propelled up the trachea into the pharynx where it is swallowed and cleared. This gel layer is composed of secreted mucins that become hydrated once reaching the airway lumen. Mucins are secreted at a baseline rate and at a stimulated rate, dependent on the amount of agonist. Baseline secretion is responsible for steady clearance of inhaled particles and pathogens. Stimulated secretion is thought to play a role in trapping helminths though mucus occlusion in small …

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations and Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Qki-Mediated Cholesterol Biosynthesis In Eye Lens And Myelin Of The Central Nervous System, Seula Shin, Seula Shin

Dissertations and Theses (Open Access)

Cells obtain cholesterol in two ways, de novo biosynthesis and uptake from circulation. While most tissues utilize both sources, eye lens and brain depend extensively on cholesterol biosynthesis due to the limited supply from circulation. Lens cell membrane consists of highest portion of cholesterol. Brain is the most cholesterol-rich organ, which accounts for 23% of total cholesterol. Genetic mutations of cholesterol biosynthesis enzymes in humans and animal models present cataracts and hypomyelinating disorders linked to neurological impairment. Yet, it remains unclear how gene expression of cholesterol biosynthesis is regulated in lens and brain. Therefore, studying cholesterol biosynthesis in both tissues …

Fibroblast Heterogeneity In Pancreatic Cancer Immunity, Josephine Darpolor

Dissertations and Theses (Open Access)

Fibroblasts are a unique cell type defined by their mesenchymal phenotype and exclusion from epithelial, immune, and endothelial cell subsets. Although well studied in wound healing, cancer associated fibroblasts (CAFs) are incredibly heterogeneous, leading to contradictions as to the roles CAFs play in the tumor microenvironment (TME). CAFs were thought to be a barrier to treatment of pancreatic ductal adenocarcinoma (PDAC). However, general stromal targeting strategies have largely failed in the clinic likely due to the heterogeneity of CAFs in the TME. Therefore, our groups and others have worked to unravel the heterogeneity of CAFs in PDAC. In the works …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations and Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

Combined Inhibition Of Ddr1 And Cdk4/6 Induces Synergistic Effects In Er-Positive, Her2-Negative Breast Cancer With Pik3ca/Akt1 Mutations, Maryam Shariati, Maryam Shariati

Dissertations and Theses (Open Access)

COMBINED INHIBITION OF DDR1 AND CDK4/6 INDUCES SYNERGISTIC EFFECTS IN ER-POSITIVE, HER2-NEGATIVE BREAST CANCER WITH PIK3CA/AKT1 MUTATIONS

Maryam Shariati, M.S. Advisory Professor: Funda Meric-Bernstam, M.D.

Molecular alterations in the phosphatidylinositol 3‑kinase (PI3K)/ serine/threonine protein kinase B (AKT) signaling pathway occur frequently in estrogen receptor–positive (ER-positive) breast tumors. Patients with ER-positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer are often treated with cyclin-dependent kinase (CDK4/6) inhibitors such as palbociclib in combination with endocrine therapy. Although this is a very effective regimen, disease progression ultimately occurs in most patients. Further, the modulators of palbociclib sensitivity remain unclear. The purpose …

Qki-Mediated Cholesterol Biosynthesis In Eye Lens And Myelin Of The Central Nervous System, Seula Shin, Seula Shin

Dissertations and Theses (Open Access)

Cells obtain cholesterol in two ways, de novo biosynthesis and uptake from circulation. While most tissues utilize both sources, eye lens and brain depend extensively on cholesterol biosynthesis due to the limited supply from circulation. Lens cell membrane consists of highest portion of cholesterol. Brain is the most cholesterol-rich organ, which accounts for 23% of total cholesterol. Genetic mutations of cholesterol biosynthesis enzymes in humans and animal models present cataracts and hypomyelinating disorders linked to neurological impairment. Yet, it remains unclear how gene expression of cholesterol biosynthesis is regulated in lens and brain. Therefore, studying cholesterol biosynthesis in both tissues …

Determining The Utility Of Hl7® Fast Healthcare Interoperability Resources (Fhir®) Standards In Supporting Ehr And Edc-Agnostic Esource Implementations For Clinical Research, Maryam Garza

Dissertations and Theses (Open Access)

Advances in efficiency while maintaining or improving quality are immediately needed in clinical research, specifically for multicenter clinical studies. Though recent evidence points toward electronic health record (EHR) to electronic data capture (EDC) system (EHR to EDC) data collection as a viable contribution, there are many unanswered process and outcome-level questions regarding quality, site burden, and cost within the context of multicenter clinical trials. Direct extraction and use of EHR data in multicenter clinical studies is a long-term and multifaceted endeavor that includes design, development, implementation and evaluation of methods and tools for semi-automating tasks in the research data collection …

The Direct Primary Care Model: Practice Characteristics And Patient Experience, James David Miller

Dissertations and Theses (Open Access)

The Direct Primary Care practice model has been growing in both number of practices and public awareness. However, there has been little academic research about this emerging practice model. This research is aimed to describe the current state of the DPC practice model by examining the services provided, geographic distribution of practices, statistical distribution of membership fees, demographic characteristics of physicians using the model and to determine whether regional pricing variation existed. In addition, differences were analyzed between the patient satisfaction levels in DPC and fee-for-service practices. A dataset was created by visiting the website of all known, non-corporate, DPC …

Cross-Sectional Analysis Of The Relationship Between Violent Crime And Mental Health Disorders In A Sample Of Homeless Adults Recently Released From Jail, Addison Ransom

Dissertations and Theses (Open Access)

Adverse mental health conditions among incarcerated populations are high, and treatment for these conditions is particularly low. Additionally, there is a culture of stigma in the United States towards those with mental health conditions and violent criminal history, contributing to mass incarceration. The present cross-sectional study sought to assess the association between violent criminal history and mental health symptoms among recently incarcerated homeless adults in Dallas, Texas. This study included 230 participants, taking place at The Bridge Homeless Recovery Center, evaluating non-violent versus violent criminal history. Outcome measures of positive screens for post-traumatic stress disorder, generalized anxiety disorder, and depression …

Development And Preliminary Psychometric Testing Of The Drake Atrial Electrogram Assessment Survey: Daegas©, Jeanette Drake

Dissertations and Theses (Open Access)

Background: Critical care nurses (CCNs) who care for postoperative cardiac surgery patients need specialty knowledge, for example, knowledge of atrial electrograms (AEGs). An inadequate audit trail exists for psychometric performance of instruments to measure CCN knowledge of AEGs. A 29-item survey previously pilot tested with a convenience sample of CCNs in the Pacific Northwest had a Kuder-Richardson-20 estimate of internal consistency of .75. The survey was revised to 20 items (14 knowledge and 6 AEG interpretation) and named the Drake Atrial Electrogram Assessment Survey (DAEGAS).

Objectives: The study objectives were to assess evidence for content validity (content validity …

The Impact Of Bullying Victimization And Sexual Orientation On The Severity Of Suicidal Behavior, Annalyn Demello

Dissertations and Theses (Open Access)

Background: Lesbian, gay, and bisexual (LGB) youth face a disproportionate risk of suicidal ideation and attempt compared to their heterosexual counterparts. The Minority Stress Theory and Interpersonal Theory of Suicide posit that chronic stress, which can occur as a result of bullying victimization, can lead to loneliness, self-hate, and suicidal ideation. The escalation from ideation to attempt can occur quickly, and most youth who survive suicide attempts pursue subsequent, riskier attempts. It is crucial to intervene when behaviors are less severe. The primary aim of this study was to compare the magnitudes of association between independent variables (bullying and sexual …

Molecular Diagnosis Of Intestinal Parasites: Impact On Growth Among Preschool-Age Children In Rural Ecuador, Patricia Bryan

Dissertations and Theses (Open Access)

Background: Gastrointestinal (GI) parasites may have important influences on growth outcomes during early childhood. Previous studies investigating the effects of GI parasites on growth have predominantly used microscopy-based diagnostic methods with low sensitivity. Few accurate epidemiologic data are available on GI parasitic infections among rural Ecuadorian children. To investigate the impact of single and multiple GI parasite infections on growth during early childhood data from a longitudinal birth cohort in Ecuador were analyzed.

Purpose: The aims of this study were to determine the prevalence of GI parasites (soil-transmitted helminths and intestinal protozoa) and to describe associations between GI parasitic infections …

Atitiudes Tow Ards Computer Games For Learning And Pl.A Yer Archetypes: An Exploration Of Measures On Preintervention Player Characteristics For Serious Game-Based Interventions, Benjamin Lee

Dissertations and Theses (Open Access)

Serious game-based interventions offer promising health outcome results with the aid of pre-intervention player tailoring and the development of measurements that evaluate pre-intervention player characteristics and subgroups. Video gaming measures can potentially provide helpful tailoring information that discerns individual video gaming preferences which could influence their overall user experience. It is critical that measures that target adolescent video gaming be psychometrically validated. There is a gap in the literature with psychometrically validated measures evaluating adolescent attitudes towards computer games for learning and gaming archetypes. Therefore the aims of this dissertation were to 1) evaluate the psychometric properties (i.e., reliability and …

Costs Of Coronary Artery Bypass Grafting And Percutaneous Coronary Intervention In Texas, Saleh Hamed Alsarhan

Dissertations and Theses (Open Access)

Background: Coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) procedures have been associated with substantial financial costs in Texas. The annual hospital charges in 2016 for CABG surgeries and PCI procedures in Texas were $3.6 billion and $4.1 billion, respectively. Recently, these two procedures have become a target for bundled payment initiatives. Due to the lack of information about the demographics and variations associated with CABG and PCI episode payments for commercially insured patients, more research needs to be conducted to understand the magnitude of payments and the drivers of variation in payments in Texas. Objective: This …

Semiparametric Methods To Improve Risk Assessment And Dynamic Prediction, Wen Li

Dissertations and Theses (Open Access)

Incorporating promising biomarkers to improve risk assessment and prediction is the central goal in many biomedical studies. Cost-effective designs and longitudinal designs are often utilized for measuring biomarker information, but they pose challenges to the data analyses. Statistical analyses for these kinds of data are routinely performed using parametric models. When the model assumptions are violated, parametric models may lead to substantial bias in parameter estimation, risk evaluation and prediction. In this dissertation, we will develop robust, exible statistical methods for risk assessment for matched case-control, nested case-control, and case-cohort designs, as well as a dynamic prediction tool for longitudinal …

A Qualitative Inquiry Exploring Help-Seeking Behaviors And Resilience Strategies Women With Disabilities Utilize When Experiencing Gender-Based Violence In Rural Communities, Kimberly Ann Aguillard

Dissertations and Theses (Open Access)

Women with disabilities (WWD) are at pronounced risk of experiencing multiple forms of severe and prolonged violence, and they face barriers to accessing help. A multitude of factors associated with disability and rurality may compound the experience of violence, including geographic and social isolation, forcing WWD in rural settings to navigate extremely dangerous situations with limited avenues for accessing help and securing safety. This research explored how women with disabilities experiencing violence while living in rural communities navigate programs and policies, make decisions about seeking and securing help, and build resilience despite experiencing violence. The current study methodology empowers this …

A Comparison Of Interdisciplinary Palliative Care Teams And Leadership Attitudes Of Nci-Designated And Non-Nci-Designated Cancer Centers In The United States From 2009-2018, Joseph Chen

Dissertations and Theses (Open Access)

Background: Interdisciplinary palliative care (PC) teams (IDTs) are essential to improving patient outcomes while cancer center executives have a key role in defining the future of PC. Objectives: To compare PC team compositions and executives’ attitudes towards PC between NCI (National Cancer Institute)-designated cancer centers (NCI-CCs) and non-NCI-designated cancer centers (non-NCI-CCs) in 2018 and to compare changes in team composition and executives’ attitudes and beliefs between 2009-2018. Methods: PC program leaders (PL) and cancer center executives at all 62 NCI-CCs and a random sample of 60 of 1252 non-NCI-CCs were surveyed from April-August 2018. The PL survey examined team composition …

Disparities In Patient Safety Events For Hospitalized Patients, Nnabuchi Anikpezie

Dissertations and Theses (Open Access)

Background: Twenty years post IOM’s landmark publication, “To Err is Human: Building a Safer Health System”, still no consensus on case definition for patient safety events (PSEs). Available data on incidence and magnitude of PSEs are more than 10 years old, while data on disparities are ambiguous. Objective: To examine the racial and socioeconomic disparities in reported patient safety events (PSEs) among hospitalized individuals. Design, Setting, and Participants: Cross-sectional study of patient safety events using the 2016 National Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project (HCUP). A total of 6,753,100 discharges were identified as being at risk …

Determining The Racial And Ethnic Differences In Neonatal Intensive Care Unit Admission Rates, Youngran Kim

Dissertations and Theses (Open Access)

Background: Recent trends show that the utilization of neonatal intensive care unit (NICU) has extended beyond severely ill infants and increased substantially across all birth weights. However, little is known about what drives the growth of NICU admission rates and whether these trends differ by race/ethnicity. Methods: The study used 2008-2018 Natality Files with restricted use of state and county-level information. Crude and risk-adjusted NICU admission rates, overall and stratified by birth weight group, were compared between black and white infants and between Hispanic and white infants. Kitagawa decomposition and Oaxaca-Blinder decomposition analyses were conducted for the temporal increase in …

Causal Analysis Theory And Application To Alzheimer’S Disease (Ad) And Heart Failure (Hf), Shudi Li

Dissertations and Theses (Open Access)

Alzheimer's disease (AD) and heart failure (HF) are two complex diseases that are caused by the combination of genetic and epigenetic, environmental and other lifestyle factors. Understanding the relationships between genetic and epigenetic variants and other factors of such complex diseases could assist researchers discover disease mechanisms and develop targeted therapies. Much of the research in genetics/epigenetics studies regarding AD and heart diseases have been focused on association analysis. Many researchers have identified genetic/epigenetics variants and phenotypes that are significantly associated with disease pathology. While most of these studies utilize association analysis as the analytical platform, the signals identified by …

Heat Stress Related Symptoms And Pulmonary Function In Oil Spill Response And Cleanup Workers Following The Deepwater Horizon Disaster, Yiyou Li

Dissertations and Theses (Open Access)

The objective of this study was to estimate the relationship between heat stress and pulmonary function among OSRC workers following the Deepwater Horizon (DWH) disaster. Methods: Pulmonary function test results were analyzed from a cohort of oil spill response and cleanup workers 1-3 years following the DWH disaster (N=5,131). Proxies for heat stress was employed by using information on heat stress-related symptoms as well as a questionnaire on stopping work due to heat reported during a structured telephone enrollment questionnaire. Associations between heat stress proxies and lung function were estimated using multivariable linear models and binomial logistic regression models while …

Epidemiology Of No -Syndromic, Orofacial Clefts In A Registry­Based, Birth-Cohort In Texas: Differences By Cleft Type And Presence Of Additional Defects, Maria Luisa Navarro Sanchez

Dissertations and Theses (Open Access)

Although orofacial clefts, which include cleft palate alone (CP) and cleft lip with or without cleft palate (CL±P), are among the most common birth defects, their etiology is complex and is generally not well understood. While some clefts are caused by rare syndromes, the majority occur in the absence of a syndrome, either in association with co-occurring defects or as isolated defects. Among these non-syndromic cases, epidemiologic studies have identified demographic variables that are associated with CP and/or CL±P, such as geographic location and infant sex, as well as several maternal characteristics, though some of these associations have been weak …

Heat Stress Related Symptoms And Pulmonary Function In Oil Spill Response And Cleanup Workers Following The Deepwater Horizon Disaster, Yiyao Li

Dissertations and Theses (Open Access)

Objective: The objective of this study was to estimate the relationship between heat stress and pulmonary function among OSRC workers following the Deepwater Horizon (DWH) disaster. Methods: Pulmonary function test results were analyzed from a cohort of oil spill response and cleanup workers 1-3 years following the DWH disaster (N=5,131). Proxies for heat stress was employed by using information on heat stress-related symptoms as well as a questionnaire on stopping work due to heat reported during a structured telephone enrollment questionnaire. Associations between heat stress proxies and lung function were estimated using multivariable linear models and binomial logistic regression models …

Area-Level Landfill Density And Asthma Prevalence In Urban Texas Areas, Jessica Meighan Herrin

Dissertations and Theses (Open Access)

Environmental exposures, especially air pollutants, pose a threat for an increase in asthma prevalence. In particular, hydrogen sulfide (H2S) gas can cause severe health effects closely resembling asthmatic symptoms. Ambient concentrations of H2S gas correlates with the amount of solid waste found in landfills. The potential for adverse health risks associated with H2S emitted from landfills is of concern for those populations living in close proximity to landfills. Asthma is one of the adverse health effects that can occur due to H2S exposure. However, there is a lack of detailed studies characterizing possible associations between the density of landfills and …

Impact Of Substance Use In Social Networks On Antiretroviral Therapy Adherence For Hiv-Positive Younger Men Who Have Sex With Men, Natascha Del Vecchio

Dissertations and Theses (Open Access)

The community of young men who have sex with men (YMSM) has higher rates of substance use than the general population and the use of alcohol, cannabis, and illicit drugs has been shown to have a negative impact on the HIV care continuum. Our first aim was to understand the prevalence of substance use in the community through the use of self-reported, RDS-II, and RDS-SS estimates. We used multivariable logistic and negative binomial GEE with QIC selection to determine the factors important to having a prescription and staying adherent, respectively. Selected variables were included with a subset of substance use …

Effect Of The Expanded Prospective Payment System On Dialysis Initiation, The Usage Of Erythropoiesis-Stimulating Agents, And Medicare Expenditures, Lu Zhang

Dissertations and Theses (Open Access)

In January 2011, the U.S. Centers for Medicare & Medicaid Services (CMS) implemented the expanded prospective payment system (PPS) for financing the management of end-stage renal disease (ESRD). Expanded PPS may not only change healthcare providers’ decisions about patient care by removing the financial incentives associated with the previous composite rate payment methodology, but also change the Medicare expenditures associated with various treatment patterns by using a constant base rate for all dialysis modalities. This study aimed to examine the effect of the expanded PPS on providers’ decisions on timing of dialysis initiation and ESA utilizations in ESRD patients as …

Hospital Market Analysis Using A Cohort Of Privately Insured Patients With Total Hip And Knee Replacement Procedures, Elifnur Yay Donderici

Dissertations and Theses (Open Access)

Background: Several recent studies have analyzed the contribution of hospital inpatient prices and utilization to variation in medical spending. However, it is still unknown how the drivers of spending for specific procedures differ within privately insured patients. Next, the market concentration of hospitals has been a matter of concern for several decades. However, researchers usually calculate Herfindahl-Hirschman index (HHI) as a measure of market concentration or power, but there is a drawback of using this measure. Hospitals sell differentiated products, and the HHI measure does not take this differentiation into account in its formulation (Gaynor and Town, 2011). Objective: First …