Medicine and Health Sciences Commons^™

Long-Term Outcomes After Endovascular Stent Placement For Long-Segment Superficial Femoral Artery Lesions, Nader Zamani

Dissertations and Theses (Open Access)

Objective: Endovascular intervention is commonly pursued as first-line management of symptomatic, long-segment superficial femoral artery (SFA) disease. The relative effectiveness and comparative long-term outcomes among bare metal stents (BMSs), covered stents (CSs), and drug-eluting stents (DESs) for long-segment SFA lesions remain uncertain.

Methods: A retrospective cohort study identified patients with symptomatic SFA lesions measuring at least 15cm who successfully received an endovascular stent (BMS, CS, or DES). The outcomes were patency, patient presentation upon stent occlusion, amputation free survival (AFS), and all-cause mortality. Proportional hazards regressions and a multinomial logistic regression model were used to control for significant confounders.

Results: …

Lymphocyte-Specific Tyrosine Kinase Expression In Ovarian Cancer: A Valuable Prognostic Indicator, Emily Moss Hinchcliff

Dissertations and Theses (Open Access)

Cellular immune response, specifically tumor infiltrating lymphocytes (TILs), has been correlated to survival in epithelial ovarian cancer; however, specific gene expression patterns for this response remain poorly understood. The objective of this research was to investigate the prognostic and biologic significance of immune-related gene expression in high grade serous ovarian cancer (HGSOC). To do so, a panel of immune related gene expression was evaluated in HGSOC utilizing The Cancer Genome Atlas (TCGA) and validated in an independent cohort of ovarian tumors. Based on the strong association with survival, the cohort was grouped into LCK (lymphocyte specific tyrosine kinase) high and …

Clinical Diagnostic Whole Exome Sequencing For Infants In Intensive Care Settings: Outcomes Analysis And Economic Evaluation, Hadley Stevens Smith

Dissertations and Theses (Open Access)

Whole exome sequencing (ES) is an extensive form of genetic testing and increasingly used as a diagnostic tool. Clinical uptake of genome-scale sequencing occurred without clear guidelines for application or robust information regarding potential impact on patient health outcomes or cost of care. For infants in intensive care with suspected genetic conditions, ES can be especially powerful to identify a specific diagnosis and inform crucial decisions about medical care. However, little is known about the cost-effectiveness of ES compared to other diagnostic strategies. This project first assessed the literature on pediatric clinical ES. Then, using electronic medical record, diagnostic laboratory, …

Fire Department Support And Physical Activity Of Volunteer Firefighters: A Cross-Sectional Examination, Sarah Wagner

Dissertations and Theses (Open Access)

Greater health and fitness of volunteer firefighters protects them from cardiovascular disease-related deaths, reduces risk of injury, and improves job performance, which subsequently provides better protection for the majority of the U.S. population who is served by volunteers. Given the strong social support system characteristic of the U.S. fire service, there seems to be potential opportunity to influence the behaviors of firefighters by creating a culture that promotes healthy habits rather than unhealthy. Objective: Determine the association between fire department culture’s encouragement of physical activity and volunteer firefighters’ moderate- to vigorous-intensity aerobic activity. Methods: A cross sectional analysis was performed …

Evaluating The Impact Of Early Initiation Of Antiretroviral Therapy (Art) On Patient Outcomes Among Hiv-Infected Adolescents And Young Adults In Uganda, Hilda Sekabira Nakalema

Dissertations and Theses (Open Access)

Introduction: Since the introduction of anti-retroviral therapy (ART), treatment initiation criteria have continually been revised to start these lifesaving drugs before onset of advanced disease and optimize ART benefits for people living with HIV. However, little is known about the effect of these changes on treatment outcomes among young people. We evaluated the effect of such a policy change on long term adherence and treatment outcomes among young people, aged 15-24 years.

Methods: We conducted a retrospective cohort analysis of young people, 15-24years old, who started ART from January 2012 – December 2016. We used administrative data from the District …

Ends Device Types And Subsequent Use Of Combustible Tobacco Products Among Texas Youth, Aslesha Sumbe

Dissertations and Theses (Open Access)

The aims of the study were to determine whether ENDS device types (i.e., disposable devices, replaceable cartridges, and refillables) at initial, or first ENDS use is longitudinally associated with subsequent initiation of combustible tobacco products (cigarettes, hookah, cigars) and continued, past 30-day use of combustible and ENDS products. This study is a secondary analysis of data from the Texas Adolescent Tobacco and Marketing Surveillance system (TATAMS) study, a longitudinal cohort study of students who were in the 6th, 8th, and 10th grades (n = 3907) during the 2014-2015 academic year. Data were collected every 6 months, from 2014-2018. Using data …

Dynamic Competing Risk Model For Multi-Type Recurrent Events With Dependent Termination, Alokananda Ghosh

Dissertations and Theses (Open Access)

Cardiovascular disease (CVD), defined by the World Health Organization (WHO) as diseases that involve the heart and/or blood vessels is the number one cause of morbidity and mortality worldwide. In the United States more health care dollars are spent managing and treating CVD and/or its complications than any other disease process. Coronary heart disease (CHD) is the leading cause of deaths (43.8%) attributable to CVD, followed by stroke (16.8%), hypertension (9.4%) and heart failure (HF) (9%). CVD-related deaths and attendant morbidities, which include lifelong disability are in many cases preventable. This research proposes a dynamic risk model that handles multi-type …

Exploring The Potential Yield Of Prenatal Testing By Evaluating A Postnatal Population With Structural Abnormalities, Peyton Busby

Dissertations and Theses (Open Access)

After identification of one or more structural abnormalities in a fetus, pregnant women are offered a host of different testing options to identify a possible genetic cause for the structural abnormality(ies). When considering what type of test to undertake, there is limited information on the diagnostic yield of the varying testing options. Some women may miss an opportunity to gain the information they are seeking or make a less informed decision when they choose a testing option after identification of a structural abnormality due to this lack of information. This study aimed to identify the potential diagnostic yield of all …

Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer

Dissertations and Theses (Open Access)

Stem cells are integral for tissue maintenance and fertility. Therefore, understanding how stem cells are regulated under stress is imperative. When confronted with acute starvation, stem cells must conserve energy and metabolites to cope with the lack of an external source. Caenorhabditis elegans germline stem cells (GSCs) are an excellent model for studying stem cell properties and regulation as they can divide throughout the life of the organism. While GSCs are an adult stem cell population, their cell cycle structure more closely mimics mouse and human embryonic stem cells with short G1 and long S phases. In this thesis, I …

Identifying Interest In And Barriers To Psychiatric Genetic Counseling, Samantha Montgomery

Dissertations and Theses (Open Access)

Mental illness is common in the United States and genetic counseling for psychiatric indications can help individuals understand multifactorial inheritance, recurrence risk estimates, and identify ways to protect their future mental health. Despite interest in and efficacy of the service documented in populations outside of the United States, individuals with personal and/or family histories of psychiatric conditions are very rarely accessing psychiatric genetic counseling services. The purpose of our study was to identify interest in and barriers to psychiatric genetic counseling with the hopes of better characterizing this population and improving access to this beneficial service in the future. An …

Multimodality Somatostatin Analog For Fluorescence-Guided Surgery In Cancer, Servando Hernandez Vargas

Dissertations and Theses (Open Access)

Cancer surgery remains the primary curative treatment for most solid cancers and has major therapeutic implications for patients with neuroendocrine tumors (NETs). Anatomical and functional imaging technologies are widely used during the pre- and postoperative stages, but intraoperative disease recognition relies on direct visual inspection and the hands of surgeons. The limited number of clinical tools for real-time intraoperative visual feedback restricts the ability to remove the complete cancer source and is partially responsible for the high rate of disease recurrence in patients. Intraoperative imaging with fluorescent contrast agents has the potential to improve the ability of surgeons to detect …

Quantitative Imaging For Precision Medicine In Head And Neck Cancer Patients, Rachel Ger

Dissertations and Theses (Open Access)

The purpose of this work was to determine if prediction models using quantitative imaging measures in head and neck squamous cell carcinoma (HNSCC) patients could be improved when noise due to imaging was reduced. This was investigated separately for salivary gland function using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), overall survival using computed tomography (CT)-based radiomics, and overall survival using positron emission tomography (PET)-based radiomics. From DCE-MRI, where T1-weighted images are serially acquired after injection of contrast, quantitative measures of diffusion can be obtained from the series of images. Radiomics is the study of the relationship of voxels to …

Development Of Automated Radiotherapy Treatment Planning For Cervical And Breast Cancer For Resource-Constrained Clinics, Kelly Kisling

Dissertations and Theses (Open Access)

Globally, cancer rates are on the rise, especially in low- and middle-income countries (LMICs). However, many of these countries lack access to radiotherapy, which is due in part to a substantial shortage of the staff necessary to deliver safe and effective radiotherapy. This staff shortage could be mitigated by the automation of the radiation treatment planning process. To this end, we developed automated planning for cervical and postmastectomy breast cancer radiotherapy, the two most common types of cancer in women in many LMICs.

For radiotherapy of cervical cancer in resource-constrained clinics, the recommended treatment technique is a four-field box. We …

The Impacts Of Insurance And Billing Considerations On The Practice And Attitudes Of Genetic Counselors, Emily Krosschell

Dissertations and Theses (Open Access)

Genesurance counseling has been identified as an integral part of many genetic counseling sessions, but little is known about the workflow impacts and genetic counselor perceptions of genesurance-related tasks. In this study, we aimed to characterize how insurance and billing considerations for genetic testing are being incorporated into genetic counselors’ practice; as well as describe current attitudes and challenges associated with their integration. An electronic survey was sent by email to members of the National Society of Genetic Counselors (NSGC). A total of 325 genetic counselors that provided direct patient care were included in data analysis. Results showed that the …

Metabolic Control, Quality Of Life, And Body Image In Patients With Glycogen Storage Disease Type Ia, Alexa Bream

Dissertations and Theses (Open Access)

Glycogen storage disease is a group of inborn errors of metabolism, with type Ia being the most common form of the disorder. Glycogen storage disease type Ia (GSDIa) is a multisystemic condition in which individuals have various complications secondary to an inability to properly break down glycogen and to perform gluconeogenesis. Complex management is then necessary for patients and includes dietary modification, frequent cornstarch usage, and evaluation for additional complications such as hepatic adenomas, hypertriglyceridemia, and kidney disease. Previous studies have found lower scores in quality of life and body image in GSDIa patients; however, the specific factors influencing this …

Hypoglycemia In Mitochondrial Disorders, Allison Moats

Dissertations and Theses (Open Access)

INTRODUCTION: The electron transport chain (ETC) in mitochondria functions to produce energy in the form of adenosine triphosphate (ATP). Defects in the mitochondrial or nuclear DNA that codes for components of the ETC lead to mitochondrial disorders (MTDs). MTDs are multi-system conditions affecting the heart, muscles, and especially brain. The endocrine system is commonly affected in MTDs, and diabetes and hyperglycemia are established secondary diagnoses. Rates of non-iatrogenic hypoglycemia have not been studied in individuals with MTDs. This study aims to investigate the frequency of hypoglycemia in patients with MTDs.

METHODS: Individuals diagnosed with a ‘definite’ or ‘probable’ …

Il-6/Jak1 Drives Pd-L1 Phosphorylation And Glycosylation To Promote Cancer Immune Evasion, Li-Chuan Chan

Dissertations and Theses (Open Access)

Glycosylation of immune receptors and ligands, such as T-cell receptor (TCR), major histocompatibility complex (MHC), and co-inhibitory molecules, regulates immune signaling activation, antigen presentation, and immune surveillance. Recent studies revealed that the glycan structures of co-inhibitory molecules are required for receptor-ligand interaction, a critical feature for activating cancer immune evasion. However, it is unclear how oncogenic signaling initiates glycosylation of co-inhibitory molecules to induce immunosuppression. Here we show interleukin (IL)-6-activated Janus kinase 1 (JAK1) phosphorylates programmed death-ligand 1 (PD-L1)-Tyr112, leading to the recruitment of endoplasmic reticulum (ER)-associated N-glycosyltransferase, STT3A, which catalyzes the glycosylation of PD-L1, contributing to its stability. A …

Termination For Fetal Anomaly: What Is The Impact Of Genetic Counseling On Coping?, Cayleen Smith

Dissertations and Theses (Open Access)

Pregnancy termination for fetal anomaly (TFA) is a unique experience that can cause women to develop long-term, complicated grief. Although a woman’s experience with her healthcare providers has been previously identified as an important factor in coping, studies have shown that many women report their healthcare as lacking to some extent. Given the overlap in patient needs and the practice scope of a genetic counselor (GC), this study aimed to examine how genetic counseling may impact coping as well as explore patient expectations of GCs pre- and post-TFA. An online survey, which included the Brief COPE and The Short Version …

Genetic Counselor Utilization And Interpretation Of Somatic Tumor Testing In Evaluation For Lynch Syndrome, Danielle Williams

Dissertations and Theses (Open Access)

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome characterized by increased risk for colorectal and uterine cancers. Individuals with pathogenic variants in the mismatch repair (MMR) genes (MLH1, MSH2/EPCAM, MSH6, PMS2) are diagnosed with LS and subsequently recommended to proceed with high risk screening protocols to increase prevention and early detection of LS-related cancers. Various tumor studies can help identify those at high risk for LS, but sometimes create uncertainty with discordant screening and germline results, leading to unexplained mismatch repair deficiency (UMMRD). Somatic testing of the MMR genes has created opportunities for resolving …

Identifying Pathogenic Variants In Hereditary Cancer Syndrome Genes Via Tumor Molecular Profiling, Carol Nowlen

Dissertations and Theses (Open Access)

Tumor molecular profiling is often performed in order to direct cancer treatment options. However, because many of the genes analyzed on tumor molecular profiling overlap with genes known to be associated in the germline with hereditary cancer predisposition syndromes, tumor molecular profiling can unknowingly uncover germline predisposition to cancer development. In this study, we determined the number of patients with pathogenic variants (PVs) identified in BRCA1 and BRCA2 (BRCA1/2) via tumor molecular profiling at The University of Texas MD Anderson Cancer Center, then performed a retrospective chart review to determine the proportion of such patients that received germline …

Investigating The Role Of The P63 Isoform Δnp63 In Lung Stem Cell Populations And Lung Cancer, Sarah J. Wu

Dissertations and Theses (Open Access)

Cell of origin studies have determined separate populations of lung progenitor cells that give rise to lung adenocarcinoma and squamous cell carcinoma. ΔNp63 is known to regulate lung development but its role in lung cancer progression remains unclear. We utilized a ΔNp63-specific conditional knockout mouse model to determine ΔNp63’s role in lung progenitor cells and lung cancer. In vivo and in vitro experiments revealed a role for ΔNp63 in maintaining lung progenitor cells. ChIP-seq results indicate that deletion of ΔNp63 results in robust loss of enhancer histone marks at cell identity genes for lung progenitor populations of basal cells and …

Current Practices And Perspectives Of Genetic Counselors And Reproductive Endocrinologists Regarding Transfer Of Mosaic Embryos, Angelica Starnes

Dissertations and Theses (Open Access)

With the recent transition in testing methodology used for preimplantation genetic testing for aneuploidy (PGT-A) from array comparative genomic hybridization to next generation sequencing, mosaic embryos are being identified more readily. Given the limited clinical guidance and information regarding outcomes after the transfer of mosaic embryos (TME), a mosaic test result can present challenging scenarios for providers and patients. The current landscape of this area of reproductive medicine must be described before a consensus can be determined and areas for improvement can be identified. This cross-sectional descriptive study aimed to define the current practices regarding TME as reported by prenatal …

Exploring Experiences & Expectations Of Prenatal Healthcare And Genetic Counseling/Testing In Immigrant Latinas, Georgiann Garza

Dissertations and Theses (Open Access)

In recent years, the Latino population of the United States has continued to increase, but the specific needs of Latinos in the genetic counseling setting have yet to be explored. Genetic counselors tailor sessions to the needs of the patient, and more information regarding general attitudes of a population can assist in building rapport. We aimed to investigate the relationship between acculturation, prenatal care, genetic testing experiences, and expectations for their prenatal care in an immigrant Latino population. A total of 20 Spanish-speaking, pregnant Latinas from various Latin American countries were interviewed after completing a prenatal genetic counseling session. The …

Hsp70-Mediated Regulation Of Hsf1 Transcriptional Activity In Saccharomyces Cerevisiae, Sara Peffer

Dissertations and Theses (Open Access)

In eukaryotic cells, protein homeostasis and cellular fitness is promoted by the transcription factor heat shock factor 1 (HSF1) during exposure to proteotoxic stress. HSF1 controls the basal and stress-induced expression of molecular chaperones and other protective targets. Dynamic regulation of HSF1 involves the major heat shock proteins Hsp70 and Hsp90. Recent advances in the understanding of this regulatory circuit in Saccharomyces cerevisiae have shown that the Hsp70 Ssa1 acts as a sensor for some proteotoxic stresses and is capable of a direct interaction with Hsf1. This work continues to explore the complex regulatory interaction between Hsf1 and Ssa1. I …

Development Of A High-Throughput System For Screening Of Anti-Prion Molecules, Katherine Do

Dissertations and Theses (Open Access)

The misfolded prion protein causes and transmits disease in both humans and animals. As other infectious agents, prions display strain variation, which can generate different pathological outcomes in affected individuals. Unfortunately, there are no known therapies for these diseases, which at present are invariably fatal. In this work, the Protein Misfolding Cyclic Amplification technology (PMCA, an in vitro test that replicates minimum quantities of infectious prions) has been modified to screen for small molecules inhibiting prion protein misfolding in a strain-specific manner. In order to approach a high-throughput PMCA system, technical aspects in PMCA has been optimized for application of …

Sequence-Specific Gene Correction Of Cystic Fibrosis Airway Basal Cells, Varada Anirudhan

Dissertations and Theses (Open Access)

Cystic fibrosis (CF) is a lethal monogenic disease resulting from mutations in the CFTR gene which encodes a protein involved in regulating anion trans-epithelial transport. A three-base deletion in CFTR (termed as ΔF508 mutation), wherein CFTR protein is misfolded leading to its pre-mature degradation in the endoplasmic reticulum (ER), is the most common cause of this debilitating disease. Since CFTR is expressed in multiple body systems, CF affects different organs, but lung pathology is the greatest cause of death in affected patients. We achieved site-specific gene correction with an efficiency of ~10 % in CF airway basal cells homozygous for …

Cross-Presentation Is A Source Of Tumor Antigens For Multiple Myeloma Immunotherapy, Alexander A. Perakis

Dissertations and Theses (Open Access)

Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here …

Computational Genomic Models For Spatio-Temporal Investigation Of Early Lung Cancer Pathology, Smruthy Sivakumar

Dissertations and Theses (Open Access)

Lung cancer, of which non-small cell lung cancer (NSCLC) is the most common form, is the second most prevalent cancer and the leading cause of cancer-related deaths. NSCLCs primarily comprise adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). Advances in early detection and prevention have been limited by the lack of early-stage biomarkers and targets. A comprehensive molecular characterization of premalignant lesions and tumor-adjacent normal tissue can aid in better understanding NSCLC pathogenesis. However, these investigations are further challenged by limited tissue availability and low cellular fractions of detectable somatic mutations.

Therefore, there is a dearth of knowledge about the pathogenesis …

The Impact Of The Aca Cost-Sharing Elimination Provision On The Utilization Of Breast, Cervical, And Colorectal Cancer Screening Services Among Insured Individuals In The United States, Sara Salah Atallah

Dissertations and Theses (Open Access)

Preventive cancer screenings are essential to early detect cancer and subsequently save lives. However, out-of-pocket expenditures for cancer screening services deter individuals from obtaining them. In an effort to improve the utilization of cancer screening, the Affordable Care Act (ACA) implemented a cost-sharing elimination provision that removes all forms of cost sharing including copayments, co-insurance and deductibles from certain preventive care services that are recommended by widely known scientific figures such as the United States Preventive Services Task Force (USPSTF). This study evaluated the impact of the ACA cost-sharing elimination provision for preventive care services from 2008 through 2016 using …

Spatial Analysis Of Exposure To Soil Heavy Metals, Oral Bioaccessibility And Risk Assessment In Houston, Texas, Tsai Shu Chu

Dissertations and Theses (Open Access)

Chronic exposure to heavy metals could lead to adverse health effects such as cancer, neurological development diseases and immunological diseases. The ingestion pathway has been considered the major exposure route for heavy metal contaminated soils. Heavy metals may be proportionally bioaccessible for the human body to absorb. There are no risk assessment studies done in Houston to evaluate health risks from exposure to heavy metals and no spatial analysis done yet. The aims of this dissertation are (1) to characterize 13 heavy metals: magnesium (Mg), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc …