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A Global Slc7a7 Knockout Mouse Model Demonstrates Characteristic Phenotypes Of Human Lysinuric Protein Intolerance, Chih-Wei Hsu, Cheng-Yen Chang, Luan D Truong, Brian Dawson, Ingo Grafe, Yuqing Chen, Ming-Ming Jiang, Denise Lanza, Jennie Rose Green, Qin Sun, J P Barrish, Safa Ani, Audrey E Christiansen, John R Seavitt, Mary E Dickinson, Farrah Kheradmand, Jason D Heaney, Brendan Lee, Lindsay C Burrage

Faculty, Staff and Students Publications

Lysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary alveolar proteinosis, autoimmune disorders and osteoporosis, are limited. Given the early lethality of the only published global Slc7a7 knockout mouse model, a viable animal model to investigate global SLC7A7 deficiency is needed. Hence, we generated two mouse models with global Slc7a7 deficiency (Slc7a7em1Lbu/em1Lbu; Slc7a7Lbu/Lbu and Slc7a7em1(IMPC)Bay/em1(IMPC)Bay; Slc7a7Bay/Bay) using CRISPR/Cas9 technology by introducing a deletion of exons …

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 …

Predicting Quality Of Clinical Performance From Cardiology Fellowship Applications, Michael W Cullen, Thomas J Beckman, Kristine M Baldwin, Gregory J Engstler, Jay Mandrekar, Christopher G Scott, Kyle W Klarich

The Texas Heart Institute Journal

Variables in cardiology fellowship applications have not been objectively analyzed against applicants' subsequent clinical performance. We investigated possible correlations in a retrospective cohort study of 65 cardiology fellows at the Mayo Clinic (Rochester, Minn) who began 2 years of clinical training from July 2007 through July 2013. Application variables included the strength of comparative statements in recommendation letters and the authors' academic ranks, membership status in the Alpha Omega Alpha Honor Medical Society, awards earned, volunteer activities, United States Medical Licensing Examination (USMLE) scores, advanced degrees, publications, and completion of a residency program ranked in the top 6 in the …

Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li

Dissertations and Theses (Open Access)

In recent years, technological advancements, such as next-generation sequencing and single-cell interrogation techniques, have enriched our understanding in tumor heterogeneity. By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic and extrinsic mechanisms, and the variable responses of clones to perturbations in the environment, especially therapeutics, underlie disease progression and relapse. Thus, there exists a pressing need to understand the molecular mechanisms that determine the functional heterogeneity of tumor sub-clones …

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 …

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 …

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 …

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 …

The Multilevel Factors Facilitating Or Impeding Healthcare Access Among Refugees Residing In Bexar County Texas, Howaida Werfelli

Dissertations and Theses (Open Access)

The goal of this study was to increase understanding of healthcare access among refugees by investigating the multilevel factors that facilitate or impede healthcare access among refugees who have resettled in Bexar County, Texas. The multilevel factors facilitating or impeding access to healthcare for refugees resettled in Bexar County were identified as follows: health literacy, level of educational attainment, proficiency (reading, writing and, speaking) in English, proficiency (reading, writing and speaking) in native language, translation services, public transportation, income level, a shortage of healthcare providers, navigation of the healthcare system, the fragmentation of the healthcare system, insurance status, staff shortages …

Health Disparities Across Funcitonal Disability Groups, Katherine Sanches

Dissertations and Theses (Open Access)

Background: People with disabilities experience higher rates of chronic disease and poor health status compared to those without disability. People with disabilities do not participate in community health programs to the same degree as those without disability due to social, programmatic, and environmental barriers. The Community Health Inclusion Index (CHII) is a community health assessment tool which evaluates the degree to which community-level health promoting opportunities to promote nutrition and physical activity are inclusive and accessible to people with disabilities. The CHII assess barriers to inclusion across five domains: build environment, equipment, program/services, staff, and policies. Objective: The purpose of …

Covariate-Adaptive And Response-Adaptive Clinical Trial Designs, Lu Wang

Dissertations and Theses (Open Access)

Most of the research on Response-adaptive randomization(RAR) designs has been focused on clinical trials with a single endpoint. However modern clinical trials are often complex, with multiple competing objectives and multiple endpoints. We overcome the obstacles introduced by the large number of unknown parameters and the possible correlations between the multiple endpoints. We obtained the optimal allocation proportions for the following two optimization problems: (1) maximizing the power of the test of homogeneity with a xed sample size, and (2) minimizing the expected weighted number of failures with a fixed power. Further, we implemented these optimal allocations through response-adaptive randomization …

Alcohol Ablation Of Cardiac Tissues Quantified And Evaluated Using Cielab Euclidean Distances, Ashley Rook, Mathews M John, Allison Post, Mehdi Razavi

The Texas Heart Institute Journal

Ethanol solubilizes cell membranes, making it useful for various ablation applications. We examined the effect of time and alcohol type on the extent of ablation, quantified as Euclidean distances between color coordinates. We obtained biopsy punch samples (diameter, 6 mm) of left atrial appendage, atrial, ventricular, and septal tissue from porcine hearts and placed them in transwell plates filled with ethanol or methanol for 10, 20, 30, 40, 50, or 60 min. Control samples were taken for each time point. At each time point, samples were collected, cut transversely, and photographed. With use of a custom MATLAB program, all images …

Profound And Redundant Functions Of Arcuate Neurons In Obesity Development, Canjun Zhu, Zhiying Jiang, Yuanzhong Xu, Zhao-Lin Cai, Qingyan Jiang, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qi Wu, Gang Shu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

The current obesity epidemic faces a lack of mechanistic insights. It is known that the acute activity changes of a growing number of brain neurons rapidly alter feeding behaviour; however, how these changes translate to obesity development and the fundamental mechanism underlying brain neurons in controlling body weight remain elusive. Here, we show that chronic activation of hypothalamic arcuate GABAergic (GABA

Identification Of Trim24 Domain Essentiality In Primary Trim24coe Carcinosarcoma Cell Lines, Cem Dede

Dissertations and Theses (Open Access)

Regulation of transcriptional control is a critical feature for organismal development and survival. Because of its effects on chromatin-controlled expression, disruptions of this delicately tuned mechanism are an important factor in development of tumorigenesis. Therefore, there is a growing interest in targeting these control mechanisms for their potential therapeutic values.

Our lab previously discovered the epigenetic regulator function of Tripartite motif protein 24 (TRIM24) through its H3K4me0 and H3K23ac dual histone signature reader function, its negative regulatory effect on the p53 tumor suppressor, in addition to its shown oncogenic driving capacity on immortalized mammary epithelial cells when overexpressed. Although TRIM24 …

Aging Lowers Pex5 Levels In Cortical Neurons In Male And Female Mouse Brains, Ndidi-Ese Uzor

Dissertations and Theses (Open Access)

Peroxisomes are small organelles with critical functions: lipid synthesis, breakdown of reactive oxygen species by antioxidant enzymes, and amino acid degradation. In the brain, peroxisomal lipids make up the myelin sheath. Brain peroxisomal dysfunction leads to lipid disruption or neurological consequences if key peroxisomal proteins are absent. Still, it is unclear how peroxisomes are affected in neurodegenerative diseases and in normal brain aging. This work examines peroxisomal markers in three settings: 1) in a neuronal and 2) animal model of Huntington disease (HD), where mutant huntingtin (mHtt), the causative protein in Huntington disease pathogenesis is expressed, and 3) in the …

Characterization Of Treatment Planning System Photon Beam Modeling Errors In Iroc Houston Phantom Irradiations, Mallory Glenn

Dissertations and Theses (Open Access)

In radiation therapy, proper commissioning of the treatment planning system’s (TPS) dose calculation algorithm is critical because any errors in this process impact all treatment plans prepared in the system. Previously, TPS errors have been identified as a major cause for poor phantom irradiation performance, which may also mean that patients are treated suboptimally. The purpose of this work was to investigate the TPS beam modeling developed by the radiotherapy community to understand where inconsistencies may arise, which variables are most susceptible to variations, and in what way changing these variables can alter dose calculations.

Using the Imaging and Radiation …

Bringing Til Therapy Beyond Melanoma: Advancing The Treatment Of Advanced Pancreatic And Ovarian Cancers, Donald Sakellariou-Thompson

Dissertations and Theses (Open Access)

The success of checkpoint blockade immunotherapy (CBI) has reinvigorated the cancer therapy field, particularly for advanced melanoma which has doubled the survival rates compared to 20 years ago. However, there are many solid tumor types that are yet to receive substantial benefit from this groundbreaking therapy, two of which are pancreatic cancer (PDAC) and ovarian cancer (OvCa). As such, the 5-year survival rate for PDAC and OvCa stand at 9% and 28% respectively. Despite the lack of efficacy of CBI so far, there is still evidence for the role of immune control in these cancers as evidenced by presence of …

Directed Evolution Of Macrocyclic Peptides For Inhibition Of Autophagy, Joshua Gray

Dissertations and Theses (Open Access)

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of …