Medicine and Health Sciences Commons^™

Pediatric Intensive Care Hospitalization: Sibling Experience, Karla Abela

Dissertations & Theses (Open Access)

Prior research on the impact of pediatric intensive care unit (PICU) hospitalization on families have been predominantly focused on the parents, yet siblings who visit the ill child in the PICU environment remain understudied. The aim of this study was to describe the experiences of 9- to 17-year-old siblings of acutely critically ill or injured children. A generic qualitative approach using one-to-one interviews, observations, and clinician notes was used to gain an understanding of the experience of siblings who visited the PICU. Qualitative analytic methods were used to analyze the data. The findings from 16 siblings (mean age 6.3 years) …

Left Ventricular Assist Device Adjustment Impacted By Patient Trajectory: A Qualitative Exploratory Study, Brittany Rhoades

Dissertations & Theses (Open Access)

Background: Left Ventricular Assist Devices (LVADs) are used as advanced therapy for advanced heart failure in order to sustain patients until a heart transplant is available (bridge to transplant, ‘BTT’) or until the end of life (destination therapy, ‘DT’). Despite the differences in treatment trajectory, BTT and DT patients are provided the same education. Currently it is unknown if the two groups compare to living with the LVAD regarding adjustment.

Aims: The aim of this study was to explore LVAD patient experience, describe how patients construct the impact of the LVAD on daily life and self-care and compare the findings …

Understanding Motivation To Lead In Nurses, Janete Sheiner

Dissertations & Theses (Open Access)

Background: Nurse leaders are indispensable to the delivery of quality, patient-centered care. They are influential in the practice environment, contributing to front-line staff job satisfaction. They work to improve retention, turnover, organizational health, and patient outcomes. Yet, there is a dearth of research investigating the motivating factors that appeal to, encourage, discourage, and help retain nurse leaders in their roles. The forecast of a shortage of nurse leaders, along with the reluctance of nurses to assume leadership roles, is affecting healthcare organizations throughout the United States. An in-depth understanding of the underlying factors related to motivation that appeal to, encourage, …

Caregivers Of Medically Fragile Children With Technology Needs, Vuong Prieto

Dissertations & Theses (Open Access)

Background: Medically fragile children (MFC) with technology needs have complex and challenging health care needs in the home setting. Providing care can have both negative and positive psychological and social impacts on the caregivers’ health related quality of life (HRQOL).

Aims: a) To examine the relationship between caregiver burden, caregiving satisfaction, and HRQOL in caregivers of MFC with technology needs. b) To identify caregiver and child related variables of caregiver burden and caregiving satisfaction.

Methods: A cross sectional study was conducted over four months at a children’s hospital and outpatient clinics. Caregivers completed three one-time surveys (Zarit Burden Interview, Caregiving …

Factors That Impact Uptake Of Carrier Screening By Male Reproductive Partners Of Female Prenatal Patients, Wendi Betting

Dissertations & Theses (Open Access)

Carrier screening is a genomic technology that is used to identify individuals who are carriers of autosomal recessive conditions. Despite published recommendations, the majority of male partners do not complete carrier screening after their female partner is identified to be a carrier. Previous studieshave examined reasons why women elect or decline carrier screening, but there have been few published studies that examine factors that influence a male partner’s decision to elect or decline carrier screening, particularly when the female has been identified as a carrier. The aim of the study was to determine the factors that influence the uptake of …

Genetic Counselors' Experiences With And Approaches To Discordant Genotypic And Phenotypic Sex Detected Via Non-Invasive Prenatal Testing, Emily Stiglich

Dissertations & Theses (Open Access)

As the use of non-invasive prenatal testing becomes more ubiquitous during pregnancy, genetic counselors (GCs) will see clients more frequently for discordant sex identification via non-invasive prenatal testing (NIPT-DSI). Thus, it is imperative to investigate what GCs consider important when counseling about NIPT-DSI and assess how GCs perceive their role in such cases. Prenatal and pediatric GCs were surveyed regarding previous experiences of NIPT-DSI, comfort levels of topics relating to NIPT-DSI, and perceived importance of potential discussion topics in a counseling session (n = 108). The survey consisted of two vignettes, presenting cases of NIPT-DSI identified prenatally in one …

Preclinical Studies Of A Novel Idh1 Inhibitor In Acute Myeloid Leukemia (Aml), Vivian Salama

Dissertations & Theses (Open Access)

LY3410738, a novel covalent Isocitrate Dehydrogenase 1 (IDH1) inhibitor in Acute Myeloid Leukemia, it is more effective than Ivosidenib (AG120) and has a potent anti-leukemic effect against IDH1 mutant acute myeloid leukemia in combination with Venetoclax (ABT-199).

Acute myeloid Leukemia (AML) is an aggressive neoplastic blood disorder characterized by proliferation of poorly differentiated cells of myeloid lineage. IDH1 is a cytoplasmic enzyme that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the citric acid cycle. Somatic gain-of-function mutations in IDH1 occur in ~10% of the newly diagnosed AML patients. The neo-enzymatic activity of mutant IDH1 results in accumulation …

Development Of Fully Balanced Ssfp And Computer Vision Applications For Mri-Assisted Radiosurgery (Mars), Jeremiah Sanders

Dissertations & Theses (Open Access)

Prostate cancer is the second most common cancer in men and the second-leading cause of cancer death in men. Brachytherapy is a highly effective treatment option for prostate cancer, and is the most cost-effective initial treatment among all other therapeutic options for low to intermediate risk patients of prostate cancer. In low-dose-rate (LDR) brachytherapy, verifying the location of the radioactive seeds within the prostate and in relation to critical normal structures after seed implantation is essential to ensuring positive treatment outcomes.

One current gap in knowledge is how to simultaneously image the prostate, surrounding anatomy, and radioactive seeds within the …

Genetic Counselors' Approaches To Direct-To-Consumer Genetic Testing For Hereditary Breast Cancer, Sarah Burke

Dissertations & Theses (Open Access)

Given the increasing availability of health-related direct-to-consumer genetic testing (DTC-GT) and third-party interpretation (TPI) services, it is likely that genetic counselors (GCs) will continue to encounter consumers that require follow-up counseling for their results. The National Comprehensive Cancer Network recommends clinical-grade genetic testing to confirm commercial results; however, the type of testing that GCs select remains uncharacterized. Therefore, we aimed to describe the specific recommendations that cancer GCs make for confirmatory genetic testing in probands who have already obtained DTC-GT results or TPI data that reported a BRCA1/2 pathogenic variant. We recruited 80 GCs specializing in hereditary cancer and administered …

Exosomal Communication By Metastatic Osteosarcoma Cells Modulates Alveolar Macrophages To An M2 Tumor-Promoting Phenotype And Inhibits Tumoricidal Functions, Kerri Wolf

Dissertations & Theses (Open Access)

Osteosarcoma metastasizes to the lung, and there is a link between the predominance of tumor promoting immunosuppressive M2 macrophages in the metastases and poor patient survival. By contrast, M1macrophage predominance correlates with longer survival. M2 macrophages can be induced by various stimuli in the tumor microenvironment, including exosomes, which are 40- to 150-nm vesicles that are involved in intercellular communication and contribute to tumor progression and immune evasion. Recognizing that tumor cells can influence the tumor microenvironment to make it more permissive and because of the link between M2 dominance and curtailed patient survival, we evaluated the effect of …

Statistical Methods For Functional Annotation-Based Rare Variant Association Analysis, Yiding Ma

Dissertations & Theses (Open Access)

Despite ongoing large-scale population-based whole-genome sequencing (WGS) projects such as the TOPMed program, WGS-based association analysis of complex traits remains a tremendous challenge. External biological knowledge, such as functional annotations based on the ENCODE, Epigenomics Roadmap and GTEx projects, may be helpful in distinguishing causal rare variants from neutral ones; however, each functional annotation can only provide certain aspects of the biological functions. Our knowledge for selecting informative annotations a priori is limited and incorporating non-informative annotations will introduce noise and lose power. In the first part of this dissertation, we propose FunSPU, a versatile and adaptive test that incorporates …

Economic Evaluation Of Implementing Hpv Vaccine Promotion Interventions For Cervical Cancer In The United States, Chi-Fang Wu

Dissertations & Theses (Open Access)

The HPV vaccine has been proven as a safe and effective method for preventing cervical cancer. However, the HPV vaccine coverage rate in the U.S. is suboptimal. Various interventions have been implemented to improve HPV vaccine coverage. However, evidence of the cost-effectiveness of HPV vaccine promotion interventions is lacking. We conducted an economic evaluation to assess HPV vaccine promotion interventions of cervical cancer in the U.S. Firstly, a systematic review was conducted to review evidence on interventions aimed at increasing HPV vaccine coverage and to summarize the cost and effectiveness of these interventions. We included 56 HPV vaccine promotion studies …

A Mixed- Methods Examination Of The Healthcare, Social Support, And Religious Needs Of Sexual And Gender Minority (Sgm) Older Adults In Texas, Jennifer Lynn Holcomb

Dissertations & Theses (Open Access)

Shared historical and social contexts influence a generational group’s needs, risk factors, and resiliency mechanisms. Sexual and gender minority (SGM) older adults have experienced structural exclusion and systematic discrimination throughout their lifetime. The minority stress model posits that SGM individuals experience stressors, like discrimination, unique to their social status which affect physical and mental health. SGM older adults experience worse physical and mental health outcomes than their heterosexual peers suggesting unique needs for SGM older adults. Research also points to resiliency mechanisms that offset the impact of stressors on SGM older adults. The examination of these needs and resiliency mechanisms …

The Association Between Assorted Hormonal Contraceptive Methods And Advanced-Stage Epithelial Ovarian Cancer: A Systematic Review, Cheng Cheng

Dissertations & Theses (Open Access)

Epithelial ovarian cancer, the most lethal of the gynecological cancers, is typically diagnosed at advanced stages. Women diagnosed with advance-staged (i.e., stage III and IV according to the International Federation of Gynecology and Obstetrics) epithelial ovarian cancer are more likely to have recurrent episodes within 18 months17. According to a 2012 2016 case analysis conducted by the surveillance, epidemiology, and end results, or SEER program, the incidence of ovarian cancer was 11.4 per 100,000 women in all races per year with the highest incidence in non-Hispanic whites, of 11.9 per 100,000 women and the lowest incidence in Asians / Pacific …

Raft-Versus-Host Disease Occurrence Among Cord Blood Transplantation Recipients In Relation To Human Leukocyte Antigen Match Grade, Sarah Chowdhury

Dissertations & Theses (Open Access)

Umbilical cord blood (UCB) transplantation has been consistently found to have low rates of graft-versus-host disease (GVHD), high rates of engraftment, and faster turnaround times in terms of finding suitable donors. In addition, it serves as a viable option for individuals with no matched donor options especially due to its flexible human leukocyte antigen matching criteria. Despite its advantages, there has been an overall decrease in UCB transplantation. However, its advantages emphasize the need for further research and investment in resources such as cord blood banking especially since pediatric populations are most likely to benefit from continued research due to …

Vestigial-Like 1 Is A Shared Targetable Cancer-Placenta Antigen Expressed By Pancreatic And Basal-Like Breast Cancers, Sherille Denae Bradley

Dissertations & Theses (Open Access)

Cytotoxic T lymphocyte (CTL)-based cancer immunotherapies have shown great promise for inducing clinical regression by targeting tumor-associated antigens (TAA). To expand the TAA landscape of pancreatic ductal adenocarcinoma (PDAC), we performed tandem mass spectrometry analysis of HLA class I-bound peptides from tumors of PDAC patients. This led to the identification of a shared HLA-A*0101 restricted peptide derived from co-transcriptional activator Vestigial-like 1 (VGLL1), a novel putative TAA demonstrating overexpression in multiple tumor types and low or absent transcript expression in normal tissues with the exception of placenta. VGLL1-specific CTL isolated and expanded from the blood of a male PDAC patient …

Molecular Mechanisms Of Antimicrobial Resistance In Multi-Drug Resistant Enterococci, Ayesha Khan

Dissertations & Theses (Open Access)

Antibiotic resistance is a major global public health threat. Enterococci are recalcitrant, nosocomial pathogens that can be intrinsically resistant to valuable antibiotics, like beta-lactams, or evolve resistance to all existing antimicrobials. The LiaFSR system regulates resistance to cell membrane (CM) stressors like daptomycin (DAP), a front-line drug for multi-drug resistant infections. DAP resistance (DAP-R) in E. faecalis is mediated by CM phospholipid alterations. Emergence of DAP-R often leads to b-lactam resensitization, a phenomenon called the seesaw effect. The molecular mechanism of DAP-R and the seesaw effect are unknown. Here we show that LiaX is a surface exposed protein whose C-terminal …

Hypothalamic Circuits Mediating Consumption And Anxiety, Ryan Cassidy

Dissertations & Theses (Open Access)

From 1960-2016, U.S. obesity prevalence increased 13-40% and diabetes increased from 3-15%. There is an epidemic of metabesity, the aggregate metabolic disorders produced by chronic overeating. Drugs for metabesity were developed in the 1930s with limited effectiveness; agents today rely on the same principles and are similarly ineffective. Particularly surprising has been the failure of satiety enhancers; this indicates it may not be that physiologic hunger drives chronic overeating. Although hunger and satiety affect traditional reward circuitry (Cassidy & Tong 2017), evidence for the primacy of this effect is mixed. Being hungry reduces anxiety-like behavior in mice; whether the …

Mcp-1 Release Modulation Through Interaction Of Pulmonary Endothelial Cells And Mesenchymal Stromal Cells, Kaavya Giridhar

Dissertations & Theses (Open Access)

Background: Ischemic stroke is a leading cause of death and long-term disability

around the world. Current treatment options are limited to the administration of

tissue plasminogen activator (tPA) and/or endovascular therapy, administered within

a limited time window. However, cell-based therapies such as mesenchymal stromal

cells (MSCs) have increasingly shown great promise for ischemic stroke recovery

with some therapies already in various stages of clinical trials. Intravenous (IV)

administration of the MSCs leads to the entrapment of these MSCs in the lungs.

These entrapped MSCs interact with the pulmonary endothelial cells (PECs) and

could modulate the immune response through the release …

Frequency Of Copy Number Variants Involving The Sex Chromosomes In A Clinical Setting, Autumn Vara

Dissertations & Theses (Open Access)

Copy number variants (CNVs) are a common finding in the clinical setting and contribute to both genetic variation as well as disease. Recently, studies have described the accumulation of multiple CNVs as a disease modifying mechanism. While it has been characterized how additional CNVs may play a role in phenotype, in which ways and to what extent sex chromosomes are involved has not been fully described. We performed a secondary data analysis using the DECIPHER database on 2,273 de-identified individuals with 2 CNVs. CNVs were designated primary and secondary based on our criteria and characteristics of both CNV groups were …

An Exploration Of Neuroanatomical Signatures Of Pediatric Bipolar Disorder Using Structural Neuroimaging, Jonika Tannous

Dissertations & Theses (Open Access)

Bipolar Disorder (BD) is diagnosed using the Diagnostic and Statistical Manual (DSM) criteria, which relies heavily on symptomatology. This method, however, lends itself to error due to variance in symptom expression and is further complicated during childhood and adolescence- a period marked by major anatomical and behavioral changes. Therefore, in order to institute early and effective interventions, it is imperative that we develop more objective methods of mood disorder characterization and diagnosis. Two proposed solutions for accomplishing this task include 1) the generation of normative development models to assess BD risk and 2) data-driven clustering of patients based on specific …

Loss Of Caspase-8 Function In Combination With Smac Mimetic Treatment Sensitizes Head And Neck Squamous Carcinoma To Radiation Through Induction Of Necroptosis., Burak Uzunparmak

Dissertations & Theses (Open Access)

Caspase-8 (CASP8) is one of the most frequently mutated genes in Head and Neck Squamous Carcinomas (HNSCC), and mutations of CASP8 are associated with poor overall survival. The distribution of these mutations in HNSCC suggests that they are likely to be inactivating. Inhibition of CASP8 has been reported to sensitize cancer cells to necroptosis, a unique cell death mechanism. Here, we evaluated how CASP8 regulates necroptosis in HSNCC using cell line models and syngeneic mouse xenografts. In vitro, knockdown of CASP8 rendered HNSCCs susceptible to necroptosis induced by a second mitochondria-derived activator of caspase (SMAC) mimetic, Birinapant, when combined …

Implementation Of Genetic Carrier Screening In The Ob Population: Healthcare Cost Impact And Recommendation Adherence, Aranza Gonzalez Cendejas

Dissertations & Theses (Open Access)

Background. The recent increases in availability of and demand for genetic testing have been observed alongside concerns regarding the appropriate ordering of such tests by providers, and subsequent unnecessary costs to the healthcare system. Professional organizations, such as ACOG and ACMG, develop guidelines to aid providers in ordering appropriate genetic testing. In this study, the ordering of carrier screening by obstetricians and genetic counselors was used to determine if duplicate genetic testing was taking place at a large academic institution along with adherence to ACOG and ACMG carrier screening guidelines.

Methods. A retrospective chart review of primigravida and multigravida women …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations & Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

Receptor Tyrosine Kinases-Mediated Acquired Parp Inhibitor Resistance In Breast Cancer, Mei-Kuang Chen

Dissertations & Theses (Open Access)

Leveraging compromised DNA damage repair (DDR) pathways commonly found in tumor cells, a classic strategy in cancer therapy is inducing excessive DNA damage to cause cancer cell death. Small molecule poly(ADP-ribose) polymerase (PARP) inhibitors (PARP-is) have been approved for clinical use in treating breast cancer and ovarian cancer patients bearing DDR-deficient tumors with mutations in breast cancer susceptibility genes (BRCA^m). However, accumulating evidences show that both intrinsic and acquired resistances to PARP-is exist in clinic and pre-clinical animal models. Therefore, I developed panels of cells with acquired PARP-is resistance from PARP-is-sensitive triple negative breast cancer (TNBC) cell …

Investigating Medical Examiners' Practices: Genetic Evaluation For Fatal Acute Aortic Dissection, Bradley Power

Dissertations & Theses (Open Access)

Acute thoracic aortic dissection (TAD) is a life-threatening event with a hereditary component. Currently, pathogenic variants in 11 genes associated with aortic aneurysm and dissection predispose to a heritable form of disease thereby conferring an increased risk for TAD. Genetic testing plays a pivotal role not only in diagnosis, but also in risk stratification for relatives and medical management to prevent premature death from dissection. Due to its high fatality rate, medical examiners and coroners (ME/Cs) may be the first to identify TAD cases and initiate genetic testing for the decedent and at-risk relatives. ME/Cs were surveyed using three clinical …

Table-To-Text: Generating Descriptive Text For Scientific Tables From Randomized Controlled Trials, Qiang Wei

Dissertations & Theses (Open Access)

Unprecedented amounts of data have been generated in the biomedical domain, and the bottleneck for biomedical research has shifted from data generation to data management, interpretation, and communication. Therefore, it is highly desirable to develop systems to assist in text generation from biomedical data, which will greatly improve the dissemination of scientific findings. However, very few studies have investigated issues of data-to-text generation in the biomedical domain. Here I present a systematic study for generating descriptive text from tables in randomized clinical trials (RCT) articles, which includes: (1) an information model for representing RCT tables; (2) annotated corpora containing pairs …

Patient, Hospital And State-Level Policy Characteristics Associated With Prevalence Of Treating Opioid Use Disorder In United States Emergency Departments, Rafeek Adeyemi Yusuf

Dissertations & Theses (Open Access)

The opioid crisis in the United States was declared a public health emergency due to escalating and untoward human, financial, and systemic consequences and effects on the nation. Opioid use disorder (OUD) comprising opioid abuse and dependence is devastating because of its associated chronic relapsing nature, overutilization of healthcare services, rising morbidity and mortality rates, and high cost of care. Efforts to address this have not made significant positive impacts. It is thus imperative to reassess the influence of factors associated with OUD. This study answered the question, what patient-, hospital-, and state-level policy factors were associated with prevalence of …

Identifying Risk Factors For Chronic Kidney Disease Of Unknown Origin In Six Central American Countries And Houston, Texas, Erika Figueroa-Solis

Dissertations & Theses (Open Access)

Chronic kidney disease (CKD) is a public health problem that is recognized worldwide. The type of CKD in Central America does not fit the “usual” CKD encountered in countries with upper middle-income economies, and is also often referred to as CKD of undetermined cause (CKDu). Evidence suggests that CKDu is a disease of occupational origin that can be brought on by a combination of exposures: hot environments, high physical job demands, inadequate hydration protocols, and effects of other nephrotoxic agents. Many gaps remain in knowledge related to CKDu and its putative risk factors, geographic distribution, distributions of renal function in …

Predictors Of Kidney Transplant Receipt And Medicare Costs For Patients, Parisa Asgarisabet

Dissertations & Theses (Open Access)

Background: The objectives of this study were to first understand whether a dialysis center’s ownership status modified the association between informing end-stage renal disease (ESRD) patients about transplantation options and patients’ transplantation status; and second, to understand whether Medicare’s Prospective Payment System (PPS) implementation affected the cost of care for ESRD patients from Medicare’s perspective.

Method: This study used the United States Renal Data System (USRDS) data containing information on all ESRD patients in the US, linked to Medicare claims. To address the first objective, a multi-level analysis using mixed effect multinomial logistic regression model was conducted with …