Medicine and Health Sciences Commons^™

Clinical And Demographic Factors Associated With Peg-Asparaginase-Related Toxicities In Patients With Acute Lymphoblastic Leukemia, Priyadarshani Dharia

Dissertations and Theses (Open Access)

Introduction: Polyethylene glycol (PEG)-asparaginase is one of the first-line drugs in pediatric ALL treatment. Although a complete and prolonged treatment with PEGasparaginase has been instrumental in improving the survival of ALL patients, it is associated with four common toxicities: hypersensitivity, hyperbilirubinemia, pancreatitis, and venous thromboembolism (VTE). PEG-asparaginase-related toxicities may require modifications and delays in treatment, which often leads to poor treatment outcomes. Previous studies of PEG-asparaginase-related toxicities have mainly focused on individual toxicities. Further, these studies were conducted in study populations which were predominantly self-reported non-Hispanic whites. Therefore, there is a gap in the knowledge regarding the cumulative burden of …

Quantifying The Financial & Clinical Impact Of Annual Vs. Biennial Mammography Screening, Danmeng Huang

Dissertations and Theses (Open Access)

Current guidelines for screening mammography recommend different start ages and intervals for women with average cancer risk. Longer intervals between mammograms allow more time for a tumor to grow, to become symptomatic and clinically detectable, and more likely to be at advanced stage. Existing literature on the associations between mammography screening frequency and risk of more advanced breast cancer have mixed results. Studies have showed that advanced breast cancer costs more to treat, but real-world cost estimates following different mammography screening frequencies are unavailable. To fill the gaps, this dissertation aimed to quantify the clinical and financial impact following annual …

Characterizing Risk & Burden Of Lower Cranial Neuropathy (Lcnp) As Late Effect Among Oropharyngeal Cancer Survivors, Puja Aggarwal

Dissertations and Theses (Open Access)

Background: Lower cranial neuropathy (LCNP) is a rare but potentially disabling late effect of radiotherapy (RT) and other head and neck cancer therapies. Survivors who develop late LCNP may experience profound functional impairment with deficits in swallowing, speech, and voice. The aims of this research were: 1) to quantify the cumulative incidence of late LCNP and identify clinical predictors of late LCNP; 2) to investigate the impact of late LCNP on severity of cancer treatment-related symptoms, general functional impairment (GFI), and single item scores of the most severe symptoms; and 3) to quantify the association of late LCNP with swallowing-related …

Moving Beyond The Single Gene: Integrative Gene Set Analysis For Rna-Seq, Andrew Richard Aschenbrenner

Dissertations and Theses (Open Access)

RNA-seq is the next-generation sequencing technology for gene expression and while many tools have been developed to assess differential expression, most focus on gene-level statistics. Gene-level statistics implicitly ignore any dependence among genes. In order to directly incorporate correlation into testing for differential expression, genes are sorted into networks using Ingenuity Pathway Analysis (IPA) and the gene expression of each network is modeled using Generalized Estimating Equations (GEE). Since the gene network data often exhibits correlation structures containing positive and negative values, a new intermediate correlation structure is developed. This structure provides a compromise between an exchangeable (one parameter for …

Physical Activity Among Preschool-Aged Children: Considerations For Waking Activity Patterns And Health, Erin Dooley

Dissertations and Theses (Open Access)

With nearly one-quarter (23%) of U.S. preschool children (ages 3-5 years) having overweight or obesity, supporting healthy growth and development is paramount. Hispanic children have the highest prevalence within this age group (15.6%) and a large projected population growth. Energy expenditure through physical activity is one way to combat excess development of obesity and poor health outcomes. Yet there is limited evidence about the correlates associated with physical activity and health within this population. The three studies of this dissertation examined sociodemographic-, cultural-, and context-related factors related to waking activity patterns and the subsequent impact on health indicators. The overall …

Quantifying The Financial & Clinical Impact Of Annual Vs. Biennial Mammography Screening, Danmeng Huang

Dissertations and Theses (Open Access)

Current guidelines for screening mammography recommend different start ages and intervals for women with average cancer risk. Longer intervals between mammograms allow more time for a tumor to grow, to become symptomatic and clinically detectable, and more likely to be at advanced stage. Existing literature on the associations between mammography screening frequency and risk of more advanced breast cancer have mixed results. Studies have showed that advanced breast cancer costs more to treat, but real-world cost estimates following different mammography screening frequencies are unavailable. To fill the gaps, this dissertation aimed to quantify the clinical and financial impact following annual …

Epidemiological Evaluation Of The National Sickle Cell Screening Program In The Republic Of Uganda, Arielle G. Hernandez

Dissertations and Theses (Open Access)

Sickle cell anemia contributes substantially to childhood morbidity and mortality in sub-Saharan Africa, where there are scarce health resources and inadequate awareness among healthcare providers and the community. Without early diagnosis and initiation of preventive treatments, most infants will die of acute complications before their fifth birthday. Information on the mortality associated with sickle cell anemia is excluded from global statistical summaries due to the lack of accurate data, making sickle cell anemia an invisible killer of children on the African continent. Information from long-term large-scale sickle cell screening efforts is not yet available in Africa; therefore, a mixed-methods study …

The Associations Between Fat And Clinical Outcomes Among Lung Cancer Patients: Dietary Intake And Genetic Determinants, Fang Yu Lin

Dissertations and Theses (Open Access)

Higher dietary fat intake and alterations in fatty acid metabolism may affect cancer development and progression. This dissertation conducted a series of studies examining whether dietary fat intake and genetic variants in fatty acid metabolism genes have an impact on clinical outcomes among non-Hispanic whites newly diagnosed with non-small cell lung cancer (NSCLC). First, a cohort of 2,262 NSCLC patients was prospectively examined for intakes of total, saturated, monounsaturated, and polyunsaturated fat in relation to overall survival and recurrence. Dietary fat intake at diagnosis was assessed with a previously validated food frequency questionnaire and categorized by Dietary Reference Intakes. Multivariable …

External Environmental Dimensions And Financial Performance Of Major Teaching Hospitals In The U.S, Karima Lalani

Dissertations and Theses (Open Access)

Background: Teaching hospitals have a unique mission to not only deliver graduate medical education, but to also provide both inpatient and ambulatory care, and to conduct clinical and medical research; therefore, they are under constant financial pressure, and it is important to find out what types of external environmental components affect their financial performance. No recent studies have been comprehensively conducted for all major teaching hospitals in the U.S. to examine if there is an association between the external environmental dimensions based upon Resource Dependence Theory (Munificence, Uncertainty, Complexity) and the short-term financial performance, measured by days cash on hand …

Access To Antibiotics Without Prescription For Travelers And Colombian Citizens At Community Pharmacies In Bogota, Colombia, Marie Kasbaum

Dissertations and Theses (Open Access)

The misuse of antibiotics has been shown to exacerbate the global antibiotic resistance crisis, which could have major consequences on public health worldwide (Auta et al., 2018). In Bogotá, Colombia, the non-prescription sale of antibiotics still occurs in pharmacies despite national regulations requiring a prescription from a physician or health agency before dispensing antibiotics to a patient (Vacca et al., 2011). The purpose of this study was to investigate the non-prescription sale of antibiotics in community pharmacies to foreign travelers and Colombian citizens in Bogotá, Colombia. Trained Simulated Clients (SCs) gathered experimental data in pharmacies distributed throughout 20 geographic districts …

Examining Differences In Physical Activity By Socio-Demographics, Employment, And Social Support Among U.S. Adolescents, Ashleigh Marie Johnson

Dissertations and Theses (Open Access)

The overall decline in physical activity levels during adolescence supports the examination of intrapersonal-, interpersonal-, and behavior-level factors that may influence physical activity behavior among this population. The three papers within this dissertation aimed to examine associations of socio-demographics and socio-environmental factors with physical activity among U.S. adolescents. Papers 1 and 3 used data from the Family Life, Activity, Sun, Health, and Eating (FLASHE) Study. Paper 1 examined differences in adolescent physical activity by gender and race/ethnicity, and examined modification by grade and socioeconomic status (SES). Paper 3 examined the association of parent- and adolescent-reported parental social support with adolescent …

Nonlinear Functional Models On Causal Inference, Rong Jiao

Dissertations and Theses (Open Access)

Statistical analysis has experienced significant progress on association study, but it remains elusive to understand the etiology and mechanism of complex phenotypes. As a major analytical platform, association analysis may hamper the theoretic development of biomedical science and its application. Thus, many researchers suggest making the transition from association to causation. The mainstream of research in genetics and epigenetics data analysis focuses on statistical association or exploring statistical dependence between variables. Despite significant progress in dissecting the genetic architecture of complex diseases by genome-wide association studies (GWAS), the signals identified by association analysis can only explain a small proportion of …

Understanding The Relatlonships Between Survivorship Care Plans And Survivor Level Outcomes Among Breast And Colorectal Cancer Survivors, Jessica Danielle Austin

Dissertations and Theses (Open Access)

PURPOSE: Cancer survivors have complex journeys following the completion of active treatment. The Institute of Medicine and other high-profile organizations have recommended and mandated the use of a survivorship care plan (SCP) despite mixed evidence supporting the impact of SCPs on key survivor-level outcomes. The purpose of this dissertation was to understand the complex relationship linking the delivery of SCPs and to relevant survivorlevel outcomes. STUDY GROUP: This dissertation focuses on breast and colorectal cancer survivors because they comprise nearly 30% of the entire cancer survivor population in the US and are the two most prevalent cancers in men and …

The Role Of Gamma Oscillations And Cortical Inhibition In The Development Of Working Memory In Adolescence, Christopher P. Walker

Dissertations and Theses (Open Access)

Adolescence is a dynamic period of social, cognitive, and biological changes. In particular, working memory, the ability to actively encode and maintain information over a short period of time, develops early in childhood and gradually increases in capacity and stability during adolescence. The precise neurophysiological mechanism by which working memory capacity increases during adolescence is unclear. The objective of this investigation was to evaluate the role of cortical gamma-band (> 30 Hz) oscillations—which are associated with working memory in adults—for the development of working memory capacity in adolescents, and to identify the extent to which the temporal profile of gamma-aminobutyric …

A Novel Switch-Like Function Of Delta-Catenin In Dendrite Development, Ryan Baumert

Dissertations and Theses (Open Access)

The formation of neuronal networks in the brain is tightly regulated, and dependent on the morphology of dendrites, the branch-like signal-receiving structures extending from neurons. Disruptions in dendrite development, or dendritogenesis, can lead to the atypical neuronal connectivity associated with multiple neurodevelopmental diseases. My research addresses molecular processes that underlie dendritogenesis via analysis of a pair of novel interactions involving the protein delta-catenin.

In neurons, delta-catenin localizes to dendrites and synapses, where it functions in their development and maintenance. Structurally, delta-catenin possesses a central Armadillo domain and a C-terminal PDZ-binding motif. This motif associates with PDZ domain-containing proteins, and is …

Uncovering The Zeb1 Interactome To Identify Novel Regulators Of Metastatic Non-Small Cell Lung Cancer, Roxsan Manshouri

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States, due in part to the robust affinity of lung cancer cells to metastasize. Understanding the processes that contribute to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-tomesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell adhesion and polarity is reduced, allowing epithelial cancer cells to dissociate from the primary tumor and invade distant organs. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) has been reported to uniquely correlate with NSCLC disease progression and to …

The Effect Of Traumatic Brain Injury On Tau Pathology By A Potential Seeding Mechanism, George Edwards Iii

Dissertations and Theses (Open Access)

The misfolding, aggregation and accumulation of specific proteins is the overarching concept in protein misfolding disorders (PMDs). The microtubule associated protein tau is known to form insoluble filaments known as neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (pTau) found in a subset of PMDs called tauopathies, such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE), among others. Misfolded tau engenders a structurally alternative intermediate conformation that is prone to aggregate having amyloidogenic properties. Formation of amyloids, such as tau aggregates, is proposed to follow a nucleation-polymerization model where misfolded, soluble oligomeric seeds can trigger native proteins to misfold and …

The Role Of Membrane Domains In Protein And Lipid Sorting During Endocytic Traffic, Blanca B. Diaz-Rohrer

Dissertations and Theses (Open Access)

The lipid and protein composition of the plasma membrane (PM) must be tightly controlled to maintain cellular functionality, despite constant, rapid endocytosis. Because de novo synthesis of proteins and lipids is energetically costly, the cell depends on active recycling to return endocytosed membrane components back to the PM. For most proteins, the mechanisms and pathways of their PM retention remain unknown. The work presented here shows that association with ordered membrane microdomains is fully sufficient for PM recycling and that abrogation of raft partitioning leads to their degradation in lysosomes. These findings support a model wherein ordered membrane domains mediate …

Determination Of Thymic Epithelial Cell Composition And Proliferation During The Perinatal To Adult Transition, Scott Casey

Dissertations and Theses (Open Access)

T-cells develop in the thymus based on signaling from multiple stromal cell types, particularly thymic epithelial cells (TECs). The thymus develops rapidly during the perinatal time period (birth – 10 days in mice) before reaching a period of homeostasis (10 days – 6 weeks). The mechanisms that initially promote and subsequently limit expansion of the TEC compartment are not known. However, previous reports from our lab suggest that the Cyclin D1-RB-E2F pathway plays a key role in regulating the perinatal to adult transition. We have previously shown that inactivation in TEC of retinoblastoma (RB) family members through deletion of RB …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations and Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

A Signature Enrichment Design With Bayesian Adaptive Randomization For Cancer Clinical Trials, Fang Xia

Dissertations and Theses (Open Access)

Clinical trials in the era of precision medicine demand more flexible and efficient trial designs. Adaptive clinical trial designs allow pre-specified modifications of an on-going clinical trial and could shorten the trial duration. We reviewed five common types of adaptive clinical trials based on adaptation methods. In particular, outcome-randomization becomes more popular as it can assign more patients to the promising treatments based on the accumulated trial data. This data-driven allocation allows more patients to benefit from the trial, which is especially important for cancer patients. We compared different Bayesian outcome-adaptive randomization methods and discussed them from both methodological and …

Assessment Of New Innovations In Pet/Ct For Respiratory Motion Correction, Joseph Meier

Dissertations and Theses (Open Access)

In oncological imaging, Positron Emission Tomography/Computed Tomography (PET/CT) is a vital tool used for stating and treatment response assessment of patients due to its ability to visualize and accurately quantify the bio-distribution of radiolabeled pharmaceuticals. However, due to the long acquisition times, respiratory motion blur is unavoidable in PET images especially in the lower lung and upper abdomen. This leads to reductions in measured radiotracer concentration and lesion detectability all of which can potentially result in incorrect management of patients. Multiple methods exist to correct for respiratory motion but are rarely used in the routine clinical setting because of: 1) …

Deconvolute Brain Tumor Genomic Alterations Based On Dna Methylation, Jie Yang

Dissertations and Theses (Open Access)

Molecular classification based on mutations, expression subtypes, and copy number variants has improved diagnosis and treatment decision-making for patients with brain tumors, particularly malignant gliomas. However, the association between epigenetic signature and genetic alterations is poorly understood. For example, mutation of isocitrate dehydrogenase (IDH) is associated with genome-wide hypermethylation of CpG islands in gliomas. But other subtype-associated alterations, including telomerase reverse transcriptase (TERT) promoter mutation, alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation, chromosome 1p19q co-deletion (chr1p19q codel), and gene expression subtypes, have yet to be associated with any epigenetic signature. Therefore, we hypothesized that …

Relevance Of Fgfr1 And Its Isoforms In Prostate Cancer Bone Metastases, Estefania Labanca

Dissertations and Theses (Open Access)

The fibroblast growth factor receptor (FGFR) 1 is implicated in prostate cancer (PCa) progression. Various FGFR1 isoforms have been described and we demonstrate here that the well-characterized FGFR1 a and b isoforms are correlated with the expression of different genes and pathways in human PCa. Direct injection of PC3 PCa cells overexpressing FGFR1 isoforms into the femur of mice resulted in enhanced tumor growth and reduction in bone volume when compared with PC3 expressing empty vector. However, only PC3 overexpressing FGFR1 b was associated with increased osteoclast parameters, suggesting that each isoform may mediate diverse biological effects (similar findings were …

Utilizing Temporal Information In The Ehr For Developing A Novel Continuous Prediction Model, Kang Lin Hsieh

Dissertations and Theses (Open Access)

Type 2 diabetes mellitus (T2DM) is a nation-wide prevalent chronic condition, which includes direct and indirect healthcare costs. T2DM, however, is a preventable chronic condition based on previous clinical research. Many prediction models were based on the risk factors identified by clinical trials. One of the major tasks of the T2DM prediction models is to estimate the risks for further testing by HbA1c or fasting plasma glucose to determine whether the patient has or does not have T2DM because nation-wide screening is not cost-effective.

Those models had substantial limitations on data quality, such as missing values. In this dissertation, I …

Design And Architecture Of An Ontology-Driven Dialogue System For Hpv Vaccine Counseling, Amith Faheem Muhammad

Dissertations and Theses (Open Access)

Speech and conversational technologies are increasingly being used by consumers, with the inevitability that one day they will be integrated in health care. Where this technology could be of service is in patient-provider communication, specifically for communicating the risks and benefits of vaccines. Human papillomavirus (HPV) vaccine, in particular, is a vaccine that inoculates individuals from certain HPV viruses responsible for adulthood cancers - cervical, head and neck cancers, etc. My research focuses on the architecture and development of speech-enabled conversational agent that relies on series of consumer-centric health ontologies and the technology that utilizes these ontologies. Ontologies are computable …

Ashtanga For Addiction: A Qualitative Web-Based Open-Ended Survey To Assess Outcomes From Ashtanga Yoga Practice In Individuals In Long-Term Recovery From Substance Abuse Disorder, Shaun M. Jones

Dissertations and Theses (Open Access)

Over 72,000 people die from overdose or secondary health issues related to substance use disorder (SUD) annually. Studies support mind-body interventions in reducing stress, anxiety, depression, and craving symptoms. There is a growing body of literature supporting yoga as a mind-body intervention for individuals recovering from SUD. These interventions promote improved physical awareness, greater awareness of mental states, non-reactivity, and reduced perception of pain, allows for more successful coping with cravings. Ashtanga yoga (AY) is a tradition of yoga wherein students work on a one-on-one basis with highly qualified teachers following an invariant sequence of yoga postures. AY is characterized …

Mhealth Childhood Obesity Prevention: A Look Into The Hispanic Mother’S Perspective, Veronica Isabel Gonzalez

Dissertations and Theses (Open Access)

Along with increasing physical activity, improving nutrition is an important behavior to target to reduce the risk of obesity in children and adolescents. To date, a nutrition-focused mHealth intervention used to promote obesity prevention and healthy living among Hispanic children and adolescents has not been specifically developed for Hispanic mothers. The purpose of this study was to provide information on feasibility and acceptability of a mHealth child nutrition intervention among Hispanic mothers. The data was collected from an online survey and telephone interviews from 30 mothers of 8-12-year-old Hispanic girls. Most mothers were 40 years old or younger (70%), identified …

Climate Change And Chagas Disease In The Americas: A Qualitative Systematic Review, Brittany N. Graves

Dissertations and Theses (Open Access)

While many studies have found associations between climate change and factors affecting Chagas disease transmission, the future impact of climate change on the global spread of Chagas disease remains debatable. A qualitative, systematic review was conducted to assess the impact of climate change on Chagas disease transmission in the Americas (Central America, South America, and North America). The literature search was performed in January 2019 using the keywords climate, Chagas, and “trypanosoma cruzi” and the electronic databases PubMed, Scopus, and Ovid. Searches retrieved records from 1982 through 2019. The initial electronic database search identified a total of 191 record documents …

Perceived Discrimination From Providers On Latina Mothers’ Decision-Making On Hpv Vaccination Initiation And Completion In Houston, Tx, Fatima Frausto

Dissertations and Theses (Open Access)

Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections (STI) in the United States (US). Certain HPV strains have the potential to develop into cervical, anal, penile, vulvar, and throat cancers. Latinos in the U.S. have the highest rates of cervical and penile cancers compared to non-Hispanic Whites. Despite the availability of HPV9v, uptake of the vaccine is suboptimal in the Latino community. Previous research has found factors such as provider recommendation and communication are important in HPV vaccine series initiation and completion. Discrimination in the medical setting is linked to poorer health outcomes and delayed …