Digital Commons Network^™

Reassessing Replication: Addressing The Replication Crisis From A Statistical Perspective, Alicia Richards Phd

Theses and Dissertations

In 2015, Open Science Framework directly replicated 100 psychology studies and found astonishingly low replication rates. Since, researchers have suggested factors that may have influenced the low rates, including the metrics used to assess replications. The definitions used to decide whether a replication study was successful all suffer from flaws. Therefore, we propose a new metric for assessing replication that can estimate the likelihood a study successfully replicated rather than forcing a binary choice and accounts for study design limitations.

Using equivalence study techniques, we first propose a new metric to assess replication, defining a successful replication as one where …

Witnessing Community Violence And Its Consequences: Changes Across Middle School, Sarah Pittman

Theses and Dissertations

Community violence exposure is prevalent among youth residing in economically marginalized communities that have high rates of violence. Witnessing community violence has been concurrently associated with persistent adverse consequences. However, few studies have applied a developmental psychopathology framework and examined dynamic developmental processes between witnessing community violence and outcomes over time. Moreover, most prior studies have used analyses that assume that associations between witnessing violence and outcomes are the same for all adolescents, which is inconsistent with both developmental theories and theories specific to community violence exposure. The goal of this study was to apply a developmental psychopathological framework to …

Studying Gene Function In Streptococcus Sanguinis Using Rna-Sequencing Analysis, Ahmed Ismail

Theses and Dissertations

The oral cavity hosts hundreds of bacterial species, amongst them are the Streptococci family. More specifically, S. sanguinis is a benign bacteria in the oral cavity to protect the tooth surface from S. mutans. which is a pathogen causing dental caries. While S. sanguinis is harmless in the oral cavity, it becomes pathogenic once entering the bloodstream and causing Infective Endocarditis (IE). To further study S. sanguinis and eventually develop an effective drug to treat IE caused by S. sanguinis, a gene expression study was conducted. In order to study gene expression, RNA-sequencing was conducted, and appropriate methods to remove …

Investigating Tgf-Β1 And Fibronectin Signaling In Low Oxygen Environments, Caitlin E. Williams

Theses and Dissertations

Breast cancer is the second leading cause of death in women, second to lung cancer. It’s one of the most well-known cancers, with almost 300,000 new cases estimated to be diagnosed in 2023. Breast cancer often begins in ductal epithelial cells, and these cells will typically undergo a cellular transformation process known as epithelial-mesenchymal transition (EMT) in early stages. Breast cancer becomes deadly when it reaches a metastatic stage. As a part of the metastatic process, transformed cells will conduct remodeling of the extracellular matrix (ECM) to allow for migration of an otherwise non-migratory cell type.

As dense tumors form, …

Transcriptional Coregulation Among Diabetes-Associated Pathways By Genome Organization, Musaddiq K. Lodi

Theses and Dissertations

There are currently 96 million individuals affected by diabetes in the United States alone. Crucial information such as biomarkers, regulatory networks, and metabolic pathways in diabetes still remain an active area of research. The primary focus of this study is on a phenomena known as transcription factor co-regulation. Transcription factors (TFs) are DNA-binding proteins that can control the rate of transcription of genetic information from DNA to mRNA, hence misregulation of one of them can lead to misregulation of many of its target genes and associated pathways. In this study I propose a framework to quantify transcriptional coherence in co-regulated …

Effectiveness Of Financial Incentives In Improving Breast Cancer Screening Among Medicaid Recipients, James B. Sherwood

Theses and Dissertations

Breast cancer remains one of the leading causes of death among women. Roughly 2.4 million women are diagnosed annually with breast cancer throughout the world. Although breast cancer survival rates are favorable for the United States compared to other nations (90% 5-year survival for non-metastatic disease), it comes at a high cost. The United States spends an estimated $30 billion annually on breast cancer treatment. In addition, disparities in breast cancer survival rates also exist in the United States. Women Medicaid recipients, who are predominately minorities (60%), are more likely to die of breast cancer due to their high rates …

Genomic Comparison Of Dba/2j And C57bl/6j Strains Of Mus Musculus And Best Practice Of Genome Alignment For Bioinformatics Analyses, Dustin J. Zeliff

Theses and Dissertations

Alcohol use disorder is known to have significant genetic components that contribute to an individual’s susceptibility to the disease. Mouse models are commonly used to study the mechanisms underlying alcohol use disorder, with C57BL/6J (B6) and DBA/2J (D2) being two of the more prominently used inbred strains. Research in the Miles Laboratory has used these two strains, and genetic panels of mice derived from them, to identify potential genes associated with variance in ethanol-related behaviors using quantitative trait loci (QTL) analysis. For example, Ninein (Nin) was identified as a potential candidate gene for the anxiolytic effects of ethanol, discovered because …

Protacs – A Novel And Rapidly Developing Field Of Targeted Protein Degradation, Hannah R. Gatley

Theses and Dissertations

There is a continued need for new technology and strategies for tackling cancer and other diseases, and within the current century a novel therapeutic strategy has emerged in the realm of targeted protein degradation called Proteolysis-Targeting Chimeras (PROTACs). This technology specifically targets and degrades disease-causing proteins via the ubiquitin-proteasome system, and has seen an explosion of research and intrigue in both academia and industry over the past two decades. The diversity of PROTAC classes based on the E3 ligase recruiting ligand and the target protein allows for a universal molecular structure that can be customized for a specific target and …

Examining Genetically-Informed Etiologic Models Of Co-Occurring Posttraumatic Stress Disorder And Recreational Cannabis Use Among College Students, Terrell A. Hicks

Theses and Dissertations

The college years encompass a period of increased risk recreational cannabis use (RCU), as well as a time of increased risk for trauma exposure and developing posttraumatic stress disorder (PTSD). Given the high co-occurrence between RCU and PTSD, and the potentially negative consequences of the two (e.g., worse academic outcomes), there is a need to understand the etiologic mechanisms of these commonly co-occurring conditions. Two primary phenotypic models exist: self-medication model (i.e., PTSD to RCU) and the high-risk model (i.e., RCU to PTSD). To date, there are two existing studies longitudinally examining the etiologic models proposed to explain co-occurring RCU …

Factors Associated With Turnover Intention Of Medical Laboratory Professionals During The Covid-19 Pandemic: A Mixed Methods Approach, Keandra Walthall

Theses and Dissertations

The COVID-19 pandemic disrupted and strained healthcare systems worldwide. Frontline healthcare workers have experienced increased rates of psychological distress and burnout during the COVID-19 pandemic, which have led to high turnover intention and workforce shortages. Medical Laboratory Professionals have endured similar experiences during the COVID-19 pandemic; however, there has been limited research exploring these factors for this group of professionals. This study utilized a convergent mixed methods approach to investigate the impact of psychological distress and burnout on the turnover intentions of Medical Laboratory Professionals in the United States during the COVID-19 pandemic, as well as to explore motivational factors …

Fascism In Sci-Fi: "Mobilizing Passions" In Robert A. Heinlein's Starship Troopers, Alton C. Ayers

Theses and Dissertations

This thesis responds to criticism of Robert A. Heinlein’s Starship Troopers (1959) as a “fascist” novel by further investigating the claim through a close reading of the novel that applies political theory scholarship on fascism. Chapters I and II introduce the novel along with its general reception and controversy. These chapters consider the accusations of “fascism” given to the novel while at the same time understanding that a clear, exact definition of “fascism” has long been grappled with by scholars since the rise of the regimes in Nazi Germany and Fascist Italy. Chapters III and IV apply political theory to …

Wrestling With The One Drop Rule: Exploring Multiraciality In Social Work Education, Britney Pitts

Theses and Dissertations

This three paper dissertation aims to provide a baseline understanding of how multiraciality is understood in social work education. The first paper, a fusion autoethnography, explores how my own perception of my multiracial identity was clarified throughout my social work education. This exploration led to the development of incongruent logic in/validation (ILV), a new aspect of racial identity invalidation (RII). The second paper, a multimethod qualitative case study, explores master of social work (MSW) students’ knowledge, attitudes, and anticipated professional behaviors with multiracial individuals and families. Themes from this study include: never explicitly learned about multiraciality; non-ecological endorsements of multiracial …

Characterizing 3-O-Sulfation-Induced Novel Compact Topologies In Heparan Sulfate And Their Interactions With Proteins, Samuel Holmes

Theses and Dissertations

Heparan sulfate (HS) is highly-charged, linear polysaccharide that interacts with numerous proteins in humans as consituents of proteoglycans. The action of sulfotransferase enzymes during the biosynthesis of HS can generate a combinatorially massive library of differentially sulfated sequences. Furthermore, the number and position of these sulfate groups are key to their biological activity, modulating their selectivities for certain proteins at the cell surface or ECM. The installation of a sulfate on the C3 hydroxyl of a glucosamine residue in HS represents the rarest of the sulfations, despite the HS 3-O-sulfotransferase (3OST) family being the most diverse of the other sulfotransferases. …

Tgif1 Physiological Levels Limit Β-Cell Distress And Neonatal Diabetes, Creighton J. Friend

Theses and Dissertations

TGIF1 belongs to the superfamily of homeodomain proteins, which regulate a wide variety of biological functions, including cell stemness and specification of cell fate during early development. Perhaps surprisingly, we found that enforced expression in pancreatic progenitor cells during embryogenesis resulted in severe diabetes, hinting at the possibility that TGIF1 might regulate pancreas development. Subsequent genetic experiments targeting β-cells showed that TGIF1 affected β-cell function and homeostasis. Transcriptomic analysis revealed that TGIF1 expression inhibits the expression of essential components of UPR signaling, underscoring a potential mechanism in which TGIF1 disrupts protein folding and secretion. Congruently, TGIF1 expression led to a …

Using Bovid Tribe Proportions To Reconstruct Paleoenvironments Of Eastern African Paranthropus, Lisa Day

Theses and Dissertations

There are conflicting theories about the eating habits and corresponding environmental needs of Paranthropus boisei and Paranthropus aethiopicus, two species of extinct hominins that existed ~2.8 to ~1 Ma in eastern Africa. Paranthropus species are well-known for their unusually large molars and sagittal crest (a bony ridge on their skulls which allowed for large chewing muscle attachments), these skeletal adaptations were once thought to be due to their feeding on hard foods; however, recent isotope data and dental microwear studies question the simplicity of this assumption. This has revealed a gap in our understanding of the environmental needs of …

The Impact Of Patient Characteristics On Dysphagia Therapy Utilization And Feeding Outcomes For Premature Infants In The Neonatal Intensive Care Unit, Tiana Nguyen

Theses and Dissertations

Medical advances have significantly increased the survival rates of preterm infants at lower gestational ages. However, infants born at lower gestational ages have an increased risk for developmental disabilities and oral feeding difficulties. A stay in the neonatal intensive care unit (NICU) is very costly and inadequate oral feeding is the most common barrier to discharge for premature infants. Infants can receive dysphagia therapy services during their NICU stay that focuses on the development of oral feeding and swallowing skills. However, literature to this date has mainly focused on the impact of therapy services for premature infants after NICU discharge. …

Mitigation Of Nicotine Reward And Withdrawal By The N-Acyl Amino Acids: N-Oleoyl Glycine And N-Oleoyl Alanine, Kimberly Karin

Theses and Dissertations

A growing body of research is exploring the efficacy of N-acyl amino acids (N-oleoyl glycine; OlGly and N-oleoyl alanine; OlAla) in rodent models of drug reward and dependence. In particular, OlGly attenuated the reinforcing effects of nicotine in the mouse nicotine-induced conditioned place preference (CPP) paradigm and reduced somatic and affective signs of mecamylamine-precipitated withdrawal in nicotine-dependent mice. Based on the addition of a methyl group on the head group, OlAla was proposed to have increased metabolic stability compared to OlGly. While OlAla has been assessed in assays of reward and withdrawal of opioids, cocaine, and …

Anti-Immigration-Related Stressors And Latine Immigrant Well-Being: The Role Of Family & Community Resilience, Lisa S. Fuentes

Theses and Dissertations

Anti-immigrant rhetoric and policies have continued to adversely impact Deferred Action for Childhood Arrivals (DACA) and Temporary Protection Status (TPS) beneficiaries (Arevalo et al., 2015; Cleary, 2017; Li, 2015; Sangalang et al., 2018). There have been numerous attempts to revoke DACA, TPS, and other policies that temporarily protect immigrant families. Although the number of resilience literature has grown, more strength-based approaches are still needed. Additionally, given that familismo (familism) and collectivism are key cultural values for Latine families (Campos et al., 2019; Corona et al., 2017), it is imperative to explore family and community resilience among Latine immigrants to gain …

Strength Scaling A Generic Upper Limb Musculoskeletal Model To Represent Individuals With Paraplegia, Yeajin Cho

Theses and Dissertations

Musculoskeletal (MSK) modeling and simulation of human movement is needed to estimate biomechanical quantities which cannot be directly measured, including muscle and joint contact forces during wheelchair propulsion. When accurate representation of an individual's muscle strength and musculoskeletal anatomy is needed, a generic upper limb MSK model can be scaled, or a subject-specific model can be developed. A generic MSK model can be scaled with regard to strength to represent an individual nonimpaired adult or child based on limb lengths and muscle volumes, or other techniques. Developing a subject-specific model requires MSK and physiologic data typically derived from medical imaging …

Qvoices: Queer Voices In Oncology Igniting Change Through Empowered Stories Of Survivorship, Viktor Clark

Theses and Dissertations

Background: Each year in the United States there are roughly 2 million new cancer diagnoses, with over 600,000 deaths due to cancer. The National Cancer Institute developed a six-stage cancer control continuum framework ranging from etiology to survivorship to organize the cancer experience. Sexual and gender minorities (SGM) are comprised of multiple communities representing ~23.6 million adults in the US, SGM face disparities at each stage of the cancer control continuum. This study emphasizes three stages, prevention, detection, and treatment. Engagement in prevention can prevent or prolong cancer, early detection through engagement in cancer screening improves cancer trajectories and compliance …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

Building A Macrosystems Ecology Framework To Identify Links Between Environmental And Human Health, Felisha N. Walls

Theses and Dissertations

The structure and functions of natural systems continue to be degraded by human activities such as land-use change. One potential consequence that has received relatively little attention is a corresponding decline in human health. Altered ecosystems can present a host of risks to human health. Yet the consequences of environmental degradation are rarely considered in national-scale research on human well-being. The guiding objective of this work is to compare stream health and socioeconomic metrics with spatially congruent human health metrics throughout the conterminous United States, then to identify potential links between environmental health, socioeconomic factors and human health. Environmental health …

Population Demography Of A Neotropical Migratory Songbird In The Face Of A Changing Climate, Adele Balmer

Theses and Dissertations

This dissertation investigates the population dynamics and demographic trends of the Prothonotary Warbler (Protonotaria citrea), a migratory songbird that breeds in North America during the spring and summer and overwinters in Central and northern South America. The primary objective of this dissertation is to examine the combined implications of variation in weather and individual traits on demographic traits and to project the effects of climate change on population trajectories of the Prothonotary Warbler.

The analyses conducted in this dissertation centered around female Prothonotary Warblers; however, visual identification of a nestling’s sex is impossible in most altricial bird species, …

Model-Based Imputation Of Below Detection Limit Missing Data And Group Selection In Bayesian Group Index Regression, Matthew Carli

Theses and Dissertations

Investigations into the association between chemical exposure and health outcomes are increasingly focused on the role of chemical mixtures, as opposed to individual chemicals. The analysis of chemical mixture data required the development of novel statistical methods, one of these being Bayesian group index regression. A statistical challenge common to all chemical mixture analyses is the ubiquitous presence of below detection limit (BDL) data. We propose an extension of Bayesian group index regression that treats both regression effects and missing BDL observations as parameters in a model estimated through a Markov Chain Monte Carlo algorithm that we refer to as …

Moderators Of Response To Intervention For College Students With Adhd: Integrating Personal And Contextual Factors, Cathrin D. Green

Theses and Dissertations

College students with attention deficit/hyperactivity disorder (ADHD) are at increased risk for educational, interpersonal, and comorbid mental health difficulties. Although growing evidence suggests that psychosocial interventions can effectively improve ADHD symptoms and functioning in college students with ADHD, there is almost no research investigating individual differences in intervention response. Numerous factors ranging from participant characteristics, as well as social and contextual factors could lead some people to respond more positively than others. Understanding individual differences in intervention response may help to better target intervention efforts and to determine where intervention refinement is needed. This study evaluates whether personal and contextual …

Integrative Post-Gwas Analyses Of Psychiatric Disorders: Identifying Putative Risk Genes And Gene Sets Using Transcriptome, Proteome And Methylome Information, Huseyin Gedik

Theses and Dissertations

Genome-wide association studies (GWAS) of psychiatric disorders (PD) yield numerous loci with significant signals, but often they do not implicate specific protein coding genes. Because GWAS risk loci are enriched in expression/protein/methylation quantitative loci (e/p/mQTL, hereafter xQTL), transcriptome/proteome/methylome-wide association studies (T/P/MWAS, hereafter XWAS), which integrate information from GWAS and x-level (mRNA, protein or DNA methylation levels) coming from largest xQTL studies, can link GWAS signals to effects on specific genes. For gene level analyses, researchers use mendelian randomization (MR) methods to fine-map the association between x-levels and trait. However, none of the previous studies ever jointly analyzed XWAS of multiple …

A Learning Health System For Radiation Oncology, Rishabh Kapoor

Theses and Dissertations

The proposed research aims to address the challenges faced by clinical data science researchers in radiation oncology accessing, integrating, and analyzing heterogeneous data from various sources. The research presents a scalable intelligent infrastructure, called the Health Information Gateway and Exchange (HINGE), which captures and structures data from multiple sources into a knowledge base with semantically interlinked entities. This infrastructure enables researchers to mine novel associations and gather relevant knowledge for personalized clinical outcomes.

The dissertation discusses the design framework and implementation of HINGE, which abstracts structured data from treatment planning systems, treatment management systems, and electronic health records. It utilizes …

Kpt-330 Synergizes With Everolimus To Reduce Mtorc1-Overactive Basal-Like Triple-Negative Breast Cancer Brain Metastasis Burden, Aaron D. Valentine

Theses and Dissertations

Triple-negative breast cancer (TNBC), a highly metastatic breast cancer subtype, accounts for approximately 20% of all breast cancer diagnoses. Basal-like TNBC is notably difficult to treat due to the lack of actionable drug targets such as estrogen and progesterone receptors, as well as HER2. Due to the deficiency in TNBC-targeting drugs that are able to cross the blood-brain barrier (BBB) for breast-to-brain metastasis, there is a need to develop novel BBB-permeable treatments. After preliminary testing, KPT-330 (XPO1 inhibitor) and everolimus (FKBP1A/mTOR inhibitor) were selected as drug candidates for this study. Patient-derived xenograft (PDX) models for in vitro and in vivo …

Impact Of Portal Of Exit On The Prevalence Of Apical Periodontitis In Root Canal Treated Maxillary Molars With Missed Second Mesiobuccal Canals: A Cbct Study, Jing Ye

Theses and Dissertations

Objective: To evaluate the association of portal of exit (POE) of the second mesiobuccal (MB2) canal with the prevalence of apical periodontitis (AP) in previously treated maxillary molars

Methods: Cone beam computed tomography (CBCT) scans of 106 previously treated maxillary molars seen for either recall or retreatment in the past 3 years were included in the study. Scans were reviewed by one endodontic resident and one board-certified endodontist to determine the POE (separate versus common) of the missed MB2 canal and the presence or absence of a periapical hypo-dense area. Association between AP and portal of exit was assessed using …

Examining Allostatic Load As A Biological Mechanism Linking Childhood Adversity And Pediatric Pain, Angela Pascale

Theses and Dissertations

Despite a strong literature base relating childhood adversity to pain, the biological mechanisms underlying these associations remain unclear. Theoretical and preliminary empirical evidence supports allostatic load as a potential biological mechanism, though prior studies investigating associations between childhood adversity and elevated allostatic load and/or between elevated allostatic load and poorer pain outcomes have primarily focused on adult populations and individual allostatic load indicators rather than a comprehensive index. Thus, the current study built upon prior literature by testing longitudinal relationships between childhood adversity and multiple biological indicators spanning across physiological systems (i.e., comprehensive allostatic load index) and pediatric pain outcomes …