Digital Commons Network^™

Therapeutic Implications Of The Gut-Cns Axis In Promoting Recovery Following Cervical Spinal Cord Injury, Jessica Wilson

Theses and Dissertations--Neuroscience

Nearly 60% of all spinal cord injuries (SCI) occur at the cervical level. These high-level injuries can interrupt the descending respiratory pathways required for breathing. Indeed, therapies in animal studies have been successful at restoring breathing after SCI; however, these interventions appear to be more effective at chronic time points. One potential cause for this observation is the impact of the injury on the gut microbiome. Neurotrauma can induce gut dysbiosis, an imbalance of pathogenic and beneficial gut microbiota, which has previously been shown to negatively impact the central nervous system (CNS) and impair recovery. We aimed to build upon …

Foster Caregiving: How Interactions With The Child Welfare Agency Impact Foster Parent Satisfaction, Recruitment, And Retention, Ethan Engelhardt

Theses and Dissertations--Social Work

Professionals of the child welfare system in Kentucky have continuously worked to retain and recruit new foster parents for the foster care system. Foster parents are uniquely placed in a surrogate caring position for children removed from their homes for reasons of abuse or neglect. Foster parents accept this role and step in to provide a safe and loving household for many children. There are more than 9,000 children placed in Out of Home Care (OOHC) on any given day in Kentucky, leaving many children in need of a loving and supportive household. Foster parents hang in the balance between …

Factors Associated With Successful Military-To-Civilian Transition Among Special Forces Veterans, Edward Richter

Theses and Dissertations--Social Work

The purpose of this study was to explore the military-to-civilian transitional experience in a sample of Special Forces veterans. Acknowledging challenges in accessing the veteran population, most existing research on the military-to-civilian transition consolidates military occupations into a single sample. This method fails to address the intricacies that may exist within individual military occupations, especially that of U.S. Army Special Forces soldiers. Special Forces qualified soldiers represent the largest portion of all U.S. Military Special Operations Forces and are responsible for the majority of all Special Operations activities, yet their experience in transitioning out of the Army is largely unknown. …

Sensory Marketing For Consumer Wellbeing, Josh Lundberg

Theses and Dissertations--Marketing and Supply Chain

Chapter 1. Many consumer decisions – from trying a new brand to trying a new recipe – involve some risk. However, although consumers’ appetite for risk has received over fifty years of investigation, the impact of situational variables (e.g., atmospherics) on consumer decision making involving risk remains relatively unexplored. To address this gap, the current work examines the influence of temperature, a ubiquitous situational influence, on consumers’ inclination toward risk. Across four studies, we find evidence for a positive relationship between temperature and risk taking, using multiple manipulations of temperature and measurements of risk. Evidence suggests that this effect is …

When The Past Comes Knocking: An Alter-Centric Perspective On Network Mobilization In Prosocial Occupations, Jason Ross

Theses and Dissertations--Management

Networks are vital to our ability to access resources. However, scholars have often overlooked just how social networks are mobilized. Underexplored in the literature is how individuals think and feel about mobilizing networks with little attention directed towards the person (alter) being reached out to. In this dissertation, I use a basic, interpretive design to better understand how people think and feel about receiving requests for task-related help, paying particular attention to when those requests originate from people from one’s past. To do so, I conducted interviews with 40 animal rescuers given their passion for helping, but their inability to …

Placing Rural Poverty In The Political Economy: Farm Policy In The American Midwest, Aimee Imlay

Theses and Dissertations--Sociology

Approaches to explaining rural poverty highlight the social, economic, and political processes that contribute to poverty in rural communities, yet the political economy of agriculture has rarely been considered a determinant of rural poverty. Within rural sociology, peasant studies, and rural poverty are distinct subdisciplines; thus, farm and nonfarm poverty are viewed as mutually exclusive. This dissertation uses a three-paper format to: 1) examine the impact of changes to commodity programs on rural poverty rates in the Midwest; 2) investigate the impact of direct payments on rural poverty rates in the Midwest; and 3) explore the linkages between peasant studies, …

Tolerance Intervals For Various Regression Models, Xitong Zhou

Theses and Dissertations--Statistics

Among statistical intervals, confidence intervals and prediction intervals are well-known and commonly used. In many applications, the problem becomes finding an interval that covers at least a certain proportion $P$ of the population for a characteristic of interest with a specified confidence level $(1-\alpha)$. And such interval is named a $P$-content, $(1-\alpha)$-confidence Tolerance Interval (TI). The topic of the dissertation is the utility of tolerance intervals for various regression models. We begin with a discussion of tolerance intervals for linear and nonlinear regression models. We then propose a bootstrap method of constructing TIs for Tobit regression to deal with censored …

High Dimensional Data Analysis: Variable Screening And Inference, Lei Fang

Theses and Dissertations--Statistics

This dissertation focuses on the problem of high dimensional data analysis, which arises in many fields including genomics, finance, and social sciences. In such settings, the number of features or variables is much larger than the number of observations, posing significant challenges to traditional statistical methods.

To address these challenges, this dissertation proposes novel methods for variable screening and inference. The first part of the dissertation focuses on variable screening, which aims to identify a subset of important variables that are strongly associated with the response variable. Specifically, we propose a robust nonparametric screening method to effectively select the predictors …

Methodologies And Computational Tools For Zero-Inflated Discrete Weibull Models, Peng Yeh

Theses and Dissertations--Statistics

Count data with excess zeros is common in many fields, such as ecology, healthcare, and insurance. Excess zeros data are often causing the inaccurate fit from the count models. While zero-inflated models have been developing for over two decades, one should also consider a more flexible model that can handle the excess zeros and further over- or under-dispersion. In this talk, we discuss zero-inflated discrete Weibull model and some novel computational contributions. The flexibility and competitiveness of the ZIDW model are illustrated by simulation studies and a real data analysis. We also investigate the performance of the proposed model through …

Adverse Childhood Experiences, Nicotine Dependence, And Depressive Symptoms Among A Community Sample Of People With Mental Illnesses, Bassema Abufarsakh

Theses and Dissertations--Nursing

Adverse childhood experiences (ACEs) pose a major public health issue as they are associated with poor mental and physical health outcomes. In the United States (US), more than 60% of adults report at least one ACE, and around 15% experienced four or more. Repeated exposure to ACEs stressors can convert ACEs to toxic stress by altering the brain's architecture and function. Evidence suggests that exposure to four or more ACEs, which are indicators of exposure to toxic stressors, is associated with nicotine dependence (ND) and depressive symptoms. Moreover, people with mental illnesses (MI) often have greater exposure to toxic stressors …

Investigating The Use Of Mpges-1 Inhibitors For The Treatment Of Abdominal Aortic Aneurysms, Lauren M. Weaver

Theses and Dissertations--Pharmacy

The cardiovascular field is still searching for a treatment for abdominal aortic aneurysms (AAA). This inflammatory disease is a deadly, permanent ballooning of the aortic artery. It often goes undiagnosed until a late stage where associated rupture has a high mortality rate. Surgery is the only option available to patients, but it is risky. There are currently no FDA-approved pharmacological treatments for AAA available. Historically, drugs that have been examined in interventional clinical trials for treatment of AAA were repurposed therapeutics. Novel treatments have been unable to reach the clinic, stalling out in pre-clinical studies. Exceedingly few murine studies have …

Effectiveness Of A Long-Acting Cocaine Hydrolase In Metabolizing Cocaine And Its Physiologically Active Metabolites, Linyue Shang

Theses and Dissertations--Pharmacy

Cocaine is a widely abused, hepatotoxic drug without an FDA-approved pharmacotherapy specific for cocaine addiction or overdose. Cocaine-induced toxicity in animals and humans is due to its multiple physiological effects on the central nervous system, cardiovascular system, etc. The toxicity of cocaine is highly complex, as its metabolites also contribute to the toxicity. Notably, the combination of cocaine and alcohol is common among drug users and can produce additional metabolites. Some of the metabolites are more toxic than cocaine itself. Hence, to develop an ideal therapeutic candidate, the candidate should not only account for cocaine but should also detoxify other …

Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana

Theses and Dissertations--Pharmacy

Cancer remains a real and present threat to global health. In the United States, according to cancer statistics, almost 40% of people will be diagnosed with cancer at some point in their lifetime. Conventional chemotherapy has become the mainstay for cancer treatment option. However, chemotherapeutic agents are plagued with problems such as poor aqueous solubility, chemical degradation, Bio instability, and off-site toxicity due to non-specificity. New drug modalities are needed to tackle the ever-growing burden on cancer. In recent times, the promise of nanotechnology has aided to develop drug delivery vehicles to facilitate the administration of potent chemotherapeutics. Nanoformulations such …

Striving For Appropriate Antibiotic Use: A Biomarker Initiative, And Outcomes Associated With Azithromycin Exposure, Amanda Gusovsky

Theses and Dissertations--Pharmacy

The introduction of antibiotics into clinical practice is considered the greatest medical breakthrough of the 20^thcentury. However, the use of antibiotics can contribute to the development of resistance. In the United States (U.S.), approximately 2.8 million people are infected with antibiotic-resistant bacteria each year, and more than 35,000 people die as a result. Moreover, some antibiotics are known to cause cardiac side effects including QT prolongation, hypotension, and ventricular arrythmias. The U.S. Centers for Disease Control and Prevention (CDC) defines appropriate antibiotic use as the effort to use “the right antibiotic, at the right dose, for the right …

Optimization Of Orally Bioavailable Inhibitors Of Defective In Cullin Neddylation 1 (Dcn-1), Leah Kovalic

Theses and Dissertations--Pharmacy

Ubiquitin (UB) and ubiquitin-like protein (UBL) pathways have emerged as important targets for oncology drug discovery based on the success of proteasome inhibitors (bortezomib or carfilzomib), E3 inhibitors, and the NEDD8 E1 inhibitor pevonedistat (MLN42924). Chemical inhibitors have also proven to be useful probes for identifying and dissecting multifactor UB and UBL regulatory networks. Toward this end, we have pursued approaches to target NEDD8 ligation to Cullins, through developing small molecule inhibitors of DCN1 (defective in Cullin Neddylation 1). DCN1 was discovered as a potentiating RBX1-dependent NEDD8-ligation, through recognizing the acetylated N-terminal methionine of the NEDD8 E2s UBE2M and UBE2F. …

Genetic And Pharmacogenetics Associations Of Cancer Disparities In Appalachia, Nan Lin

Theses and Dissertations--Pharmacy

Individuals residing in Appalachian regions have significant health disparities, including higher cancer incidence and mortality rates. Previous studies have addressed the impact of socioeconomic status and environmental risk factors on Appalachia cancer disparities, while few studies have evaluated genetic risk factors.

Germline whole exome sequencing samples from 7,078 individuals with cancer (759 Appalachians) were evaluated. Demographics and relatedness were assessed using KING. Ethnicity was verified by principal component analysis using TRACE, which included 6,034 individuals (85%) of European genetic ancestry. After QC filtering, 5,980 individuals were analyzed. To assess the overall predisposition of hereditary disease, gene level frequency of likely …

Bioinformatic Analysis Of Proteomic And Genomic Data From Nsclc Tumors On Prognostic And Predictive Factors Of Immunotherapy Treatment, Mark Wuenschel

Theses and Dissertations--Pharmacy

Recent lung cancer research has led to advancements in molecular immunology, resulting in development of small molecule inhibitors, or immune checkpoint inhibitors, that propagate an anti-tumor T cell response. Despite increased overall and progression-free survival with reduced adverse effects compared to traditional chemotherapy, treating advanced stage lung adenocarcinoma patients remains non-curative, and evidence of non-responders or tumor recurrence to immune checkpoint inhibitor therapy is growing. Also, compared to traditional chemotherapy, there is a lower percentage of patients who respond to small molecule inhibitors. In this analysis of proteomic and genomic data from The Cancer Proteome Atlas and Global Data Commons …

Population-Based Evaluation Of Treatment Patterns, Drug-Drug Interactions, And Cardiovascular Risk In Patients With Metastatic Castration-Resistant Prostate Cancer, Yue Cheng

Theses and Dissertations--Pharmacy

Prostate cancer has the highest increasing rate and new cases among all cancer in men in the United States and has a higher risk in elderly men. Metastatic castration-resistant prostate cancer (mCRPC) is the late stage of prostate cancer and associated with poor prognosis (median survival 13 months). Androgen deprivation therapy (ADT) use with novel hormone therapy or standard chemotherapy are recommended for mCRPC treatment. Although, the treatment options expanded significantly in recent years, new challenges are present because of the aging population, larger treatment spectrum and co-administrated medication use for other underlying medical conditions, especially for cardiovascular disease (CVD), …

Design And Synthesis Of Small Molecular Inhibitors Of Dcn1-Ube2m Interaction, Tucker J. Moseley

Theses and Dissertations--Pharmacy

Over the last century, advancements in medicine have been made to improve cancer patients' outcomes. The discovery of new druggable targets is essential to achieving this goal. Defective in Cullin Neddylation 1 is a proven oncogenetic driver that may lead to better clinical outcomes when targeted. In efforts to further improve a series of novel small molecular inhibitors of the DCN1 and UBE2M protein-protein interaction, the Guy lab has designed and synthesized 26 new compounds. These compounds were designed to specifically target the UBE2M N-Acetyl sub-pocket on DCN1 that was not occupied by compounds previously described in the literature.

Investigation Of Folate-Poly(Glutamic Acid)/Polyethylenimine/Dna Complexes For In Vitro Gene Delivery, Caleb Akers

Theses and Dissertations--Pharmacy

Gene therapy is currently being studied as a treatment for a variety of indications, including cancer, infectious disease, and cardiovascular diseases, among others. While many of the early treatments in the field involved the use of viral delivery methods, various safety, ethical, and financial concerns limit the potential uses of this methodology. As such, more recent research has focused on developing non-viral delivery platforms to alleviate some of the issues inherent in viral delivery. Recently, the release of the COVID-19 vaccines from Pfizer and Moderna represents a promising use of non-viral delivery as both utilized a lipid-based delivery vector.

Despite …

An Epidemiological And Pharmacokinetic-Pharmacodynamic Investigation Into The Impact Of Carbapenem-Resistant Enterobacterales, Justin Clark

Theses and Dissertations--Pharmacy

Background: According to the 2019 CDC Antibiotic Resistance Threats Report, more than 2.8 million antibiotic-resistant infections occur in the United States each year, leading to more than 35,000 deaths. Among the most urgent threats identified by the CDC are carbapenem-resistant Enterobacterales (CRE). Despite efforts to control the spread of these organisms, the number of estimated cases between 2012 and 2017 remained stable. In 2017, an estimated 13,100 hospitalized cases of CRE led to approximately 1,100 deaths and $130 million attributable healthcare costs. This dissertation seeks to address this issue from both a pharmacokinetic/pharmacodynamic and epidemiological perspective.

Methods: We evaluated the …

Developing A Biocatalytic Toolbox To Aid In Understanding Nucleoside Antibiotics, Jasmine Brianna Woods

Theses and Dissertations--Pharmacy

Antibiotic resistance happens when bacteria develop the ability to survive medications that normally terminate them. Instead, these super germs are able to survive in the body and produce a community of antibiotic resistance germs which can cause human fatalities. It is important to discover and develop new compounds and molecules that will improve this clinical obstacle. This research focused on analyzing the biosynthesis that incorporates distinctive chemical characteristic of various nucleoside antibiotics, ß-hydroxy amino acids and α-methyl-amino acids. ß-hydroxy amino acids and α-methyl-amino acids are considered an important class of industrially useful compounds, particularly for pharmaceutical development, and are found …

New Tools For Biocatalysis: Studies On The Carminomycin 4-O-Methyltransferase Dnrk, Elnaz Jalali

Theses and Dissertations--Pharmacy

Methyltransferases (MTs) are ubiquitous enzymes commonly involved in biosynthesis and regulation. The fundamental goal of this thesis was to explore the permissive nature of methyltransferases and leverage this unique biocatalytic feature to develop a new platform for chemoselective intramolecular cyclization reactions. To realize this ambitious goal, this thesis project set out to probe the substrate specificity of multiple natural product tailoring enzymes (MTs and glycosyltransferases), identify model substrates common to multiple such tailoring enzymes and subsequently establish multi-enzyme tandem reactions that would set the stage for a subsequent chemoselective intramolecular cyclization reaction. Chapter One highlights current state of the art …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Studies Of Polypharmacy And Medication Therapy Management In Population-Based Cohorts, Ximena A. Oyarzun Gonzalez

Theses and Dissertations--Epidemiology and Biostatistics

According to the United States Census Bureau, 16.8% of the population was 65 years and older in 2021, and it is expected that by 2060 that number will increase to about 30% (about 114 million people). Aging is associated with physiological changes in all systems of the body. These changes impact the pharmacodynamics and pharmacokinetic characteristics of drugs. Furthermore, older adults usually have several chronic conditions, which increases their exposure to medications. Increased vulnerability combined with increasing exposure puts elderly people at higher risk for drug interactions and adverse events.

Charlesworth et al. (2014) found that the prevalence of polypharmacy, …

Clustering Hospital Performance Using Group-Based Multi-Trajectory Modeling With Singular Bayesian Information Criterion, Gaixin Du

Theses and Dissertations--Epidemiology and Biostatistics

Hospital performance is complex and patient-experience oriented. Currently, the Centers for Medicare and Medicaid Services (CMS) evaluate hospitals yearly with a single score of one to five ("Star Rating") using composite measures from five domains. However, a single composite score cannot fully describe it, and alternative measures should be considered. Healthcare quality improvement needs long-term data to validate effectiveness. Group-based multi-trajectory modeling (GBMTM) estimates probabilities of latent group membership based on longitudinal profiles from multiple outcomes. We use GBMTM to identify groups of hospitals with similar performance in SAS PROC TRAJ.

We downloaded Medicare-eligible hospitals (N=5,111) that provided patient care …

Evaluating The Impact Of Mental Health Needs And Services Disruption: Covid-19 & Wisconsin Children’S Welfare Services, Gavin Rienne

Theses and Dissertations--Epidemiology and Biostatistics

Children’s traumatic experiences have lifelong impacts on their mental health and quality of life, therefore mental health services are a critical part of necessary community resources. The increased frequency and severity of natural disasters such as hurricanes, tornadoes, and pandemics reinforces the need to examine and understand the importance of mental health and child services in response to disaster events. This research assesses the relationship between disasters and subsequent health service utilization amongst children and adolescents. We investigated current research on the relationship between children’s mental health and community mental health resource efficacy and accessibility after a major disaster by …

Maternal Occupation And Pediatric Brain Cancer In Kentucky, Mary Elizabeth Begley

Theses and Dissertations--Epidemiology and Biostatistics

Pediatric brain cancer is a rare and potentially deadly diagnosis that affects children in Kentucky at a higher incidence than those nationally. Limited exposures in children early in life to warrant the development and progression of brain cancer point to the role parental exposures experienced in the period prior to conception and throughout pregnancy may play in its development. Many of these exposures may be experienced through occupation.

Data on a subset of pediatric brain cancer cases in Kentucky was compared to all cases diagnosed in the state from 1995 to 2019. Survey data of the study sample was collected …

Potential Alzheimer's Disease Plasma Biomarkers, Taylor Estepp

Theses and Dissertations--Epidemiology and Biostatistics

In this series of studies, we examined the potential of a variety of blood-based plasma biomarkers for the identification of Alzheimer's disease (AD) progression and cognitive decline. With the end goal of studying these biomarkers via mixture modeling, we began with a literature review of the methodology. An examination of the biomarkers with demographics and other health factors found evidence of minimal risk of confounding along the causal pathway from biomarkers to cognitive performance. Further study examined the usefulness of linear combinations of biomarkers, achieved via partial least squares (PLS) analysis, as predictors of various cognitive assessment scores and clinical …

Prediction Of Dynamic Subsidence In The Proximity Of Longwall Panel Boundaries, Jesus David Romero Benitez

Theses and Dissertations--Mining Engineering

The development of mining subsidence has a dynamic character, and it is related to the mining rate and a time coefficient. Reliable prediction of dynamic deformations is important when planning to undermine important structures that cannot account for large relative deformations and or large horizontal strains. This thesis discusses subsidence development for a number of points over a retreating longwall panel in the eastern US. The prediction points are at different distances from the excavation rib and, therefore, present a different response in terms of dynamic movements. Final movements, i.e., measurements after the panel was fully extracted, were used to …