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Barriers And Facilitors Of Healthcare Use Among People Who Inject Drugs, C. Brooke Kuns-Adkins

Theses and Dissertations--Nursing

Hepatitis C Virus (HCV) is an infection that can have grave consequences when left untreated. Hepatitis C can be easily eradicated with direct acting antiviral therapy. People who inject drugs (PWID) and inmates are among those with the highest incidence of HCV. However, cure rates among this population remains low. This is, in part, related to an interruption in the HCV care cascade such that only 30% of PWID are linked to care and only 8% of those receive treatment. Inadequate screening and failure to be linked to HCV care remain the largest impediments to treatment success. There is limited …

Actinomycin Familial Diversity Driven By Phenoxazinone-Core Reactivity, Matthew Richard Mcerlean

Theses and Dissertations--Pharmacy

Actinomycins are a class of compounds consisting of phenoxazinone-like core attached to two peptidolactone rings, denoted as α and β. A unique component of a few families—actinomycins G, Y, and Z—is a chlorinated β-ring threonine residue. Families G and Y also contained an actinomycin that possess a β-ring heterocycle (actinomycins G₅ and Y₅, respectively); prior to this work, no β-ring heterocycle-containing actinomycins were reported for the Z family. Unlike other actinomycin derivatives, Y₅’s cytotoxicity was abolished while still maintaining some antibacterial potency.

We constructed a model compound to probe the physical properties of the actinomycin …

Developing A Workflow To Evaluate Medications For Repurposing Using Health Claims Data: Application To Substance Use Disorders, Emily Ruth Hankosky

Theses and Dissertations--Pharmacy

Healthcare big data are a growing source of real-world data with which to identify and validate medications with repurposing potential. Previously, we developed a claims-based workflow to evaluate medications with potential to treat stimulant use disorders. In order to test the workflow, the framework was applied in the context of opioid use disorders (OUDs), for which there are medications with known efficacy. Using the Truven Marketscan Commercial Claims Database, a nested case-control analysis was conducted to determine the association between OUD medications (buprenorphine, naltrexone) and remission. Cases were defined as enrollees with a remission diagnosis and matched (1:4) to controls …

Phase Behavior Of Amorphous Solid Dispersions: Miscibility And Molecular Interactions, Kanika Sarpal

Theses and Dissertations--Pharmacy

Over the past few decades, amorphous solid dispersions (ASDs) have been of great interest to pharmaceutical scientists to address bioavailability issues associated with poorly water-soluble drugs. ASDs consist of an active pharmaceutical ingredient (API) that is typically dispersed in an inert polymeric matrix. Despite promising advantages, a major concern that has resulted in limited marketed formulations is the physical instability of these complex formulations. Physical instability is often manifested as phase heterogeneity, where the drug and carrier migrate and generate distinct phases, which can be a prelude to recrystallization. One important factor that dictates the physical stability of ASDs is …

The Development Of Novel Proteasome Inhibitors For The Treatment Of Multiple Myeloma And Alzheimer’S Disease, Min Jae Lee

Theses and Dissertations--Pharmacy

Over a decade, proteasome inhibitors (PIs), bortezomib, carfilzomib (Cfz) and ixazomib, have contributed to a significant improvement in the overall survival for multiple myeloma (MM) patients. However, the response rate of PI was fairly low, leaving a huge gap in MM patient care. Given this, mechanistic understanding of PI resistance is crucial towards developing new therapeutic strategies for refractory/relapsed MM patients.

In this dissertation work, we found H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). It indicated H727 cells may serve as a …

Carbapenem-Resistant Enterobacteriaceae: Epidemiology, Genetics, In Vitro Activity, And Pharmacodynamic Modeling, Brandon Kulengowski

Theses and Dissertations--Pharmacy

Background: Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) such as Escherichia coli and Klebsiella pneumoniae are among the most urgent threats of the infectious disease realm. The incidence of these infections has been increasing over the years and due to very limited treatment options, mortality is estimated at about 50%. By 2050, mortality from antimicrobial resistant infections is expected to surpass cancer at 10 million deaths annually.

Methods: We evaluated 18 contemporary antimicrobials against 122 carbapenem-resistant Enterobacteriaceae using a variety of antimicrobial susceptibility testing methods according to Clinical Laboratory Standards Institute guidelines. Time-kill studies were performed on clinical isolates with variable …

Therapeutic Video Games And The Simulation Of Executive Function Deficits In Adhd, Markus Tiitto

Theses and Dissertations--Pharmacy

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by difficulty paying attention, impulsivity, and hyperactivity. Diagnosis of ADHD rose 42% from 2003–2004 to 2011–2012. In 2011, 3.5 million children were treated with drugs. Optimizing therapy can take a year, and may not be completely effective.

A clinical trial is currently being conducted of a device/drug combination using the computer game Minecraft, to determine how certain activities affect executive function, working memory, and restraint in patients diagnosed with ADHD. The human subjects’ responses are being modeled using artificial neural networks (ANNs), an artificial intelligence method that can be utilized …

Pharmacokinetic And Pharmacodynamic Evaluation Of Cocaine Hydrolases For The Treatment Of Cocaine Overdose And Cocaine Addiction Using Rodent Models, Xirong Zheng

Theses and Dissertations--Pharmacy

Overdose and addiction are two medical complications of cocaine abuse. To date, there is no FDA approved pharmacotherapy specific for cocaine abuse. Cocaine hydrolases (CocHs) have been extensively investigated for its potential in anti-cocaine therapy. Previous studies have demonstrated that CocHs efficiently hydrolyze cocaine to generate biologically inactive metabolites both in vivo and in vitro. However, it has not been studied whether there is gender difference in the therapy using CocHs. In addition, the effectiveness of CocHs is unknown for treating cocaine toxicity when alcohol is co-administered.

The main purpose of this dissertation is to characterize and evaluate efficient …

Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel

Theses and Dissertations--Pharmacy

Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.

The goals of …

Discovery Of Novel Pharmacotherapeutics For Substance Use Disorders, Na-Ra Lee

Theses and Dissertations--Pharmacy

Substance use disorders are serious health concerns in the United States. Furthermore, the National Survey on Drug Use and Health reports a continuous increase in substance use disorders in the United States during the last 10 years. However, there are not many effective pharmacotherapeutics available for substance use disorders. The current dissertation is focused on research aimed at discovering pharmacotherapeutics for substance use disorders. First part of dissertation focused on discovering methamphetamine (METH) use disorder therapeutics targeting specific mechanism of METH action on dopaminergic neurons. The second part of dissertation focused on opioids and cocaine use disorder therapeutics targeting rewarding …

Trends And Patterns In Use Of Medications For Opioid Use Disorder In A Commercially Insured Population In The U.S., Catherine Serratore

Theses and Dissertations--Pharmacy

Opioid use disorder (OUD) and opioid overdose are pervasive public health problems in the U.S. Medications for opioid use disorder (MOUD) have been shown effective to reduce OUD morbidity and mortality. Two distinct approaches to MOUD are currently used: agonist therapy (methadone or buprenorphine) or antagonist therapy (naltrexone). Limited information is available about the patterns of use, adherence to therapy, and characteristics of those who use agonist vs. antagonist therapy. The objective of this study is to assess recent trends in MOUD, adherence in use of MOUD, and the characteristics of those who use agonist vs. antagonist therapy in a …

Development Of Mithramycin Analogues With Improved Efficacy And Reduced Toxicity For Treatment Of Ets-Dependent Tumors In Ewing Sarcoma And Prostate Cancer, Joseph Michael Eckenrode

Theses and Dissertations--Pharmacy

Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor …

Computational Modeling Guided Discovery Of Novel Inhibitors Of Mpges-1 And Butyrylcholinesterase As Drug Candidates, Shuo Zhou

Theses and Dissertations--Pharmacy

Ever since the advent of computer-aided drug design (CADD), in silico simulation methods have greatly accelerated the drug discovery process and lead to the discovery of numerous drug candidates. With the exponential growth of computational power, we nowadays simulate biologic systems at a scale unimaginable a decade ago and thus provides perspectives for drug design. In this dissertation research, combining in silico simulation methods like molecular docking and molecular dynamics (MD) simulation with organic synthesis, in vitro/in vivo experiments and clinical data mining, we developed new drug discovery strategies. These strategies were applied in our drug discovery projects and led …

Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber

Theses and Dissertations--Pharmacy

Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …

Investigation Of Factors Influencing Protein Stability In Lyophilized Formulations Using Solid-State Nmr Spectroscopy, Ashley Lay-Fortenbery

Theses and Dissertations--Pharmacy

Many proteins are unstable in solution and must be formulated in the solid state. This has led to an increase in the use of lyophilized dosage forms. Lyophilization is a complicated processing method consisting of three major steps: freezing, primary drying, and secondary drying. This can lead to several formulation stability challenges including changes in ionization within the matrix, phase separation of the protein drug from added stabilizers, sufficient mobility within the system for movement of reactive species and protein side chains, and crystallization of excipients upon storage. Solid-State Nuclear Magnetic Resonance Spectroscopy (SSNMR) is used to characterize many important …

Estimating Disease Severity, Symptom Burden And Health-Related Behaviors In Patients With Chronic Pulmonary Diseases, Radmila Choate

Theses and Dissertations--Epidemiology and Biostatistics

Chronic pulmonary diseases include a wide range of illnesses that differ in etiology, prevalence, symptomatology and available therapy. A common link among these illnesses is their impact on patients’ vital function of breathing, high symptom burden and significantly impaired quality of life.

This dissertation research evaluates disease severity, symptom burden and health behaviors of patients with three different chronic pulmonary conditions. First, alpha-1 antitrypsin deficiency (AATD) is an inherited condition that typically is associated with an increased risk of early onset pulmonary emphysema. This study examines differences in demographic, health, and behavioral characteristics and compares clinical outcomes and health related …

Social Workers’ And Teachers’ Feelings Of Self-Efficacy In Dealing With School Bullying, Sharon Lynn Simmons

Theses and Dissertations--Social Work

Bullying continues to be a serious problem in schools. School social workers and teachers face challenges daily to deal with bullying. This author examined school social workers’ and teachers’ perceptions about their feelings of efficacy to deal with bullying and what may account for those feelings in a population of 71 teachers and 26 social workers employed in Kentucky schools. Research was gathered using a self-report, electronic survey consisting of subscales of the Teachers’ Attitudes about Bullying Questionnaire (Beran, 2005), the School Bullying Questionnaire (Nicolaides, Toda & Smith, 2002), the Toronto Empathy Questionnaire (Spreng, McKinnon, Mar & Levine, 2009) and …

Veterans' Treatment Courts In Kentucky: Examining How Personal Characteristics And During-Program Occurrences Influence Program Completion And Criminal Recidivism, Monica Lynn Himes

Theses and Dissertations--Social Work

Military veterans are disproportionately represented in United States (U.S.) jails and prisons, with nearly 10% of current inmates being veterans. Veterans’ criminal justice involvement is often precipitated by underlying mental health and substance abuse that are connected to their military service. Veterans’ treatment courts are the judicial response to a need for more coordinated provision of mental health and substance abuse services to veterans involved in the criminal justice system. Modeled after drug courts and mental health courts, veterans treatment courts are a judicial innovation that aim to honor the service of veterans by providing them an alternative to incarceration. …

Suicide Attitudes And Terror Management Theory, Athena Kheibari

Theses and Dissertations--Social Work

Virtually every mental health problem carries stigma, but suicide appears to run so counter to our accumulative, achievement-oriented society, that it poses even greater threat of stigma. While suicide is inherently troubling in that it opposes the fundamental human instinct for self-preservation, the tendency to stigmatize and reject individuals affected by suicide appears to be counterproductive and excessive. Hence, the purpose of this three-manuscript dissertation is to gain a more nuanced understanding of suicide attitudes from an exploratory and terror management theory perspective. More specifically, this dissertation attempts to answer three general questions: (1) how do suicide attitudes differ from …

Predictive Modeling Of Dc Arc Flash In 125 Volt System, Austin Cody Gaunce

Theses and Dissertations--Mining Engineering

Arc flash is one of the two primary hazards encountered by workers near electrical equipment. Most applications where arc flash may be encountered are alternating current (AC) electrical systems. However, direct current (DC) electrical systems are becoming increasingly prevalent with industries implementing more renewable energy sources and energy storage devices. Little research has been performed with respect to arc flash hazards posed by DC electrical systems, particularly energy storage devices. Furthermore, current standards for performing arc flash calculations do not provide sufficient guidance when working in DC applications. IEEE 1584-2002 does not provide recommendations for DC electrical systems. NFPA 70E …

Simplifying Techniques Applied To Computational Fluid Dynamics Modeling Of Methane Explosions, Laura Steeves

Theses and Dissertations--Mining Engineering

Traditional methods of studying underground coal mine explosions are limited to observations and data collected during experimental explosions. These experiments are expensive, time-consuming, and require major facilities, such as the Lake Lynn Experimental Mine. The development of computational fluid dynamics (CFD) modeling of explosions can help minimize the need for large-scale testing. This thesis utilized the commercial CFD software, SC/Tetra, to examine three case studies. The first case study modeled the combustion of methane in a scaled shock tube, measuring approximately 1 foot by 1 foot, by 20.5 feet long, with a methane cloud of 2.5 feet in length, at …

The Redesigned Vortecone: A Maintenance-Free Wet Scrubber Device, Allison Taylor

Theses and Dissertations--Mining Engineering

Dust creates health and safety issues in mining and there are several different ways to reduce the amount of respirable dust created. Dust particles also affect the operation and efficiency of mining equipment. One device currently used to reduce dust in a coal mine is a flooded-bed dust scrubber. These type of scrubbers are found on continuous miners and are designed to capture dust particles close to the cutting head. However, the fibrous screens on the flooded-bed dust scrubber clog easily reducing both production and the quality and quantity of air miners are exposed too. The flooded-bed dust scrubber was …

Dust Transportation And Settling Within The Mine Ventilation Network, Anand Kumar

Theses and Dissertations--Mining Engineering

Dust is ubiquitous in underground mine activities. Continuous inhalation of dust could lead to irreversible occupational diseases. Dust particles of size lower than 75.0 µm, also known as float coal dust, can trigger a coal dust explosion following a methane ignition. Ventilation air carries the float coal dust from the point of production to some distance before it’s deposited on the surfaces of underground coal mine. Sources of dust are widely studied, but study of dust transportation has been mainly based on experimental data and simplified models. An understanding of dust transportation in the mine airways is instrumental in …

Influence Of Water Injection Rate On The Vortecone, An Impingement Screen, And A Conventional Filter Screen Cleaning Efficiency, Oscar Velasquez

Theses and Dissertations--Mining Engineering

Industrial produced respirable particles are known to affect the respirable tract of workers causing serious illness or even death. These particles can be found in any mining operation’s environment, new regulations by the Mine Safety and Health Administration (MSHA) in 2014 reduced the allowable limit of dust exposure for underground workers. Dust control practices have been improving over the years to lower the number of incidents caused by these particles. In underground mining, water sprays and scrubber systems have become the most used dust control methods. Water sprays create numerous fine water droplets to capture dust once it has become …

Quantification Of Myocardial Mechanics In Left Ventricles Under Inotropic Stimulation And In Healthy Right Ventricles Using 3d Dense Cmr, Zhan-Qiu Liu

Theses and Dissertations--Mechanical and Aerospace Engineering

Statistical data from clinical studies indicate that the death rate caused by heart disease has decreased due to an increased use of evidence-based medical therapies. This includes the use of magnetic resonance imaging (MRI), which is one of the most common non-invasive approaches in evidence-based health care research. In the current work, I present 3D Lagrangian strains and torsion in the left ventricle of healthy and isoproterenol-stimulated rats, which were investigated using Displacement ENcoding with Stimulated Echoes (DENSE) cardiac magnetic resonance (CMR) imaging. With the implementation of the 12-segment model, a detailed profile of regional cardiac mechanics was reconstructed for …

Enhanced Surface Integrity With Thermally Stable Residual Stress Fields And Nanostructures In Cryogenic Processing Of Titanium Alloy Ti-6al-4v, James R. Caudill

Theses and Dissertations--Mechanical and Aerospace Engineering

Burnishing is a chipless finishing process used to improve surface integrity by severe plastic deformation (SPD) of surface asperities. As surface integrity in large measure defines the functional performance and fatigue life of aerospace alloys, burnishing is thus a means of increasing the fatigue life of critical components, such as turbine and compressor blades in gas turbine engines. Therefore, the primary objective of this dissertation is to characterize the burnishing-induced surface integrity of Ti-6Al-4V alloy in terms of the implemented processing parameters. As the impact of cooling mechanisms on surface integrity from SPD processing is largely unexplored, a particular emphasis …

Quantification Of Papillary Muscle Motion And Mitral Regurgitation After Myocardial Infarction, Connor R. Ferguson

Theses and Dissertations--Mechanical and Aerospace Engineering

Change in papillary muscle motion as a result of left ventricular (LV) remodeling after posterolateral myocardial infarction is thought to contribute to ischemic mitral regurgitation. A finite element (FE) model of the LV was created from magnetic resonance images acquired immediately before myocardial infarction and 8 weeks later in a cohort of 12 sheep. Severity of mitral regurgitation was rated by two-dimensional echocardiography and regurgitant volume was estimated using MRI. Of the cohort, 6 animals (DC) received hydrogel injection therapy shown to limit ventricular remodeling after myocardial infarction while the control group (MI) received a similar pattern of saline injections. …

A Computational Study Of Patch Implantation And Mitral Valve Mechanics, Dara Singh

Theses and Dissertations--Mechanical and Aerospace Engineering

Myocardial infarction (i.e., a heart attack) is the most common heart disease in the United States. Mitral valve regurgitation, or the backflow of blood into the atrium from the left ventricle, is one of the complications associated with myocardial infarction. In this dissertation, a validated model of a sheep heart that has suffered myocardial infarction has been employed to study mitral valve regurgitation. The model was rebuilt with the knowledge of geometrical changes captured with MRI technique and is assigned with anisotropic, inhomogeneous, nearly incompressible and highly non-linear material properties. Patch augmentation was performed on its anterior leaflet, using a …

Indoor-Wireless Location Techniques And Algorithms Utilizing Uhf Rfid And Ble Technologies, Ann M. Whitney

Theses and Dissertations--Mechanical and Aerospace Engineering

The work presented herein explores the ability of Ultra High Frequency Radio Frequency (UHF RF) devices, specifically (Radio Frequency Identification) RFID passive tags and Bluetooth Low Energy (BLE) to be used as tools to locate items of interest inside a building. Localization Systems based on these technologies are commercially available, but have failed to be widely adopted due to significant drawbacks in the accuracy and reliability of state of the art systems. It is the goal of this work to address that issue by identifying and potentially improving upon localization algorithms.

The work presented here breaks the process of localization …

Trade-Off Balancing For Stable And Sustainable Operating Room Scheduling, Amin Abedini

Theses and Dissertations--Mechanical and Aerospace Engineering

The implementation of the mandatory alternative payment model (APM) guarantees savings for Medicare regardless of participant hospitals ability for reducing spending that shifts the cost minimization burden from insurers onto the hospital administrators. Surgical interventions account for more than 30% and 40% of hospitals total cost and total revenue, respectively, with a cost structure consisting of nearly 56% direct cost, thus, large cost reduction is possible through efficient operation management. However, optimizing operating rooms (ORs) schedules is extraordinarily challenging due to the complexities involved in the process. We present new algorithms and managerial guidelines to address the problem of OR …