Digital Commons Network^™

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Three Essays On Trade, Environment, And Health, Sookti Chaudhary

Theses and Dissertations--Economics

My dissertation consists of three essays on trade, environment and health. The first essay empirically evaluates domestic facilities' environmental response to Chinese import competition in the United States (US) manufacturing sector from 2000 to 2010. Using facility-level data on chemical emissions and employing an instrumental variables approach, the paper finds that industry/regional exposure to increased import competition had very little impact on the environmental decisions of domestic facilities.

The second essay empirically explores a possible link between the environmental justice efforts during the Obama administration and the change in environmental inequity by examining the change in US facilities' underlying environmental …

Three Essays On The Economics Of Education Expansion, Xiaozhou Ding

Theses and Dissertations--Economics

My dissertation consists of three essays that study the unintended consequences of education policies. The first two essays examine the impact of higher education expansion in China on household saving rate and individual migration rate. The third essay looks into the impact of a school redistricting plan and the construction a new school on housing prices in Fayette County, Kentucky.

In the first essay, I utilize the large national expansion on higher education in China which exogenously increase the enrollment of college students, to estimate the induced change in the expected college probability and how it affects saving rates for …

Semiparametric And Nonparametric Methods For Comparing Biomarker Levels Between Groups, Yuntong Li

Theses and Dissertations--Statistics

Comparing the distribution of biomarker measurements between two groups under either an unpaired or paired design is a common goal in many biomarker studies. However, analyzing biomarker data is sometimes challenging because the data may not be normally distributed and contain a large fraction of zero values or missing values. Although several statistical methods have been proposed, they either require data normality assumption, or are inefficient. We proposed a novel two-part semiparametric method for data under an unpaired setting and a nonparametric method for data under a paired setting. The semiparametric method considers a two-part model, a logistic regression for …

Nonparametric Analysis Of Clustered And Multivariate Data, Yue Cui

Theses and Dissertations--Statistics

In this dissertation, we investigate three distinct but interrelated problems for nonparametric analysis of clustered data and multivariate data in pre-post factorial design.

In the first project, we propose a nonparametric approach for one-sample clustered data in pre-post intervention design. In particular, we consider the situation where for some clusters all members are only observed at either pre or post intervention but not both. This type of clustered data is referred to us as partially complete clustered data. Unlike most of its parametric counterparts, we do not assume specific models for data distributions, intra-cluster dependence structure or variability, in effect …

Residential Radon Exposure, Its Contribution To Lung Cancer, And Social Determinants Of Radon Testing, Stacy Stanifer

Theses and Dissertations--Nursing

Lung cancer is a highly preventable form of cancer. Cigarette smoking is the leading cause of lung cancer followed by radon gas exposure and exposure to secondhand smoke. Kentucky leads the nation in both incidence and mortality from lung cancer. Tobacco use in Kentucky continues to be a major public health concern as nearly one-quarter of adults report current tobacco use and just over one-third of Kentucky homes with children lack rules which prohibit smoking in the home. Radon, a colorless, odorless radioactive gas, occurs naturally from the decay of uranium found in rocks and soil and is harmful when …

Associations Between Psychosocial Stressors, Genes, And Cardiovascular Disease In At-Risk Adults, Kaitlin Voigts Key

Theses and Dissertations--Nursing

Psychosocial stressors have a significant adverse impact on cardiovascular health. While better medical treatments and increased emphasis on healthy lifestyle have improved cardiovascular health for many in the United States over the past 50 years, there are persistent inequities in cardiovascular disease (CVD) rates, with the highest rates among populations burdened by chronic exposure to psychosocial stressors such as discrimination and anxiety, among others. Genetic factors may interact with these stressors further influencing the rates of CVD in these populations. The purpose of this dissertation is to examine associations among psychosocial stressors and other CVD risk factors, and the influence …

Tobacco Use And Nicotine Withdrawal Among Patients With Mental Illness, Yazan Daher Al-Mrayat

Theses and Dissertations--Nursing

People with mental illness (MI) are disproportionately affected by tobacco use compared to the general population. In fact, it is estimated that people with MI consume approximately 44% of cigarettes smoked in the United States. Moreover, the MI population is at greater risk for the negative social, economic, and health consequences associated with tobacco use and are reported to have 25-year shorter life expectancies than the general population. The impact of tobacco use is further noticeable among patients with MI who require psychiatric hospitalization. Quitting smoking in this population has been linked to fewer discharges against medical advice, better quality …

Establishing Exclusive Breastfeeding And The Influence Of Hospital Support, Martha Monroe

Theses and Dissertations--Nursing

Maternal-child health authorities recommend that infants breastfeed exclusively for the first six months of life. Currently, 25% of infants in the United States do so. Breastfeeding specific care that mothers receive from their postpartum nurses and lactation specialists is integral to successfully initiating exclusive breastfeeding. Due to the time sensitive nature of establishing milk supply, interrupting the process of lactogenesis with supplementation puts infants at high risk for early termination of breastfeeding. The purpose of this dissertation is to examine the relationship of breastfeeding care received during the postpartum hospital stay, defined as the first 48-72 hours of life, and …

Responses To Symptoms Among Patients With Heart Failure, Chin-Yen Lin

Theses and Dissertations--Nursing

Patients with heart failure (HF) suffer from chronic and progressive symptoms. Failure to respond appropriately to escalating symptoms of HF causes a delay in seeking care, which results in worse symptom status, frequent rehospitalizations, and contributes to higher mortality. In order to enhance HF self-care, promote timely care-seeking, and improve outcomes, identification of factors that affect patients’ responses to symptoms and their decisions to seek care is essential. Thus, the purposes of this dissertation were to (1) identify factors associated with patients’ responses to worsening HF symptoms, and (2) determine the impact of responses to symptoms on outcomes in patients …

It Matters Who You Live With. The Relationship Of Living Arrangement And Medication Adherence In Patients With Heart Failure, Rana Lindsay-Rahman

Theses and Dissertations--Nursing

Medication adherence is an ongoing challenge for patients with heart failure (HF) that can adversely affect mortality, morbidity, and quality of life. Living with a spouse has been associated with better adherence while living alone has been associated with poor adherence. Other factors demonstrated to affect adherence include medication complexity, perceived barriers to adherence, and depressive symptoms. Interestingly, the effect of these latter factors on adherence has not been examined in the context of the patient’s living arrangement. The purpose of this dissertation was to investigate the relationships among medication complexity, perceived barriers, and depressive symptoms with medication adherence across …

Meaningful Measurement Matters: Defining Potentially Inappropriate Medication Use To Target Cognitive Outcomes, Ashley I. Martinez

Theses and Dissertations--Pharmacy

Preventable and unintended consequences of medication use occur in more than 25% of ambulatory and hospitalized patients, and nearly half of long-term care patients. Unfortunately, many medications used to treat common health conditions in older adults (such as anxiety, behavioral disturbances, incontinence, insomnia, depression, and pain) have also been linked to cognitive impairment and decline. Recently, substantial efforts to investigate medications and medication classes that may be associated with cognitive impairment and decline in older adults have been undertaken. Unfortunately, studies have used a wide variety of different tools to define “potentially inappropriate medication” (PIM) use, and no published literature …

Relationship Between Initial Prescription Opioid Exposure Length And Future Opioid Use Disorder Diagnosis In Opioid Naive Adolescents, Eric Lindahl

Theses and Dissertations--Pharmacy

Objectives: The long-term risks associated with the use of short-term prescription opioids in opioid naïve adolescents in not well characterized. The purpose of this study was to explore the potential association between the days’ supply of the initial prescription opioid exposure and the rates of diagnosed OUD in the subsequent 3-year period. Methods: We conducted a retrospective cohort study using a nationwide database of commercially-insured adolescents aged 12-17 at the time of the index opioid fill. A multivariable Cox Proportional Hazard regression model was developed to analyze the association of interest while accounting for known risk factors for the development …

The Impact Of Bone Marrow Transplantion On Patients With Psychiatric Diagnoses: Medication Adherence Assessment, Brittany Galop

Theses and Dissertations--Pharmacy

Objectives: We investigated whether there is a measurable difference in medication utilization for psychiatric conditions before and after bone marrow transplantation (BMT). Previous studies have identified a potential association between psychiatric conditions and immune function. We hypothesized that medication utilization for psychiatric diagnoses would be impacted by BMT.

Methods: This study was a retrospective, quasi-experimental cohort design. De-identified data was compiled from the Truven database for patients ranging from January 2009 through December 2016. Two measurements of medication utilization, proportion of days covered (PDC) and medication possession ratio (MPR) were calculated for each included Medispan-defined class of medications before analyzing …

Antiresorptive Bone Therapy Use In Advanced Lung Cancer And Associated Outcomes, Noor Naffakh

Theses and Dissertations--Pharmacy

Background/Rationale: Studies have shown antiresorptive agents decrease skeletal related events in metastatic non-small cell lung cancer. However, two prevalence studies have found low utilization rates of antiresorptive therapy in advanced lung cancer. The first study reported a rate of 14.8% during the 1995-2009 time period, while the second study reported a 33% usage rate during the time frame of 2002-2011. We believe these low utilization rates are associated with the poor prognosis of these patients. The prognosis of advanced lung cancer has improved significantly since these trials were conducted, and the utilization of denosumab has not been evaluated. We hypothesize …

Population Pharmacokinetic Modeling And Genetic Association Analysis In Infants With Neonatal Abstinence Syndrome Receiving Morphine Or Clonidine, Fei Tang

Theses and Dissertations--Pharmacy

Neonatal abstinence syndrome, or NAS, is a postnatal opioid withdrawal syndrome occurring in 55% to 94% of neonates as a result of in utero exposure to opioids. It has emerged as a significant public health issue, as its incidence more than quadrupled in the past decade. There is significant variability in disease severity and treatment outcomes in neonates with NAS due to patient-specific factors and treatment- or site-specific factors. To understand what contributes to variability in length of hospital stay and other outcomes in neonates with NAS, we assessed population pharmacokinetics (PK) of clonidine and morphine, and we investigated potential …

Extensively Drug-Resistant Pseudomonas Aeruginosa In Vitro Susceptibility And Mechanisms Of Resistance, Chanah Gallagher

Theses and Dissertations--Pharmacy

Pseudomonas aeruginosa causes severe healthcare-associated infections. Forty-eight extensively drug-resistant (XDR)-P. aeruginosa isolates were selected from 287 isolates collected for evaluation based on clinical susceptibility data. In vitro activity of commonly utilized antimicrobials (i.e. antipseudomonal beta-lactams, aminoglycosides, fluoroquinolones, and polymyxins) plus ceftolozane-tazobactam, ceftazidime-avibactam, and aztreonam-avibactam against XDR-P. aeruginosa were determined. The mechanism of resistance profile was determined through phenotypic expression analysis. Overall, polymyxin B and colistin were 100% susceptible. Apart from the polymyxins, ceftolozane-tazobactam had the highest susceptibility (94%) followed by ceftazidime-avibactam (90%) and amikacin (83%). Ceftolozane-tazobactam activity was not significantly different from ceftazidime-avibactam (p=0.6831). Only 40% of isolates …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

Novel Small Molecule Antifungals For Invasive Fungal Infections, Emily Dennis

Theses and Dissertations--Pharmacy

Human fungal pathogens cause a range of diseases from benign skin conditions (i.e., ringworm) to thrush, mucosal membrane infections, and life-threatening systemic infections including bloodstream infections (i.e., aspergillosis and candidiasis) and Cryptococcal meningitis. These systemic infections occur most often in immunocompromised individuals and have high mortality rates. Current antifungal agents used in the clinic belong to three main classes: the polyenes (e.g., amphotericin B (AmB)), the echinocandins (e.g., caspofungin (CFG)), and the azoles (e.g., fluconazole (FLC)). In addition, the antimetabolite pyrimidine analogue flucytosine is used in combination with AmB. The …

Characterization And Engineering Of Interrupted Adenylation Domains, Taylor A. Lundy

Theses and Dissertations--Pharmacy

Nature has historically served as a prolific source of biologically active molecules produced by plants, fungi, and bacteria termed natural products (NPs). These NPs often serve as therapeutic leads due to their structural diversity and unique mechanisms of action. However, many need modifications to make them more effective or safer for human use. This can be a daunting and complicated task to do via traditional organic chemistry because of their complexity, copious stereocenters, and a multitude of reactive functional groups. For this reason, enzymatic modification of these NP during their biosynthesis is an appealing option. One major class of NPs …

Opioid Use In Vulnerable Populations, Gyeon Oh

Theses and Dissertations--Epidemiology and Biostatistics

Opioid-related negative health outcomes, such as substance use disorder, misuse, and overdose deaths, have risen as long-term opioid use has increased. The benefit of using long-term opioids for pain is yet to be established. The Centers for Disease Control and Prevention provides guidelines for opioid prescribing in chronic pain, but detailed recommendations on opioid prescribing for vulnerable populations are missing due to lack of evidence-based studies. The purpose of this dissertation is to describe patterns and predictors of opioid use and assess outcomes related to prescribing opioid medications in vulnerable populations, specifically older adults with various levels of cognitive function, …

Olmstead Mandated Statewide Implementation Of Assertive Community Treatment: Precipitating Factors And Participant Experiences, Elizabeth Nelson-Cooke

Theses and Dissertations--Social Work

Evidence-based practices for individuals with serious mental illness have not been widely implemented in United States public mental health systems. Mental health advocates have used the Supreme Court’s Olmstead decision to force states with underfunded community mental health services to develop more robust treatment systems. Using a case study, this article-based dissertation examines the process of mandated widespread implementation of Assertive Community Treatment (ACT) in Kentucky through the experiences of individuals involved in ACT creation and documents related to implementation and the state mental health system. Study 1 identifies precipitating factors to the Kentucky Olmstead settlement agreement that contributed to …

Investigating Whether Ecological Models Of Community-Oriented Variables Improve Prediction Of Childhood Resilience Over A Set Of Personal Characteristic Variables Such As Impulse Control, Emotional Regulation, Relational Motivation, And Self-Reliance, Vinod Kumar Srivastava

Theses and Dissertations--Social Work

Children experiencing trauma and entering child protective services have been continuously increasing. Problems associated with childhood trauma, such as neurodevelopmental disorder, trauma and stress-related disorders, personality disorders, substance use disorder, externalizing and internalizing disorders, academic problems, relational difficulties, and delinquent behaviors, have been found increasing despite advances in trauma and translational research. Children’s trauma is mostly interpersonal in nature and nested in their immediate environment. There is a need for a change in focus from helping children to overcome challenges and adversities to strengthening the resilience-building process by utilizing functional strengths in the environment to achieve sustainable outcomes. This study’s …

Embodying Inequality: Three Papers On The Role Of Gender And Discrimination In The Lives Of Women, Stefana I. Moldovan

Theses and Dissertations--Social Work

Women experience different forms of discrimination throughout their lives such as unfair treatment in interpersonal interactions in the public spheres and in the private sphere, as prescribed by societal gender roles, women can also experience inequality and discrimination as a disproportionate share of household work and caregiving, limited participation in decision making, unequal access and share of financial resources and leisure, and as well as in cases, of emotional, and physical, or sexual abuse. Limited research explored the potential joint effect of these forms of discrimination. The questions explored in this dissertation were: (1) How does gendered intra-household inequality, experienced …

National Guard Members With Suicide Ideation: The Impact Of Stigma, Mental Health, And Trauma History On Treatment-Seeking Outcomes, Amy Brown

Theses and Dissertations--Social Work

Background. Veterans are overrepresented among suicide deaths in the United States, representing 20% of annual suicide deaths but only about 1% of the U.S. population (Department of Veteran Affairs, 2010). Of all military suicide deaths in 2016, one-third (33.4%) were in the National Guard or Reserves (Department of Defense, 2018). Previous suicidal ideation or behavior (SIB) has been shown to increase risk of subsequent ideation or behavior in both active duty and veteran samples (Bryan, Rudd, & Wertenberger, 2016; Hazlett et al., 2016) but studies of SIB specific to National Guard service members were not found.

Access and Barriers to …

Investigation Into Mine Pillar Design And Global Stability Using The Ground Reaction Curve Concept, Ravi Chandan Ray

Theses and Dissertations--Mining Engineering

Pillars form an important support structure in any underground mine. A bulk of the overburden load is borne by the mine pillars. Thus, the strength of pillars has been a subject of detailed research over more than 6 decades. This work has led to the development of largely empirical pillar design formulations that have reduced the risk of pillar failures and mine collapse. Current research, however, has drawn attention to the fact that some of the assumptions used in the development of conventional pillar design methodologies are not always valid. Conventional pillar design methodology assumes that the pillars carry the …

Numerical Approximation Of The Ground Reaction And Support Reaction Curves For Underground Limestone Mines, Jesus Castillo Gomez

Theses and Dissertations--Mining Engineering

Pillar stability has been a matter of study for the last 70 years. The determination of pillar strength had taken different solutions and approaches over that time. This research has led to numerous empirical formulations that have reduced the number of pillar failures worldwide. However, new numerical approaches are being studied. In the last 20 years, the Ground Reaction Curve concept has been examined as a way of understanding the convergence of the rock-mass. Although the Ground Reaction Curve was first introduced in the civil tunneling industry, several authors have introduced the Ground Reaction Curve concept as an approach for …