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Anxiolytic Intervention: Modulation Of Cell Types Due To Nicotine Withdrawal, Taylor Elder

Theses and Dissertations--Pharmacy

Nicotine use disorder (NUD) remains a leading cause of preventable disease, yet the neurobiological mechanisms underlying nicotine withdrawal are incompletely understood. Emerging evidence implicates neuroimmune signaling and astrocytic regulation of glutamate in shaping the withdrawal-associated affective phenotype. This dissertation investigated these processes using multiple nicotine administration paradigms including osmotic minipump implant, cigarette smoke exposure, and nicotine vapor inhalation to model diverse routes of human nicotine intake.

Chapter 2 examines the effects of these three modes of administration on neuroinflammation and validation of nicotine delivery. Nicotine exposure was confirmed through receptor [³H]Epibatidine nAChR binding assay and serum cotinine measurements. …

Investigating The Role Of Dynamic Signaling Of Nrg3-Erbb4 In The Prefrontal Cortex In Mediating Nicotine Withdrawal Phenotypes, Emily Prantzalos

Theses and Dissertations--Pharmacy

While several pharmacotherapies are currently available for nicotine use disorder (NUD), smoking cessation success rates remain below 10% each year. The molecular mechanisms underlying failed quit attempts continue to represent a critical gap in our knowledge. However, recent advances in understanding the genetic contributions to nicotine dependence offer a promising avenue for developing more effective cessation therapies. Prior research has identified genetic variation in Neuregulin 3 (Nrg3) and its cognate receptor ErbB4 as potential contributors to affective nicotine withdrawal (WD) phenotypes and cessation outcomes. Therefore, this dissertation aims to systematically investigate the region-specific, functional role of the Neuregulin Signaling Pathway …

Leveraging Transcriptomics And Behavior To Investigate Potential Neuronal And Glial Drivers Of Substance Use Disorder Endophenotypes, Jack V. Keady

Theses and Dissertations--Pharmacy

Over 54 million Americans needed substance use treatment in 2023. While there are many facets of substance use disorder, two major issues of interest are the negative reinforcing aspects of substances of abuse, manifesting in part as withdrawal symptomologies, and why a subset of people who use substances of abuse escalate to a use disorder. Nicotine exposure models were used to investigate the mechanisms of withdrawal endophenotypes, as smoking is the leading cause of preventable death in the United States, and a fentanyl self-administration model was used to probe individual differences in escalation phenotypes, as 80% of overdose deaths in …

The Impact Of Maternal Environmental Exposures On The Immune Landscape Of The Maternal-Fetal Interface, Heather E. True

Theses and Dissertations--Pharmacy

Maternal environmental exposures and inflammation are known to impact fetal development in utero as well as increase the risk for chronic diseases later in life. Therefore, it is essential that we understand how the maternal environment alters placental structure and immune function.

Therefore, we isolated fetal (chorionic villous) tissues from the placentas of healthy pregnant participants (control) and those with inflammatory conditions, including SARS-COV-2 infection, pregravid obesity, and opioid use disorder. Isolated placental leukocytes were subjected to a series of assays to uncover the phenotypic, functional, and transcriptional (single-cell RNA-sequencing) landscape of placental immune cells. Additional placental tissues were subjected …

Collision Avoidance Information System Utilizing Machine Learning Image Recognition, Michael W. Long

Theses and Dissertations--Mining Engineering

This thesis addresses significant safety challenges presented by powered haulage fatalities in underground mining by developing and evaluating a machine learning-driven Collision Avoidance Information System (CAIS). The research utilized a ZED 2i camera to capture both RGB and depth data for enhanced spatial awareness in visually limited underground environments. A specialized dataset of underground mining equipment was captured from limestone and zinc mines, annotated, and used to train a segmentation network. The CAIS was field-tested in diverse underground settings, achieving an accuracy of 82% in a limestone mine similar to the training data, but a lower accuracy of 45% in …

Temporal Machine Learning For Predicting Accidents And Violations In The Mining Industry, Nathan T. Kelley

Theses and Dissertations--Mining Engineering

This thesis examines the predictive capability of a temporal machine learning model for forecasting future accidents and violations at individual mines, based on historical data. Mine accidents were categorized by accident classification and violations were categorized by the Part Section. The primary datasets utilized were the mine safety and health administration’s (MSHA’s) Accident Injuries and Violations datasets. The available datasets were cleaned and organized by mine type and commodity, then divided into separate subsets for training, validating, and testing. Different models, cutoff metrics, learning rates, number of hidden layers, data processing methods, data processing divisions, number of points observed …

An Autonomous Robotic Inspection System For Underground Mines Using Unmanned Aerial Vehicles (Uavs), Kiazoa M. Joao

Theses and Dissertations--Mining Engineering

Underground mining environments pose unique safety challenges for workers due to poor visibility, unstable ground conditions, and the absence of GPS signals. To adhere to safety and health standards, underground mines are required to perform safety inspections regularly. Conventional safety inspections require personnel to enter the hazardous environment, highlighting the need for a safer, remote alternative. The use of UAVs for safety inspection in underground mines is a somewhat novel idea but has shown great promise. While Unmanned Aerial Vehicles (UAVs) cannot eliminate all hazards associated with mining, they provide critical support by accessing hazardous or restricted zones that are …

Simplified Molecular Diagnostics Methods For Environmental Testing Of Pathogens And Other Applications, Mohammad Dehghan Banadaki

Theses and Dissertations--Mechanical and Aerospace Engineering

Environmental Surveillance (ES) has emerged as a powerful tool to monitor the emergence and persistence of a pathogen within a facility or community using wastewater/water analysis. Over the past four years, implementation of ES has experienced an explosive acceleration, driven by efforts to monitor the spread of SARS-CoV-2, which has made ES a routinely used public health tool in many locations. We can now use ES to measure the emergence/presence/abundance of different viruses (e.g., SARS-CoV-2, influenza, mpox), bacteria (e.g., E. coli, V. cholerae, antibiotic-resistant strains), fungi (e.g., C. auris), and other biological markers indicative of infectious diseases. However, its broad …

Acoustic Characterization Of A Quadcopter Using A Test Stand, Jared Schmal

Theses and Dissertations--Mechanical and Aerospace Engineering

Unmanned Aerial Vehicles (UAVs) with multirotor propulsion and control, commonly called drones or multicopters, generate a complex acoustic field that is not entirely understood. Many components and their interactions contribute to the overall noise level and behavior of the acoustic field. However, performing acoustic measurements on a multicopter in a confined space, such as a small anechoic chamber, can be an extremely difficult and time-consuming process. A test stand was developed to allow for rapid and safe acoustic measurements in a controlled environment. The design, development, and initial measurements are discussed. The performance and acoustic response are assessed to examine …

In-Situ Informed Modeling And Characterization Of Friction And Built-Up Edge In Machining Of Aerospace Alloys, Avery Hartley

Theses and Dissertations--Mechanical and Aerospace Engineering

Machining is by no means a new manufacturing process. However, it is separated from other traditional deformation processes by its extreme temperatures and strain rates. The function and life of a multitude of products and mechanical components are dependent on the material properties induced by changing the surface through machining. Furthermore, the tools used within machining are often expensive and material reserves are sparse. The understanding the mechanics of the machining process, especially related to the friction of the tool and workpiece, helps to further the life of tools and parts to minimize economic and environmental impact.

Current friction modeling …

High-Altitude Balloon-Launched Uncrewed Aircraft System Measurements Of Atmospheric Turbulence And Qualitative Comparison With Infrasound Microphone Response, Anisa Haghighi

Theses and Dissertations--Mechanical and Aerospace Engineering

This study explores the use of a balloon-launched uncrewed aircraft system (UAS) to measure atmospheric turbulence in the troposphere and lower stratosphere using both wind velocity measurements and infrasonic acoustic energy. The UAS, a glider configured for autonomous descent along a predefined trajectory, had on board, in situ sensors to capture thermodynamic and kinematic atmospheric parameters. Additionally, it carried an infrasonic microphone to evaluate its potential for remotely detecting clear-air turbulence by capturing infrasonic waves. The system’s performance was assessed over the course of three test flights conducted in New Mexico, USA, in 2021. The descent enabled high-resolution profiling, with …

The Dying Swan: How To Predict And Evaluate The Survival Rate And Longevity Of Small Dance Companies In The United States, Evemarie N. Bessenbach

Theses and Dissertations--Arts Administration

Smaller dance organizations are an integral component of the arts and culture sector in the United States, making valuable artistic, economic, and social contributions despite limited resources. They provide employment for professional artists, contribute to a region’s economic vitality, and increase accessibility to quality arts-related programming. However, there are numerous professional dance companies that have permanently closed these past ten years alone, such as Dance Theatre of Tennessee, Ballet Theatre of Indiana, and Missouri Ballet Theatre, to just name a few—all of which can be considered smaller dance organizations.

The purpose of this interdisciplinary, exploratory study is to address the …

Come Hell Or High Water: A Constructed Grounded Theory Of Disaster Preparedness In Nonprofit Arts Management, Leah D. Hamilton

Theses and Dissertations--Arts Administration

This dissertation study constructs a grounded theory of disaster preparedness in nonprofit arts management, a research area that is underrepresented in broader disaster science research, and underrecognized by US government emergency management policy. Using the Constructivist Grounded Theory methodology, this qualitative study involves a systematic document review of more than 20 years of US practices and standards related to arts preparedness in combination with a two-year inquiry using a purposive sample of nonprofit arts managers who have recently been affected, directly or indirectly, by disasters in the state of Kentucky. The findings and the subsequent Theory of Performative Preparedness provide …

Impact Of Hyperthermia And Mitomycin C On Heat Shock Proteins, Mismatch Repair Proteins, And Cytotoxicity In Colon Cancer, Anna M. Reagan

Theses and Dissertations--Clinical and Translational Science

Cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) is a treatment used for primary peritoneal malignancy or metastases, including colon cancer. We aimed to explore the effects of hyperthermia and/or mitomycin C (MMC) on mismatch repair (MMR) proteins and heat shock proteins (hsps) and the potential for post-HIPEC treatment with pembrolizumab treatment. Colon cancer cells were treated with hyperthermia and/or MMC for 90 minutes. Subcellular fractionation and immunofluorescent imaging were performed to identify protein abundance and localization of MSH2, MLH1, hsp70, and hsp27. Proteomics analysis was performed for HT29 cells. HT29 cells and patient-derived organoids (PDOs) underwent simulated HIPEC and treatment …

Early Adversity, Impulsivity, And Health Behaviors, Amy Lynn Meadows

Theses and Dissertations--Clinical and Translational Science

Childhood trauma and early adversity are associated with a variety of negative health outcomes, some of which may be mediated by changes to impulsivity as described by the cumulative risk model. The purpose of this project is to provide insight into the effects of cumulative adverse childhood experience on impulsivity in various populations. Three studies examine the effects of early adversity on impulsivity in normal volunteers, parents caring for a child with medical needs, and in patients with diabetes or pre-diabetes with data collected through crowdsourcing. The strongest effects for early adversity on impulsivity were seen in the patients with …

Enhancing Public Health Surveillance: Development And Validation Of Machine Learning Models For Suspected Opioid Overdose Detection In Emergency Medical Services Data, Peter J. Rock

Theses and Dissertations--Clinical and Translational Science

The ongoing opioid overdose crisis in the United States requires timely and accurate surveillance systems to inform public health responses. Traditional public health surveillance methods rely on hospital discharge data and death certificates, which suffer from significant reporting delays and miss cases where patients refuse hospital transportation. Emergency Medical Services (EMS) data presents a promising alternative with advantages in timeliness and case ascertainment but lacks validated definitions for suspected opioid overdose (SOO).

This dissertation addresses this critical gap through the development, validation, and fairness assessment of machine learning models with natural language processing (ML-NLP) for identifying SOOs in EMS data. …

Exploring Healthcare Access In Telehealth Through Spanish-Speaking Patients’ Perspectives: A Scoping Review, Abigail J. Verst

Theses and Dissertations--Communication Sciences and Disorders

Background: Telehealth offers a potential solution to addressing access barriers experienced by Spanish-speaking patients. This scoping review aimed to explore whether a comprehensive view of healthcare access is being considered when creating telehealth programs for Spanish-speakers. The Conceptual Framework of Access to Healthcare (Levesque et al., 2013) was used to guide access analysis.

Methods: A literature search was conducted across three databases to identify empirical studies in the United States that reported Spanish-speaking patients’ perspectives of telehealth through quantitative questions. Data was collected from the included articles to characterize the type of healthcare providers and telehealth modalities examined in the …

Holding Space For Two Truths: Thematic Analysis Of Speech Language Pathologists’ And Teachers’ Philosophies And Practices In Reading Comprehension, Ryan Foote

Theses and Dissertations--Communication Sciences and Disorders

Introduction: Reading is a doorway to life participation. Only about one-third of fourth graders have read at grade level for the last three decades. Multiple views on what constitutes skilled reading emphasize decoding and greater variability among comprehension-related skills. Scarborough’s Reading Rope is the most specific in defining discrete skills necessary for adequate reading comprehension. This study aims to understand how elementary-level general education teachers and speech-language pathologists define “reading comprehension” and describe their practices in assessing and developing these skills. Methodology: Elementary school speech-language pathologists and teachers were interviewed about their conceptualizations and applications of the discrete skills in …

Practicing Clinicians' Views Of The Life Participation Approach To Aphasia Therapy, Stephanie H. Mays

Theses and Dissertations--Communication Sciences and Disorders

The Life Participation Approach to Aphasia therapy (LPAA) aligns with a person-centered, functional approach to speech therapy. Past research has demonstrated that persons with aphasia (PWA) benefit from this approach and prefer it when compared to the traditional medical model to therapy. However, a disconnect between PWA preferences and SLP treatment approaches in therapy persists. This study aims to identify both barriers and facilitators that SLPs face when implementing LPAA. Five CCC-SLPs practicing in the state of KY with experience working with PWA were recruited as participants. Participants were placed into two focus groups, with each group meeting for 2-3 …

M1 Macrophage-Engineered Vesicles Have Anti-Cancer Activity In Ovarian Cancer, Connie Du Cao

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer typically presents at an advanced stage, has a poor prognosis, and is a leading cause of cancer-related deaths in women. Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles that function in specific cell-to-cell communication and are under development as novel drug delivery vehicles and modulators of the tumor microenvironment. Artificial cell-derived vesicles (ACDVs) derived from M1 macrophages are able to repolarize M2 macrophages to the M1 phenotype and target tumor cells in in vitro studies.

In this study, we generated engineered EVs (EEVs) by membrane disruption of M1 macrophages (MEVs) in the presence and absence of cisplatin to generate …

Zebrafish Models To Uncover Targetable Mechanisms Of Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Relapsed T-cell Acute Lymphoblastic Leukemia (T-ALL) patients have dismal prognosis, with 5-year overall survival rates of 10% for adults and 36% for children. Relapse is attributed to the inability of chemotherapy agents to eliminate Leukemia Stem Cells (LSCs) that can repopulate the leukemia. Those cells exist with a unique genetic, transcriptomic, and metabolic profile compared to the rest of the leukemia and thus, finding targeted therapies toward this population of cells can result in disease eradication and elimination of relapse. However, investigating LSCs is challenging-particularly in T-ALL- for two reasons: 1) the lack of robust surface markers that define LSCs …

Cell-Type Specific Apoe4 To Apoe2 ‘Switching’ In Astrocytes And Microglia Alters Alzheimer’S Disease Neuropathology, Lesley R. Golden

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). APOE exists in three common protein isoforms throughout the population: ApoE2 (E2), ApoE3 (E3), and ApoE4 (E4). While APOE allele frequencies and the degree of AD-associated risk vary across different ethnic groups, when compared to the ‘neutral’ and most common E3 allele, the E4 allele confers up to a 33-fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by up to 67%. Here, we aimed to determine the therapeutic potential of cell-type specific APOE allele ‘switching’ and explore …

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …

Biochemical Properties Of Cardiac Sarcomeres In Human Heart Failure, Austin Grey Wellette-Hunsucker

Theses and Dissertations--Physiology

Heart failure (HF) exhibits considerable heterogeneity, posing significant challenges for research involving human cohorts. Diastolic dysfunction is a common pathophysiological feature; however, its molecular mechanisms remain incompletely elucidated. Sarcomeric proteins are integral to cardiac contraction and relaxation. Nonetheless, the phosphoproteome and the structural remodeling effects of these proteins on diastolic function within the context of HF have not been comprehensively characterized. This study examined sarcomeric modifications in diastolic dysfunction in human HF, focusing on Dilated and Ischemic HF, with non-failing donor hearts as controls. Analyzing myocardial samples from ~150 patients using electrophoretic and biochemical techniques, it found significant titin remodeling …

Development And Clinical Validation Of Automated Same-Day Stereotactic Treatment Procedures For Multiple Brain Metastases And Recurrent Head And Neck Cancers, Shane Mccarthy

Theses and Dissertations--Radiation Medicine

As technology advances, more and more cancer patients are benefiting from the use of stereotactic radiosurgery and radiotherapy (SRS/SRT) to treat their disease. One such technology, Varian’s HyperArc high-definition radiosurgery module, a tool to help facilitate the treatment of brain metastases on a medical linear accelerator (LINAC), has been demonstrated to achieve comparable low dose spillage and target conformity compared to the current gold standard for intracranial malignancies, the Elekta Gamma Knife. Furthermore, due to HyperArc’s single-isocenter multiple lesion approach, the treatment can be delivered in a significantly shorter amount of time. Unfortunately, the manual process of creating these stereotactic …

Assessing The Effectiveness Of A Modified Cook Together Eat Together Program On Food Resource Management Behaviors In A Rural Setting, Johanna K. Poysti

Theses and Dissertations--Nutrition and Food Systems

This study evaluated the effectiveness of a modified, hybrid Cook Together, Eat Together (CTET) program on food resource management behaviors in a rural setting. A six-week intervention combining virtual and in-person sessions aimed to improve health behaviors, food resource management skills, and self-efficacy. Although most behavioral changes were not statistically significant, participants reported increased confidence in cooking healthy meals on a budget. Positive qualitative feedback from focus group discussions indicated program feasibility and engagement. Strengths and limitations of the study were discussed as well as recommendations for future research were given.

Therapist Perspective Of Therapeutic Alliance And Treatment Outcome In Systemic Psychotherapy, Benjamin Larkin Mize Patterson

Theses and Dissertations--Family Sciences

One of the most robust findings in psychotherapy outcome research has been the relationship of a strong therapeutic alliance with improvement in treatment. Most research, however, has measured therapeutic alliance from the client’s point of view, disregarding the therapist’s perspective of this phenomenon. In this naturalistic study of adults in systemic individual, couple, or family psychotherapy (N = 627), both client- and therapist-ratings of alliance were assessed for their associations with treatment outcomes. Multilevel modeling was employed to analyze data from the Marriage and Family Therapy Practice Research Network (MFT-PRN). Client-ratings of the therapeutic alliance and general functioning/relationship satisfaction …

Dinotefuran Resistance In The German Cockroach (Blattella Germanica L.), Hannah F. Blevins

Theses and Dissertations--Entomology

German cockroaches (Blattella germanica L.) are one of the most prevalent and pervasive indoor pest species in the world. Infestations can lead to many negative impacts on humans, including sensitization to allergens, increase in asthmatic symptoms, mental health declines, and potentially, the spread of diseases. While insecticides remain the most effective and affordable option for German cockroach control, resistance to many commonly used insecticide active ingredients (AIs), such as pyrethroids, has been observed globally at high levels across different populations. Given such resistance to pyrethroids, inclusion of insecticides with alternative modes of action into insecticidal treatments could potentially improve cockroach …

Bed Bugs: Health Risks And Control, Simona Principato

Theses and Dissertations--Entomology

Bed bugs are blood-feeding hemipterans strongly associated with humans. Their detection in indoor environments, such as homes, hotels, trains, and public facilities, has increased gradually over the past 20 years. The exact cause of their resurgence is still unclear, but the increase of international travel and insecticide resistance are thought to have contributed to it.

Although bed bugs are not known to transmit diseases, the EPA, CDC, and USDA have classified them as a pest of significant public health concern, mainly due to the dermatitis that they can cause. Beyond the dermatological burden of the bites, other health implications often …

Family And Social Factors In Emotion Regulation And Adjustment In Adolescents, Julia J. Morgan

Theses and Dissertations--Family Sciences

Adolescents face many challenges during this unique phase of development. Because of this, it is important to identify how to promote resilience and positive adjustment for these individuals. The present dissertation includes three studies which focused on familial and social factors in promoting emotion regulation and ultimately adjustment among middle and late adolescents.

The first study focused on the importance of alexithymia in the relationships between closeness and communication and internalizing problems, namely depression, anxiety, and self-esteem. Results showed that closeness was negatively associated with depression and positively associated with self-esteem. Communication was not associated with any of the studied …