Digital Commons Network^™

Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie

Theses and Dissertations

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …

Spillover Theory: Unintended Consequences Of Provisions In The Affordable Care Act, Robert T. Braun

Theses and Dissertations

Objective: To examine spillovers from a federal policy, managed care market, and community perspective.

Data Sources/Study Setting: We studied spillovers from a federal policy and managed care market perspective using the Health Care Utilization Project’s (HCUP) State Inpatient Database (SID). American Hospital Association (AHA) data, Interstudy Commercial Managed Care, and Area Health Resource File (AHRF). Medicare Advantage county-level payment schedules originate from CMS. We examined community uninsurance spillovers using 2011-2015 Medical Expenditure Panel Survey (MEPS), the Area Health Resource File (AHRF), and the Small Area Health Insurance Estimator (SAHIE).

Study Design: Ordinary Least Squares (OLS) and difference-in-difference regression analyses were …

Outcomes Associated With The Utilization Of Antidepressants And Psychotherapy Amongst Cancer Patients With Depression, Purva N. Parab

Theses and Dissertations

Objective: To determine patterns of use, prescription medicine costs, office-based visit costs and quality of life (QOL) across classes of antidepressants/psychotherapy in elderly cancer patients. Methods: Medical Expenditure Panel Survey data files from 2005-2015 for cancer patients with depression aged 18 years or older were used for the study. Frequencies of patients under specific classes of antidepressants/psychotherapy were identified. Costs and QOL scores were compared using Analysis of Variance (ANOVA). Generalized linear models, linear/multinomial logistic regression were used for analyses adjusted for demographics, overall health status, number and type of comorbidities. Results: The study sample consisted of 17,671 cancer patients …

Mass Spectrometry-Based Proteomics Analysis Of Secreted Proteins, Emmanuel K. Cudjoe Jr

Theses and Dissertations

Secreted proteins play important roles in many cellular functions and molecular processes. Because secreted proteins potentially enter the blood stream, they can serve as valuable measures of health and disease useful for disease diagnosis and prognosis, therapeutic target identification, and patient stratification in personalized medicine. Consequently, significant interest exists in secreted protein analysis within complex biospecimens, particularly blood but significant bioanalytical challenges including the wide protein dynamic range >10 orders of magnitude remain. The cellular secretome therefore represents a viable alternative to direct biomarker discovery in biofluids. Finally, cellular systems are amenable to labeling for the production of intact stable …

Housing Status, Patient Characteristics, And Ed Utilization Associated With Medication Prescribing At Ed Discharge Among Homeless And Nonhomeless Adults In Urban Hospitals In The United States, Lauren Cox

Theses and Dissertations

This cross-sectional study used a weighted sample of ED visits contained in the 2010-2015 years of the National Hospital Ambulatory Care Survey-Emergency Department (NHAMCS-ED) dataset. The purpose of this study was to: 1) identify differences in predisposing, enabling, and need characteristics, and ED use and medication prescribing characteristics between homeless and nonhomeless ED users; 2) assess the association between housing status and medication prescribing at ED discharge, and identify variables contributing to the disparity in medication prescribing between homeless and nonhomeless ED users; and 3) assess the predisposing, enabling, need, and ED use characteristics that predict medication prescribing at ED …

Metal-Organic Frameworks And Graphene-Based Support Materials For Heterogeneous Catalysis, Andrew Lin

Theses and Dissertations

Nanoparticles are involved in a broad range of applications, including heterogeneous catalysis. Nanoparticles tend to quickly lose their well-defined shapes and facets due to aggregation under duress such as heat.

A series of highly studied materials are explored as support materials for nanoparticle supports. These supports include metal-organic frameworks (MOF), graphene oxide (GO), and a MOF-PRGO (partially reduced graphene oxide) hybrid. The inclusion of a support with the palladium increased lifespan of the catalyst by separation of nanoparticles. The choice of support material not only allowed for supporting of palladium nanoparticles, but allowed for rational catalyst synthesis in order to …

Integral Measurement Of Atmospheric Particulate Matter (Pm), Di Liu

Theses and Dissertations

Atmospheric aerosol particles also known as atmospheric particulate matter or particulate matter (PM) are microscopic particles (solid or liquid) suspended in air, which is one of six air pollutants in US air quality standard. PM is classified as coarse particles with diameters between 2.5 to 10 mm, fine particles with a diameter less than 2.5 mm (PM_2.5), and ultrafine particles with the diameter less than 0.1 mm (PM_0.1). Epidemiological studies have already showed the adverse health effects (such as asthma, lung cancer and respiratory and cardiovascular disease) resulted from exposure to the fine and ultrafine particles. …

Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin

Theses and Dissertations

The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On …

In Vitro Genetic Code Expansion And Selected Applications, Emil S. Iqbal

Theses and Dissertations

The ability of incorporation non-canonical amino acids (ncAAs) using translation offers researchers the ability of extend the functionality of proteins and peptides for many applications including synthetic biology, biophysical and structural studies, and discovery of novel ligands. Here we describe the three projects where the addition of ncAAs to in vitro translation systems creates useful chemical biology techniques. In the first, a fluorinated histidine derivative is used to create a novel affinity tag that allows for the selective purification of peptides from a complex mixture of proteins. In the second, the high promiscuity of an editing-deficient valine-tRNA synthetase (ValRS T222P) …

Investigating Racial Bias In Perceptions Of Free Will, Courtney J. Alderson

Theses and Dissertations

The overarching goal of this study was to examine whether perceptions of others’ free will would differ depending on perceiver race as well as target race. The current study proposed that such a racial bias may be one mechanism by which racial disparities in medical treatment recommendations arise. By bridging findings from four different lines of research (i.e., the literatures on racial health and medical treatment disparities, racial bias, free will beliefs, and social identity), it was hypothesized that: (1) participants would perceive greater amounts of free will for a hypothetical racial ingroup patient than an outgroup patient; (2) such …

An Investigation Of Electronic Cigarette Aerosol Mixture On Craniofacial Development In Mouse Embryos, Suraj Kandalam

Theses and Dissertations

E-cigarette (e-cig) use has increased in recent years among teenagers and young adults. E-cigs are battery-powered nicotine delivery systems that vaporize e-liquids, a solution composed of propylene glycol (PG), vegetable glycerin (VG), nicotine, flavoring, and coloring agents. The aim of this study was to determine the effects of exposure to e-cig aerosol mixtures (e-cigAMs) on proliferation, migration, and differentiation of NCCs in vitro and craniofacial development in mouse embryos in vivo. E-cigAM was produced by bubbling e-cig aerosol into saline. E-cigAMs were generated for unflavored e-liquid of increasing PG: VG ratio. Metabolic activity (MA), gene expression, migration, and proliferation …

Elucidation Of Substrate Binding Interactions For Human Organic Cation Transporters 1 (Slc22a1) And 2 (Slc22a2) Using In Silico Homology Modeling In Conjunction With In Vitro Site-Directed Mutagenesis And Kinetic Analysis, Raymond E. Lai

Theses and Dissertations

The organic cation transporters (OCTs) play a critical role in the absorption, distribution and elimination of many drugs, hormones, herbal medicines, and environmental toxins. Given the broad substrate specificity of OCTs, they fall victim to the high susceptibility for contributing to harmful drug-drug interactions. Further defining how human (h)OCTs mechanistically bind to its broad array of substrates will provide significant insight to the understanding and prediction of drug-drug interactions in polypharmacy patients and the advancement of future rational drug design for therapeutics targeting OCTs. The goal of the current study was to elucidate the critical amino acid residues for transporter-substrate …

Perceived Financial Burden, Self-Management Behaviors, And Glycemic Control In Adults With Type 1 Diabetes, Megan Peter

Theses and Dissertations

People with type 1 diabetes must perform frequent self-management behaviors to maintain glycemic control. Those with higher diabetes distress tend to have worse glycemic control, indicated by higher A1C. Financial stress is common in adults with chronic diseases, but little is known about perceived financial burden in adults with type 1 diabetes or its associations with diabetes distress, self-management behaviors, or A1C. It is also unknown whether diabetes self-efficacy moderates the associations between perceived financial burden or diabetes distress with self-management behaviors.

Surveys were collected from 235 adults with type 1 diabetes. Structural equation modeling tested whether perceived financial burden …

Why Local Governments Collaborate: Perspectives From Elected Officials And Local Government Managers On Regional Collaboration, Stephanie D. Davis

Theses and Dissertations

This study examined the factors that influence a local government’s decision to engage in regional collaborations. Analysis of 7 local government managers and eleven elected officials revealed that the decision to engage in regional collaboration was influenced by external factors, organizational factors, and internal motivations. Elected officials and local government managers identified a disaster occurrence, fiscal stress, outside agencies, jurisdictional benefit, and communication as key factors. Further, this research highlights the importance of the role of the elected official in intergovernmental arrangements, the role of the local government manager as the policy entrepreneur, and the influence of shared norms and …

International Student Participation In Postsecondary U.S. English Language Programs, Valeriana Colon

Theses and Dissertations

Postsecondary English language education is a growing industry in the United States. While there has been considerable research on international student mobility in higher education, there is limited research on the population’s participation in U.S. English language programs (ELPs). The purpose of the study was to apply existing theories and data analysis to understand postsecondary English language program participation and create a foundation for future studies. This exploratory study examined the characteristics of international students enrolled in U.S. postsecondary ELPs. The researcher investigated the relationship between ELP enrollment with U.S. higher education enrollment as well as the relationship between ELP …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Communicating Colorectal Cancer Risk To Average Risk Adults: Examining The Impact On Risk Perceptions And Health Behavior Intentions, Carrie A. Miller

Theses and Dissertations

Background. CRC risk can be reduced though lifestyle modification and regular screenings. Providing CRC risk feedback that promotes preventive behaviors to those at average risk has the potential to significantly reduce CRC morbidity and mortality.

Purpose. The purpose of this dissertation was to examine the impact of CRC risk assessment feedback among adults aged 50-75 with no personal or family history of the disease. The specific aims were to: (1a) test personalized (vs. generic) risk assessment feedback on individuals’ risk perceptions and intentions to engage in three risk-reducing behaviors (e.g., physical activity, diet, and screening); (1b) determine if the provision …

Validation Of Virginia's Juvenile Risk Assessment Instrument, Jessica P. Schneider

Theses and Dissertations

Utilizing a validated risk assessment tool to predict future offending is recommended as best practices in corrections by a number of professional organizations (Latessa & Lovins, 2010). Guided by the risk-needs-responsivity model, risk assessment tools have evolved to help inform criminal justice practitioners by identifying offenders most in need of intervention or supervision, guiding the case plan to optimize outcomes (Bonta & Andrews, 2007). The Virginia Department of Juvenile Justice (DJJ) utilizes the Youth Assessment and Screening Instrument (YASI) at all stages of contact with youthful offenders, including intake, probation, commitment, and parole (DJJ, 2016). However, risk assessment instruments do …

Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks

Theses and Dissertations

Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14⁺⁺CD16^-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14⁺⁺CD16⁺) and non-classical (CD14^LowCD16⁺⁺) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression …

Discovering Driver Mutations In Biological Data, Yahya Bokhari

Theses and Dissertations

Background

Somatic mutations accumulate in human cells throughout life. Some may have no adverse consequences, but some of them may lead to cancer. A cancer genome is typically unstable, and thus more mutations can accumulate in the DNA of cancer cells. An ongoing problem is to figure out which mutations are drivers - play a role in oncogenesis, and which are passengers - do not play a role. One way of addressing this question is through inspection of somatic mutations in DNA of cancer samples from a cohort of patients and detection of patterns that differentiate driver from passenger mutations. …

Trna Profiling Of Mesenchymal Stem Cell Exosome, Khin Mimi San

Theses and Dissertations

Background: Exosomes have great potential in regenerative medicine through the

transfer of their bioactive cargos, such as RNA. tRF RNA and tiRNA are tRNAderived

non-coding RNA. Here, we sought to identify the tRF/tiRNA profile in human

mesenchymal stem cell (hMSC) exosomes. Methods: Bone marrow hMSCs were

cultured with/without osteogenic differentiation medium and exosomes were

harvested. RNA was extracted from: 1) control cells (Cell-NT); 2) control exosomes

(EXO-NT); 3) differentiated cells (Cell-OM); 4) exosomes produced by differentiated

cells (EXO-OM). RNA was sequenced to profile the small RNA with a focus on

tRF/tiRNA. Results: tRF/tiRNA was highly enriched in hMSC exosomes. Less …

Genomic Instability In Severe Congenital Neutropenia, A Leukemia Predisposition Syndrome, Adya Sapra

Theses and Dissertations

Severe congenital neutropenia (SCN) is a rare blood disorder characterized by abnormally low levels of circulating neutrophils. Mutations in multiple genes like neutrophil elastase gene (ELANE) and granulocyte colony stimulating factor receptor (CSF3R) may cause SCN. The treatment of choice for SCN is the administration of granulocyte-colony stimulating factor (G-CSF) which elevates the neutrophil count and hence improves the survival and quality of life. Long term survivorship on G-CSF is however linked to development of MDS (myelodysplastic syndrome)/AML (acute myeloid leukemia). About 70% of MDS/AML patients acquire nonsense mutations affecting the cytoplasmic domain of CSF3R. …

Integrating Obesity And Eating Disorder Prevention: A Pilot And Feasibility Trial Of Inspire, Courtney C. Simpson

Theses and Dissertations

Obesity and eating disorders are pervasive concerns among young adult women, and profoundly impact physical and psychological functioning. Weight-related disorders are typically chronic conditions; their treatment is often complex and frequently ineffective. Moreover, Black and Latina women have disproportionately high rates of obesity, and experience rates of eating disorders comparable to those of their White peers; yet, they are less likely to be referred to appropriate treatment. Given the intractability of weight-related concerns and their detrimental consequences, attempts to prevent unhealthy eating attitudes and behaviors are essential. To date, few prevention programs have significantly reduced both obesity risk and eating …

Predicting Arterial Oxygen Desaturation Events Via Patient Journal And Pulse Oximetry Data In Postoperative Ambulatory Surgery Patients, Charles R. Elam Iv

Theses and Dissertations

Associations between patient and procedural factors on the nature and quality of the immediate in-home recovery from anesthesia following ambulatory orthopedic surgery are unknown. Further, there is a paucity of outcomes research quantitatively categorizing in-home

patient recovery and safety following discharge from same-day orthopedic procedures. Tools are available, however, to shed light on outcomes in this population, and integration of such available measures is critical.

Ambulatory orthopedic surgery is a burgeoning specialty, with growth expected over the foreseeable future. The expected increased patient caseload subsequent to implementation of the Affordable Care Act and aging Baby Boom generation suggests greater morbidity …

The Experiences That Promote Success For Students With Intellectual Disability In Postsecondary Education, Kimberly S. Handsome

Theses and Dissertations

This in-depth qualitative, phenomenological (Smith & Fowler, 2009) research study attempted to understand the experiences of young adults with intellectual disability who had completed a 2-year, inclusive postsecondary education program. 13 participants (4 former students with ID, 5 parents, and 4 Postsecondary Education staff members) participated in semi-structured interviews. Interviews were coded to provide themes amongst each individual group of participants. A document review was also conducted to better understand the program components and add validity to self-reports from interviews. Results were analyzed and used to provide implications for future research and program development.

An Exploration Of Identity Negotiation In Adult English Learners’ Communities Of Practice, Kathleen D. Rolander

Theses and Dissertations

This study utilizes Lave and Wenger’s (1991) communities of practice (COP) model to explore how ELLs navigate their positions within and between their many language learning communities. Drawing on Norton’s (1995, 2013) work on ELLs’ identity negotiation and Wenger’s 1998 work on the reinforcing impacts of identities between multiple COPs, this study explores what adults consider to be their COPs, how they perceive themselves within and between them, and how past, current, and imagined or possible COPs impact each other.

A constructivist, multiple case study design was used to focus on participants’ perceptions of their identity negotiation processes through their …

A Practice Elements-Based Approach To Adherence Measurement, Stephanie Violante

Theses and Dissertations

The measurement of treatment adherence (i.e., the frequency and thoroughness with which a therapist delivers a treatment as designed) is critical to the field of implementation science, as adherence is often considered an indicator of successful implementation. Most existing instruments of treatment adherence are treatment protocol specific; however, this approach is costly, inefficient, and disallows cross-treatment and cross-study comparisons. Thus, there is a need for adherence instruments that can be used across treatment protocols. It has been suggested that an instrument that captures adherence at the practice element level would meet this need, as it would have utility across protocols …

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Spatial Learning And Memory In Brain-Injured And Non-Injured Mice: Investigating The Roles Of Diacylglycerol Lipase-Α And -Β., Lesley D. Schurman

Theses and Dissertations

A growing body of evidence implicates the importance of the endogenous cannabinoid 2-arachidonyl glycerol (2-AG) in memory regulation. The biosynthesis of 2-AG occurs primarily through the diacylglycerol lipases (DAGL-α and -β), with 2-AG serving as a bioactive lipid to both activate cannabinoid receptors and as a rate limiting precursor for the production of arachidonic acid and subsequent pro-inflammatory mediators. Gene deletion of DAGL-α shows decrements in synaptic plasticity and hippocampal neurogenesis suggesting this biosynthetic enzyme may be important for processes of normal spatial memory. Additionally, 2-AG is elevated in response to pathogenic events such as traumatic brain injury (TBI), suggesting …

Influence Of Muscle Strength On Mobility In Critically Ill Adult Patients On Mechanical Ventilation, Audrey R. Roberson

Theses and Dissertations

Patients in the intensive care unit (ICU) setting are prone to develop muscle weakness and the causes are multi-factorial. Muscle strength in adult, critically ill patients on mechanical ventilation decreases with immobility. The influence of muscle strength on different muscle groups and its influence on progressive mobility in the adult, critically ill patient on mechanical ventilation has not been examined. Identifying muscle strength in this patient population can benefit overall muscle health and minimize muscle deconditioning through a progressive mobility plan. The objective of this dissertation was to describe muscle strength in different muscle groups and to describe the influence …