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Synthesis Of 2,4,6-Substituted Pyrrolo[2,3-D]Pyrimidines As Potential Anticancer Agents, Si Yang

Electronic Theses and Dissertations

This thesis mainly focuses on the introduction of the background and work have been done in the areas of antifolates development, such as folate function, its three uptake mechanisms inside human cells, antifolates’ role in chemotherapy, et. al. In addition, the Structure-Activity-Relationship design rationale for the series of antifolates will also be discussed. Nevertheless, the details of synthesizing these pyrrolo[2,3-d]pyrimidines as potential antifolates have been described, including chemistry reviews on the pyrrolo[2,3-d]pyrimidine scaffold, and the challenges encountered and the solutions how to solve or improve in order to achieve better yield.

Retention And Attrition In Bariatric Surgery Research: A Qualitative Study, William F. Gourash

Electronic Theses and Dissertations

Problem: Longitudinal bariatric surgical research studies often lack information on retention and attrition of study participants and the strategies utilized to optimize these. The potential for attrition bias with adverse effects on validity, reliability, and generalizability increases over time. The many factors potentially affecting retention and attrition in research, have been under studied.

Purpose: The purpose was to explore factors affecting research participation of bariatric surgical patients who are subjects in the Longitudinal Assessment of Bariatric Surgery (LABS) study. The research questions explored research participants’ perceptions, motivations, and attitudes concerning participation in the study, specifically participation in annual in-person visits …

Burden Of Illness And Pharmacoeconomic Evaluation Of Lumacaftor/Ivacaftor In Cystic Fibrosis, Pratyusha Vadagam

Electronic Theses and Dissertations

Objectives: (1) To estimate the burden of illness in cystic fibrosis (CF) using 2010-2014 Medical Expenditure Panel Survey (MEPS) data, and (2) to conduct a pharmacoeconomic evaluation of lumacaftor/ivacaftor in the treatment of CF.

Methods: The study was conducted in two parts. Part 1 involved a retrospective analysis using individuals in MEPS database with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code of 277.00 for a principal diagnosis of CF. Dependent variables were cumulative and out-of-pocket (OOP) expenditures and independent variables included patient demographics and clinical characteristics. Unweighted and weighted estimates of expenditure in CF group, …

Target Based Design And Synthesis Of Fused Pyrimidines In The Potential Treatment Of Cancer And Opportunistic Infection, Khushbu Shah

Electronic Theses and Dissertations

This dissertation describes an introduction, background and research progress in the areas of agents designed as (a) selective Pneumocystis jirovecii dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection; (b) inhibitors of microtubule polymerization and multiple receptor tyrosine kinase (RTK) for potential treatment of cancer; and (c) substrates for tumor-targeted therapy for cancer.

PCP is a host species-specific infection. Most of the drugs, synthesized and evaluated so far, have been tested against Pneumocystis carinii dihydrofolate reductase (the causative organism in rats), which would not necessarily be effective against pjDHFR (the causative organism in humans). Trimethoprim-sulfamethoxazole (TMP-SMX) combination, which has been …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

Mammography Utilization In African American Women, April D. Kidd

Electronic Theses and Dissertations

Purpose: Breast cancer presents differently among women causing breast cancer health disparities with women of color disproportionally shouldering later-stage screening, incidence, and treatment, and greater mortality. This study assessed 10 predictors and rates of recent and long-term mammography utilization for women 43-79 years of age to better understand differences among age strata and races. This was the first study to use both the calculated Gail Risk scores (calculates absolute breast cancer risk over time intervals) from the 2010 National Health Interview Survey (NHIS) and a temporary homelessness variable in predicting mammography utilization using national-level data.

Theoretical Framework: A modified Behavioral …

Parents Of Children Who Had Hypoxic-Ischemic Encephalopathy: A Mixed-Methods, Exploratory Study, Natalene Kramer

Electronic Theses and Dissertations

Background: There is scant literature addressing the parents of children who had hypoxic-ischemic encephalopathy (HIE). therefore only inferences may be made as to issues of that experience affecting parents.

Purpose: The purposes of this study was to uncover the lived experiences of parents of children who had HIE, evaluate issues of stress, depression, coping, and impact of neurologic disability in order to better care for them and thus their families

Methods: A parallel, convergent mixed-methods design was used to explore experiences and perceptions of these parents regarding their experiences and life changes. The quantitative strand addressed four research questions which …

A Systems Approach To Moral Distress In Long Term Care, Margaret Lemley

Electronic Theses and Dissertations

Abstract: The question that this dissertation seeks to answer is whether or not a Systems Approach to Moral Distress can serve to positively address issues of moral distress within the Long-Term Care setting. Because moral distress has largely been understood as a phenomenon of the individual, efforts to address and reduce incidents of moral distress have focused almost entirely on the individual and his or her reaction to specific triggers. Building upon the existing literature this dissertation argues that previous efforts to understand moral distress within the healthcare setting have been limiting in two very important aspects. The first …

Phylogeny, Psychology, And The Vicissitudes Of Human Development: The Anxiety Of Atavism, Frank Pittenger

Electronic Theses and Dissertations

This cross-disciplinary dissertation provides a missing intellectual history of an ostensibly dead idea. Once widely held and no less elegant for its obsolescence, the principle of biogenetic recapitulation is best remembered by its defining mantra, “ontogeny recapitulates phylogeny.” Among psychologists and sociologists as well as embryologists, the notion that the development of any individual organism repeats in compressed, miniaturized form the entire history of its species enjoyed broad (if not uncontested) acceptance through the early twentieth century. The author reexamines the origins of this theory in the work of Charles Darwin and Ernst Haeckel, and traces its influence in psychology …

Occupational Profiles Of At-Risk Youth: A Multi-Case Study, Abigail Catalano

Electronic Theses and Dissertations

Occupational therapy’s work with at-risk and adjudicated youth is a practice area currently possessing a limited base of evidence. One significant need in this body of literature is for examination of evidence-based evaluation practices. This project describes implementation and results of an evaluation protocol, Primary Occupations for Work and Employment Readiness (POWER), designed to elicit comprehensive occupational profiles from participants. POWER consists of five assessment tools, supplemented by clinical observations and program data. The assessments included are the Occupational Self-Assessment (OSA), Model of Human Occupation Screening Tool (MOHOST), Double OT (DOT), Kawa River Model, and Role Checklist Version 3 (RCV3). …

The Challenge Of Enhancement & Adaptability In Healthcare: An Ethical Framework For Organizations, Gary Edwards

Electronic Theses and Dissertations

This work defends enhancements that aim at promoting adaptability and formulates a framework for how healthcare organizations can cope with these sorts of enhancements. It begins by defending explicit approaches to defining enhancements and sketches a tripartite conception of enhancements dependent on well-being, social, and perception approaches. After assessing several major arguments for and against enhancement, it defends an adaptability justification for enhancements. In light of this justification, the remaining sections explore the adaptability argument’s implications for healthcare, justify an organizational approach for dealing with these implications, and finally formulate an organizational ethics framework for coping with the adaptability argument’s …

Emotions, Intuitions And Risk Perception In Critical Care, Oleksandr Dubov

Electronic Theses and Dissertations

The theory of decision-making as it applies to bioethics and healthcare assumes a rational decision maker: someone who knows all his alternatives, has clear preferences, can rank and weigh risks and benefits of an intervention, and always acts in his own best interests. However, the growing body of research from the field of decision science shows that, in reality, such a purely rational decision maker does not exist. Instead, patients are rational within personal or environmental constraints such as uncertainty or ambiguity in which non-rational approaches such as emotion and intuition are instrumental. This issue is particularly important in critical …

An Organizational Ethics Framework To Balance Individual Privacy And Population Interests Regarding Genetic Technologies, Christine Trani

Electronic Theses and Dissertations

The American culture holds the right to privacy as one of the most esteemed rights for individuals. As such, the culture adamantly defends the right to privacy to ensure individuals have the opportunity to live freely. In the American healthcare system, the right to privacy is critical for individual autonomy. However, genetic science has pushed this boundary as it emphasizes the interdependency between individual and population health. Genetic technologies for healthcare have been increasing at an exponential rate since the early 2000s. Their implantation into clinical care has been a slower process due to ethical dilemmas. Specifically, ethical dilemmas revolve …

A Bioethics Tool For The Implementation Of Global Principles By The Pharmaceutical Industry, Daniel J. Hurst

Electronic Theses and Dissertations

Due to scandals of scientific misconduct, a climate of mistrust of science exists amongst the general public. This becomes of concern when we acknowledge that it is difficult for science and technology to flourish without broad societal trust. The pharmaceutical industry has often felt the brunt of such mistrust and has suffered many reputational setbacks over the past several years. Such reputational decline has a strong moral dimension, as it stems from issues such as the questionable conduct of clinical trials, pricing schemas, and access to medicines for low- or middle-income countries. The end product of such issues is the …