Medicine and Health Sciences Commons^™

Synthesis Of Novel Azetidines, Amber Thaxton

University of New Orleans Theses and Dissertations

Azetidine is a four-membered nitrogen-containing heterocyclic ring that has recently received a great deal of attention as a molecular scaffold for the design and preparation of biologically active compounds. Structure-activity studies employing functionalized azetidines have led to the development of variety of drug molecules and clinical candidates encompassing a broad spectrum of biological activities.

Herein, the synthesis a novel series of 3-aryl-3-arylmethoxyazetidines is described. Selected 3-aryl-3-arylmethoxyazetidines were evaluated for their binding affinity to multiple monoaminergic transporters for the potential treatment of methamphetamine addiction. It was discovered that this scaffold exhibits high binding affinity (nM) for both the serotonin and dopamine …

Modeling Fecal Bacteria In Oregon Coastal Streams Using Spatially Explicit Watershed Characteristics, Paul Bryce Pettus

Dissertations and Theses

Pathogens, such as Escherichia coli and fecal coliforms, are causing the majority of water quality impairments in U.S., making up ~87% of this grouping's violations. Predicting and characterizing source, transport processes, and microbial survival rates is extremely challenging, due to the dynamic nature of each of these components. This research built upon current analytical methods that are used as exploratory tools to predict pathogen indicator counts across regional scales. Using a series of non-parametric methodologies, with spatially explicit predictors, 6657 samples from non-estuarine lotic streams were analyzed to make generalized predictions of regional water quality. 532 frequently sampled sites in …

Design And Synthesis Of Novel Sultams As Non-Nucleoside Inhibitors Of Hiv Reverse Transcriptase, Brian Chadwick Lecroix

Doctoral Dissertations

The compound 2-methyl-3-phenyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (NSC 108406) was identified as an HIV-1 reverse transcriptase inhibitor by the National Cancer Institute. Using this lead, the Baker group has developed a series of analogues with various groups at the 3-position that show a spectrum of biological activities. In the end, the substituents used could not compare to the biological activity of the inhibitor efavirenz (Sustiva^® [trademark]), and so it was decided to synthesize sultams with alkylethynyl substituents at the 3-position of the sultams in an attempt to mimic the activity of efavirenz.

Previous research analyzed the proposed novel sultams in the modeling …

Transcending Microbial Source Tracking Techniques Across Geographic Borders: An Examination Of Human And Animal Microbiomes And The Integration Of Molecular Approaches In Pathogen Surveillance In Brazil And The United States, Amber Mae Koskey

Theses and Dissertations

Waterborne illnesses, attributed to the ingestion or contact with contaminated water, present a significant global health concern. Surface water sources can be impacted by wide array of pollution inputs, but fecal pollution generates the most significant and acute threat to human health. Therefore, the detection of fecal bacteria in surface water sources remains an important public health objective. Current surface water monitoring employs the use of fecal indicator bacteria (FIB) including E. coli and enterococci as proxies for pathogenic organisms carried in fecal pollution. These traditional indicators, detected by culture-based microbiological methods, do not discriminate fecal sources from another. New …

Factors Associated With Parental Decision Making And Childhood Vaccination, Zuwen Qiu-Shultz

UNLV Theses, Dissertations, Professional Papers, and Capstones

In order to better understand factors affecting immunization status, logistic regression was used to assess the association of various socio-demographic factors and whether parents would have their child immunized if not a state mandate. Factors included in the study were race, household income, number of children in the household, number of adults in the household, if the child had a primary provider, if the child had a health check-up in the last twelve months, and medical insurance status of the child. The combined Nevada Kindergarten Health Survey Result of 2009-2010 (Year Two) and 2010-2011 (Year Three) conducted by the Nevada …

Evaluation Of Vdr-Coactivator Inhibitors Using Biochemical And Cell-Based Assays, Athena Marie Baranowski

Theses and Dissertations

ABSTRACT

EVALUATION OF VDR–COACTIVATOR INHIBITORS USING BIOCHEMICAL AND CELL–BASED ASSAYS

by

Athena Baranowski

The University of Wisconsin–Milwaukee, 2013

Under the Supervision of Dr. Alexander Arnold

The vitamin D receptor (VDR) is a ligand–dependent transcription factor, which belongs to the nuclear receptor superfamily. VDR–mediated gene regulation is governed by coregulators (coactivators and corepressors). VDR coregulator binding inhibitors (CBIs), which were discovered using high throughput screening (HTS), were evaluated using cell–based assays and biochemical assays to determine their ability to inhibit the interaction between VDR and steroid receptor coactivator–2 (SRC–2). Determining their ability to inhibit the VDR–SRC–2 interaction can lead to the …

Dynamic Queue Management For Hospital Emergency Room Services, Kar Way Tan

Dissertations and Theses Collection (Open Access)

The emergency room (ER) – or emergency department (ED) – is often seen as a place with long waiting times and a lack of doctors to serve the patients. However, it is one of the most important departments in a hospital, and must efficiently serve patients with critical medical needs. In the existing literature, addressing the issue of long waiting times in an ED often takes the form of single-faceted queue-management strategies that are either from a demand perspective or from a supply perspective. From the demand perspective, there is work on queue design such as priority queues, or queue …

Developing A Presumptive Test For Select Synthetic Cannabinoids, Carrie Snyder

Graduate Theses and Dissertations

Synthetic cannabinoids (SC's) began to gain popularity around the world in 2009. Since then, many of the compounds have been outlawed and methods developed to detect them and their metabolites using mass spectrometry. Our work investigated the possibility of developing a colorimetric presumptive test. The SC JWH-019 was synthesized and its ketone targeted as a possible reaction site. Many SC's contain ketones and thus a reaction at this site would be applicable to many of the compounds. Since JWH-019 is costly and time consuming to synthesize, much of the experimental work was done using benzophenone (BP). BP contains a diaryl …

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations & Theses (Open Access)

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some …

Consumer Adoption Of Health Information Systems, Sankara Subramanian Srinivasan

Graduate Theses and Dissertations

At nearly 18 percent of the country's GDP, the U.S. healthcare industry continues to wrestle with growing cost and a quality of care that does not match the increased spending. The dominant focus to date has been on promoting Health IT (HIT) system implementation and digitizing health records at the provider's end, with scant attention to the role of the patient in the healthcare process. The source of inefficiency in the healthcare system is not only on account of shortcomings at the provider's end but also due to non-compliance (such as failing to adhere to medication advice and follow-up visits) …

Formulation Development Of A Polymer-Drug Matrix With A Controlled Release Profile For The Treatment Of Glaucoma, Eric W. Tsoi

Master's Theses

Glaucoma is the leading cause of blindness in the United States accounting for 9-12% of all cases of blindness. Currently, the front line treatment for glaucoma are prostaglandins that may have to be taken up to several times a day. Even with proper treatment, roughly 11% of the patients using the treatment are non-compliant and lose their vision. In this project, ForSight Laboratories has developed a pharmaceutical drug delivering implant with the capability of sustaining long-term release of a prostaglandin as a new way to treat the condition. This project reports the product development of a polymer drug matrix with …

Radiogenic Second Cancer Risk Differences In Female Hodgkin Lymphoma Patients Treated With Proton Versus Photon Radiotherapies, Kenneth L. Homann

Dissertations & Theses (Open Access)

Hodgkin Lymphoma (HL) is the most common cancer diagnosis of young adults in the United States. Advances in curative treatments for HL, including the use of photon radiation therapy (RT) techniques, have increased 10 year survival rates to approximately 90% among young patients. These RT treatments, however, contribute to an increased incidence of radiogenic second cancer (RSC) formation to the healthy tissue surrounding the tumor volume relative to the general population. These RSCs are the leading cause of death among long-term HL survivors. Proton therapy has been shown to reduce the therapeutic dose, and therefore, the risk of developing a …

An Evaluation Of The Consistency Of Imrt Patient-Specific Qa Techniques, Elizabeth M. Mckenzie

Dissertations & Theses (Open Access)

To ensure the integrity of an intensity modulated radiation therapy (IMRT) treatment, each plan must be validated through a measurement-based quality assurance (QA) procedure, known as patient specific IMRT QA. Many methods of measurement and analysis have evolved for this QA. There is not a standard among clinical institutions, and many devices and action levels are used. Since the acceptance criteria determines if the dosimetric tools’ output passes the patient plan, it is important to see how these parameters influence the performance of the QA device. While analyzing the results of IMRT QA, it is important to understand the variability …

Investigation Of The Structure And Dynamics Of Regioisomeric Eu³⁺ And Gd³⁺ Chelates Of Nb-Dotma: Implications For Mri Contrast Agent Design, Benjamin Charles Webber

Dissertations and Theses

The detection of disease and abnormal pathology by magnetic resonance imaging (MRI) has been aided significantly by the use of gadolinium (Gd³⁺)-based contrast agents (CAs) over the past three decades. MRI and MRI CAs play a critical role in diagnosing tumors and diseases of the central nervous system. The agents used clinically have been shown to safely increase MRI contrast despite the toxicity of Gd³⁺, owing to the high kinetic and thermodynamic stability of these chelates. However, current CAs enhance contrast at a small fraction of what is theoretically possible. This leads to the necessity of …

An Epidemic Model Structured By The Time Since Last Infection, Jorge Alturo Alfaro Murillo

Open Access Dissertations

Epidemiological models structured by time since infection have their origin in the seminal work of 1927 by Kermack and McKendrick. Compared to ordinary differential equations (ODE) models, they are able to capture differences in infectivity of the individuals in a more suitable manner. Their use declined in the second half of the 20th century, probably because the theory for ODE models is more robust, complete and has proved successful in providing insights and predictions for many epidemiological problems. Nevertheless, it is important to understand in what occasions the inclusion of time since infection may alter the outcomes in a significant …

Altered Cholesterol Metabolism In Human Cancers Unraveled By Label-Free Spectroscopic Imaging, Shuhua Yue

Open Access Dissertations

Despite tremendous scientific achievements, cancer remains the second leading cause of death in the United States. Metabolic reprogramming has been increasingly recognized as a core hallmark of cancer. My dissertation work identified novel diagnostic markers and therapeutic targets for human cancers through the study of cholesterol in cancer cells.

Enabled by label-free Raman spectromicroscopy, we performed the first quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases, but not in normal prostate, benign prostatic hyperplasia, or …

Use Of Immersive Visualization For The Control Of Dental Anxiety During Dental Hygiene Treatment, Carmelo Padrino-Barrios

Dental Hygiene Theses & Dissertations

Purpose: The purpose of this study was to determine the effectiveness of immersive visualization (IV) therapy, a technique that provides visual and stereoscopic display through the use of eyewear, in anxious patients during an oral prophylaxis. Methods: A convenience sample of thirty adults was enrolled. A split mouth design was utilized. Subjects were randomly divided into two groups: group A (use of IV for the right side of the mouth), and group B (use of IV for the left side of the mouth). Subjects received a full mouth oral prophylaxis (removal of supra and subgingival calculus and selective polishing), always …

Image Quality Of Energy-Dependent Approaches For X-Ray Angiography, Jesse Evan Tanguay

Electronic Thesis and Dissertation Repository

Digital subtraction angiography (DSA) is an x-ray-based imaging method widely used for diagnosis and treatment of patients with vascular disease. This technique uses subtraction of images acquired before and after injection of an iodinated contrast agent to generate iodine-specific images. While it is extremely successful at imaging structures that are near-stationary over a period of several seconds, motion artifacts can result in poor image quality with uncooperative patients and DSA is rarely used for coronary applications.

Alternative methods of generating iodine-specific images with reduced motion artifacts might exploit the energy-dependence of x-ray attenuation in a patient. This could be performed …

Never Smokers -- Are They More Sensitive To The Respiratory Health Effects Of Ambient Air Pollution?, Zuhair Saleh Natto

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Several studies show an association between ambient particulate matter (PM) and all-cause mortality. The Adventist Health and Smog 1 (AHSMOG-1) study (N=6,338) has previously found associations between ambient air pollution and incident chronic obstructive pulmonary disease (COPD) using the spatial interpolation method from the three nearest fixed monitoring stations to residence and workplace. However, few studies have assessed the risk of death among disease specific subgroups such as those with COPD.

Objectives: The aims of this study were 1) to assess the effect of chronic exposure to ambient air pollutants on risk of all-cause mortality among persons with COPD …

Perceived Attitudes And Staff Roles Of Community Based Outpatient Clinics In Disaster Management, Pauline Antoinette Hodge-Hilton

Loma Linda University Electronic Theses, Dissertations & Projects

Objective: Natural and manmade disasters have claimed the lives of thousands of individuals in the US and caused billions of dollars in property damage. First responders carry the responsibility of disaster management, leaving other health care professionals such as medical clinic staff underutilized to support the clinic staff. We explored how medical and support staff in Community-based Outpatient VHA Clinics (CBOC) perceive their roles in disaster response, their attitudes about clinic readiness and continuity of care during disasters, and their ability to function in a post disaster environment.

Methods: A mixed method study was conducted to answer questions related to …

The Impact Of Lateral Electron Disequilibrium On Stereotactic Body Radiation Therapy Of Lung Cancer, Brandon Disher

Electronic Thesis and Dissertation Repository

Stereotactic Body Radiation Therapy (SBRT) is an effective treatment option for patients with inoperable early-stage lung cancer. SBRT uses online image-guidance technology [e.g. cone-beam CT (CBCT)] to focus small-fields of high energy x-rays onto a tumour to deliver ablative levels of radiation dose (e.g. 54 Gy) in a few treatment fractions (e.g. 3). For the combination of these treatment parameters and a low density lung, lateral electron disequilibrium (LED) can potentially occur, reducing lung and tumour doses. The goal of this thesis was to determine the impact of LED on stereotactic body radiation therapy for lung cancer.

The effect of …

Optimization Of A Boundary Element Approach To Electromagnet Design With Application To A Host Of Current Problems In Magnetic Resonance Imaging, Chad T. Harris

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging (MRI) has proven to be a valuable methodological approach in both basic research and clinical practice. However, significant hardware advances are still needed in order to further improve and extend the applications of the technique. The present dissertation predominantly addresses gradient and shim coil design (sub-systems of the MR system).

A design study to investigate gradient performance over a set of surface geometries ranging in curvature from planar to a full cylinder using the boundary element (BE) method is presented. The results of this study serve as a guide for future planar and pseudo-planar gradient systems for …

Polysaccharide-Based Nanocarriers For Improved Drug Delivery, Nan Zhang

Dissertations - ALL

The field of drug delivery has provided a solution to the limited efficacy and high toxicity of many drugs. Nano-sized drug carriers are popular because their size allows for selective accumulation in the diseased area. Polysaccharides are non-toxic and biodegradable natural polymers that can serve as the basis for these nano-sized carriers. Polysialic acid (PSA) is such a polysaccharide with strong hydrophilicity that may reduce uptake by the reticuloendothelial system and prolong drug circulation. In this study, we developed PSA-based nanocarriers, specifically micelles and nanoparticles, for improved drug delivery with improved efficacy and minimized toxicity. PSA-based micelle systems were developed …

Renal Cryoablation: Investigation Of Periprocedural Visualization Tools And Treatment Response Quantification, Katherine L. Dextraze

Dissertations & Theses (Open Access)

Cryoablation for small renal tumors has demonstrated sufficient clinical efficacy over the past decade as a non-surgical nephron-sparing approach for treating renal masses for patients who are not surgical candidates. Minimally invasive percutaneous cryoablations have been performed with image guidance from CT, ultrasound, and MRI. During the MRI-guided cryoablation procedure, the interventional radiologist visually compares the iceball size on monitoring images with respect to the original tumor on separate planning images. The comparisons made during the monitoring step are time consuming, inefficient and sometimes lack the precision needed for decision making, requiring the radiologist to make further changes later in …

Successful Aging And Creativity : An Investigation On Functional Status And Psychological Wellbeing In Older Adults, Mirie E. Levy

Loma Linda University Electronic Theses, Dissertations & Projects

Objectives: While the literature supports the maintenance of functional status as integral to successful aging, the relationship of creativity on functional status has received little attention. Creativity has been associated with health and aging in the research but only a small number of studies have examined creativity interventions to enhance functional status and boost psychological wellbeing.

Methods: A pretest-posttest quasi-experimental design was used to investigate an 8-week creativity intervention on functional status and psychological wellbeing in older adults. Sample subjects were 92 men and women all over age 60. A series of two-way mixed ANOVAs measured differences between treatment and …

Biophysical Understanding Of Novel Synthetic Amyloid-Β (Aβ) Prions In Alzheimer's Disease, Amit Kumar

Dissertations

Oligomers of amyloid-β (Aβ) peptide are the primary toxic agents that play a pivotal role in the pathogenesis of Alzheimer’s disease (AD). Oligomers are the intermediates formed during the Aβ aggregation process leading up to insoluble fibrils. It is important to know that oligomers can also be formed via pathways that do not lead to fibril formation. Such ‘off-pathway’ oligomers would have significantly longer half-lives than the ‘on-pathway’ ones, which may result in prolonged toxicity to neuronal cells. Furthermore, neither the mechanism of neurotoxicity nor the potential mechanisms of propagation and proliferation to neighboring cells are well understood. Moreover, recent …

Developing Thyronamine Analog Pharmaceuticals Targeting Taar1 To Treat Methamphetamine Addiction, Troy Andrew Wahl

Dissertations and Theses

As a part of the overall program in the Grandy laboratory at Oregon Health & Science University (OHSU), studying the underlying chemical biology of methamphetamine (Meth) addiction, this dissertation reports on the development of six new thyronamine analogs which were synthesized and assayed against trace amine associated receptor 1 (TAAR1), giving preliminary results consistent with the analogs being inverse agonists. Due to highly variable TAAR1 expression levels in the assays, based on inter-assay response to control Meth stimulation as well as other possible factors, kinetic models were developed to qualitatively explain the assay results. The models set approximate limits on …

Maternal Smoking, Weight Status And Preecalmpsia And Eclampsia Risk Among Women Living In San Bernardino County, Fiona Bedelia Lewis

Loma Linda University Electronic Theses, Dissertations & Projects

Preeclampsia is defined as pregnancy-induced hypertension affecting between 2% and 8% of pregnancies and accounting for about 10-15% of maternal deaths worldwide. Eclampsia is defined as the occurrence of one or more episodes of seizures in a pregnant woman related only to a preeclampsia diagnosis. Preeclampsia, if poorly managed, can progress to eclampsia resulting in injury and death to both mother and infant. The etiology of preeclampsia is not completely understood. Oxidative stress leading to abnormal placenta development and endothelial dysfunction are thought to be key components in the biological mechanism of preeclampsia.

Modifiable risk factors include maternal body weight …

Urban Agriculture Stormwater Management In California Cities, Rachel L. Cohen

Master's Theses

Cities within California are beginning to incorporate urban agriculture into their land use designations. Prompted by residents and local organizations, cities are hoping to capture the benefits that urban agriculture provides. Research has shown that urban agriculture renews and beautifies neighborhoods, provides healthy food choices, increases public health, has the potential to help with stormwater runoff, creates jobs, and fosters community. In the last few years, several California cities have made headlines as they have adopted new zoning codes that include urban agriculture.

In reviewing these new zoning codes and exploring the topic of urban agriculture, it became evident that …

Geographic And Temporal Epidemiology Of Campylobacteriosis, Jennifer Weisent

Doctoral Dissertations

Campylobacteriosis is a leading cause of gastroenteritis in the United States. The focus of this research was to (i) analyze and predict spatial and temporal patterns and associations for campylobacteriosis risk and (ii) compare the utility of advanced modeling methods. Laboratory-confirmed Campylobacter case data, obtained from the Foodborne Diseases Active Surveillance Network were used in all investigations.

We compared the accuracy of forecasting techniques for campylobacteriosis risk in Minnesota, Oregon and Georgia and found that time series regression, decomposition, and Box-Jenkins Autoregressive Integrated Moving Averages reliably predict monthly risk of infection for campylobacteriosis. Decomposition provided the fastest, most accurate, user-friendly …