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2015

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Decoding Nf1 Intragenic Copy-Number Changes, Meng-Chang Hsiao Jan 2015

Decoding Nf1 Intragenic Copy-Number Changes, Meng-Chang Hsiao

All ETDs from UAB

Genomic rearrangements may cause both Mendelian and complex disorders. Currently, several major mechanisms causing genomic rearrangements have been proposed such as non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR). However, to what extent these mechanisms contribute to gene-specific pathogenic copy-number changes (CNCs) remains understudied. Furthermore, only few studies resolved these pathogenic alterations at the nucleotide-level. Accordingly, our aim was to explore which mechanisms contribute to a large, unique set of locus-specific non-recurrent genomic rearrangements causing the genetic neurocutaneous disorder neurofibromatosis type 1 (NF1). Through breakpoint-spanning PCR as well as …

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A Bio-Inspired Hybrid Nanosack For Pancreatic Islet Transplantation In The Omentum, Patrick Tj Hwang Jan 2015

A Bio-Inspired Hybrid Nanosack For Pancreatic Islet Transplantation In The Omentum, Patrick Tj Hwang

All ETDs from UAB

Pancreatic islet transplantation (PIT) has demonstrated consistent and sustained reversal of type 1 diabetes, generating optimism for its wider application as a potential cure for type 1 diabetes. However, the clinical efficacy is still lacking because of a substantial loss of islets during or shortly after transplant to the implantation site. The liver has been widely used as an implantation site for PIT, but it has serious risks for islet loss, such as massive islet destruction by instant blood-mediated inflammatory reaction, progressive attrition of islet cells due to exposure to the toxic environment. The omentum has gained significant attention as …

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Mechanisms Of Heme Oxygenase-1-Mediated Protection Against Tissue Injury, Travis David Hull Jan 2015

Mechanisms Of Heme Oxygenase-1-Mediated Protection Against Tissue Injury, Travis David Hull

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Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in the catabolism of heme, which is released by necrotic cells in injured tissue. HO-1 expression is protective in cardiac and renal injury because it coordinates the degradation of pro-oxidant heme with the generation of equimolar quantities of iron (Fe2+) and the cytoprotective mole-cules carbon monoxide and biliverdin. While many studies have demonstrated that HO-1 expression is protective in numerous disease states, relatively few have examined the specific cellular compartment(s) through which HO-1 expression confers its protective effects. Our objective was to define the cellular compartments in which HO-1 expression is critical to …

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Mechanisms Of Resistance To Oncolytic Herpes Simplex Viruses In Malignant Peripheral Nerve Sheath Tumors, Joshua Douglas Jackson Jan 2015

Mechanisms Of Resistance To Oncolytic Herpes Simplex Viruses In Malignant Peripheral Nerve Sheath Tumors, Joshua Douglas Jackson

All ETDs from UAB

Malignant peripheral nerve sheath tumors (MPNSTs) are rare but highly aggressive cancer of the peripheral nervous tissue. Median patient survival is approximately two years following diagnosis due in part to the ineffective options for treatment. As an alternative therapeutic approach to conventional radio- and chemotherapy, oncolytic herpes simplex viruses type-1 (oHSVs) have been proposed to treat MPNSTs. These oHSVs have been shown safe in clinical trials with associated tumor regression. However, there is evidence that resistance to the therapy should be anticipated in a subset of patients. Therefore, the goal of this dissertation has been to identify the primary obstacles …

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Zebrafish Wnt9b Patterns The First Pharyngeal Arch Into D-I-V Domains And Promotes Anterior-Medial Outgrowth, Henry Jackson Jan 2015

Zebrafish Wnt9b Patterns The First Pharyngeal Arch Into D-I-V Domains And Promotes Anterior-Medial Outgrowth, Henry Jackson

All ETDs from UAB

The secondary mouth and its associated face and jaws were an important evolutionary adaptation in the vertebrate lineage. The secondary mouth is formed from facial prominences including the fronto-nasal prominence and the 1st pharyngeal-arch derived maxillary and mandibular prominence. Cranial neural crest cells within these prominences give rise to the connective tissues of face and jaws, and strict spatio-temporal regulation of cranial neural crest cell fate patterning and subsequent prominence outgrowth is vital to normal facial development. Oral-facial clefting (OFC) is a common morbid human birth disorder characterized by disrupted oral and craniofacial morphogenesis. Our previous studies demonstrate that a …

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Hospital Community Orientation: Predictors And Performance Outcomes, J'Aime Jennings Jan 2015

Hospital Community Orientation: Predictors And Performance Outcomes, J'Aime Jennings

All ETDs from UAB

The three publishable manuscripts contained within this dissertation examine the predictors and performance outcomes of hospital community orientation. Community orientation is the customization of hospital services to meet identified community health needs. Together, these papers fill gaps in the literature regarding the factors that assist or hinder hospitals from being community-oriented, as well as the effects of community orientation. The first paper uses longitudinal data to examine the organizational and environmental factors that may influence how engaged hospitals are in a community orientation strategy based on the number of activities performed. The remaining papers consider the performance outcomes of community …

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Exploring Body Image And The Association Between Body Image Dissatisfaction And Waist Circumference Among Overweight And Obese Rural African American Women Participating In A Weight Loss Program, Erica Rayshelle Johnson Jan 2015

Exploring Body Image And The Association Between Body Image Dissatisfaction And Waist Circumference Among Overweight And Obese Rural African American Women Participating In A Weight Loss Program, Erica Rayshelle Johnson

All ETDs from UAB

African American (AA) women are disproportionately burdened by obesity, an epidemic with implications that reach beyond physiological consequences. Given that perceptions of body image may impact health-promoting behaviors and weight management efforts, we sought to evaluate the presence and magnitude of body image dissatisfaction (BID) and explore its relationship with waist circumference (WC), independent of weight among overweight and obese treatment-seeking rural AA women. Participants referred to images from the Pulvers Figure Rating Scale that included nine body silhouettes to answer: “How I think I look now” (i.e., current body image) and “How I would like to look” (i.e., desired …

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Prevalence And Determinants Of High Risk Human Papillomavirus (Hpv) Among Wives Of Migrant Workers - A Study In Far - West Nepal, Derek Johnson Jan 2015

Prevalence And Determinants Of High Risk Human Papillomavirus (Hpv) Among Wives Of Migrant Workers - A Study In Far - West Nepal, Derek Johnson

All ETDs from UAB

This dissertation research focuses on the risk factors associated with high-risk HPV infection (HR-HPV) and abnormal cervical cytology in Nepali women residing in Nepal’s Far-West district of Achham. The first part of this dissertation assesses the HR-HPV test concordance of self-collected vs. clinician-collected cervico-vaginal specimens. Of 261 women with both clinician- and self-collected cervical samples, 25 tested positive for HR-HPV, resulting in an overall HR-HPV prevalence of 9.6% (95% Confidence Interval [CI]: 6.3 – 13.8). The overall Kappa value for clinician- and self-collected tests was 0.64 (95% CI: 0.48 – 0.84), indicating a “good” level of agreement. The second part …

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Towards An Understanding Of Patient Satisfaction In The Military Health System, Alan Alexander Jones Jan 2015

Towards An Understanding Of Patient Satisfaction In The Military Health System, Alan Alexander Jones

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The Military Health System (MHS) is the most expansive health care system in the world. The MHS provides health care services to 9.7 million eligible beneficiaries spread across six continents. The MHS budget exceeded $52 billion in 2013 or 10 percent of the total 2013 Defense budget. The cost of health care in the MHS is of great concern to the Department of Defense and the US Congress. The MHS needs a strong framework to measure the value of the health care it provides. The purpose of this study was to develop a framework to better understand Patient Satisfaction in …

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Simulation Of Bridge Responses To Heavy Vehicles, Rahul Kalyankar Jan 2015

Simulation Of Bridge Responses To Heavy Vehicles, Rahul Kalyankar

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The main objective of this dissertation is to simulate dynamic heavy vehicle bridge interaction using advanced numerical models of heavy vehicle and bridges for the Next Generation Bridge Weigh in Motion (B-WIM) system. The traditional B-WIM system uses a simplified approach where the bridge is considered as a beam and the heavy vehicle is considered as a stable mass moving with constant speed. On the contrary, the moving heavy vehicle consists of a series of complex parts such as tire assembly, springs and dampers, rigid bodies, and types of materials. Along with the complexities of the heavy vehicle, the bridge …

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Examining The Interplay Of Diet Composition, Cardiometabolic Diseases, And Economics, Kenneth Patton Kell Jan 2015

Examining The Interplay Of Diet Composition, Cardiometabolic Diseases, And Economics, Kenneth Patton Kell

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Despite the invaluable contributions that both randomized controlled trials and longitudinal studies have made to our understanding of the relationships between diet and cardiovascular disease (CVD), a comprehensive understanding of these relationships does not yet exist from birth to death. Furthermore, the longest running of these longitudinal studies have not included a representative portion of racial minority participants. Lastly, given the financial impacts of CVD, as well as how socioeconomic status (SES) can influence diet, the interplay between these three merits consideration. Therefore, the objective of this dissertation was to evaluate the associations between diet and cardiovascular disease (CVD): 1) …

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The Influence Of State Politics On State Rainy Day Funds, Nathaniel Franklin Kelley Jan 2015

The Influence Of State Politics On State Rainy Day Funds, Nathaniel Franklin Kelley

All ETDs from UAB

States often find themselves facing fiscal hardships due to such issues as their own revenue volatility or through federal recessions. The methods taken by the states have varied over the years, but rainy day funds are becoming one of the leading mechanisms for coping with economic disparity. As more state officials look to rainy day funds as a solution, the field for research regarding rainy day funds has expanded. The existing studies have focused on the best way to build and maintain these types of funds, but there has been little information put forth that helps understand how they work. …

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Automated Processing Of Continuous Glucose Monitor (Cgm) Data To Study Onset Of Diabetes, Aman Khatri Jan 2015

Automated Processing Of Continuous Glucose Monitor (Cgm) Data To Study Onset Of Diabetes, Aman Khatri

All ETDs from UAB

Diabetes is a long term condition that causes high levels of blood glucose, and it is necessary to get a complete picture of glucose levels which can lead to better treatment decision and better glucose control. The advent of Continuous Glucose Monitoring (CGM) is helping researches to track the blood glucose levels continuously and to understand the effects of impaired glucose levels on human body which in turn can lead to better treatment of diabetes. Current CGM systems process enormous amounts of data and have limitations in regards to data accuracy, precision, and reliability of raw glucose data. The inaccuracy …

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Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar Jan 2015

Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar

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Cks1 is a crucial cell cycle regulator which plays pleiotropic roles in cancer cell growth and is highly expressed at both the protein, and mRNA levels, in cancer cells. In contrast, normal cells exhibit barely detectable levels of this protein, even though they express substantial Cks1 mRNA. One reason for high Cks1 protein in cancers appears to be its stabilization in these cells. Cks1 is known to be ubiquitinated and degraded by the proteasome. Coordinated ubiquitination dependent proteasomal degradation of cell cycle proteins is a major mechanism that regulates their activity. Therefore aberrant accumulation of Cks1, frequently observed in cancer, …

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Evaluation Of Sample Size Re-Estimation Procedures For Non-Inferiority Designs With Time-To-Event Outcomes, Hwasoon Kim Jan 2015

Evaluation Of Sample Size Re-Estimation Procedures For Non-Inferiority Designs With Time-To-Event Outcomes, Hwasoon Kim

All ETDs from UAB

Study designs that allow sample size review may potentially save a study by identifying misspecified assumptions, modifying the planned sample size, and reinforcing the study’s power. Most sample size re-estimation (SSR) methods in non-inferiority trials have been developed for continuous or binary outcomes. In many medical domains studying cancer, heart failure, and other chronic diseases, most phase III trials use censored endpoints (e.g. survival or event-free survival). Non-inferiority designs have inherent complexity by the introduction of the non-inferiority margin and therefore understanding of strategies in these methods is essential. In our first paper, we detail the issues related to misspecification …

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Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough Jan 2015

Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough

All ETDs from UAB

Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …

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The Impact Of Cultural Competency On Patient Experience Of Care, Emily Lane Koudelka Jan 2015

The Impact Of Cultural Competency On Patient Experience Of Care, Emily Lane Koudelka

All ETDs from UAB

The impact of hospitals’ cultural competency on inpatient experience of care will be examined. Enhanced patient experience of care may alter an individual’s willingness to use health services, thereby increasing access and decreasing health disparities. As a result, to the extent that cultural competency influences patient experience of care, the integration of cultural competency into healthcare organizations has emerged as a critical issue for researchers, industry leaders, and policymakers. Findings from this study will inform policies, practices, and processes across the broad spectrum of healthcare industry stakeholders.

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An Nphp-4 Enhancer Mutagenesis Screen For Modifiers Of Cilia Phenotypes Reveals Novel Mks Alleles, Uncovers, A Specific Genetic Interaction Between Osm-3 And Nphp-4, And A Novel Ciliary Calcium Channel., Dawn Landis Jan 2015

An Nphp-4 Enhancer Mutagenesis Screen For Modifiers Of Cilia Phenotypes Reveals Novel Mks Alleles, Uncovers, A Specific Genetic Interaction Between Osm-3 And Nphp-4, And A Novel Ciliary Calcium Channel., Dawn Landis

All ETDs from UAB

Nephronophthisis (NPHP) is a ciliopathy with diverse clinical features likely caused by genetic modifiers. To identify NPHP modifiers, a screen was conducted on nphp-4(tm925) mutant C. elegans to reveal mutations that exacerbate the NPHP ciliary defects. Ten loci were generated, five of which have now been identified. Three are mutations in ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66) is a missense mutation (S316F) in OSM-3, a kinesin required for cilia distal segment assembly. As in osm-3 null mutants, nphp-4(tm925);osm-3(yhw66) mutants lack distal segments, are dye-filing defective (Dyf), and have osmotic avoidance defects (OSM). The osm-3(yhw66) mutant alone …

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14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley Jan 2015

14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley

All ETDs from UAB

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson’s disease (PD), and LRRK2 is a risk factor for idiopathic PD. How LRRK2 function is regulated is not well understood. Recently, the highly-conserved 14-3-3 proteins, which play a key role in many cellular functions including cell death, have been shown to interact with LRRK2. In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening and kinase activity. In the presence of 14-3-3θ overexpression, neurite length of primary neurons from BAC transgenic G2019S-LRRK2 mice returned back to wildtype levels. Similarly, 14-3-3θ overexpression …

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Changes In The Frontal Soft Tissue Of The Lower Face By Age And Sex, Maggie Law Jan 2015

Changes In The Frontal Soft Tissue Of The Lower Face By Age And Sex, Maggie Law

All ETDs from UAB

The purpose of this study is to determine age-related changes of the lower face by age and by gender. The secondary purpose of this study is to stress the importance of the clin-ical exam for orthodontic patients in the frontal view, the way most patients perceive themselves. Also, individualized treatment planning with age-appropriate incisor display is crucial for esthetic outcomes. Materials and Methods: Specific dimensions of the lower face were measured at patients initial clinical exam before starting orthodontic treatment. All patients were from Dr. David Sarver's private practice in Vestavia Hills, AL collected from 1/1/2002-11/4/2014. The following parameters were …

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Gene Replacement Therapy For Sickle Cell Disease, Chao Li Jan 2015

Gene Replacement Therapy For Sickle Cell Disease, Chao Li

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Sickle Cell Disease (SCD) is a devastating inherited disorder resulting from a single DNA base pair (bp) mutation in the sixth codon of the β-globin gene. It causes severe tissue damage that can result in strokes, splenic infarction, kidney failure, liver and lung disorders, painful crises, and other complications. Currently, the only cure for the disease is allogenic stem cell transplantation, which is only available to limited patients with histocompatible donors. In order to overcome this limitation, CRISPR/Cas enhanced gene correction in sickle patient iPS and CD34+ hematopoietic stem/progenitor cells as a therapy strategy was explored. Keratinocytes from skin biopsies …

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Linking Adiponectin And Autophagy In The Regulation Of Breast Cancer Metastatic Potential, Emily Libby Jan 2015

Linking Adiponectin And Autophagy In The Regulation Of Breast Cancer Metastatic Potential, Emily Libby

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Curative approaches for metastatic breast cancer remain elusive. Adiponectin is the most abundant of the adipocyte-secreted adipokines, and there is recent interest in development of adiponectin-based therapies for this disease. Yet, while multiple epidemiological studies have indicated that low levels of circulating plasma adiponectin portend poorer prognosis, recent work has reported that elevated adiponectin expression in breast tissue correlates with advanced disease. Further, isoform-specific roles of this molecule are not well understood. Thus, the overarching purpose of this work was to elucidate how adiponectin isoforms contribute to the microenvironmental regulation of the early steps of breast cancer metastasis. We show …

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The Jak/Stat Pathway In Neuroinflammatory Diseases, Yudong Liu Jan 2015

The Jak/Stat Pathway In Neuroinflammatory Diseases, Yudong Liu

All ETDs from UAB

Dysregulation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is critically involved in the pathogenesis of multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE). Suppressor Of Cytokine Signaling (SOCS) proteins are the negative regulators of the JAK/STAT pathway. To determine the role of SOCS3 in myeloid cells in EAE, mice with conditional SOCS3 deletion in myeloid cells (LysMCre-SOCS3fl/fl) were created and tested. LysMCre-SOCS3fl/fl mice develop a severe, non-resolving atypical form of disease, characterized by lesions and extensive neutrophil and other inflammatory cell infiltrates in the cerebellum and brainstem, elevated STAT activation, elevated cytokine, chemokine and iNOS expression, and prominent …

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Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu Jan 2015

Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu

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Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease (PD) , with pathogenic mutations located within each of the two catalytic cores of the protein, the GTPase and kinase domains. The most prevalent pathogenic mutation, G2019S increases kinase activity up to 5-fold, causing significant changes in the protein’s biochemical behavior. Other mutations such as R1441G and I2020T have also been demonstrated to increase LRRK2 kinase activity, however, the detailed mechanisms remains unclear. A major limitation in the field is the lack of structural information of LRRK2. This dissertation detailed …

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Spatial Analysis Of Hypertension Prevalence Using A Large Us Cohort, Matthew Loop Jan 2015

Spatial Analysis Of Hypertension Prevalence Using A Large Us Cohort, Matthew Loop

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Stroke mortality rates are highest in the Southeast US, and the cause for this "Stroke Belt" is not well understood. We investigate the spatial distribution of hypertension, an important risk factor for stroke. This investigation explores statistical issues in performing spatial analysis in a large cohort (over 30,000 participants), relating to type 1 error rate control and geocoding error. Recommendations for handling these statistical issues are made. In an applied analysis, we find that hypertension prevalence varies across the continental US, and is highest in northeast Louisiana, southeast Arkansas, west Mississippi, and east Michigan. These areas are not concordant with …

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Assessing Potential Diesel Exhaust Exposure In Truckers Resting At Truck Stops, Gumindenga Farayi Mabvuta Jan 2015

Assessing Potential Diesel Exhaust Exposure In Truckers Resting At Truck Stops, Gumindenga Farayi Mabvuta

All ETDs from UAB

The nature of long haul truck driving places workers in this occupation in a peculiar setting for chronic exposure to diesel exhaust which is a known carcinogenic. These drivers endure exposure to diesel exhaust in traffic and potentially greater exposure at truck stops where they park for rest breaks as mandated by DOT regulations. This study looked at the potential exposure to diesel exhaust in long haul truck drivers resting at truck stops where up to two hundred trucks are left idling for air conditioning and other reasons. Two different trucks were used consecutively over the 21 days of sampling. …

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Some Contributions To Bayesian Regularization Methods With Applications To Genetics And Clinical Trials, Himel Mallick Jan 2015

Some Contributions To Bayesian Regularization Methods With Applications To Genetics And Clinical Trials, Himel Mallick

All ETDs from UAB

Variable selection refers to the class of problems where one tries to find an optimal subset of relevant variables, which can be used to accurately predict the outcome of a certain response variable. Typically, a large number of variables are often collected; however, all but a few important variables are relevant for the prediction of the outcome, so the underlying representation is sparse. To this end, variable selection is fundamental in high-dimensional data analysis, playing a crucial role in important scientific discovery and decision-making, and has received enormous attention in the literature. Regularization method is one attractive approach that has …

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Synaptic And Neurochemical Profiles Of The Nucleus Accumbens In Postmortem Schizophrenia, Lesley Mccollum Jan 2015

Synaptic And Neurochemical Profiles Of The Nucleus Accumbens In Postmortem Schizophrenia, Lesley Mccollum

All ETDs from UAB

Schizophrenia is a mental illness affecting 1% of the population worldwide. Treatment options are limited for patients, due in part to the lack of understanding of the pathophysiological mechanisms of schizophrenia. In order to improve treatment, it is vital to gain a better understanding of the underlying pathology of the disorder. One region of particular interest is the nucleus accumbens (NAcc). Part of the ventral striatum, this region is thought to play a role in schizophrenia pathology for multiple reasons: afferent input of many brain regions implicated in schizophrenia is integrated here; the dopamine and glutamate systems, both known to …

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Emergency Department Wait Time Communication Strategies And Patient Throughput Efficiency, Tom R. Mcdougal Jan 2015

Emergency Department Wait Time Communication Strategies And Patient Throughput Efficiency, Tom R. Mcdougal

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This study investigates hospital strategies used to inform patients of anticipated wait times in the Emergency Department (ED) and the association of such strategies with patient throughput efficiency. When hospitals are inefficient in ED patient throughput, conditions of overcrowding often occur. Overcrowding of the ED is a problem for many hospitals. When such conditions exist, there is evidence in the literature that it leads to lower patient satisfaction, care quality, and financial position of the hospital. Therefore, improving patient throughput efficiency is a priority for hospitals. To improve patient throughput efficiency, hospitals use a variety of strategies. This study focuses …

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A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown Jan 2015

A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown

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In the first step in light perception, rod and cone photoreceptors convert photon absorption into an electrical impulse that is transmitted through the visual pathway. While the biochemistry and the signaling physiology have largely been defined in dark-adapted, isolated mammalian rods, there are still unanswered questions regarding photoreceptor light adaptation processes that involve extracellular components. In particular, the proteins of the interphotoreceptor matrix have not been considered in the studies of rod signaling and adaptation. This thesis details a new form of light adaptation, now known as adaptive potentiation (AP), in which extracellular components act on rods to transiently increase …

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