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GSBS Dissertations and Theses

2014

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Full-Text Articles in Medicine and Health Sciences

Characterization Of Innate Immune Pathways In Dna Vaccine-Induced, Antigen-Specific Immune Responses: A Dissertation, John J. Suschak Iii Dec 2014

Characterization Of Innate Immune Pathways In Dna Vaccine-Induced, Antigen-Specific Immune Responses: A Dissertation, John J. Suschak Iii

GSBS Dissertations and Theses

A major advantage of DNA vaccination is the ability to induce both humoral and cellular immune responses. DNA vaccines are currently used in veterinary medicine, but their tendency to display low immunogenicity in humans has hindered their usage, despite excellent tolerability and safety profiles. Various approaches have been used to improve the immunogenicity of DNA vaccines. Recent human study data re-established the value of DNA vaccines, especially in priming high-level antigen-specific antibody responses. Data suggests that innate immune responses to the DNA vaccine plasmid itself contribute to the immunogenicity of DNA vaccines, however the underlying mechanisms responsible remain unclear. In ...


Raav-Mediated Gene Transfer For Study Of Pathological Mechanisms And Therapeutic Intervention In Canavan's Disease: A Dissertation, Seemin Seher Ahmed Dec 2014

Raav-Mediated Gene Transfer For Study Of Pathological Mechanisms And Therapeutic Intervention In Canavan's Disease: A Dissertation, Seemin Seher Ahmed

GSBS Dissertations and Theses

Canavan’s Disease is a fatal Central Nervous System disorder caused by genetic defects in the enzyme – aspartoacylase and currently has no effective treatment options. We report additional phenotypes in a stringent preclinical aspartoacylase knockout mouse model. Using this model, we developed a gene therapy strategy with intravenous injections of the aspartoacylase gene packaged in recombinant adeno associated viruses (rAAVs). We first investigated the CNS gene transfer abilities of rAAV vectors that can cross the blood-brain-barrier in neonatal and adult mice and subsequently used different rAAV serotypes such as rAAV9, rAAVrh.8 and rAAVrh.10 for gene replacement therapy. A ...


Gli-Ikbke Requirement In Kras-Induced Pancreatic Tumorigenesis: A Dissertation, Mihir S. Rajurkar Nov 2014

Gli-Ikbke Requirement In Kras-Induced Pancreatic Tumorigenesis: A Dissertation, Mihir S. Rajurkar

GSBS Dissertations and Theses

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by KRAS activation. Here, we find that transcriptional activation mediated by the GLI family of transcription factors, although dispensable for pancreatic development, is required for KRAS induced pancreatic transformation. Inhibition of GLI using a dominant-negative repressor (Gli3T) inhibits formation of precursor Pancreatic Intraepithelial Neoplasia (PanIN) lesions in mice, and significantly extends survival in a mouse model of PDAC. Further, ectopic activation of the GLI1/2 transcription factors in mouse pancreas accelerates KRAS driven tumor formation and reduces survival, underscoring the importance of GLI transcription ...


Amphiphilic Degradable Polymer/Hydroxyapatite Composites As Smart Bone Tissue Engineering Scaffolds: A Dissertation, Artem B. Kutikov Nov 2014

Amphiphilic Degradable Polymer/Hydroxyapatite Composites As Smart Bone Tissue Engineering Scaffolds: A Dissertation, Artem B. Kutikov

GSBS Dissertations and Theses

Over 600,000 bone-grafting operations are performed each year in the United States. The majority of the bone used for these surgeries comes from autografts that are limited in quantity or allografts with high failure rates. Current synthetic bone grafting materials have poor mechanical properties, handling characteristics, and bioactivity. The goal of this dissertation was to develop a clinically translatable bone tissue engineering scaffold with improved handling characteristics, bioactivity, and smart delivery modalities. We hypothesized that this could be achieved through the rational selection of Food and Drug Administration (FDA) approved materials that blend favorably with hydroxyapatite (HA), the principle ...


The Three-Dimensional Structure Of The Cystic Fibrosis Locus: A Dissertation, Emily M. Smith Nov 2014

The Three-Dimensional Structure Of The Cystic Fibrosis Locus: A Dissertation, Emily M. Smith

GSBS Dissertations and Theses

The three dimensional structure of the human genome is known to play a critical role in gene function and expression. I used chromosome conformation capture (3C) and 3C-carbon copy (5C) techniques to investigate the three-dimensional structure of the cystic fibrosis transmembrane conductance regulator (CFTR) locus. This is an important disease gene that, when mutated, causes cystic fibrosis. 3C experiments identified four distinct looping elements that contact the CFTR gene promoter only in CFTR-expressing cells. Using 5C, I expanded the region of study to a 2.8 Mb region surrounding the CFTR gene. The 5C study shows 7 clear topologically associating ...


A Population-Based Perspective On Clinically Recognized Venous Thromboembolism: Contemporary Trends In Clinical Epidemiology And Risk Assessment Of Recurrent Events: A Dissertation, Wei Huang Nov 2014

A Population-Based Perspective On Clinically Recognized Venous Thromboembolism: Contemporary Trends In Clinical Epidemiology And Risk Assessment Of Recurrent Events: A Dissertation, Wei Huang

GSBS Dissertations and Theses

Background: Venous thromboembolism (VTE), comprising the conditions of deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common acute cardiovascular event associated with increased long-term morbidity, functional disability, all-cause mortality, and high rates of recurrence. Major advances in identification, prophylaxis, and treatment over the past 3-decades have likely changed its clinical epidemiology. However, there are little published data describing contemporary, population-based, trends in VTE prevention and management.

Objectives: To examine recent trends in the epidemiology of clinically recognized VTE and assess the risk of recurrence after a first acute episode of VTE.

Methods: We used population-based surveillance to monitor ...


Oncogene Function In Pre-Leukemia Stage Of Inv(16) Acute Myeloid Leukemia: A Dissertation, Liting Xue Oct 2014

Oncogene Function In Pre-Leukemia Stage Of Inv(16) Acute Myeloid Leukemia: A Dissertation, Liting Xue

GSBS Dissertations and Theses

The CBFbeta-SMMHC fusion protein is expressed in acute myeloid leukemia (AML) samples with the chromosome inversion inv(16)(p13;q22). This fusion protein binds the transcription factor RUNX with higher affinity than its physiological partner CBFbeta and disrupts the core binding factor (CBF) activity in hematopoietic stem and progenitor cells. Studies in the Castilla laboratory have shown that CBFbeta-SMMHC expression blocks differentiation of hematopoietic progenitors, creating a pre-leukemic progenitor that progresses to AML in cooperation with other mutations. However, the combined function of cumulative cooperating mutations in the pre-leukemic progenitor cells that enhance their expansion to induce leukemia is not ...


Role Of Mycobacterium Tuberculosis-Induced Necrotic Cell Death Of Macrophages In The Pathogenesis Of Pulmonary Tuberculosis: A Dissertation, Teresa S. Repasy Oct 2014

Role Of Mycobacterium Tuberculosis-Induced Necrotic Cell Death Of Macrophages In The Pathogenesis Of Pulmonary Tuberculosis: A Dissertation, Teresa S. Repasy

GSBS Dissertations and Theses

Mycobacterium tuberculosis, the causative agent of tuberculosis, can manipulate host cell death pathways as virulent strains inhibit apoptosis to protect its replication niche and induce necrosis as a mechanism of escape. In vitro studies revealed that similar to lytic viruses, M. tuberculosis has the ability to induce cytolysis in macrophages when it reaches an intracellular burden of ~25 bacilli. Base on this finding, we proposed the burst size hypothesis that states when M. tuberculosis invades a macrophage at a low multiplicity of infection it replicates to a burst size triggering necrosis to escape the cell and infect naïve nearby phagocytes ...


Psychometric Evaluation Of Joint-Specific Patient-Reported Outcome Measures Before And After Total Knee Replacement: A Dissertation, Barbara L. Gandek Sep 2014

Psychometric Evaluation Of Joint-Specific Patient-Reported Outcome Measures Before And After Total Knee Replacement: A Dissertation, Barbara L. Gandek

GSBS Dissertations and Theses

Background: Patient reports of pain and function are used to inform the need for and timing of total knee replacement (TKR) and evaluate TKR outcomes. This dissertation compared measurement properties of commonly-used patient surveys in TKR and explored ways to develop more efficient knee-specific function measures.

Methods: 1,179 FORCE-TJR patients (mean age=66.1, 61% female) completed questionnaires before and 6 months after TKR. Patient surveys included the knee-specific Knee injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and generic SF-36 Health Survey. Tests of KOOS and WOMAC measurement properties included evaluations ...


A Feedback Loop Couples Musashi-1 Activity To Omega-9 Fatty Acid Biosynthesis: A Dissertation, Carina C. Clingman Sep 2014

A Feedback Loop Couples Musashi-1 Activity To Omega-9 Fatty Acid Biosynthesis: A Dissertation, Carina C. Clingman

GSBS Dissertations and Theses

All living creatures change their gene expression program in response to nutrient availability and metabolic demands. Nutrients and metabolites can directly control transcription and activate second-­‐messenger systems. In bacteria, metabolites also affect post-­‐transcriptional regulatory mechanisms, but there are only a few isolated examples of this regulation in eukaryotes. Here, I present evidence that RNA-­‐binding by the stem cell translation regulator Musashi-­‐1 (MSI1) is allosterically inhibited by 18-­‐22 carbon ω-­‐9 monounsaturated fatty acids. The fatty acid binds to the N-­‐terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA association. Musashi ...


Long-Term Survival And Prognostic Factors In Patients With Acute Decompensated Heart Failure According To Ejection Fraction Findings: A Population-Based Perspective: A Master Thesis, Andrew H. Coles Aug 2014

Long-Term Survival And Prognostic Factors In Patients With Acute Decompensated Heart Failure According To Ejection Fraction Findings: A Population-Based Perspective: A Master Thesis, Andrew H. Coles

GSBS Dissertations and Theses

Limited data exists describing the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to currently recommended ejection fraction (EF) findings. In addition, little is known about the magnitude of, and factors associated with, long-term prognosis for these patients. Based on previously validated and clinically relevant criteria, we defined HF-REF as patients with an EF value ≤40%, HF-PEF was defined as an EF value > 50%, and HF-BREF was defined as patients with an EF value during their index hospitalization between 41 and 49%. The hospital medical records of residents of the Worcester (MA) metropolitan area who ...


Comparative Effectiveness Of Lithium And Valproate For Suicide Prevention And Associations With Nonsuicide Mortality: A Dissertation, Eric G. Smith Aug 2014

Comparative Effectiveness Of Lithium And Valproate For Suicide Prevention And Associations With Nonsuicide Mortality: A Dissertation, Eric G. Smith

GSBS Dissertations and Theses

Background: The mood stabilizer lithium has long been reported to be associated with reduced suicide risks, but many studies reporting associations between lithium and reduced suicide risks also have been nonrandomized and lacked adjustment for many potential confounders, active controls, uniform follow-up, or intent-to-treat samples. Concerns also have been raised that medications being considered as potential suicide preventative might increase risks of nonsuicide mortality while reducing risks of suicide.

Methods: Three studies of Veterans Health Administration (VHA) patients were conducted combining high-dimensional propensity score matching with intent-to-treat analyses to examine the associations between lithium and valproate and one-year suicide and ...


Approaches And Considerations Towards A Safe And Effective Adeno-Associated Virus Mediated Therapeutic Intervention For Gm1-Gangliosidosis: A Dissertation, Cara M. Weismann Aug 2014

Approaches And Considerations Towards A Safe And Effective Adeno-Associated Virus Mediated Therapeutic Intervention For Gm1-Gangliosidosis: A Dissertation, Cara M. Weismann

GSBS Dissertations and Theses

GM1 gangliosidosis is a lysosomal storage disorder caused by a deficiency in the catabolizing enzyme β-galactosidase (βgal). This leads to accumulation of GM1-ganglioside (GM1) in the lysosome inducing ER stress and cell death. GM1 gangliosidosis is primarily a disorder of the central nervous system (CNS) with peripheral organ involvement. In this work we report two major findings, 1) systemic treatment of GM1 gangliosidosis with an adenoassociated virus (AAV9) encoding mouse-βgal (mβgal) in a GM1 gangliosidosis mouse model (βGal-/-), and 2) an investigation into an intracranial injection of a therapeutic AAVrh8 encoding mβgal. Systemic treatment of GM1 gangliosidosis with AAV9 resulted ...


Hypertensive Acute Decompensated Heart Failure Presentations: On The Decline? : A Master's Thesis, Chad E. Darling Jul 2014

Hypertensive Acute Decompensated Heart Failure Presentations: On The Decline? : A Master's Thesis, Chad E. Darling

GSBS Dissertations and Theses

Background: The initial systolic blood pressure (SBP) in patients with acute heart failure (AHF) can be used as a guide when choosing specific pharmacologic treatments by helping identify the underlying type of HF (e.g., HF with preserved ejection fraction). Clinical experience and research data from our medical center suggests that AHF with elevated SBP may be presenting less frequently than in the past. This may call into question the utility of initial SBP as a clinical guide. The goal of this Master’s Thesis is to test the hypothesis that the frequency of AHF patients with a SBP>160mmhg ...


Impact Of Copd On The Mortality And Treatment Of Patients Hospitalized With Acute Decompensated Heart Failure (The Worcester Heart Failure Study): A Masters Thesis, Kimberly A. Fisher Jul 2014

Impact Of Copd On The Mortality And Treatment Of Patients Hospitalized With Acute Decompensated Heart Failure (The Worcester Heart Failure Study): A Masters Thesis, Kimberly A. Fisher

GSBS Dissertations and Theses

Objective: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with heart failure, yet little is known about the impact of this condition in patients with acute decompensated heart failure (ADHF), especially from a more generalizable, community-based perspective. The primary objective of this study was to describe the in-hospital and post discharge mortality and treatment of patients hospitalized with ADHF according to COPD status.

Methods: The study population consisted of patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 4 study years: 1995, 2000, 2002, and 2004.

Results: Of the 9,748 patients hospitalized ...


Caspase-8 And Rip Kinases Regulate Bacteria-Induced Innate Immune Responses And Cell Death: A Dissertation, Dan Weng Jul 2014

Caspase-8 And Rip Kinases Regulate Bacteria-Induced Innate Immune Responses And Cell Death: A Dissertation, Dan Weng

GSBS Dissertations and Theses

Yersinia pestis (Y. pestis), as the causative agent of plague, has caused deaths estimated to more than 200 million people in three historical plague pandemics, including the infamous Black Death in medieval Europe. Although infection with Yersinia pestis can mostly be limited by antibiotics and only 2000-5000 cases are observed worldwide each year, this bacterium is still a concern for bioterrorism and recognized as a category A select agent by the Centers for Disease Control and Prevention (CDC). The investigation into the host-pathogen interactions during Y. pestis infection is important to advance and broaden our knowledge about plague pathogenesis for ...


The Cellular Consequences Of Fus/Tls Depletion: A Loss Of Function Model For Amyotrophic Lateral Sclerosis: A Dissertation, Catherine L. Ward Jul 2014

The Cellular Consequences Of Fus/Tls Depletion: A Loss Of Function Model For Amyotrophic Lateral Sclerosis: A Dissertation, Catherine L. Ward

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons, generally leading to paralysis and death within 3-5 years of onset. Over 50 different mutations in the gene encoding FUS/TLS (or FUS) will result in ALS, accounting for ~4% of all inherited cases. FUS is a multifunctional protein with important functions in DNA/RNA processing and stress response. How these mutations affect the structure or function of FUS protein and ultimately cause ALS is not known. The fact that mutations cause the protein to mislocalize from the nucleus to the cytoplasm of cells ...


Clinical And Financial Impact Of Hospital Readmissions Following Colorectal Resection: Predictors, Outcomes, And Costs: A Thesis, Rachelle N. Damle Jun 2014

Clinical And Financial Impact Of Hospital Readmissions Following Colorectal Resection: Predictors, Outcomes, And Costs: A Thesis, Rachelle N. Damle

GSBS Dissertations and Theses

Background: Following passage of the Affordable Care Act in 2010, 30-day hospital readmissions have come under greater scrutiny. Excess readmissions for certain medical conditions and procedures now result in penalizations on all Medicare reimbursements. We examined the risk factors, outcomes, and costs of 30-day readmissions after colorectal surgery (CRS).

Methods: The University HealthSystem Consortium database was queried for adults (≥ 18 years) who underwent colorectal resection for cancer, diverticular disease, inflammatory bowel disease, or benign tumors between January 2008 and December 2011. Our outcomes of interest were readmission within 30-days of the patient’s index discharge, hospital readmission outcomes, and total ...


Differences In Access To Care And Healthcare Utilization Among Sexual Minorities: A Master's Thesis, Tan Phu Pham Jun 2014

Differences In Access To Care And Healthcare Utilization Among Sexual Minorities: A Master's Thesis, Tan Phu Pham

GSBS Dissertations and Theses

BACKGROUND: The barriers in accessing healthcare for gay, lesbian and bisexuals individuals are not well explored. These challenges as well as a lack of knowledge concerning this understudied group has prompted the Institute of Medicine to create a research agenda to build a foundational understanding of gay, lesbian and bisexual health and the barriers they encounter.1 the primary aim of this study will be to compare the differences in health care access and utilization between gay/lesbian, bisexual and heterosexual individuals using a large, nationally representative dataset of the U.S. population.

METHODS: Data from 2001 to 2012 from ...


Outpatient Emergency Department Utilization: Measurement And Prediction: A Dissertation, Lisa M. Lines Apr 2014

Outpatient Emergency Department Utilization: Measurement And Prediction: A Dissertation, Lisa M. Lines

GSBS Dissertations and Theses

Approximately half of all emergency department (ED) visits are primary-care sensitive (PCS) – meaning that they could potentially be avoided with timely, effective primary care. Reducing undesirable types of healthcare utilization (including PCS ED use) requires the ability to define, measure, and predict such use in a population.

In this retrospective, observational study, we quantified ED use in 2 privately insured populations and developed ED risk prediction models. One dataset, obtained from a Massachusetts managed-care network (MCN), included data from 2009-11. The second was the MarketScan database, with data from 2007-08. The MCN study included 64,623 individuals enrolled for at ...


Espfu, An Enterohemorrhagic E. Coli Secreted Effector, Hijacks Mammalian Actin Assembly Proteins By Molecular Mimicry And Repetition: A Dissertation, Yushuan (Cindy) Lai Apr 2014

Espfu, An Enterohemorrhagic E. Coli Secreted Effector, Hijacks Mammalian Actin Assembly Proteins By Molecular Mimicry And Repetition: A Dissertation, Yushuan (Cindy) Lai

GSBS Dissertations and Theses

Enterohemorrhagic E. coli (EHEC) is a major cause of food borne diarrheal illness worldwide. While disease symptoms are usually self-resolving and limited to severe gastroenteritis with bloody diarrhea, EHEC infection can lead to a life threatening complication known as Hemolytic Uremic Syndrome (HUS), which strikes children disproportionately and is the leading cause of kidney failure in children. Upon infection of gut epithelia, EHEC produces characteristic lesions called actin pedestals. These striking formations involve dramatic rearrangement of host cytoskeletal proteins. EHEC hijacks mammalian signaling pathways to cause destruction of microvilli and rebuilds the actin cytoskeleton underneath sites of bacterial attachment. Here ...


Depression In Rheumatoid Arthritis And An Estimation Of The Bi-Directional Association Of Depression And Disease Burden: A Dissertation, Alan M. Rathbun Apr 2014

Depression In Rheumatoid Arthritis And An Estimation Of The Bi-Directional Association Of Depression And Disease Burden: A Dissertation, Alan M. Rathbun

GSBS Dissertations and Theses

Depression is a common comorbidity in rheumatoid arthritis (RA), yet it may not be adequately recognized during routine clinical care. RA symptoms may confer a risk for depression, and vice versa; depression may affect RA disease activity and response to treatment. The study aims were to compare patient- and physician-reported depression measures, evaluate the temporal bi-directional association between RA disease activity and depressive symptomology, and assess depression as a moderator of RA treatment.

Patients were identified using a national RA registry sample (Consortium of Rheumatology Researchers of North America; CORRONA). Depression prevalence and incidence rates were estimated, and concordance and ...


Regulation Of Type Ii Responses In Lung Fibrosis And Systemic Autoimmunity: A Dissertation, Tia Bumpus Brodeur Apr 2014

Regulation Of Type Ii Responses In Lung Fibrosis And Systemic Autoimmunity: A Dissertation, Tia Bumpus Brodeur

GSBS Dissertations and Theses

Preclinical models of lupus indicate that T cell-B cell collaboration drives antinuclear antibody (ANA) production and sustains T cell activation. Autoreactive B lymphocytes are present in the normal repertoire but persist as ignorant or anergic cells. Mechanisms that normally limit T cell activation of autoreactive B cells remain incompletely resolved, but potentially include the absence of autoreactive effector T cell subsets and/or the presence of autoAgspecific regulatory T cells (Tregs). Several studies have addressed this issue by using experimental systems dependent on transgenic autoreactive B cells, but much less is known about the activation of autoreactive B cells present ...


Adhd-200 Patient Characterization And Classification Using Resting State Networks: A Dissertation, Suzanne M. Czerniak Mar 2014

Adhd-200 Patient Characterization And Classification Using Resting State Networks: A Dissertation, Suzanne M. Czerniak

GSBS Dissertations and Theses

Attention Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder of childhood that is characterized by symptoms of inattention, impulsivity/hyperactivity, or a combination of both. Intrinsic brain dysfunction in ADHD can be examined through various methods including resting state functional Magnetic Resonance Imaging (rs-fMRI), which investigates patients’ functional brain connections in the absence of an explicit task. To date, studies of group differences in resting brain connectivity between patients with ADHD and typically developing controls (TDCs) have revealed reduced connectivity within the Default Mode Network (DMN), a resting state network implicated in introspection, mind-wandering, and day-dreaming. However, few studies ...


Fus/Tls In Stress Response - Implications For Amyotrophic Lateral Sclerosis: A Dissertation, Reddy Ranjith Kumar Sama Mar 2014

Fus/Tls In Stress Response - Implications For Amyotrophic Lateral Sclerosis: A Dissertation, Reddy Ranjith Kumar Sama

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease is a fatal neurodegenerative disease. ALS is typically adult onset and is characterized by rapidly progressive loss of both upper and lower motor neurons that leads to death usually within 3-5 years. About 90% of all the cases are sporadic with no family history while the remaining 10% are familial cases with mutations in several genes including SOD1, FUS/TLS, TDP43 and C9ORF72.

FUS/TLS (Fused in Sarcoma/Translocated in Liposarcoma or FUS) is an RNA/DNA binding protein that is involved in multiple cellular functions including DNA damage ...


Identification And Characteristics Of Factors Regulating Hepatocellular Carcinoma Progression And Metastasis: A Dissertation, Leanne G. Ahronian Mar 2014

Identification And Characteristics Of Factors Regulating Hepatocellular Carcinoma Progression And Metastasis: A Dissertation, Leanne G. Ahronian

GSBS Dissertations and Theses

Hepatocellular carcinoma (HCC) is a common malignancy of the liver that is one of the most frequent causes of cancer-related death in the world. Surgical resection and liver transplantation are the only curative options for HCC, and tumor invasion and metastasis render many patients ineligible for these treatments. Identification of the mechanisms that contribute to invasive and metastatic disease may enlighten therapeutic strategies for those not eligible for surgical treatments. In this dissertation, I describe two sets of experiments to elucidate mechanisms underlying HCC dissemination, involving the activities of Krüppel-like factor 6 and a particular p53 point mutation, R172H.

Gene ...


Cognitive Status And Initiation Of Lifestyle Changes Following Acute Coronary Heart Syndrome: A Dissertation, Alexandra M. Hajduk Mar 2014

Cognitive Status And Initiation Of Lifestyle Changes Following Acute Coronary Heart Syndrome: A Dissertation, Alexandra M. Hajduk

GSBS Dissertations and Theses

Background: Cognitive impairment is prevalent in survivors of acute coronary syndrome (ACS) and increases risk for poor outcomes. Lifestyle changes are recommended to patients after ACS to reduce their risk for recurrent events, but cognitively impaired patients may encounter difficulties initiating these changes. This dissertation had three aims: (1) to examine cognitive status as a predictor of lifestyle changes after ACS, (2) to examine whether caregiver support moderates the association of cognitive status and initiation of lifestyle changes, and (3) to assess the reliability of self-reported lifestyle changes in cognitively impaired patients through comparison of their reports of lifestyle change ...


Developing Three New Pathophysiologically Based Measures Of Nicotine Dependence: A Dissertation, W. W. Sanouri A. Ursprung Jan 2014

Developing Three New Pathophysiologically Based Measures Of Nicotine Dependence: A Dissertation, W. W. Sanouri A. Ursprung

GSBS Dissertations and Theses

BACKGROUND: Of the 22 known measures of nicotine dependence (ND), none capture the overall disease severity of physical dependence alone. Instead, they capture constructs related to dependence, such as perceived risk, psychological addiction, smoker motivations, or smoking related behaviors, but none of the measures include only physical withdrawal symptoms to capture physical dependence on nicotine.

AIM: To develop a range of nicotine dependence measures that capture physical dependence on nicotine.

METHODS: The final measures were developed in a cross-sectional study conducted in three phases: 1) candidate item development through literature review and cognitive interviews, 2) developing and pre-testing the survey ...


From Neurodegeneration To Infertility And Back - Exploring Functions Of Two Genes: Armc4 And Tardbp: A Dissertation, Wei Cheng Jan 2014

From Neurodegeneration To Infertility And Back - Exploring Functions Of Two Genes: Armc4 And Tardbp: A Dissertation, Wei Cheng

GSBS Dissertations and Theses

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset progressive neurodegenerative disease that causes degeneration in both upper and lower motor neurons. ALS progresses relentlessly after the onset of the disease, with most patients die within 3-5 years of diagnosis, largely due to respiratory failure. Since SOD1 became the first gene whose mutations were associated with ALS in 1993, more than 17 ALS causative genes have been identified. Among them, TAR DNA-binding protein (TARDBP) lies in the central of ALS pathology mechanism study, because TDP43 proteinopathy is observed not only in familial ALS cases carrying TARDBP mutations, but also in most of ...