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Immunosuppression And Risk Prediction Of Sepsis Following Solid Organ Transplantation, John Patrick Donnelly Jan 2018

Immunosuppression And Risk Prediction Of Sepsis Following Solid Organ Transplantation, John Patrick Donnelly

All ETDs from UAB

Solid organ transplant (SOT) recipients typically need immunosuppressive therapy (IST) to protect graft function and regimens may include an induction agent (e.g., anti-thymocyte globulin [ATG] or alemtuzumab) with maintenance medications (e.g., tacrolimus, mycophenolate mofetil [MMF], mycophenolic acid [MPA], or azathioprine [AZA]). Sepsis, or organ dysfunction resulting from a dysregulated host response to infection, is a common complication among SOT recipients. Using national data from the United States Renal Data System (USRDS), we sought to determine the associations of IST regimens and maintenance medication exposure with sepsis risks and outcomes among kidney transplant recipients (KTRs). Using USRDS and single center data, …

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Constraint-Induced Movement Therapy To Improve Gait And Mobility Of People With Chronic Stroke: A Mixed Methods Study, Sarah Monteiro Dos Anjos Jan 2018

Constraint-Induced Movement Therapy To Improve Gait And Mobility Of People With Chronic Stroke: A Mixed Methods Study, Sarah Monteiro Dos Anjos

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Walking impairment after stroke impacts on participation and quality of life. Different techniques have been developed in the last decades to overcome walking difficulties after stroke, however, few have been shown to be efficacious. Constraint-induced Movement Therapy (CIMT) is a family of techniques that has been reported as one the most effective intervention for improving functional use and motor skills of a more-affected upper extremity (UE). The intervention protocol includes: 1) intensive supervised training; 2) use of shaping as a strategy for the motor training, 3) a group of behavioral strategies called the transfer package, and 4) procedures to increase …

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Drive-By Bridge Damage Inspection And Monitoring, Ahmed Elhattab Jan 2018

Drive-By Bridge Damage Inspection And Monitoring, Ahmed Elhattab

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Recently, drive-by bridge inspection has become an intriguing topic in the bridge health monitoring domain. The technique utilizes indirect measurements from the suspension system of a vehicle passes over the bridge to infer the bridge structural health condition. A number of studies have given confidence, hypothetically, in the feasibility of the approach in detecting, quantifying and localizing the damage. However, there is a scarcity of work investigating the fidelity of this technique to full-scale field applications. Whereas the wide number of uncertainties that governs the vehicle bridge interaction dynamics could significantly impact hypothetical techniques when applied in the field, the …

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Endodontic Post Retention With Resin Cements (Ilumi Fiber Post), Faimeena Farheen Jan 2018

Endodontic Post Retention With Resin Cements (Ilumi Fiber Post), Faimeena Farheen

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Objectives: Loss of post retention is the leading cause in the cemented post. There is no good method of bonding a fiber post in a post space with resin cements because adhesive cementation into a prepared post space is difficult- due to an inability to place, dry and light cure the adhesive and the cement. A new post system (iLumi) that transmits light to the apex of the post has recently been developed. We want to know if this system will improve post retention in each section (coronal, middle and apical) of the prepared post space and if this curing …

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Simulation Of Correlated Variables, Mixture Distributions, And Repeated Measures And Comparison Of Pharmacogenetic Prediction With Machine Learning Methods, Allison Cynthia Fialkowski Jan 2018

Simulation Of Correlated Variables, Mixture Distributions, And Repeated Measures And Comparison Of Pharmacogenetic Prediction With Machine Learning Methods, Allison Cynthia Fialkowski

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Pharmacogenetics aims to improve individualized medicine by combining genetic information with clinical data when assigning drug treatments. Different diseases are often associated with different factors, each with its own distributional characteristics. For rare or complex diseases, these characteristics may not be well understood and standard analysis methods may not be appropriate. In psychiatric disorders, for example, multiple drug treatments need to be compared across small sample sizes with heterogeneous patient populations, making implementation of standard methods difficult. Simulating data that mirrors clinical data is important because it allows investigators to determine which method is best suited for data from their …

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An Interdisciplinary Model For The Development Of Alabama Oil Sands, Daniel Edward Smith Jan 2018

An Interdisciplinary Model For The Development Of Alabama Oil Sands, Daniel Edward Smith

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In July 2013, a memorandum of understanding (MOU) was signed by the Governors of the states of Alabama and Mississippi to jointly conduct a comprehensive geologic, engineering, and legal assessment of oil sands resources associated with the Hartselle Sandstone formation including the identification of environmental best practices associated with developing these resources. Pursuant to the MOU, the Geological Survey of Alabama (GSA) began a limited geological evaluation of the potential development of Alabama’s oil sand resources. This dissertation compliments those GSA efforts by identifying and assessing environmental and social sustainability risks associated with the potential development of Alabama’s oil sands …

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The Influence Of Perceived Stress And Sleep Disturbance On Fatigue And Blood Pressure As Mediated By Cortisol In Children With Sickle Cell Disease, Heather Carol Soistmann Jan 2018

The Influence Of Perceived Stress And Sleep Disturbance On Fatigue And Blood Pressure As Mediated By Cortisol In Children With Sickle Cell Disease, Heather Carol Soistmann

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ABSTRACT Introduction: Life expectancy is improving for those with sickle cell disease (SCD); however, with this improvement come increasing risks for long-term health complications. Early identification of health concerns could lead to improved long-term health outcomes. Two health concerns in school-age children with SCD are fatigue and blood pressure (BP). Previous research with other populations indicates perceived stress and sleep disturbance may influence outcomes of fatigue and BP. Further, cortisol, a stress hormone, may mediate the proposed relationships. Therefore, the purpose of the study was to determine effect sizes of relationships between fatigue, BP, perceived stress, and sleep disturbance in …

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The Primary Cilium Regulates Interstitial Immune Cells During Renal Cystogenesis, Cheng Song Jan 2018

The Primary Cilium Regulates Interstitial Immune Cells During Renal Cystogenesis, Cheng Song

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Renal cysts are a pathological condition that can lead to end-stage renal failure and death. The mechanisms that underlie renal cyst development are under active investigation, and emerging evidence has revealed defects in a number of proteins required for cilia assembly or signaling, such as intraflagellar transport (IFT) proteins and the polycystins. Characterization of mice harboring conditional IFT mutations suggests that the rate of cyst formation is dependent upon the timing of cilia loss. Induction of cilia loss in juvenile mice results in rapid cyst development, while induction of cilia loss in adult mice leads to a slower progressing form …

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The Role Of Pim Kinases In Hepatoblastoma Tumorigenicity, Stem Cell-Like Cancer Cell Maintenance, And Chemoresistance, Laura Lee Stafman Jan 2018

The Role Of Pim Kinases In Hepatoblastoma Tumorigenicity, Stem Cell-Like Cancer Cell Maintenance, And Chemoresistance, Laura Lee Stafman

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Hepatoblastoma is the most common primary liver malignancy in children. Despite increasing incidence, treatment has not changed significantly in the past 20 years, making the need for novel therapeutics imperative. Proviral Integration site for Moloney murine leukemia virus (PIM) kinases are a family of serine/threonine kinases that have been implicated in multiple other cancer types including the adult liver cancer, hepatocellular carcinoma. Emerging evidence has begun to elucidate a role for PIM kinases in stem-cell like cancer cells (SCLCCs). This subpopulation of cells is thought tobe responsible for tumor maintenance, recurrence, metastasis, and chemoresistance. Chemoresistance is a significant barrier to …

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Morphological And Functional Characterization Of A Murine Garp2-Specific Knockout, Delores Stacks Jan 2018

Morphological And Functional Characterization Of A Murine Garp2-Specific Knockout, Delores Stacks

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GARP2, found exclusively in retinal rod photoreceptors, has been proposed to function as a structural protein, a calcium binding protein, and a modulator of the phosphodiesterase regulating visual phototransduction cascade kinetics. GARP2 is a splice variant of the Cngb1 gene which also encodes the β-subunit of the phototransduction cyclic nucleotide-gated cation channel and another glutamic acid-rich protein, GARP1. Mutations of the β-subunit and, recently discovered regions shared with the GARP en-coding regions of Cngb1cause retinitis pigmentosa (RP), while overexpression of GARP2 in the absence of the β-subunit accelerates the observed Cngb1-mediated retinal degeneration in mouse β-subunit knockout disease models. In …

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Establishing Control: An Investigation Into An Alternate Transcranial Direct Current Stimulation (Tdcs) Control Condition As A Replacement For Traditional Sham, Carl Edward Stevens Jan 2018

Establishing Control: An Investigation Into An Alternate Transcranial Direct Current Stimulation (Tdcs) Control Condition As A Replacement For Traditional Sham, Carl Edward Stevens

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Transcranial direct current stimulation (tDCS) is a neuromodulation technique with promise to improve numerous diseases, but results are inconsistent. A strong candidate explanation for conflicting evidence is that imbalances in expectation effects arise because participants frequently discern full-session current in “real” tDCS from mostly absent current in “fake” tDCS (sham, or control) conditions. Therefore, we conducted a study to test a better control procedure. The real tDCS condition targeted dorsolateral prefrontal cortex (DLPFC) with a right-anode/left-cathode montage expected to suppress food craving and eating. The control targeted sensorimotor cortex with a left-anode/right-cathode montage. Twenty-eight adults with overweight or obesity body …

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The Role Of Glycosylation Initiation By Galnac-Ts In Iga Nephropathy, Tyler Stewart Jan 2018

The Role Of Glycosylation Initiation By Galnac-Ts In Iga Nephropathy, Tyler Stewart

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The autoimmune disease IgA nephropathy (IgAN) is a common cause of primary glo-merulonephritis, often resulting in end-stage renal disease. IgAN patients have elevated serum levels of immunoglobulin A1 (IgA1) with autoantigenic galactose-deficient (gd) O-glycans. The gd-O-glycans occur at specific sites within IgA1 hinge-region. We hy-pothesized that GalNAc-Ts play a role in the formation of gd-IgA1, due to their role in determining glycosylation sites and densities. To better understand how GalNAc-Ts may change O-glycans of IgA1 in IgAN we characterized the complex glycosylation mecha-nism involved in mucin-type O-glycan synthesis of IgA1 hinge-region. In the first section of this work, we explore …

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Protein O-Glcnacylation In Hippocampal Hyperexcitability & Gabaergic Neurotransmission, Luke Thomas Stewart Jan 2018

Protein O-Glcnacylation In Hippocampal Hyperexcitability & Gabaergic Neurotransmission, Luke Thomas Stewart

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Plasticity at central synapses is a vital component of neuronal function and an intensively studied phenomenon thought to underlie learning and memory processes in brain structures including the hippocampus and cerebral cortex. A principle mechanism at work during long-term plasticity is the rapid and heavily regulated post-translational modification of synaptic proteins such as phosphorylation and ubiquitination. A comparatively understudied modification is ‘O-GlcNAcylation’, a distinct form of monoglycosylation with rapid intracellular signaling capacity as opposed to the structural and extracellular signaling roles of O- and N-linked polysaccharide chains on conventionally glycosylated proteins. O-GlcNAcylated proteins are found in every cell type/tissue system …

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The Habitual Offenders, Beth Shelburne Storr Jan 2018

The Habitual Offenders, Beth Shelburne Storr

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The Habitual Offenders is a work of literary journalism, written as a piece of first-person creative nonfiction. The collection of chapters explores a specific class of prison inmates in Alabama, sentenced to life without parole under a three strikes law. Major themes include fairness and disparity in the criminal justice system, politics, race and the community fallout from mass incarceration. This work reflects writing traditions from both investigative/narrative journalism and personal memoir.

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Centrifugal Microfluidics For Label-Free Isolation Of Leukocytes Subpopulations From Whole Blood, Yuxi Sun Jan 2018

Centrifugal Microfluidics For Label-Free Isolation Of Leukocytes Subpopulations From Whole Blood, Yuxi Sun

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Leukocytes carry critical information regarding the immediate immune and inflammation status of the patients. Analysis of leukocytes requires isolation from blood since the leukocytes only consist <1% of all blood cells. Commonly used isolation processes exploit physical or biochemical differences between different cell types to enable separations. Current isolation methods inevitably subject cells to physical or biochemical stress that can activate leukocytes and change their natural state. Thus, information contained within isolated leukocytes is a combination of the natural state of the cell and an artifact of the isolation process. Microfluidics which takes advantage of scaling effects within microscale structures can ensure rapid and gentle alternatives to conventional isolation methods and is ideal for sorting, and analysis of cells and particles. The precise control of flow/particles and scaling effects of microfluidics have been applied for blood cells sorting and isolation. However, the limited processing capability and throughput as well as complex fabrication and operations have hampered widespread adoption of these approaches for replacement of conventional methods. My goal was to develop a simple yet powerful microfluidic tool that enables rapid separation of leukocytes while ensuring sufficient throughput, and minimizing isolation process induced activation without the need any sample pre-processing. This project is divided into two specific aims: i) to miniaturize the conventional density gradient centrifugation using centrifugal microfluidics for PBMC isolation and evaluate separation efficiency and activation status of isolated cells in comparison to conventional techniques; ii) develop new approach for PBMC sorting using microfluidic phase partitioning to enable separation of cells based on differences in cell surface energy. For specific aim 1, PBMCs were isolated based on differences in densities using microfluidic density gradient centrifugation. We show that PBMCs can be isolated from 100µl whole blood within 5 minutes. Evaluation of leukocyte activation via profiling of expression of surface integrins and chemokine receptors shows that our microfluidic approach significantly reduced PBMC activation in comparison to conventional isolation approaches. In specific aim 2, we sought to isolate cells based on differenced in surface energy using two-phase partitioning of dextran (DEX) and polyethylene glycol (PEG). Proof of concept demonstrations was accomplished using with polystyrene and silicon dioxide microbeads which represent a mixture of white blood cells and red blood cells. The DEX and PEG mixtures were introduced into a circular channel and phase separated under centrifugal force into unique DEX and PEG phases. The bead mixture was isolated via differences in their affinity to the two phases.

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Cancer Survivorship In Young Adults: Addressing Disparities In An Invisible Population, Debran Tarver Jan 2018

Cancer Survivorship In Young Adults: Addressing Disparities In An Invisible Population, Debran Tarver

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Young adult survivors are an understudied group and have been considered invisible in cancer care and research. This population has unique medical and psychosocial needs that can influence health outcomes and behaviors. There are also health disparities that exist within this population in treatment and survivorship. Receiving a survivorship care plan (SCP) can equip young adults with the knowledge to advocate for risk-based cancer follow-up and impact health outcomes and behaviors. The purpose of this study is to examine the relationship between receipt of an SCP and age at diagnosis, health outcomes, and health behaviors. Study data were obtained from …

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Pharmacological Inhibition Of Thioredoxin-Interacting Protein To Protect Against Diabetes, Lance Thielen Jan 2018

Pharmacological Inhibition Of Thioredoxin-Interacting Protein To Protect Against Diabetes, Lance Thielen

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The loss of functional beta cell mass represents a major factor in the pathogenesis of type 1 and type 2 diabetes. Inadequate production of insulin, a glucose-lowering hormone, and elevated glucagon production, a gluconeogenic hormone, contribute to impaired glycemic control and hyperglycemia. This promotes a vicious cycle involving glucotoxicity and additional beta cell dysfunction. Currently there are no therapies that halt this process; however, thioredoxin-interacting protein (TXNIP) has recently emerged as a promising therapeutic target. TXNIP was found to be the top glucose-induced gene in a human pancreatic islet microarray, is increased in mouse models of diabetes and diabetic human …

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Reaching Consensus On Global Health Nursing Competencies For Baccalaureate Nursing Education In The United States: A Delphi Method Study, Herica Maria Torres-Alzate Jan 2018

Reaching Consensus On Global Health Nursing Competencies For Baccalaureate Nursing Education In The United States: A Delphi Method Study, Herica Maria Torres-Alzate

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The purpose of this study was to reach consensus among experts on global health competencies for baccalaureate nursing students in the United States. A Nursing Global Health Competencies Framework (NGHCF) was created to guide identification of the domains and competencies for BSN nursing education. A three-round modified Delphi study intersected with a mixed methods research approach to reach consensus from experts in global health on essential global health competencies in nursing. The first phase revised the original list of competencies based on: (a) qualitative responses to the surveys conducted by Wilson et al. (2012), Ventura et al. (2014), and Warren …

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The Effect Of Allergic Airway Sensitization On The Immune Response To Pulmonary Bacterial Infection., Arthur Harold Totten Jan 2018

The Effect Of Allergic Airway Sensitization On The Immune Response To Pulmonary Bacterial Infection., Arthur Harold Totten

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Asthma is a chronic respiratory disease associated with small airway obstruction and hy-perreactivity. Greater than 300 million people are estimated to live with asthma world-wide, and in the United States (US), estimated cost-of-care is over $50 billion per year. Allergic sensitization and infections have proven to be important in both asthmatic development, as well as recurrent exacerbations. Diversity and number of bacterial species are increased in asthmatics compared to non-asthmatics, and is also predictive of increased incidence of res-piratory infections. Mycoplasma pneumoniae (Mpn) is an atypical bacterial pathogen of the class Mollicutes, which lacks a cell wall and is an …

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Analysis Of The Gtp Cyclohydrolase I/Tetrahydrobiopterin Pathway In Glioblastoma Biology, Anh Tran Jan 2018

Analysis Of The Gtp Cyclohydrolase I/Tetrahydrobiopterin Pathway In Glioblastoma Biology, Anh Tran

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Glioblastomas (GBMs) are the most common primary malignant brain tumors in adults and one of the most aggressive cancers with high rates of recurrence and therapeutic resistance. In GBMs, subpopulations of highly tumorigenic cells called brain tumor initiating cells (BTICs) have the unique capacity to promote tumor maintenance, therapeutic resistance, and angiogenesis. Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and BTIC maintenance. GTP cyclohydrolase 1 (GCH1) is the rate limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in GBM. …

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Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner Jan 2018

Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner

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Loss of NF1 in different developmental and cellular contexts leads to unique physiological outcomes due to loss of neurofibromin function, including embryonic lethality, sporadic cancers, and the genetic disorder NF1. Neurofibromin acts as a tumor suppressor by modulation of RAS signaling, with other functions of this multi-domain protein being less clear. Even within the monogenic disorder of NF1, the clinical heterogeneity and mutational spectrum are immense, revealing the complexity underlying this disorder. There is a huge urgency and need for NF1 therapeutic treatments, and the same urgency to develop in vivo models to better understand NF1 that can be utilized …

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Synaptic Mechanisms Underlying The Integration Of Adult-Generated Neurons In The Dentate Gyrus, Ryan Vaden Jan 2018

Synaptic Mechanisms Underlying The Integration Of Adult-Generated Neurons In The Dentate Gyrus, Ryan Vaden

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The dentate gyrus is a region in the adult brain where new neurons continue to be generated throughout life. While most adult-generated neurons undergo apoptosis within the first few weeks of maturation, a fraction survives and integrates into the existing circuit. It is well established that γ-aminobutyric acid (GABA) receptor-mediated mechanisms contribute to the activity-dependent regulation of adult-neurogenesis. GABAergic interneurons regulate stem cell quiescence, progenitor proliferation, and the synaptic integration of newborn neurons, however the synaptic interactions underlying integration are not fully understood. Furthermore, the impact of adult-generated neurons integrating into the existing circuit is not completely known. The collective …

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Clinical And Histomorphometric Outcomes Following The Use Of Small Versus Large Particle Sized Bone Allografts In Ridge Preservation Procedures: A Randomized Clinical Trial, Gentiane Valiquette Jan 2018

Clinical And Histomorphometric Outcomes Following The Use Of Small Versus Large Particle Sized Bone Allografts In Ridge Preservation Procedures: A Randomized Clinical Trial, Gentiane Valiquette

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Alveolar ridge preservation at the time of tooth extraction is a commonly performed procedure as it significantly minimizes ridge resorption and allows for more optimal implant placement. The amount of new vital bone has been shown to vary with the use of different types of bone replacement grafts, however, the effect of bone graft particle size on the outcomes following ridge preservation has not been elucidated in the scientific literature. The present randomized clinical trial compared clinically, radiographically and histomorphometrically the use of small- (0.25-1.0mm) versus large- (1.0- 2.0mm) sized particle mineralized cortico-cancellous bone freeze-dried bone allografts (FDBAs) in ridge …

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Assessing Barriers And Facilitators To Appropriate Care For Chronic Pain And Prescription Opioid Abuse, Allyson Varley Jan 2018

Assessing Barriers And Facilitators To Appropriate Care For Chronic Pain And Prescription Opioid Abuse, Allyson Varley

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The objective of this study was to understand and assess barriers and facilitators to the uptake of appropriate care for co-occurring chronic noncancer pain (CNCP) and opioid use disorder. Rates of CNCP and opioid overdose have doubled in the past decade. When a patient transitions from appropriate use to misuse, significant changes must be made to their treatment plan. Considering most CNCP is treated with opioids in the primary care setting, primary care providers (PCPs) are potential change agents to remediate the epidemic of opioid abuse. Although studies have explored opioid stewardship, we still lack an understanding of the factors …

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Cardiovascular Disease Risk Among Breast Cancer Survivors, Jacqueline B. Vo Jan 2018

Cardiovascular Disease Risk Among Breast Cancer Survivors, Jacqueline B. Vo

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Background: There are nearly 3.5 million breast cancer survivors in the U.S., and approximately 10% are diagnosed prior to age 45 and considered “young.” The overall five-year survival rate for breast cancer survivors is approaching 90%. Living longer, many breast cancer survivors are at risk for developing cardiovascular disease due to cancer treatment, such as anthracyclines and/or trastuzumab. This study’s purpose was to examine cardiovascular disease risk, measured using excess heart age, among young breast cancer survivors. Methods: A retrospective, two-year longitudinal design was used to review electronic medical records of breast cancer survivors diagnosed between 30 and 44 years …

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Social Factors, Public Policies, And Infant Mortality, Lauren Wallace Jan 2018

Social Factors, Public Policies, And Infant Mortality, Lauren Wallace

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Despite consistent and substantial investments, the United States’ infant mortality rate (IMR) has not decreased significantly in the 21st century and disparities between racial and ethnic groups have increased. This study investigates the impact of social and health factors, and public policies on IMR at the state level. The research aims were to: 1) evaluate which state-level social factors and public policies were associated with state IMRs using principal component (PC) analysis; and 2) evaluate whether states cluster on their PC scores and IMRs using cluster analysis. The data used were six composite index scores based on social factor and …

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Assessment Of A Peer Mentoring Program At Lawson State Community College, Teneasha Washington Jan 2018

Assessment Of A Peer Mentoring Program At Lawson State Community College, Teneasha Washington

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ABSTRACT Colleges and universities have begun implementing mentoring programs to offset rising attrition rates; however, the literature on the benefits of these programs is limited particularly among community colleges with peer mentoring programs serving minority students. Further limiting our understanding of post-secondary peer mentoring programs is the lack of research on mentor’s as well as mentee’s perspectives on the mentoring experience. As mentors and mentees serve in a variety of capacities within the mentoring program, it is often difficult to identify outcomes that can be assessed within the mentoring program. Although the success of peer mentoring programs is directly affected …

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Factors Assocaited With Sedentary Lifestyle In Women Participants In Calm (Counseling And Lifestyle Management) Study, Amber Watts Jan 2018

Factors Assocaited With Sedentary Lifestyle In Women Participants In Calm (Counseling And Lifestyle Management) Study, Amber Watts

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Significant evidence has identified the importance of physical activity to the overall health and reduction in disease among humans. The World Health Organization (WHO) has implemented physical activity recommendations as guidelines to increase physical activity among the world population. However, evidence continues to show high levels of self-reported physical inactivity and growing prevalence of related chronic diseases (i.e. type 2 diabetes, stroke, and obesity), particularly among women. To increase participants߀™ knowledge of the benefits of physical activity and reduction of barriers continues to be focal point of interventions. However, studies indicate including more social, theory and cognitive aspects to these …

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Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb Jan 2018

Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb

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Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription during memory consolidation and retrieval. However, the means by which these mechanisms are themselves initiated and directed to specific gene regions, and the extent to which these marks coordinate control of gene expression, remain poorly understood. In this dissertation, we explore the role of methyl-lysine signaling in the epigenetic regulation of gene expression in two contexts. First, we investigated the role of histone H3 lysine 4 tri-methylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) during memory retrieval, finding that these marks increased globally and at CpG-enriched coding …

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Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib Jan 2018

Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib

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Two pathological hallmarks define Parkinson disease (PD) including dopaminergic neurodegeneration in substantia nigra pars compacta (SNpc) and accumulation of α-synuclein insoluble inclusions, called Lewy pathology, in surviving neurons. LRRK2 (encoding Leucine-rich repeat kinase 2) and SNCA (encoding α-synuclein (α-syn)) are two major genes linked to PD. Pathogenic mutations in these two genes cause autosomal dominant (AD) PD. Additionally, genetic variations in LRRK2 and SNCA are associated with increased risk of sporadic PD. Cellular and animal studies using preformed α-syn fibrils (PFF) demonstrate that the fibrils can be internalized by neurons and act as seeds that can recruit and corrupt endogenously …

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