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Genetic Analysis Of Ethanol Sensitivity And Tolerance In Drosophila, Robin Chan Jul 2013

Genetic Analysis Of Ethanol Sensitivity And Tolerance In Drosophila, Robin Chan

Theses and Dissertations

The genetic pathways influencing alcohol abuse and dependence are poorly characterized. Many critical discoveries about the interactions between ethanol-related behaviors and genetics have been made in the fruit fly Drosophila melanogaster. Coupling the statistical power of model organism studies to human association studies bolsters the analytical efficacy of these genomic approaches. A variety of behavioral assays are available for assessing behavioral responses to ethanol in Drosophila. However, we find our previously described eRING assay is influenced by the commonly used transgenic marker mini-white. We developed a Simple Sedation Assay (SSA) that is insensitive to the effects of white and mini-white. …

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Adam10 Overexpression Dysregulates Notch Signaling In Favor Of Myeloid Derived Suppressor Cell (Mdsc) Accumulation That Deferentially Modulates The Host Response Depending On Immune Stimuli And Interaction With Mast Cells., Sheinei Saleem Jul 2013

Adam10 Overexpression Dysregulates Notch Signaling In Favor Of Myeloid Derived Suppressor Cell (Mdsc) Accumulation That Deferentially Modulates The Host Response Depending On Immune Stimuli And Interaction With Mast Cells., Sheinei Saleem

Theses and Dissertations

Although the physiological consequences of Notch signaling in hematopoiesis have been extensively studied, the differential effects of individual notch cleavage products remain to be elucidated. Given that a disintegrin and metalloproteinase 10 (ADAM10) is a critical regulator of Notch and that its deletion is embryonically lethal, we generated transgenic mice that overexpress ADAM10 at early stages of lymphoid and myeloid development (A10Tg). ADAM10 transgene expression alters hematopoiesis post-hematopoietic Lineage-Sca-1+c-kit+ (LSK) subset differentiation but prior to lineage commitment of progenitor populations. This results in delayed T cell development, abrogated B2 cell development, and dramatic expansion of functionally active myeloid derived suppressor …

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Synthesis, Testing And Crystallographic Studies Of Allosteric Modifiers Of Hemoglobin, Tanvi Deshpande Jul 2013

Synthesis, Testing And Crystallographic Studies Of Allosteric Modifiers Of Hemoglobin, Tanvi Deshpande

Theses and Dissertations

The major physiological function of hemoglobin (Hb) is to bind, transport and deliver oxygen to tissues; made efficient by endogenous effectors, such as protons and 2,3-diphosphoglycerate. Synthetic allosteric effectors of Hb (AEHs) are also known to modulate Hb oxygen affinity, showing potential for the treatment of sickle cell disease (SCD) and ischemic-related diseases. In this project, AEHs which increase Hb affinity for oxygen, including derivatives of the anti-sickling compounds, 5HMF and benzaldehydes, as well as an AEH that decreases Hb affinity for oxygen, RSR-13, were synthesized for their effects on Hb oxygen binding property and their capability to release NO …

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S3-S4 Linker Modulation Of Voltage Sensor Relaxation In Voltage Gated Potassium Channels, W. Everett Fox Jul 2013

S3-S4 Linker Modulation Of Voltage Sensor Relaxation In Voltage Gated Potassium Channels, W. Everett Fox

Theses and Dissertations

It is commonly assumed that the voltage dependence for activation of voltage-gated channels is an intrinsic characteristic of the protein that remains unchanged during electrical activity. However, sporadic reports have suggested otherwise by showing that voltage dependence changes in a use-dependent manner resulting in a voltage dependence shift towards negative potentials (Bezanilla et al., 1982; Bruening-Wright and Larsson, 2007; Kuzmenkin et al., 2004; Labro et al., 2012; Larsson and Elinder, 2000; Olcese et al., 1997; Piper et al., 2003; Shirokov et al., 1992). Although the mechanism underlying the shift in voltage dependence remains unclear, this process seems to have two …

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The Effects Of Gain Of Function Mutant P53 And P63 On Eps8 And Cxcl5 Expression In Head And Neck Squamous Cell Carcinoma, Rubana Masood Jul 2013

The Effects Of Gain Of Function Mutant P53 And P63 On Eps8 And Cxcl5 Expression In Head And Neck Squamous Cell Carcinoma, Rubana Masood

Theses and Dissertations

Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers worldwide, with a survival rate of less than 50%. A class of mutant p53, known as gain of function (GOF) mutant p53, has been found to be expressed in tumors in these patients. GOF mutant p53 not only loses the wild type tumor suppressor functions, but also gains aberrant functions that have been linked to tumorigenesis. In this current study, we utilized a model system consisting of cells derived from HNSCC tumors in order to investigate our hypothesis that GOF mutant p53 enhances, and p63 …

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Motion Artifact Reduction In Impedance Plethysmography Signal, Sardar Ansari Jun 2013

Motion Artifact Reduction In Impedance Plethysmography Signal, Sardar Ansari

Theses and Dissertations

The research related to designing portable monitoring devices for physiological signals has been at its peak in the last decade or two. One of the main obstacles in building such devices is the effect of the subject's movements on the quality of the signal. There have been numerous studies addressing the problem of removing motion artifact from the electrocardiogram (ECG) and photoplethysmography (PPG) signals in the past few years. However, no such study exists for the Impedance Plethysmography (IP) signal. The IP signal can be used to monitor respiration in mobile devices. However, it is very susceptible to motion artifact. …

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Effectiveness Of Visual Aids On Preventive Dental Goals, Kristin Hodgson Jun 2013

Effectiveness Of Visual Aids On Preventive Dental Goals, Kristin Hodgson

Theses and Dissertations

Purpose: To assess a caregiver’s oral health attitudes, habits, and behaviors pre and post intervention, and to determine whether a particular delivery-style (verbal-only or with visual supplementation) of a motivational interviewing session is more effective in improving oral health behaviors as well as improving success of a chosen preventive goal. Methods: N=140 caregivers of pediatric dental patients were given questionnaires to assess readiness to change and current preventive oral health behaviors. Oral health education was communicated in a MI style (verbal-only or with visual supplementation). One preventive oral health goal was selected to focus on. The home preventive behavior survey …

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Cannabinoids Delta-9-Tetrahydrocannabinol (Thc) And Cp55,940 Ablate Specific Chemokine And Cytokine Inflammatory Response In Bv-2 Mouse Microglial Cells Activated With Hiv-1 Pro-Inflammatory Protein Tat, Rebecca Maddux Jun 2013

Cannabinoids Delta-9-Tetrahydrocannabinol (Thc) And Cp55,940 Ablate Specific Chemokine And Cytokine Inflammatory Response In Bv-2 Mouse Microglial Cells Activated With Hiv-1 Pro-Inflammatory Protein Tat, Rebecca Maddux

Theses and Dissertations

Despite the widespread use of Highly Active Anti-retroviral Therapy (HAART) to combat Human Immunodeficiency Virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), HIV-Associated Neurocognitive Disorders (HANDs) still remain a dire issue. HIV can enter the brain through infected monocytes and infect microglia, the resident macrophages within that compartment. Due to its pro-inflammatory properties, HIV regulatory protein Tat (Transactivating protein) may play a role in the progression of neurocognitive disorders. The aim of this project was to determine whether the select cannabinoids THC and CP55,940 could ablate the inflammatory response on BV-2 mouse microglia cells caused by Tat. Within …

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Identification Of Multiple Levels Of Trauma Induced Coagulopathy, Jason Newton Jun 2013

Identification Of Multiple Levels Of Trauma Induced Coagulopathy, Jason Newton

Theses and Dissertations

Trauma continues to be a major cause of death across the globe. While the exact causes of trauma differ greatly between the military and civilian lifestyles, the ability to stop bleeding after trauma is paramount for survival. Over the past decade coagulation research has transitioned from a classical understanding of plasma based protein coagulation to the current cell focused research. As part of this shift, platelets have become a central player in hemostasis. Unfortunately little is currently understood about how platelet function is affected by trauma. In an effort to better define platelet function during trauma and the resulting shock …

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A Systems Biology Approach For Understanding Inflammation In The Gastrointestinal Tract Of A Crohn’S Patient, Gigi Meyer Jun 2013

A Systems Biology Approach For Understanding Inflammation In The Gastrointestinal Tract Of A Crohn’S Patient, Gigi Meyer

Theses and Dissertations

A system of ordinary differential equations is developed to model the effect of fatty acids on chronic intestinal inflammation that is typical of a Crohn’s patient. Several murine studies have shown an anti-inflammatory response when specific polyunsaturated fatty acids are included regularly in the diet. It is believed that the fatty acids serve as a specific ligand that activates the Peroxisome Proliferator Activated Receptor (PPAR) which is located on multiple cell types that are active in the inflammatory response. The binding of the PPAR results in a suppression of the inflammatory pathway. Results of the model indicate a muted inflammatory …

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Impact Of Self-Fertilization On Fecundity, The Timing Of First Reproduction, And Population Genetic Structure: Is A Mate Worth The Wait?, Serena Caplins Jun 2013

Impact Of Self-Fertilization On Fecundity, The Timing Of First Reproduction, And Population Genetic Structure: Is A Mate Worth The Wait?, Serena Caplins

Theses and Dissertations

Organisms capable of self-fertilization typically exhibit two evolutionary syndromes uniting high inbreeding depression with low levels of selfing, or low inbreeding depression and high levels of selfing. This study tests for inbreeding depression in an apparent self-compatible, hermaphroditic marine nemertean worm, Prosorhochmus americanus. Fecundity and timing to first reproduction were assessed in isolated and paired worms. Isolated worms produced significantly more offspring than paired worms and did not show inbreeding avoidance. The selfing rate of natural populations was evaluated using species-specific microsatellites and is consistent with preferential selfing (mean: 0.801), though some outcrossing appears to take place. Population genetic structure …

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Genetic And Molecular Analysis Of The Maize R1 Locus, Jennifer Derkits Jun 2013

Genetic And Molecular Analysis Of The Maize R1 Locus, Jennifer Derkits

Theses and Dissertations

Canalization, the stability of phenotypes in the presence of a specific genotype and environment is important for trait selection and understanding gene expression pathways. The goal of this study was to investigate mechanisms involved in the loss of canalization at the maize r1 locus. A specific lightly colored R-sc derivative, R-sc:86-17(L), was mutagenized with ethyl methyl sulfonate (EMS), and the progeny screened for restoration of dark seed color and canalization. Putative revertants/mutants were mapped relative to the r1 locus, tested for complementation to each other to identify a minimum number of genes involved in canalization, tested for cis silencing of …

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Structural Basis Of Dna Binding Complexes, Ninad Walavalkar May 2013

Structural Basis Of Dna Binding Complexes, Ninad Walavalkar

Theses and Dissertations

The nucleosome remodeling and deacetylase (NuRD) complex is an abundant deacetylase complex, which couples histone deacetylation and chromatin remodeling ATPase activities, and has a broad cellular and tissue distribution. Although the working model of how this complex forms and functions is not well known, we have demonstrated that the coiled-coil interaction between two proteins (MBD2 and p66α) is critical for DNA methylation dependent gene silencing in vivo. Chapter one: ‘Unique features of the anti-parallel, heterodimeric coiled-coil interaction between methyl-cytosine binding domain 2 (MBD2) homologues and p66α dictate high affinity binding’ describes this unique coiled coil interaction. Coiled-coils were studied using …

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Implications Of Child Abduction For Human Rights And Child Welfare Systems: A Constructivist Inquiry Of The Lived Experience Of Guatemalan Mothers Publically Reporting Child Abduction For Intercountry Adoption, Carmen Monico May 2013

Implications Of Child Abduction For Human Rights And Child Welfare Systems: A Constructivist Inquiry Of The Lived Experience Of Guatemalan Mothers Publically Reporting Child Abduction For Intercountry Adoption, Carmen Monico

Theses and Dissertations

The Hague Convention on the Protection of Children and Co-operation in Respect of Intercountry Adoption was agreed upon in 1993 at the Hague Conference on Private International Law to address growing allegations of abduction, sale, and trafficking of children around the world. The Hague Convention guides countries to attend to the “best interest of the child” in making decisions on intercountry adoptions, and to apply the “principle of subsidiarity,” which calls for the consideration of family and kinship placement and national adoption prior to the consideration of intercountry adoption. This dissertation research focused on the experience of Guatemalan mothers reporting …

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Selection Of A Non-Phosphorylated Peptide Inhibitor Of Brca1’S (Brct)2 Domain, Railey White May 2013

Selection Of A Non-Phosphorylated Peptide Inhibitor Of Brca1’S (Brct)2 Domain, Railey White

Theses and Dissertations

A growing body of literature suggests Breast Cancer-Associated Protein 1 (BRCA1) is important not only as a cause, but also as a target in the quest for cancer treatment. BRCA1 deficient cells treated with radiation as well as PARP inhibitors and other chemotherapeutics demonstrate a greater sensitivity than cells with wild type BRCA1. Inhibitors of BRCA1 would take advantage of this synthetic lethality and represent a significant advance in cancer treatment as well as an understanding of the biology of DNA repair. Despite significant study of BRCA1 protein and function, it is a large protein (220 KDa) that is still …

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Intra-Mitochondrial Injury During Ischemia-Reperfusion, Hema Aluri May 2013

Intra-Mitochondrial Injury During Ischemia-Reperfusion, Hema Aluri

Theses and Dissertations

Cardiac injury is increased following ischemia-reperfusion. Mitochondria are the “effector organelles” that are damaged during ischemia (ISC) when there is no blood flow. Resumption of metabolism by damaged mitochondria during reperfusion (REP) results in increased cell injury. Current therapeutic interventions to pre-condition and post-condition the heart during ISC are ineffective during certain conditions like aging and diabetes due to defects in the signaling cascades. In contrast, mitochondrial-based strategies are effective in protecting the heart during ISC-REP. Hence direct therapeutic targeting of dysfunctional mitochondria will provide the potential to bypass the upstream signaling defects and intervene directly upon the effector organelle. …

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Water Soluble Polymer Solar Cells From Electrospray Deposition, Marshall Sweet May 2013

Water Soluble Polymer Solar Cells From Electrospray Deposition, Marshall Sweet

Theses and Dissertations

This dissertation reports the fabrication and characterization of thin films from the water soluble polymer sodium poly[2-(3-thienyl)-ethyloxy-4-butylsulfonate] (PTEBS) by electrospray deposition (ESD). Contiguous thin films were created by adjusting the parameters of the electrospray apparatus and solution properties to maintain a steady Taylor cone for uniform nanoparticle aerosolization and controlling the particle water content to enable coalescence with previously deposited particles. The majority of deposited particles had diameters less than 52 nm. A thin film of 64.7 nm with a root mean square surface roughness of 20.2 nm was achieved after 40 minutes of ESD. Hybrid Solar Cells (HSCs) with …

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Complex Network Growing Model Using Downlink Motifs, Ahmad Al-Musawi Jr. May 2013

Complex Network Growing Model Using Downlink Motifs, Ahmad Al-Musawi Jr.

Theses and Dissertations

Understanding the underlying architecture of gene regulatory networks (GRNs) has been one of the major goals in systems biology and bioinformatics as it can provide insights in disease dynamics and drug development. Such GRNs are characterized by their scale-free degree distributions and existence of network motifs, which are small subgraphs of specific types and appear more abundantly in GRNs than in other randomized networks. In fact, such motifs are considered to be the building blocks of GRNs (and other complex networks) and they help achieve the underlying robustness demonstrated by most biological networks. The goal of this thesis is to …

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Cytotoxic Properties Of Novel Platinum Compounds, Bbr3610-Dach And Trans-4-Nbd In Tumor Cells: Cellular Effects Of 1, 2-Dach And Nbd Ligands, Vijay Menon May 2013

Cytotoxic Properties Of Novel Platinum Compounds, Bbr3610-Dach And Trans-4-Nbd In Tumor Cells: Cellular Effects Of 1, 2-Dach And Nbd Ligands, Vijay Menon

Theses and Dissertations

Platinum-based chemotherapeutics are used for the treatment of a wide range of cancers and a number of attempts have been made toward developing compounds with better cellular stability and similar or enhanced cytotoxicity as compared to their predecessors. The first part of the work reported here focuses on the cellular effects of the metabolically stable dinuclear platinum compound, BBR3610-DACH. Comet assay showed this compound to form interstrand crosslinks, a highly toxic DNA lesion in HCT116 cells, at equimolar concentrations to its parental compound, BBR3610. Cell cycle studies showed that BBR3610-DACH causes G1/S and G2/M cell cycle arrest with S phase …

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Inhibition Of Retinoic Acid Receptors Results In Defasciculation Of The Trigeminal Nerve In Xenopus Laevis, Jeremy Thompson May 2013

Inhibition Of Retinoic Acid Receptors Results In Defasciculation Of The Trigeminal Nerve In Xenopus Laevis, Jeremy Thompson

Theses and Dissertations

The anatomy of the cranial peripheral nervous system has been studied for over a century, yet surprisingly little is known about how the nerves are guided to their targets. The study of the development of these nerves has important implications for our understanding of craniofacial anomalies and possible treatments for both injury and genetic disorders of nerve development such as Goldenhar-Gorlin syndrome. We have discovered that retinoic acid (RA) may play a role in the development of the trigeminal nerve. Inhibition of retinoic acid receptors (RAR) results in trigeminal nerves that become unbundled or defasciculated in the eye region. To …

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Fragments Of Social Life, Rachel Leah Cohn May 2013

Fragments Of Social Life, Rachel Leah Cohn

Theses and Dissertations

This paper examines selected events from biography and how those events have influenced my philosophies about art-making as well as the work I have produced while a graduate student at Virginia Commonwealth University. This thesis is an attempt to give an expanded context for my work through various lenses, including the personal, the traumatic, the historical and the material.

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The Role Of Family Organization In Family Health History Communication About Cancer, Vivian M. Rodríguez May 2013

The Role Of Family Organization In Family Health History Communication About Cancer, Vivian M. Rodríguez

Theses and Dissertations

Family health history (FHH) has been recognized as an important tool in cancer prevention and health promotion. To date, literature on FHH discussions about cancer have largely focused on patient-physician communication or the dissemination of cancer-specific genetic tests results within the family. Fewer studies have sought to identify family factors that may promote FHH discussions, yet this type of information could be used to identify families needing support in having these conversations. Thus, the present study examined relations between family organization (cohesion and flexibility), communication openness, and FHH communication about cancer within a diverse group of women recruited from an …

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Naturalis Historia, Reconstructed, Sarah Briland May 2013

Naturalis Historia, Reconstructed, Sarah Briland

Theses and Dissertations

When Pliny the Elder wrote Naturalis Historia around 70 A.D., the idea of natural history contained and connected biology, geology, and mineralogy with the history of painting and sculpture. Art was an extension of the natural world as its materials were extracted from plants, animals, and, particularly, mined and quarried pigments, stone, and metals. In my developing body of work, Incidents of Naturalis Historia, Reconstructed, I combine wasps’ nests, architectural fragments, and other found objects excavated from my surrounding environment with elements of glass that resemble lichen, crystallization, and geologic specimens. These works simulate artifacts of an alternative history; one …

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The Design And Validation Of A Computational Model Of The Human Wrist Joint, Afsarul Mir May 2013

The Design And Validation Of A Computational Model Of The Human Wrist Joint, Afsarul Mir

Theses and Dissertations

Advancements in computational capabilities have allowed researchers to turn towards modeling as an efficient tool to replicate and predict outcomes of complex systems. Computational models of the musculoskeletal system have gone through various iterations with early versions employing dramatic simplifications. In this work, a three-dimensional computational model of the wrist joint was developed. It accurately recreated the skeletal structures of the hand and wrist and represented the constraints imposed by soft tissue structures like ligaments, tendons, and other surrounding tissues. It was developed to function as a tool to investigate the biomechanical contributions of structures and the kinematic response of …

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Examining The Relations Between The Mental Health And Physical Health Of Caregivers Of Ms In A Mexican Sample, Gillian Leibach May 2013

Examining The Relations Between The Mental Health And Physical Health Of Caregivers Of Ms In A Mexican Sample, Gillian Leibach

Theses and Dissertations

Evidence suggests that caregiver health affects patient health. Consistent with the Biopsychosocial Model, mental health (anxiety, depression, satisfaction with life, self-esteem), physical health (bodily pain, general health, performance in physical role, physical functioning), burden, and social support were examined in the present study to understand the relations between these variables and the overall health of 81 caregivers of patients with multiple sclerosis (MS) in Mexico. The relation between mental health and physical health was significant. Canonical correlations revealed that depression and general health emerged as primary variables and these were entered into a series of analyses with burden and social …

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Sociodemographic Risk Factors Of Glycemic Control For Youth With T1d: Cross-Sectional And Longitudinal Patterns Of Hba1c, Priscilla Powell May 2013

Sociodemographic Risk Factors Of Glycemic Control For Youth With T1d: Cross-Sectional And Longitudinal Patterns Of Hba1c, Priscilla Powell

Theses and Dissertations

Individual growth curve (IGC) modeling evaluated longitudinal trajectories of glycemic control and diabetes care of youth with Type 1 Diabetes (T1D) over three years. IGC modeling allowed comparison of confounded sociodemographic predictors of disease outcomes that included ethnicity, SES, parent marital status, family structure, as well as disease duration, to determine the relative impact of these factors in the evolution of HbA1c and diabetes care throughout adolescence. At baseline, participants recruited from two pediatric endocrinology clinics included 198 youth, ages 9-15 (M age = 12.65, 77% Caucasian, 74% lived with married biological parents, M SES = 45.70) with average HbA1c …

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Development And Evaluation Of The Assessment Of Opioid Taking Behaviors And Adherence Scale (Aotba) In Patients With Sickle Cell Disease, Abdulkhaliq Jassem Alsalman May 2013

Development And Evaluation Of The Assessment Of Opioid Taking Behaviors And Adherence Scale (Aotba) In Patients With Sickle Cell Disease, Abdulkhaliq Jassem Alsalman

Theses and Dissertations

The rapid growth in opioid therapy for non-cancer pain has occurred without an adequate appreciation of the consequences of this growth. Few studies provide patient-centered evidence that can be used to inform the current proposed standards for efficacious (safe and effective) opioid prescribing in non-cancer pain. Furthermore, different terms may be used interchangeably in the literature to refer to opioid-taking behaviors, resulting in imprecise or vague interpretation of existing evidence. We therefore sought to explore patterns of opioid-taking behavior and their biopsychosocial-spiritual determinants in African-American adults with sickle cell disease (SCD). Many questions surround opioid use for non-cancer pain, but …

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Underlying Conditions, Mariam Eqbal May 2013

Underlying Conditions, Mariam Eqbal

Theses and Dissertations

The following is a collection of lines, curves, and dots on a plane, representing words fashioned to communicate my ideas about relationships between the thing and the nothing. This thesis is like a map, a contour drawing, an assortment of lines, speaking my thoughts about things in relation to space and time. As something moving, developing into another thing, as a thing sentient, I am viewing, performing, and processing incremental acts. I am looking at water and I can see my reflection break into a thousand pieces. It is like watching time.

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Predictors Of Agitation In The Critically Ill, Ruth Burk May 2013

Predictors Of Agitation In The Critically Ill, Ruth Burk

Theses and Dissertations

BACKGROUND: Agitation is a common complication in the intensive care unit (ICU) manifested in behavior and actions that range from simple apprehension or anxiety to frankly combative behavior.5 Agitation is associated with significant adverse outcomes.1-3 Studies report up to 71% of ICU patients have some degree of agitation during their ICU stay and that agitation is observed 32% of the time.3;4 Potential causes of agitation in critically ill patients are numerous; however, data about factors that predict agitation are limited. OBJECTIVE: The specific aim of this study was to identify predictors of agitation on admission to the ICU as well …

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Finding History In The Future, Al-Sowaidi Aisha May 2013

Finding History In The Future, Al-Sowaidi Aisha

Theses and Dissertations

Change and development over an extremely fast period of time in Qatar have shifted the atmospheric sense of the country. The distance created by the skyscrapers and their scale to people has a great impact on the behavior and interaction between the people and the city. In my research, I aim to incorporate the old experiences and behaviors with contemporary design in objects used within the house to maintain the feeling of being home through reliving the fading behaviors and traditions as well as bringing closer the modern city into the home through the use of materials. Through experimentation with …

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