Digital Commons Network^™

A Study Of Coverage Optimized Planning Incorporating Models Of Geometric Uncertainties For Prostate Cancer, Huijun Xu

Theses and Dissertations

A fundamental challenge in the treatment planning process of multi-fractional external-beam radiation therapy (EBRT) is the tradeoff between tumor control and normal tissue sparing in the presence of geometric uncertainties (GUs). To accommodate GUs, the conventional way is to use an empirical planning treatment volume (PTV) margin on the treatment target. However, it is difficult to determine a near-optimal PTV margin to ensure specified target coverage with as much normal tissue protection as achievable. Coverage optimized planning (COP) avoids this problem by optimizing dose in possible virtual treatment courses with GU models directly incorporated. A near-optimal dosimetric margin generated by …

Studies On The Reaction Of High-Dose Hydroxocobalamin And Ascorbic Acid With Carbon Monoxide: Implications For Treatment Of Carbon Monoxide Poisoning, Joseph Roderique

Theses and Dissertations

Based upon experimental evidence from the 1970’s we proposed that a reduced form of hydroxocobalamin should be capable of producing carbon dioxide (CO2) from carbon monoxide (CO) in blood, and that this conversion should be detectable. Using resonance raman spectroscopy we demonstrated that a mixture of hydroxocobalamin and ascorbic acid could create the reduced form of hydroxocobalamin. We used a closed-loop circulation system with a hollow-fiber membrane oxygenator to produce carboxyhemoglobin. Using sensitive gas monitoring equipment to the gas-out port of the oxygenator we analyzed the CO and CO2 concentrations coming from the oxygenator. The mixture of hydroxocobalamin and ascorbic …

Commonwealth Times 2013-04-08

Commonwealth Times, 1969-

No abstract provided.

Applying The Multiple Constituents’ Model And Social Justice Variables To Determine The Constituents’ Perception Of The Virginia Putative Father Registry, Tracey Jackson

Theses and Dissertations

A putative father registry represents a legal option for unmarried males who wish to secure legal notice regarding an adoption proceeding for a child they may have fathered. Putative father registries must balance the interests of the putative father against those of the child, the birth mother, and the adoptive parents. This study utilized a framework adapted from the Multiple Constituency Model and used social justice, as indicated by distributive justice and procedural justice, to determine the perceptions among primary constituency groups of the Virginia Putative Father Registry. This research utilized a mixed-methods approach to analyze qualitative data from focus …

Optimization Of Radiation Therapy In Time-Dependent Anatomy, W. Tyler Watkins

Theses and Dissertations

The objective of this dissertation is to develop treatment planning techniques that have the potential to improve radiation therapy of time-dependent (4D) anatomy. Specifically, this study examines dose estimation, dose evaluation, and decision making in the context of optimizing lung cancer radiation therapy. Two methods of dose estimation are compared in patients with locally advanced and early stage lung cancer: dose computed on a single image (3D-dose) and deformably registered, accumulated dose (or 4D-dose). The results indicate that differences between 3D- and 4D- dose are not significant in organs at risk (OARs), however, 4D-dose to a moving lung cancer target …

Correlates And Predictors Of Risky Sexual Partnering, Jennifer Nield

Theses and Dissertations

Introduction: Sexually Transmitted Diseases, including HIV/AIDS, continue to be a major burden in the United States. Sexual partnering behaviors contribute to the spread of STDs. Sexual concurrency has been shown to exponentially increase STD prevalence in populations. Serial monogamy with short periods between sexual partners also introduces risk. Methods: We identified sexually active men and women from the 2006-2010 National Survey of Family Growth (NSFG) and used sub sets for each particular study. Sexual partnering was defined as being concurrent, serially monogamous or monogamous in the previous year. Polytomous logistic regression models were developed to evaluate the associations between age …

Commonwealth Times 2013-03-28

Commonwealth Times, 1969-

No abstract provided.

Drug Delivery Microdevice: Design, Simulation, And Experiments, Jae Hwan Lee

Theses and Dissertations

Ocular diseases such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting millions of adults in US and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This research focused on an implantable ocular drug delivery device design, simulation and experiments with design requirements including constant diffusion rate, extended period of time operation, the smallest possible volume of device and reservoir. The drug delivery device concept uses micro-/nano-channels module embedded between top and bottom covers with a drug reservoir. Several microchannel …

Commonwealth Times 2013-03-21

Commonwealth Times, 1969-

No abstract provided.

Bridging The Gap: Using The Theory Of Planned Behavior To Predict Hpv Vaccination Intentions In Men, Daniel Snipes

Theses and Dissertations

Genital human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the US, with an estimated incidence rate of 6.2 million new cases each year. Men have higher instances of certain HPV related outcomes (e.g., head/neck cancers) when compared to women, so male vaccination with the HPV vaccine is also paramount to preventing cancer. The present study examined the theory of planned behavior (TPB) as a model for predicting HPV vaccination intentions among men. Results suggest the TPB was a well-fitting model to the data, but not all aspects of the TPB model were predictive of HPV vaccination …

Rehabilitation Service Utilization Among African American Women Living With Hiv/Aids: Using The Behavioral Model For Vulnerable Populations, Aisha Shamburger-Rousseau

Theses and Dissertations

African American women represent one of the largest groups disproportionately living with and affected by HIV/AIDS yet African American women have largely been unrepresented in the federal-state rehabilitation system. As pharmaceutical treatment options improve and individuals with HIV/AIDS are living longer and healthier lives, research exploring the appropriateness of rehabilitation services has increased. Accordingly, it has become more necessary to address the needs of this population. As the largest service provider for people with disabilities, the state-federal rehabilitation system has the potential to be a vital resource for African American women living with HIV/AIDS. The purpose of this study is …

Uncovering The Molecular Pathways Of Mbd5 In Neurodevelopmental Disorders, Sureni Mullegama

Theses and Dissertations

Neurodevelopmental disorders (NDs) are a growing public health concern. These complex disorders cause failure of normal brain development, which leads to intellectual disability (ID) or autism in 3% of children. Accurate diagnosis of NDs is difficult due to complex overlapping phenotypes. Moreover, associations between phenotypically similar NDs and their overlapping molecular mechanisms remain unidentified. The chromosome 2q23.1 region is a newly discovered disease region. We have recently identified a novel ND, 2q23.1 deletion syndrome. The phenotype includes severe ID, significantly delayed speech, behavioral problems, seizures and short stature. This syndrome shares characteristics in common with other genetic syndromes, including Smith-Magenis …

Youth Drug Use In Turkey: A Test Of The General Strain Theory, Fatih Cipil

Theses and Dissertations

This study examines the effect of strain on youth drug use in Turkey. With its many unexplored fields, Turkey is a haven for social researchers. Adolescent crime and especially drug use is an important yet poorly studied subject in Turkey. Of the many correlates of youth drug use, strain as asserted by the General Strain Theory of Agnew (1985) is chosen as the main explanatory variable in this research. Using Youth in Europe (YIE) survey data administered to a representative sample of high school students in Istanbul City, correlates of marijuana, LSD, amphetamine and ecstasy use among adolescents are analyzed …

The Impact Of Perpetrator Gender On Child Protective Services Sexual Abuse Cases: A National Picture, David Axlyn Mcleod

Theses and Dissertations

Child sexual assault is a problem of epidemic proportions in the United States with some research suggesting up to one fifth of our nations children being victimized before reaching adulthood. Research has suggested females could be responsible for up to 20% of child sexual abuse cases, and at the same time only represent only 1% of sexual offenders incarcerated the US. This creates a situation where a large group of relatively under-researched offenders are evading detection. Numerous calls for further research have been made, but relatively few studies have had the ability to shed significant light on this phenomenon on …

Commonwealth Times 2013-02-21

Commonwealth Times, 1969-

No abstract provided.

Antisocial Behavior From Adolescence To Early Adulthood: Heritability, Stability, And Correlates Using A Longitudinal Twin Sample, Ashley Dibble

Theses and Dissertations

The purpose of this study was to examine the heritability, stability, and outcomes of antisocial behavior from adolescence into adulthood in a longitudinal twin sample. Specifically, the genetic and environmental influences on conduct disorder, adult antisocial behavior, and alcohol dependence were examined. The influence of genes and environment on the relationship between these disorders was also examined. The study utilized a subset of FinnTwin12, a population-based twin study that consists of five consecutive birth cohorts. The subsample consisted of 1035 twin pairs (N = 2070) and of that 2070, 1854 completed the intensive interview at age 14. At age 22, …

Positive Allosteric Modulators Of Alpha4beta2 Neuronal Nicotinic Receptors: Synthesis And In Vitro Studies, Atul Jain

Theses and Dissertations

des-Formylflustrabromine (dFBr), isolated from the marine organism Flustra foliacea, is the first selective, positive allosteric modulator (PAM) of α4β2 nicotinic acetylcholine receptors that potentiates the action of the neurotransmitter acetylcholine (ACh). Most agonists for this receptor population are not selective and can activate other nACh receptors. A selective PAM, which activates α4β2 nACh receptors only in the presence of ACh, might find application in the treatment of of various neurological diseases such as Alzheimer’s disease or autism. dFBr was examined and found to produce a biphasic dose-response curve over a wide concentration range (i.e., potentiation at low concentration, but inhibition …

Characterization Of Potential Interactions Between Transferrin Binding Proteins In Neisseria Gonorrhoeae, Shreni Mistry

Theses and Dissertations

Neisseria gonorrhoeae requires iron for survival and establishment of infection in the human host. Pathogenic Neisseriae have evolved a repertoire of high-affinity iron acquisition systems to facilitate iron uptake in the human host. This requires specific outer membrane receptors and energy-harnessing cytoplasmic membrane proteins. The transferrin receptor proteins of Neisseria gonorrhoeae are necessary for iron uptake from transferrin in the host. The iron uptake system consists of two transferrin binding proteins, (Tbp) A and B. TbpA is an integral outer membrane, TonB-dependent transporter that forms the pore for iron internalization. TbpB is a surface exposed lipoprotein that makes the iron …

Impacts Of Black Box Warning, National Coverage Determination, And Risk Evaluation And Mitigation Strategies On The Inpatient On-Label And Off-Label Use Of Erythropoiesis-Stimulating Agents, Arpamas Seetasith

Theses and Dissertations

Background: FDA black box warning, Risk Evaluation and Mitigation Strategies (REMS), and CMS national coverage determination (NCD) aim to reduce inappropriate use of erythropoiesis-stimulating agents (ESAs) that are widely used in anemic patients. Previous studies have not linked specific safety interventions to changes in ESA utilization patterns in the inpatient settings nor assessed such interventions on off-label use of the drugs. Ineffectiveness of the intervention and lag time between such interventions and the observed change in clinical practice could lead to serious clinical outcomes. In addition, such interventions may unintentionally reduce on-label and some off-label use of ESAs considered “appropriate” …

Design, Syntheses, And Biological Evaluation Of 14-N-Substituted Naltrexone Derivatives As Opioid Receptor Ligands, Orgil Elbegdorj

Theses and Dissertations

Opium, the dried resin obtained from the unripe seedpods of the poppy flower, has been used for medicinal and euphoric purposes since ancient times. Morphine, the main active ingredient of opium, and other clinically useful opioid analgesics all mediate their effects through activating the mu opioid receptor. Studies involving the mu opioid receptor knockout mice showed that the interaction with the mu opioid receptor is also responsible for many notorious side effects associated with these drugs including dependence and addiction. Therefore, selective antagonists for the mu opioid receptor are needed to study its function in drug abuse and addiction. Previously, …

Commonwealth Times 2013-01-28

Commonwealth Times, 1969-

No abstract provided.

Commonwealth Times 2013-01-24

Commonwealth Times, 1969-

No abstract provided.

Klf2 Is Required For Normal Mouse Cardiovascular Development, Aditi Raghunath Chiplunkar

Theses and Dissertations

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …

Commonwealth Times 2013-01-17

Commonwealth Times, 1969-

No abstract provided.

Defining A Simplified Pharmacophore For Simocyclinone D8 Inhibition Of Dna Gyrase, Lauren Gaskell

Theses and Dissertations

The type II topoisomerase subfamily of enzymes has been clinically targeted by the widely used, broad-spectrum quinolone class of antibacterials. Due to emerging drug-resistant strains of bacteria, the quinolones’ effectiveness is threatened. The natural product simocyclinone D8 (SD8) has shown the ability to inhibit the type II topoisomerase, DNA gyrase, even when mutated to be resistant to the quinolones. In order to determine the pharmacophore required for SD8 binding to DNA gyrase, 16 compounds were synthesized. These compounds were then tested by surface plasmon resonance for their ability to inhibit the DNA – DNA gyrase binding interaction. It was found …

Improved Detection Of Common Variants Associated With Schizophrenia And Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate, Ole A. Andreassen, Wesley K. Thompson, Andrew J. Schork, Stephan Ripke, Morten Mattingsdal, John R. Kelsoe, Kenneth S. Kendler, Michael C. O'Donovan, Dan Rujescu, Thomas Werge, Pamela Sklar, J. Cooper Roddey, Chi-Hua Chen, Linda Mcevoy, Rahul S. Desikan, Srdjan Djurovic, Anders M. Dale

Psychiatry Publications

Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disease risk are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability. Epidemiological and clinical evidence suggest similar disease characteristics and overlapping genes between SCZ and BD. Here, we computed conditional …

Self-Healing Of Ionomeric Polymers With Carbon Fibers From Medium-Velocity Impact And Resistive Heating, Vishnu Baba Sundaresan, Andrew Morgan, Matt Castellucci

Mechanical and Nuclear Engineering Publications

Self-healing materials science has seen significant advances in the last decade. Recent efforts have demonstrated healing in polymeric materials through chemical reaction, thermal treatment, and ultraviolet irradiation. The existing technology for healing polymeric materials through the aforementioned mechanisms produces an irreversible change in the material and makes it unsuitable for subsequent healing cycles. To overcome these disadvantages, we demonstrate a new composite self-healing material made from an ionomer (Surlyn) and carbon fiber that can sustain damage from medium-velocity impact and heal from the energy of the impact. Furthermore, the carbon fiber embedded in the polymer matrix results in resistive heating …

Hydration Of The Pyrimidine Radical Cation And Stepwise Solvation Of Protonated Pyrimidine With Water, Methanol, And Acetonitrile, Ahmed M. Hamid, Pramod Sharma, M. Samy El-Shall, Rifaat Hilal, Shaaban Elroby, Saadullah G. Aziz, Abdulrahman O. Alyoubi

Chemistry Publications

Equilibrium thermochemical measurements using an ion mobility drift cell technique have been utilized to investigate the binding energies and entropy changes associated with the stepwise hydration of the biologically significant ions pyrimidine radical cation and protonated pyrimidine. The binding energy of the hydrated pyrimidine radical cation is weaker than that of the proton-bound dimer pyrimidineH+(H2O) consistent with the formation of a weak carbon-based CHδ+··OH2 hydrogen bond (11.9 kcal/mol) and a stronger NH+··OH2 hydrogen bond (15.6 kcal/mol), respectively. Other proton-bound dimers such as pyrimidineH+(CH3OH) and pyrimidineH+(CH3CN) exhibit higher binding energies (18.2 kcal/mol and 22.8 kcal/mol, respectively) due to the higher proton …

Ethanol Regulation Of Serum Glucocorticoid Kinase 1 Expression In Dba2/J Mouse Prefrontal Cortex, Blair N. Costin, Seth M. Dever, Michael F. Miles

Pharmacology and Toxicology Publications

Background

We previously identified a group of glucocorticoid-responsive genes, including Serum Glucocorticoid kinase 1 (Sgk1), regulated by acute ethanol in prefrontal cortex of DBA2/J mice. Acute ethanol activates the hypothalamic pituitary adrenal axis (HPA) causing release of glucocorticoids. Chronic ethanol dysregulates the HPA response in both humans and rodents, possibly contributing to important interactions between stress and alcoholism. Because Sgk1regulates ion channels and learning and memory, we hypothesized that Sgk1 contributes to HPA-dependent acute and adaptive neuronal responses to ethanol. These studies characterized acute and chronic ethanol regulation of Sgk1 mRNA and protein and their relationship with ethanol actions …

Cannabinoid Cb2 Receptors Regulate Central Sensitization And Pain Responses Associated With Osteoarthritis Of The Knee Joint, James J. Burston, David R. Sagar, Pin Shao, Mingfeng Bai, Emma King, Louis Brailsford, Jenna M. Turner, Gareth J. Hathway, Andrew J. Bennett, David A. Walsh, David A. Kendall, Aron H. Lichtman, Victoria Chapman

Pharmacology and Toxicology Publications

Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies.

Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that …