Physical Sciences and Mathematics Commons^™

Estimated Probability Of Becoming Alcohol Dependent: Extending A Multiparametric Approach, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Presentations

Background: United States (US) epidemiological studies suggest that for every 5-8 who start drinking alcoholic beverages, at least one drinker will develop an alcohol dependence (AD) syndrome within the first 10 years after onset of drinking (Lopez-Quintero et al., 2011; Wagner & Anthony, 2002). Recently, we described a multiparametric functional analysis approach for new research to estimate these transition probabilities with a one-dimensional function (1D; Vsevolozhskaya & Anthony, 2015). Here, we demonstrate extension of this analysis to two-dimensional (2D) functions that combine information about number of recent drinking days and number of drinks on the typical drinking day.

Methods: Data …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Functional Linear Models Extensions Uncover Pleiotropic Effects Of Chronic Pain Phenotypes, Dmitri V. Zaykin, L. Qing, G. D. Slade, R. Dubner, R. B. Fillingim, J. D. Greenspan, R. Ohrbach, W. Maixner, L. B. Diatchenko, Olga A. Vsevolozhskaya

Biostatistics Presentations

Growing scientific evidence suggests that intricate interactions of genetic risk factors with environmental exposures play a major role in the development of chronic pain conditions. In studies of relative contribution of an individual’s genetic composition to the perception of pain, the general characteristics of pain sensitivity are typically measured by a wide range of different, yet possibly etiologically related pain phenotypes. Testing each of these pain-perception traits individually is subject to problems of multiple testing and low statistical power. Furthermore, pain-related traits may share common etiology and comprise binary, categorical, and quantitative measurements. In the current study, we propose a …

Novel Human Abcc9/Sur2 Brain-Expressed Transcripts And An Eqtl Relevant To Hippocampal Sclerosis Of Aging, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Angela Wei, James Dimayuga, Qingwei Huang, Eseosa T. Ighodaro, Sergey C. Artiushin, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

ABCC9 genetic polymorphisms are associated with increased risk for various human diseases including hippocampal sclerosis of aging. The main goals of this study were 1 > to detect the ABCC9 variants and define the specific 3′ untranslated region (3′UTR) for each variant in human brain, and 2 > to determine whether a polymorphism (rs704180) associated with risk for hippocampal sclerosis of aging pathology is also associated with variation in ABCC9 transcript expression and/or splicing. Rapid amplification of ABCC9 cDNA ends (3′RACE) provided evidence of novel 3′ UTR portions of ABCC9 in human brain. In silico and experimental studies were performed focusing on …

Estimated Probability Of Becoming A Case Of Drug Dependence In Relation To Duration Of Drug-Taking Experience: A Function Approach, Olga A. Vsevolozhskaya, James C. Anthony

Olga A. Vsevolozhskaya

Measured as elapsed time from first use to dependence syndrome onset, the estimated 'induction interval' for cocaine clearly is short relative to the cannabis interval, but little is known about risk of becoming dependent when use persists. Published estimates for this facet of drug dependence epidemiology are from life histories elicited years after first use. To improve estimation, we turn to new data from nationally representative samples of newly incident drug users identified via probability sampling and confidential computer-assisted self-interviews for the National Surveys on Drug Use and Health, 2004-2013. Standardized modules assess first and most recent use, and dependence …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemo-Radiation Therapy Outcomes, Lixin Dong

Theses and Dissertations--Biomedical Engineering

Chemo-radiation therapy is a principal modality for the treatment of head and neck cancers, and its efficacy depends on the interaction of tumor oxygen with free radicals. In this study, we adopted a novel hybrid diffuse optical instrument combining a commercial frequency-domain tissue oximeter (Imagent) and a custom-made diffuse correlation spectroscopy (DCS) flowmeter, which allowed for simultaneous measurements of tumor blood flow and blood oxygenation. Using this hybrid instrument we continually measured tumor hemodynamic responses to chemo-radiation therapy over the treatment period of 7 weeks. We also explored monitoring dynamic tumor hemodynamic changes during radiation delivery. Blood flow data analysis …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Nonlinear Hierarchical Models For Longitudinal Experimental Infection Studies, Michael David Singleton

Theses and Dissertations--Epidemiology and Biostatistics

Experimental infection (EI) studies, involving the intentional inoculation of animal or human subjects with an infectious agent under controlled conditions, have a long history in infectious disease research. Longitudinal infection response data often arise in EI studies designed to demonstrate vaccine efficacy, explore disease etiology, pathogenesis and transmission, or understand the host immune response to infection. Viral loads, antibody titers, symptom scores and body temperature are a few of the outcome variables commonly studied. Longitudinal EI data are inherently nonlinear, often with single-peaked response trajectories with a common pre- and post-infection baseline. Such data are frequently analyzed with statistical methods …

Developments In Nonparametric Regression Methods With Application To Raman Spectroscopy Analysis, Jing Guo

Theses and Dissertations--Epidemiology and Biostatistics

Raman spectroscopy has been successfully employed in the classification of breast pathologies involving basis spectra for chemical constituents of breast tissue and resulted in high sensitivity (94%) and specificity (96%) (Haka et al, 2005). Motivated by recent developments in nonparametric regression, in this work, we adapt stacking, boosting, and dynamic ensemble learning into a nonparametric regression framework with application to Raman spectroscopy analysis for breast cancer diagnosis. In Chapter 2, we apply compound estimation (Charnigo and Srinivasan, 2011) in Raman spectra analysis to classify normal, benign, and malignant breast tissue. We explore both the spectra profiles and their derivatives to …

Reassessment Of Risk Genotypes (Grn, Tmem106b, And Abcc9 Variants) Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Wang-Xia Wang, Amanda B. Partch, Sarah E. Monsell, Otto Valladares, Sally R. Ellingson, Bernard R. Wilfred, Adam C. Naj, Li-San Wang, Walter A. Kukull, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer’s Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer’s Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 ( GRN ), rs1990622 ( TMEM106B ), and rs704180 ( ABCC9 ). Analyses of a subsample that was not previously evaluated (51 HS-Aging cases …

Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver

Theses and Dissertations--Pharmacy

Methamphetamine (METH) abuse is a serious problem in the United States and worldwide. The reward experienced by METH users is due to the increase in extracellular dopamine (DA) concentrations caused by an interaction between METH and the DA transporter (DAT) as well as the Vesicular Monoamine Transporter-2 (VMAT2). The reward felt by users of METH leads to further use of the drug and subsequent abuse. The current project examined the ability of three novel series of lobelane analogs to interact with a binding site on the Vesicular Monoamine Transporter-2 (VMAT2) in an attempt to inhibit the effects of METH. Lobelane …

A Molecular-Level View Of The Physical Stability Of Amorphous Solid Dispersions, Xiaoda Yuan

Theses and Dissertations--Pharmacy

Many pharmaceutical compounds being developed in recent years are poorly soluble in water. This has led to insufficient oral bioavailability of many compounds in vitro. The amorphous formulation is one of the promising techniques to increase the oral bioavailability of these poorly water-soluble compounds. However, an amorphous drug substance is inherently unstable because it is a high energy form. In order to increase the physical stability, the amorphous drug is often formulated with a suitable polymer to form an amorphous solid dispersion. Previous research has suggested that the formation of an intimately mixed drug-polymer mixture contributes to the stabilization …