Mapping Supply and Demand in Kentucky\u27s Health Care System

A report submitted by Timothy S. Hare to the Research and Creative Productions Committee in 2004 on the geographical distribution of supply and demand in Kentucky\u27s health care system

Healthcare Utilization, Deprivation, and Heart-Related Disease In Kentucky

A report submitted by Timothy S. Hare to the Research and Creative Productions Committee in 2005 on the relationship between patterns of healthcare facility utilization for heart-related disease in Kentucky

Plant-Expressed Cocaine Hydrolase Variants of Butyrylcholinesterase Exhibit Altered Allosteric Effects of Cholinesterase Activity and Increased Inhibitor Sensitivity

Butyrylcholinesterase (BChE) is an enzyme with broad substrate and ligand specificities and may function as a generalized bioscavenger by binding and/or hydrolyzing various xenobiotic agents and toxicants, many of which target the central and peripheral nervous systems. Variants of BChE were rationally designed to increase the enzyme’s ability to hydrolyze the psychoactive enantiomer of cocaine. These variants were cloned, and then expressed using the magnICON transient expression system in plants and their enzymatic properties were investigated. In particular, we explored the effects that these site-directed mutations have over the enzyme kinetics with various substrates of BChE. We further compared the affinity of various anticholinesterases including organophosphorous nerve agents and pesticides toward these BChE variants relative to the wild type enzyme. In addition to serving as a therapy for cocaine addiction-related diseases, enhanced bioscavenging against other harmful agents could add to the practicality and versatility of the plant-derived recombinant enzyme as a multivalent therapeutic

Measurement of the Nucleon F\u3csup\u3en\u3c/sup\u3e₂/F\u3csup\u3ep\u3c/sup\u3e₂ Structure Function Ratio by the Jefferson Lab MARATHON Tritium/Helium-3 Deep Inelastic Scattering Experiment

The ratio of the nucleon F2 structure functions, Fn2/Fp2, is determined by the MARATHON experiment from measurements of deep inelastic scattering of electrons from 3H and 3He nuclei. The experiment was performed in the Hall A Facility of Jefferson Lab using two high-resolution spectrometers for electron detection, and a cryogenic target system which included a low-activity tritium cell. The data analysis used a novel technique exploiting the mirror symmetry of the two nuclei, which essentially eliminates many theoretical uncertainties in the extraction of the ratio. The results, which cover the Bjorken scaling variable range 0.19 \u3c x \u3c 0.83, represent a significant improvement compared to previous SLAC and Jefferson Lab measurements for the ratio. They are compared to recent theoretical calculations and empirical determinations of the Fn2/Fp2 ratio

Density Changes in Low Pressure Gas Targets for Electron Scattering Experiments

A system of modular sealed gas target cells has been developed for use in electron scattering experiments at the Thomas Jefferson National Accelerator Facility (Jefferson Lab). This system was initially developed to complete the MARATHON experiment which required, among other species, tritium as a target material. Thus far, the cells have been loaded with the gas species 3H, 3He, 2H, 1H and 40Ar and operated in nominal beam currents of up to 22.5 uA in Jefferson Lab's Hall A. While the gas density of the cells at the time of loading is known, the density of each gas varies uniquely when heated by the electron beam. To extract experimental cross sections using these cells, density dependence on beam current of each target fluid must be determined. In this study, data from measurements with several beam currents within the range of 2.5 to 22.5 uA on each target fluid are presented. Additionally, expressions for the beam current dependent fluid density of each target are developed.Comment: 8 pages, 12 figures, 4 table

Molecular surveillance of Plasmodium vivax dhfr and dhps mutations in isolates from Afghanistan

<p>Abstract</p> <p>Background</p> <p>Analysis of dihydrofolate reductase (<it>dhfr</it>) and dihydropteroate synthase (<it>dhps</it>) mutations in <it>Plasmodium vivax </it>wild isolates has been considered to be a valuable molecular approach for mapping resistance to sulphadoxine-pyrimethamine (SP). The present study investigates the frequency of SNPs-haplotypes in the <it>dhfr </it>and <it>dhps </it>genes in <it>P. vivax </it>clinical isolates circulating in two malaria endemic areas in Afghanistan.</p> <p>Methods</p> <p><it>P. vivax </it>clinical isolates (n = 171) were collected in two different malaria endemic regions in north-west (Herat) and east (Nangarhar) Afghanistan in 2008. All collected isolates were analysed for SNP-haplotypes at positions 13, 33, 57, 58, 61, 117 and 173 of the <it>pvdhfr </it>and 383 and 553 of the <it>pvdhps </it>genes using PCR-RFLP methods.</p> <p>Results</p> <p>All 171 examined isolates were found to carry wild-type amino acids at positions 13, 33, 57, 61 and 173, while 58R and 117N mutations were detected among 4.1% and 12.3% of Afghan isolates, respectively. Based on the size polymorphism of <it>pvdhfr </it>genes at repeat region, type B was the most prevalent variant among Herat (86%) and Nangarhar (88.4%) isolates. Mixed genotype infections (type A/B and A/B/C) were detected in only 2.3% (2/86) of Herat and 1.2% (1/86) of Nangarhar isolates, respectively. The combination of <it>pvdhfr </it>and <it>pvdhps </it>haplotypes among all 171 samples demonstrated six distinct haplotypes. The two most prevalent haplotypes among all examined samples were wild-type (86%) and single mutant haplotype I₁₃P₃₃F₅₇S₅₈T₆₁<b>N </b>₁₁₇I_173/A₃₈₃A₅₅₃(6.4%).</p> <p>Double (I₁₃P₃₃S₅₇<b>R</b>₅₈T₆₁<b>N</b>₁₁₇I₁₇₃/A₃₈₃A₅₅₃) and triple mutant haplotypes (I₁₃P₃₃S₅₇<b>R </b>₅₈T₆₁<b>N</b>₁₁₇I₁₇₃/<b>G</b>₃₈₃A₅₅₃) were found in 1.7% and 1.2% of Afghan isolates, respectively. This triple mutant haplotype was only detected in isolates from Herat, but in none of the Nangarhar isolates.</p> <p>Conclusion</p> <p>The present study shows a limited polymorphism in <it>pvdhfr </it>from Afghan isolates and provides important basic information to establish an epidemiological map of drug-resistant vivax malaria, and updating guidelines for anti-malarial policy in Afghanistan. The continuous usage of SP as first-line anti-malarial drug in Afghanistan might increase the risk of mutations in the <it>dhfr </it>and <it>dhps </it>genes in both <it>P. vivax </it>and <it>Plasmodium falciparum </it>isolates, which may lead to a complete SP resistance in the near future in this region. Therefore, continuous surveillance of <it>P. vivax </it>and <it>P. falciparum </it>molecular markers are needed to monitor the development of resistance to SP in the region.</p

Elimination Therapy for the Endemic Malarias

Most malaria diagnosed outside endemic zones occurs in patients experiencing the consequences of what was likely a single infectious bite by an anopheline mosquito. A single species of parasite is nearly always involved and expert opinion on malaria chemotherapy uniformly prescribes species- and stage-specific treatments. However the vast majority of people experiencing malaria, those resident in endemic zones, do so repeatedly and very often with the involvement of two or more species and stages of parasite. Silent forms of these infections—asymptomatic and beyond the reach of diagnostics—may accumulate to form substantial and unchallenged reservoirs of infection. In such settings treating only the species and stage of malaria revealed by diagnosis and not others may not be sensible or appropriate. Developing therapeutic strategies that address all species and stages independently of diagnostic evidence may substantially improve the effectiveness of the control and elimination of endemic malaria

First Measurement of the Ti (e,e′) X Cross Section at Jefferson Lab

To probe CP violation in the leptonic sector using GeV energy neutrino beams in current and future experiments using argon detectors, precise models of the complex underlying neutrino and antineutrino interactions are needed. The E12-14-012 experiment at Jefferson Lab Hall A was designed to perform a combined analysis of inclusive and exclusive electron scatterings on both argon (N=22) and titanium (Z=22) nuclei using GeV-energy electron beams. The measurement on titanium nucleus provides essential information to understand the neutrino scattering on argon, large contribution to which comes from scattering off neutrons. Here we report the first experimental study of electron-titanium scattering as double-differential cross section at beam energy E=2.222 GeV and electron-scattering angle θ=15.541^{∘}, measured over a broad range of energy transfer, spanning the kinematical regions in which quasielastic scattering and delta production are the dominant reaction mechanisms. The data provide valuable new information needed to develop accurate theoretical models of the electromagnetic and weak cross sections of these complex nuclei in the kinematic regime of interest to neutrino experiments.National Science Foundation (U.S.) (CAREER Grant PHY-1352106

First Measurement of the Ti(e,e′)X(e,e^\prime){\rm X} Cross Section at Jefferson Lab

To probe CP violation in the leptonic sector using GeV energy neutrino beams in current and future experiments using argon detectors, precise models of the complex underlying neutrino and antineutrino interactions are needed. The E12-14-012 experiment at Jefferson Lab Hall A was designed to perform a combined analysis of inclusive and exclusive electron scatterings on both argon ($N = 22$) and titanium ($Z = 22$) nuclei using GeV energy electron beams. The measurement on titanium nucleus provides essential information to understand the neutrino scattering on argon, large contribution to which comes from scattering off neutrons. Here we report the first experimental study of electron-titanium scattering as double differential cross section at beam energy $E=2.222$ GeV and electron scattering angle $\theta = 15.541$ deg, measured over a broad range of energy transfer, spanning the kinematical regions in which quasielastic scattering and delta production are the dominant reaction mechanisms. The data provide valuable new information needed to develop accurate theoretical models of the electromagnetic and weak cross sections of these complex nuclei in the kinematic regime of interest to neutrino experiments.Comment: 6 pages, 5 figures. Version published in Physical Review