391 research outputs found

    Pointlike probes of superstring-theoretic superfluids

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    In analogy with an experimental setup used in liquid helium, we use a pointlike probe to study superfluids which have a gravity dual. In the gravity description, the probe is represented by a hanging string. We demonstrate that there is a critical velocity below which the probe particle feels neither drag nor stochastic forces. Above this critical velocity, there is power-law scaling for the drag force, and the stochastic forces are characterized by a finite, velocity-dependent temperature. This temperature participates in two simple and general relations between the drag force and stochastic forces. The formula we derive for the critical velocity indicates that the low-energy excitations are massless, and they demonstrate the power of stringy methods in describing strongly coupled superfluids.Comment: 17 pages, 2 figures, added a figure, a reference, and moved material to an appendi

    Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses : second panel on cost-effectiveness in health and medicine

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    Importance  Since publication of the report by the Panel on Cost-Effectiveness in Health and Medicine in 1996, researchers have advanced the methods of cost-effectiveness analysis, and policy makers have experimented with its application. The need to deliver health care efficiently and the importance of using analytic techniques to understand the clinical and economic consequences of strategies to improve health have increased in recent years.Objective  To review the state of the field and provide recommendations to improve the quality of cost-effectiveness analyses. The intended audiences include researchers, government policy makers, public health officials, health care administrators, payers, businesses, clinicians, patients, and consumers.Design  In 2012, the Second Panel on Cost-Effectiveness in Health and Medicine was formed and included 2 co-chairs, 13 members, and 3 additional members of a leadership group. These members were selected on the basis of their experience in the field to provide broad expertise in the design, conduct, and use of cost-effectiveness analyses. Over the next 3.5 years, the panel developed recommendations by consensus. These recommendations were then reviewed by invited external reviewers and through a public posting process.Findings  The concept of a “reference case” and a set of standard methodological practices that all cost-effectiveness analyses should follow to improve quality and comparability are recommended. All cost-effectiveness analyses should report 2 reference case analyses: one based on a health care sector perspective and another based on a societal perspective. The use of an “impact inventory,” which is a structured table that contains consequences (both inside and outside the formal health care sector), intended to clarify the scope and boundaries of the 2 reference case analyses is also recommended. This special communication reviews these recommendations and others concerning the estimation of the consequences of interventions, the valuation of health outcomes, and the reporting of cost-effectiveness analyses.Conclusions and Relevance  The Second Panel reviewed the current status of the field of cost-effectiveness analysis and developed a new set of recommendations. Major changes include the recommendation to perform analyses from 2 reference case perspectives and to provide an impact inventory to clarify included consequences

    Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

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    Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

    uPA is upregulated by high dose celecoxib in women at increased risk of developing breast cancer

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    <p>Abstract</p> <p>Background</p> <p>While increased urokinase-type plasminogen activator (uPA) expression in breast cancer tissue is directly associated with poor prognosis, recent evidence suggests that uPA overexpression may suppress tumor growth and prolong survival. Celecoxib has been shown to have antiangiogenic and antiproliferative properties. We sought to determine if uPA, PA inhibitor (PAI)-1 and prostaglandin (PG)E<sub>2 </sub>expression in nipple aspirate fluid (NAF) and uPA and PGE<sub>2 </sub>expression in plasma were altered by celecoxib dose and concentration in women at increased breast cancer risk.</p> <p>Methods</p> <p>NAF and plasma samples were collected in women at increased breast cancer risk before and 2 weeks after taking celecoxib 200 or 400 mg twice daily (bid). uPA, PAI-1 and PGE<sub>2 </sub>were measured before and after intervention.</p> <p>Results</p> <p>Celecoxib concentrations trended higher in women taking 400 mg (median 1025.0 ng/mL) compared to 200 mg bid (median 227.3 ng/mL), and in post- (534.6 ng/mL) compared to premenopausal (227.3 ng/mL) women. In postmenopausal women treated with the higher (400 mg bid) celecoxib dose, uPA concentrations increased, while PAI-1 and PGE<sub>2 </sub>decreased. In women taking the higher dose, both PAI-1 (r = -.97, p = .0048) and PGE<sub>2 </sub>(r = -.69, p = .019) in NAF and uPA in plasma (r = .45, p = .023) were correlated with celecoxib concentrations.</p> <p>Conclusion</p> <p>Celecoxib concentrations after treatment correlate inversely with the change in PAI-1 and PGE<sub>2 </sub>in the breast and directly with the change in uPA in the circulation. uPA upregulation, in concert with PAI-1 and PGE<sub>2 </sub>downregulation, may have a cancer preventive effect.</p

    Just how versatile are domains?

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    <p>Abstract</p> <p>Background</p> <p>Creating new protein domain arrangements is a frequent mechanism of evolutionary innovation. While some domains always form the same combinations, others form many different arrangements. This ability, which is often referred to as versatility or promiscuity of domains, its a random evolutionary model in which a domain's promiscuity is based on its relative frequency of domains.</p> <p>Results</p> <p>We show that there is a clear relationship across genomes between the promiscuity of a given domain and its frequency. However, the strength of this relationship differs for different domains. We thus redefine domain promiscuity by defining a new index, <it>DV I </it>("domain versatility index"), which eliminates the effect of domain frequency. We explore links between a domain's versatility, when unlinked from abundance, and its biological properties.</p> <p>Conclusion</p> <p>Our results indicate that domains occurring as single domain proteins and domains appearing frequently at protein termini have a higher <it>DV I</it>. This is consistent with previous observations that the evolution of domain re-arrangements is primarily driven by fusion of pre-existing arrangements and single domains as well as loss of domains at protein termini. Furthermore, we studied the link between domain age, defined as the first appearance of a domain in the species tree, and the <it>DV I</it>. Contrary to previous studies based on domain promiscuity, it seems as if the <it>DV I </it>is age independent. Finally, we find that contrary to previously reported findings, versatility is lower in Eukaryotes. In summary, our measure of domain versatility indicates that a random attachment process is sufficient to explain the observed distribution of domain arrangements and that several views on domain promiscuity need to be revised.</p

    Dynamical Boson Stars

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    The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201

    Effects of residence and race on burden of travel for care: cross sectional analysis of the 2001 US National Household Travel Survey

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    BACKGROUND: Travel burden is a key element in conceptualizing geographic access to health care. Prior research has shown that both rural and minority populations bear disproportionate travel burdens. However, many studies are limited to specific types of patient or specific locales. The purpose of our study was to quantify geographic and race-based differences in distance traveled and time spent in travel for medical/dental care using representative national data. METHODS: Data were drawn from 2001 National Household Travel Survey (NHTS), a nationally representative, cross-sectional household survey conducted by the US Department of Transportation. Participants recorded all travel on a designated day; the overall response rate was 41%. Analyses were restricted to households reporting at least one trip for medical and/or dental care; 3,914 trips made by 2,432 households. Dependent variables in the analysis were road miles traveled, minutes spent traveling, and high travel burden, defined as more than 30 miles or 30 minutes per trip. Independent variables of interest were rural residence and race. Characteristics of the individual, the trip, and the community were controlled in multivariate analyses. RESULTS: The average trip for care in the US in 2001 entailed 10.2 road miles (16.4 kilometers) and 22.0 minutes of travel. Rural residents traveled further than urban residents in unadjusted analysis (17.5 versus 8.3 miles; 28.2 versus 13.4 km). Rural trips took 31.4% longer than urban trips (27.2 versus 20.7 minutes). Distance traveled did not vary by race. African Americans spent more time in travel than whites (29.1 versus 20.6 minutes); other minorities did not differ. In adjusted analyses, rural residence (odds ratio, OR, 2.67, 95% confidence interval, CI 1.39 5.1.5) was associated with a trip of 30 road miles or more; rural residence (OR, 1.80, CI 1.09 2.99) and African American race/ethnicity (OR 3.04. 95% CI 2.0 4.62) were associated with a trip lasting 30 minutes or longer. CONCLUSION: Rural residents and African Americans experience higher travel burdens than urban residents or whites when seeking medical/dental care
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