932 research outputs found

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    An assessment of Growth of Infrastructure Booms have been a common element in the development of frontier areas in the 19th and 20th centuries. Most commonly, the booms have been associated with resource development such as the mineral booms of the western United States. Booms usually involve some type of dramatic short- term change which has wide-ranging implications (Gilmore, 1976). Since the arrival of the Russians in Alaska, six major booms have occurred: furs, whales, salmon, minerals, military, and petroleum. Each of these booms has, to some degree, created changes in the landscape of Alaska, in particular, the infrastructural base, which in turn has facilitated subsequent development, either another major boom, or a smaller development. For example, agricultural development has been enhanced by mineral, military, and petroleum booms in Alaska. The cumulative impact on infrastructure of more than one boom, or multibooms, as it is referred to here, is the focus of this paper. One problem encountered in studying booms is that there is no general agreement on what constitutes a boom. Detailed studies of booms in communities such as Dixon’s (1978) analysis of Fairbanks and Gilmore’s multi-community work in the Great Plains—Rocky •mountain regions, contained no specific definition of the term “boom”. Yet it was clear in each study that something dramatic had occurred. More general historical studies of the Western mineral bonanzas (Greever, 1963) or the Klondike gold rush (Berton, 1958) likewise suggest a number of factors such as population rise, influx of money, resource extraction, and infrastructure expansion. But in each case, there is no specific factor or define rate of something that specifically qualifies a time period as a boom. In this study, we are concerned with dramatic change of events which have had a major impact on the geographic landscape of an area, As a framework for the initial study, we review those events which have been given attention as boom-type activities in the historical literature of Alaska (Rogers, 1962; Naske and Slotnick, 1987)

    Clinical trials and basic research: defining mechanisms and improving treatment in connective tissue disease

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    Despite advances in elucidating the pathogenic factors responsible for its development, systemic sclerosis remains complex and poorly understood, and treatment options are limited. Multidisciplinary collaborative efforts are needed to better characterize clinical and prognostic parameters and to design and implement large-scale clinical trials in well defined populations with therapies that target potential disease modulators

    Systemic sclerosis and related connective tissue diseases: present and future

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    Greece, to discuss systemic sclerosis (SSc) and related connective tissue diseases (CTDs). SSc is a clinically heterogeneous and complex disease that is characterized by vascular dysfunction, vascular and extravascular fibrosis, and characteristic immune derangements, and for which few treatment options are available. The aims of the CTD International Scientific Advisory Board were threefold: to define the role of local mediators in CTDs, in particular to identify the nature of the initial insult in CTDs and to consider the role of genetic perturbations in CTDs; to translate what has been learned from clinical trials into clinical practice and to evaluate current treatment options for CTDs and their complications; and to address future directions for the management of CTDs and associated rare diseases, based on the biologic mechanisms elucidated. This supplemen

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    Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme

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    Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning

    Candida albicans Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation

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    Received 28 August 2014 Accepted 28 October 2014 Published 2 December 2014 This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license. ACKNOWLEDGMENTS We thank Janet Willment, Aberdeen Fungal Group, University of Aberdeen, for kindly providing the soluble Dectin-1-Fc reporter. All microscopy was performed with the assistance of the University of Aberdeen Core Microscopy & Histology Facility, and we thank the IFCC for their assistance with flow cytometry. We thank the Wellcome Trust for funding (080088, 086827, 075470, 099215, 097377, and 101873). E.R.B. and A.J.P.B. are funded by the European Research Council (ERC-2009-AdG-249793), and J.L. is funded by a Medical Research Council Clinical Training Fellowship.Peer reviewedPublisher PD

    IMPaCT Back study protocol. Implementation of subgrouping for targeted treatment systems for low back pain patients in primary care: a prospective population-based sequential comparison.

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    BACKGROUND: Prognostic assessment tools to identify subgroups of patients at risk of persistent low back pain who may benefit from targeted treatments have been developed and validated in primary care. The IMPaCT Back study is investigating the effects of introducing and supporting a subgrouping for targeted treatment system in primary care. METHODS/DESIGN: A prospective, population-based, quality improvement study in one Primary Care Trust in England with a before and after design. Phases 1 and 3 collect data on current practice, attitudes and behaviour of health care practitioners, patients' outcomes and health care costs. Phase 2 introduces and supports the subgrouping for targeted treatment system, via a multi-component, quality improvement intervention that includes educational courses and outreach visits led by opinion leaders, audit/feedback, mentoring and organisational support to embed the subgrouping tools within IT and clinical management systems.We aim to recruit 1000 low back pain patients aged 18 years and over consulting 7 GP practices within one Primary Care Trust in England, UK. The study includes GPs in participating practices and physiotherapists in associated services. The primary objective is to determine the effect of the subgrouping for targeted treatment system on back pain related disability and catastrophising at 2 and 6 months, comparing data from phase 1 with phase 3. Key secondary objectives are to determine the impact on: a) GPs' and physiotherapists' attitudes and behaviour regarding low back pain; b) The process of care that patients receive; c) The cost-effectiveness and sustainability of the new clinical system. DISCUSSION: This paper details the rationale, design, methods, planned analysis and operational aspects of the IMPaCT Back study. We aim to determine whether the new subgrouping for targeted treatment system is implemented and sustained in primary care, and evaluate its impact on clinical decision-making, patient outcomes and costs. STUDY REGISTRATION: International Standard Randomised Controlled Trial Number Register ISRCTN55174281.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Improvements in Blood Pressure Among Undiagnosed Hypertensive Participants in a Community-Based Lifestyle Intervention, Mississippi, 2010

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    Introduction Effective strategies are needed to reach and treat people who lack awareness of or have uncontrolled hypertension. We used data from a community-based participatory research initiative, Hub City Steps, to quantify the prevalence of undiagnosed hypertension and determine the relationship between hypertension status at baseline and postintervention improvements in blood pressure and health-related quality of life. Methods Hub City Steps was a 6-month preintervention–postintervention lifestyle intervention targeting hypertension risk factors. Outcome measures were collected at baseline, 3 months, and 6 months. Generalized linear mixed models were used to test for effects by time and hypertension status. Results Of the enrolled sample (N = 269), most were overweight or obese (91%), African American (94%), and women (85%). When considering hypertension status, 42% had self-reported diagnosis of hypertension (self-reported subgroup; 84% with antihypertensive medication use); 36% had no self-reported medical history of hypertension, but when blood pressure was measured they had a clinical diagnosis of prehypertension or hypertension (undiagnosed subgroup); and 22% had no self-reported or clinical hypertension diagnosis (no hypertension subgroup). From baseline to 6 months, systolic blood pressure significantly improved for participants with self-reported hypertension [8.2 (SD, 18.2) mm Hg] and undiagnosed hypertension [12.3 (SD, 16.3) mm Hg], with undiagnosed participants experiencing the greatest improvements (P \u3c .001). Effects remained significant after controlling for covariates. Health-related quality of life significantly improved for all 3 hypertension subgroups, with no apparent subgroup differences. Conclusion This study reveals advantages of a culturally appropriate community-based participatory research initiative to reach those with undetected hypertension and effectively improve blood pressure status and health-related quality of life
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