12 research outputs found

    Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

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    To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

    Pakistan's Public Health Surveillance System: A Call to Action

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    This assessment considered three major areas of public health surveillance: (1) communicable diseases, (2) vital registration with a focus on maternal and infant mortality, and (3) non-communicable diseases and risk factors. The key recommendations for each of these areas are summarized below. A stepwise approach to implementing these recommendations should be considered in the National Action Plan. Chapter 4 summarizes some of the major cross-cutting issues and provides a minimum package to develop the public health surveillance system

    Towards elimination of maternal deaths : maternal deaths surveillance and response

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    Current methods for estimating maternal mortality lack precision, and are not suitable for monitoring progress in the short run. In addition, national maternal mortality ratios (MMRs) alone do not provide useful information on where the greatest burden of mortality is located, who is concerned, what are the causes, and more importantly what sub-national variations occur. This paper discusses a maternal death surveillance and response (MDSR) system. MDSR systems are not yet established in most countries and have potential added value for policy making and accountability and can build on existing efforts to conduct maternal death reviews, verbal autopsies and confidential enquiries. Accountability at national and sub-national levels cannot rely on global, regional and national retrospective estimates periodically generated from academia or United Nations organizations but on routine counting, investigation, sub national data analysis, long term investments in vital registration and national health information systems. Establishing effective maternal death surveillance and response will help achieve MDG 5, improve quality of maternity care and eliminate maternal mortality (MMR ≤ 30 per 100,000 by 2030)
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