71 research outputs found

    Research and Teaching Materials in Development Studies

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    Summary The case for linking research with the preparation of teaching materials in Development Studies continues to obsess academics and practitioners. This article focuses on some current trends and problems in development research with particular reference to recent developments in the Department of Administrative Studies, Manchester. A research project was set up in 1973 to update the Department's knowledge and understanding of the changing milieu in developing countries, and to identify and prepare teaching materials in order to maintain relevant and challenging study programmes. The results of the project and some ways in which collaborative research can make a better contribution to the curricula of development studies are discussed in this article. Resume La recherche et le matérial d'enseignement dans les études sur le développement La nécessité de lier la recherche à la préparation du matériel d'enseignement pour les études sur le développement continue d'obséder les universitaires et les professionnels. Cet article est consacré à certaines des tendances actuelles et des problèmes de la recherche sur le développement, et particulièrement aux récentes réalisations dans le Département des études administratives, à Manchester. Un projet de recherche fut lancé en 1973 pour permettre au Département de mettre à jour ses connaissances en vue d'une meilleure compréhension du milieu changeant dans les pays en voie de développement et d'identifier et mettre au point le matériel d'enseignement afin d'avoir des programmes d'étude appropriés et intéressants. Cet article examine les résultats de ce projet et comment une recherche menée en collaboration peut aider plus efficacement à la mise au point de programmes pour les études sur le développement. Resumen Investigación y materiales de enseñanza en los estudios sobre desarrollo El caso de vincular la investigación con la preparación de materiales de enseñanza en los estudios sobre desarrollo continúa obsesionando a los académicos y practicantes. En este artículo se dirige la atención sobre ciertas tendencias y problemas actuales en la investigación del desarrollo con referencia especial a recientes acontecimientos en el Departmento de Estudios Administrativos, Manchester. En 1973 se estableció un proyecto de investigación para poner al día los conocimientos del departamento, así como su comprensión del ambiente cambiante en los países en vías de desarrollo y para identificar y preparar materiales de enseñanza, con objeto de mantener programas de estudio pertinentes y estimulantes. En este artículo se analizan los resultados del proyecto y algunas maneras en que la investigación colaborativa puede hacer una aportación mejor en el programa de estudios sobre el desarrollo

    Common Variants in Alzheimer’s Disease and Risk Stratification by Polygenic Risk Scores

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    Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n=409,435 and validation size n=58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.The present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain) supported by national grant from the Instituto de Salud Carlos III FI20/00215. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa”, Fundació ACE, and CIBERNED. A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—“Una manera de hacer Europa”). The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). 100-Plus study. This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Diorapthe, horstingstuit foundation, Memorabel (ZonMW project number 733050814, 733050512) and Stichting VUmc Fonds. Genotyping of the 100-Plus Study was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project numb 733051061). Longitudinal Aging Study Amsterdam (LASA) is largely supported by a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of LongTerm Care. This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND) and also funded by Inserm, Institut Pasteur de Lille, the Lille Métropole Communauté Urbaine, the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Genotyping of the German case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND (German Federal Ministry of Education and Research, BMBF: 01ED1619A). The i–Select chips was funded by the French National Foundation on AD and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant n° 503480), Alzheimer’s Research UK (Grant n° 503176), the Wellcome Trust (Grant n° 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant n° 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIA/NHLBI grants AG049505, AG058589, HL105756 and AGES contract N01–AG–12100, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer’s Association grant ADGC–10–19672

    New insights into the genetic etiology of Alzheimer's disease and related dementias

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    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE epsilon 4 allele. Meta-analysis of genome-wide association studies on Alzheimer's disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer's disease and dementia.Peer reviewe

    New Insights into the Genetic Etiology of Alzheimer’s Disease and Related Dementias

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    Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

    Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

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    Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.Peer reviewe

    Time correlations of high energy muons in an underground detector

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    We present the result of a search for correlations in the arrival times of high energy muons collected from 1995 till 2000 with the streamer tube system of the complete MACRO detector at the underground Gran Sasso Lab. Large samples of single muons (8.6 million), double muons (0.46 million) and multiple muons with multiplicities from 3 to 6 (0.08 million) were selected. These samples were used to search for time correlations of cosmic ray particles coming from the whole upper hemisphere or from selected space cones. The results of our analyses confirm with high statistics a random arrival time distribution of high energy cosmic rays.Comment: (12 pages, 7 figures, Accepted for publication in Astroparticle Physics
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