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.
Historians and demographers have long debated the existence, causes, and consequences of historical differences between urban and rural mortality levels. In Europe it has been usual to observe excess mortality in cities compared to the countryside, but in East Asia, by contrast, it has been found that urban areas had relatively favorable mortality environments. The debate continues because a number of pertinent questions remain to be resolved. For example, the way in which mortality is measured may influence the apparent extent of the differential, as may the way in which"urban" and"rural" are defined. Cultural factors need to be taken into account, including the practices of childrearing and the conventions surrounding baptism. Examples drawn from Japan, China, England, and France illustrate the issues involved in comparative analysis, while the urban-rural mortality continuum is examined for nineteenth-century England and Wales using log-normal distributions. Copyright 2003 by The Population Council, Inc..
This paper discusses the problems of defining and measuring late-fetal mortality (stillbirths). It uses evidence from 11 developed countries to trace long-term trends in fetal mortality. Issues associated with varying definitions and registration practices are identified, as well as the range of possible rates, key turning points and recent convergence. The implications for developing countries are spelt out. They emphasize the possible limitations of WHO estimation methods and survey-based data by examining the cross-sectional associations among 187 countries in the year 2000. The important role of skilled birth attendants is emphasized in both data sets, but the different effects on maternal mortality and late-fetal mortality are also noted.
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