Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Exploration of polyelectrolytes as draw solutes in forward osmosis processes

10.1016/j.watres.2011.12.043Water Research4641318-1326WATR

The Modified Fouling Index Ultrafiltration constant flux for assessing particulate/colloidal fouling of RO systems

Reliable methods for measuring and predicting the fouling potential of reverse osmosis (RO) feed water are important in preventing and diagnosing fouling at the design stage, and for monitoring pre-treatment performance during plant operation. The Modified Fouling Index Ultrafiltration (MFI-UF) constant flux is a significant development with respect to assessing the fouling potential of RO feed water. This research investigates (1) the variables influencing the MFI-UF test at constant flux filtration (membrane pore size, membrane material, flux rate); and (2) the application of MFI-UF into pre-treatment assessment and RO fouling estimation. The dependency of MFI on flux, means that to assess accurately particulate fouling in RO systems, the MFI should be measured at a flux similar to a RO system (close to 20 L/m2/h) or extrapolated from higher fluxes. The two studied membrane materials showed reproducible results; 10% for PES membranes and 6.3% for RC membranes. Deposition factors (amount of particles that remain on the surface of membrane) were measured in a full-scale plant ranging between 0.2 and 0.5. The concept of “safe MFI” is presented as a guideline for assessing pre-treatment for RO systems.Water ManagementCivil Engineering and Geoscience

Arsenic in drinking water: A worldwide water quality concern for water supply companies

For more than a decade it has been known that shallow tube wells in Bangladesh are frequently contaminated with arsenic concentrations at a level that is harmful to human health. By now it is clear that a disaster of an unheard magnitude is going on: the World Health Organization has estimated that long-term exposure to arsenic in groundwater, at concentrations over 500 ?g L?1, causes death in 1 in 10 adults. Other studies show that problems with arsenic in groundwater/drinking water occur in many more countries worldwide, such as in the USA and China. In Europe the focus on arsenic problems is currently confined to countries with high arsenic levels in their groundwater, such as Serbia, Hungary and Italy. In most other European countries, the naturally occurring arsenic concentrations are mostly lower than the European drinking water standard of 10 ?g L?1. However, from the literature review presented in this paper, it is concluded that at this level health risks cannot be excluded. As consumers in European countries expect the drinking water to be of impeccable quality, it is recommended that water supply companies optimize arsenic removal to a level of <1 ?g L?1, which is technically feasible. OA-fund TU DelftCivil Engineering and Geoscience