Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Integrated Geophysical Investigation of the St. James Fault Complex: A Case Study

We noninvasively detected the characteristics and location of a regional fault in an area of poor bedrock exposure complicated by karst weathering features in the subsurface. Because this regional fault is associated with sinkhole formation, its location is important for hazard avoidance. The bedrock lithologies on either side of the fault trace are similar; hence, we chose an approach that capitalized on the complementary strengths of very low frequency (VLF) electromagnetic, resistivity, and gravity methods. VLF proved most useful as a first-order reconnaissance tool, allowing us to define a narrow target area for further geophysical exploration. Fault-related epikarst was delineated using resistivity. Ultimately, a high-resolution gravity survey and subsequent inverse modeling using the results of the resistivity survey helped to further constrain the location and approximate orientation of the fault. The combined results indicated that the location of the fault trace needed to be adjusted 53 m south of the current published location and was consistent with a north-dipping thrust fault. Additionally, a gravity low south of the fault trace agreed with the location of conductive material from the resistivity and VLF surveys. We interpreted these anomalies to represent enhanced epikarst in the fault footwall. We clearly found that a staged approach involving a progression of methods beginning with a reconnaissance VLF survey, followed by high-resolution gravity and electrical resistivity surveys, can be used to characterize a fault and fault-related karst in an area of poor bedrock surface exposure.

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

The James Lind Library: explaining and illustrating the evolution of fair tests of medical treatments

The James Lind Library (www.jameslindlibrary.org) has been established to improve public and professional general knowledge about fair tests of treatments in healthcare and their history. Its foundation was laid ten years ago at the Royal College of Physicians of Edinburgh, and its administrative centre is in the College's Sibbald Library, one of the most important collections of historic medical manuscripts, papers and books in the world. The James Lind Library is a website that introduces visitors to the principles of fair tests of treatments, with a series of short, illustrated essays, which are currently available in English, Arabic, Chinese, French, Portuguese, Russian and Spanish. A 100-page book-- Testing Treatments--is now available free through the website, both in English and in Arabic and Spanish translations. To illustrate the evolution of ideas related to fair tests of treatments from 2000 BC to the present, the James Lind Library contains key passages and images from manuscripts, books and journal articles, many of them accompanied by commentaries, biographies, portraits and other relevant documents and images, including audio and video files. New material is being added to the website continuously, as relevant new records are identified and as methods for testing treatments evolve. A multinational, multilingual editorial team oversees the development of the website, which currently receives tens of thousands of visitors every month.