Statement LF and DAvH analysed UK GWAS data, selected SNPs and designed assays for golden gate genotyping. Substantial contributions to sample collections were made by DAvH, LD, GKTH, PH, JRFW, DSS (UK2 cases); DPS, WLMcA (1958 cohort controls); CJM, WV, MLM (DUTCH samples); VT, FMS, COM, NPK, DK (IRISH samples). UKGWAS genotyping was performed as described in PD lab2. KAH extracted UKGWAS and UK2 celiac DNA samples and performed UK2 sample golden gate genotyping. GrahamT and AWR prepared Irish DNA samples. GrahamT, AWR and KAH performed Irish sample golden gate genotyping. UK2 and IRISH genotyping was performed in CAM lab, DP performed quality control steps. AZ prepared DUTCH celiac and control DNA samples, and AZ and JR performed DUTCH sample golden gate genotyping in CW lab. DVH and KAH performed final golden gate genotype clustering on all samples, with assistance from RG. LD and DAvH collected Paxgene RNA celiac blood samples, GH extracted Paxgene RNA, GH and MB performed expression chips in CW lab, GH and LF analysed expression data. GosiaT performed IL18RAP re-sequencing. MCW processed intestinal biopsies, MB and MCW performed expression chips in CW lab, MCW and GH analysed expression data. DJP performed analysis of genes in intestinal T cell subsets. KAH and GH performed bioinformatics and annotation of celiac risk variant regions DAvH, RMM, CW were Principal Investigators and directed respectively the UK, IRISH and DUTCH sample collections and with RJP designed overall strategy and obtained funding for the study. DAvH directed the entire study, performed statistical analysis and generated the figures. DAvH and CW wrote the paper. RMcG, FT and WMMcL performed additional statistical analysis. To identify additional celiac disease susceptibility genes, we recently tested 310,605 SNPs in a genome wide association study of 778 celiac cases and 1,422 population controls from the United Kingdom (UKGWAS), using the Illumina HumanHap300 BeadChip2. The only SNP outside the HLA region demonstrating genome-wide significance was rs13119723 on 4q27, located in a ∼500 kb block of linkage disequilibrium (LD) containing the IL2 and IL21 genes2. Independent replication of SNPs from the IL2-IL21 region was established in both Dutch and Irish collections of celiac patients and controls. We estimate, using the current markers, that the IL2-IL21 region explains less than 1% of the increased familial risk to celiac disease, suggesting that there are additional unidentified susceptibility genes. Since we observed a greater number of significantly associated SNPs in the UKGWAS than would be expected by chance, we proceeded to study >1,000 of the most significant UKGWAS association results in a further 1,643 celiac cases and 3,406 controls from three independent European celiac disease collections. This two-stage strategy, involving a joint analysis of all data, substantially reduces the genotyping requirements versus performing whole genome genotyping on all samples and has been shown to maintain sufficient statistical power3. ...

A quarter of all patients with ulcerative colitis experience at least one episode of ASC; 20% come to colectomy on first admission, but 40% after two admissions. The likelihood of colectomy is related to biological severity on admission.

Background: Post-liver-transplant biliary anastomotic strictures (ASs) are currently managed with repeated endoscopic retrograde cholangiopancreatographies (ERCPs) inserting multiple plastic stents. Fully covered self-expanding metal stents (FCSEMSs) are being increasingly reported in the management of this condition, however no prospective randomized trials have been performed to date. Aim: The aim of this study was to determine whether FCSEMSs decrease overall numbers of ERCPs needed to achieve stricture resolution and to establish the safety, efficacy and costeffectiveness in this setting. Methods: Two tertiary referral centres performed this open-label prospective randomized trial. A total of 32 patients consented and subsequently 20 were randomized with 10 in the FCSEMS arm and 10 in the plastic arm. The FCSEMS arm had the stent in situ for 12 weeks with the plastic stent arm undergoing 3-monthly multiple plastic stenting with or without dilatation over a year. Results: The median number of ERCPs performed per patient in the FCSEMS was 2 versus 4.5 (p = 0.0001) in the plastic stenting arm. Stricture resolution was achieved in all 10 patients with FCSEMSs compared with 8/10 in the plastic arm [p = not significant (NS)]. Complications occurred in 1/10 patients in the FCSEMS arm versus 5/10 in the plastic arm (p = 0.051). Days in hospital for complications was 6 in the FCSEMS versus 56 in the plastic arm (p = 0.11). Cost analysis shows that the FCSEMS arm was more cost effective. No cases of FCSEMS migration were seen. Conclusions: FCSEMSs reduced the number of ERCPs needed to achieve stricture resolution with similar recurrence rates between arms. The FCSEMSs may do so with fewer complications making it cost effective.

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Background: Genome wide association studies have been hugely successful in identifying disease risk variants, yet most variants do not lead to coding changes and how variants influence biological function is usually unknown.

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A very distinctive perdicine bird was discovered in July 1991 during fieldwork in montane evergreen forests in parts of the Udzungwa Mountains in Tanzania which were so far ornithologically unexplored. The bird is described here as a new genus and species with affinities to the hill‐partridges Arborophila of the Indo‐Malayan region. The relict occurrence in Africa of taxa with affinities to Oriental biota is discussed.