Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

New U–Pb zircon ages of Nyong Complex meta‐plutonites: Implications for the Eburnean/Trans‐Amazonian Orogeny in southwestern Cameroon (Central Africa)

New LA–ICP–MS U–Pb zircon ages from the Nyong Complex of southwestern Cameroon—a part of the West Central African Fold Belt—trace Late Mesoarchean (∼2,850 Ma), Middle Palaeoproterozoic (∼2,080 Ma), and Neoproterozoic (∼605 Ma) events: Two meta‐syenites and the protolith of an amphibolite are Late Mesoarchean; two meta‐granodiorites are Middle Palaeoproterozoic; the amphibolite may have recrystallized in the Middle Palaeoproterozoic; all rocks are overprinted by the Neoproterozoic event. Integration with published data shows that our amphibolite sample has one of the oldest amphibolite‐protolith ages (∼2,810 Ma) reported so far. It shares the Middle Palaeoproterozoic metamorphism/recrystallization with other, previously dated amphibolites. An earlier reported metamorphic zircon age (∼2,090 Ma) from eclogite is somewhat older than the regional Middle Palaeoproterozoic metamorphism/recrystallization ages (∼2,040 Ma) reported from amphibolites. Thus, the eclogite–amphibolite ages may date an exhumation process. A published charnockite age, interpreted as an Early Mesoarchean crystallization age, is older than the Late Mesoarchean meta‐syenite and amphibolite‐protolith dates; its Middle Palaeoproterozoic metamorphism/recrystallization age, however, is identical with the meta‐granodiorites and amphibolites. The Neoproterozoic ages demonstrate the regional overprint of the Nyong Complex during this period. Integration of the Nyong Complex ages with published ones from the entire West Central African Fold Belt, and comparison with those from West Africa and South America, support their common origin from the Palaeoproterozoic collision between the Archean Congo and São Francisco shields.(a) South America–Africa fit, showing shields of western Gondwana (modified after Neves et al., 2006). (b) Geological sketch of Cameroon, showing its Archean, Paleo‐, and Neoproterozoic basement and the Cretaceous‐Cenozoic volcano‐sedimentary cover (modified after Castaing et al., 1994; Ngako, Affaton, Nnangue, & Njanko, 2003; Owona, Mvondo Ondoa & Ekodeck, 2013). (c) Geology of the Nyong Complex and related U‐Pb zircon ages. Abbreviations: NEFB – North Equatorial Fold belt, OC – Oubanguide Complex. Published studies: 1 – Toteu et al. (1994), 2 – Lerouge et al. (2006), 3 – Loose & Schenk (2018), 4 – Nkoumbou et al. (2015), and * – present study. (d) Normalized age probability diagrams summarizing the new and published U‐Th‐Pb ages from the West Central African fold belt (including the Nyong Complex), and those from the South American and West African equivalents. Abbreviations: CS – Congo Shield, KS – Kalahari Shield, SFS – São Francisco Shield, TS – Tanzania Shield, WAS – West African Shield. imageGerman Academic Exchange Service http://dx.doi.org/10.13039/50110000165

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)