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

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Improving age, growth, and maturity estimates for aseasonally reproducing chondrichthyans

Many species of chondrichthyans (sharks, rays and chimaeras) reproduce throughout the year, lacking a distinct seasonality in the timing of their reproduction with young born throughout the year. Since age determination in fish usually relies on counting regularly deposited growth increments on hard body parts (e.g. vertebrae, spines, otoliths) the age of an aseasonally reproducing animal after the first growth increment is formed is unknown. We explored the implications of this for the estimation of growth and maturity parameters using the milk shark, Rhizoprionodon acutus, a small, tropical, shark that reproduces aseasonally off northern Australia. Since R. acutus grows rapidly after birth, not accounting for an aseasonal reproductive cycle led to unrealistic projections of growth for this species. We describe a simple method for adjusting individual ages that improves projections of growth and reduces the level of error around growth parameter estimates. This is compared with growth estimates when ages are left unadjusted or adjusted to a mean value to account for aseasonal reproduction. Using back calculated length-at-age data, model-averaged growth across five models gave an asymptotic size (L∞) of 859 mm for females and 821 mm for males. Standard von Bertalanffy growth parameters were L∞ = 861 mm, K = 0.63, L0 = 423 mm for females and L∞ = 821 mm, K = 0.94, L0 = 424 mm for males. The oldest female and male were 8.1 and 4.5 years old, and the largest female and male measured were 940 and 931 mm. The size at which 50% of females and males were mature was 780 and 742 mm. The age at which 50% of females and males were mature was 1.8 and 1.1 years of age. Incorporating the effects of an aseasonal reproductive cycle into growth analysis is an important step for maximising the accuracy of age and growth results and is especially important for small, tropical species such as R. acutus that complete much of their growth in the first year of life

Age, growth and reproductive biology of the spot-tail shark, Carcharhinus sorrah, and the Australian blacktip shark,C. tilstoni, from the Great Barrier Reef World Heritage Area, north-eastern Australia

Understanding the life history of an exploited fish species is an integral part of successful fisheries management and this information can be used in quantitative population assessments. The present study describes the quantitative relationships among age, growth and reproductive biology of two commercially exploited sharks from the Great Barrier Reef World Heritage Area (GBRWHA), namely, the spot-tail shark, Carcharhinus sorrah (n = 659) and the Australian blacktip shark, C. tilstoni (n = 512). Longevity estimates based on vertebral ageing were 9 and 14 years for male and female C. sorrah and 13 and 15 years for C. tilstoni. However, an age-validation study failed to validate annual banding in larger individuals, suggesting that maximum age may be underestimated by vertebrae. C. sorrah grew to adult size relatively fast, reaching maturity at 2.3–2.4 years, whereas C. tilstoni grew slower, reaching maturity at 5.2–6.1 years. For both species, however, reproduction did not commence until approximately a year after maturity, at 3.4 years for C. sorrah and 7.2 years for C. tilstoni. The results of the present study suggest that in the GBRWHA, C. tilstoni, in particular, begins reproducing at an older age and lives longer than previously thought

Big fish in shallow water; use of an intertidal surf-zone habitat by large-bodied teleosts and elasmobranchs in tropical northern Australia

Shallow intertidal habitats are recognised as critical for larval and juvenile fish, and are often assumed to function as refuge areas where predation risk is reduced. Yet there is growing evidence that suggest these areas may also be regularly inhabited by large bodied fish and be the site of high levels of juvenile fish predation. In the present study we examined the use of an intermittently available surf zone habitat in tropical northern Australia by a diverse community of large-bodied teleosts (mean total length 444 mm), sharks (mean total stretched length 658 mm) and rays (mean total stretched length 1,108 mm). Drawing on the methods and ecological knowledge of a local commercial fishery, gillnets were used to capture fish as they entered the surf zone on the flooding tide. Monthly surveys over a one-year period revealed a dynamic assemblage consisting of 30 species of teleosts (mostly caught as adults) and 14 species of sharks and rays (mostly caught as juveniles or young of the year). Although it is unclear why these fish use this habitat, we conclude that it may support a broad range of biological benefits including spawning for teleosts, parturition for elasmobranchs, as well as foraging and refuge. The unique findings of this study highlight existing knowledge gaps and the need to better understand what fish use the intertidal zone and why. This should be a high priority given the increasing anthropogenic pressures on coastal margins

Demographics and length and weight relationships of commercially important sharks along the north-western coast of India

Biological data including size, sex ratios, male maturity, and length and weight relationships for four commercially important shark species, including the milk shark (Rhizoprionodon acutus Ruppell, 1837), the grey sharpnose shark (Rhizoprionodon oligolinx Springer, 1964), the spadenose shark (Scoliodon laticaudus Muller & Henle, 1838), and the bigeye smoothhound shark (Iago omanensis Norman, 1939), landed in Porbandar, Gujarat, India, are provided. All four species were landed by trawlers and gill-netters across three defined seasons, with seasonal differences. Higher proportions of mature R. acutus and S. laticaudus were observed in the pre-monsoon season, with neonates caught throughout the year, whereas higher proportions of mature R. oligolinx and I. omanensis were recorded during the monsoon season, with neonates caught in post-monsoon and pre-monsoon, respectively, showing important species-level differences. These small-bodied shark species (less than 1 m in total length) showed positive allometry in their length and weight relationships. Unlike the other three species, I. omanensis showed high disparity in total lengths (L-T) between the sexes, with females being larger than males, and with males maturing faster, with the smallest mature male of 33.58 cm L-T. Females outnumbered males except in R. acutus, and pregnant females of all species were recorded at least once. Of the 971 males recorded across species, 55.1% were mature and 44.9% were immature. Results from this study indicate that there is substantial overlap between the distributions of these species and fishing activities, and show that most, if not all, life stages are susceptible to mortality as a result of fishing. This study provides managers with a better understanding of the life-history traits of these commercially important species to support future quantitative population assessments, and provides a baseline of trends in fishing-related mortality

Identifying and mitigating potential risks for Marine Stewardship Council assessment and certification

The assessment of a fishery against the Marine Stewardship Council (MSC) standard requires a large amount of technical knowledge and fishery information. Failure to meet the minimum requirements or to provide the necessary information may result in 'conditions' being placed on a fishery, which can increase the overall cost of maintaining certification. Thus, it is prudent for the fishery client to have a thorough understanding of any potential areas of weakness prior to undergoing assessment. This study investigates patterns in the types of conditions received by MSC certified fisheries to identify common risk areas based on general fishery characteristics, such as target species, fishing method and geographic region.\ud \ud Fisheries targeting crab/lobster, large pelagic finfish and flatfish, and fisheries operating in the UK/Europe and the NE Pacific regions, received more conditions related to the target species' stock status (MSC Principle 1) than other groups investigated. Ecosystem (MSC Principle 2) conditions were more frequently received by fisheries using demersal trawl or longline methods compared to hand collection, line fishing or other types of netting. A high proportion of shrimp and crab/lobster fisheries, fisheries in the NW Atlantic region and dredge fisheries received Governance/Management (MSC Principle 3) conditions.\ud \ud Case studies from five types of frequently-certified fisheries are used to identify mitigation strategies for common high-risk areas. The identification and mitigation of risk areas has important implications particularly for small-scale and developing-country fisheries that have limited resources and therefore need to minimise the number of conditions received. Similarly, the identification of common risks areas highlights where more explicit guidance needs to be incorporated into future reviews of the MSC standard, e.g. Harvest Control Rules, to assist prospective fisheries and to ensure consistency in assessments

Life history of the common blacktip shark, Carcharhinus limbatus, from central eastern Australia and comparative demography of a cryptic shark complex

Common and Australian blacktip sharks (Carcharhinus limbatus and Carcharhinus tilstoni) occur sympatrically in Australia, where they are reported as a complex because of their morphological similarities. This study provides the first description of the life history of C. limbatus using samples from central eastern Australia, where C. tilstoni is rare. Females (68-267 cm total length (TL); n = 183) and males (65-255 cm TL; n = 292) both matured at 8.3 years and 200 cm TL, which exceeds the maximum length of C. tilstoni. Vertebral ageing revealed that female and male C. limbatus lived to 22 and 24 years respectively, exceeding known longevity in C. tilstoni. The mean (±s.d.) intrinsic rate of population increase calculated using a Euler-Lotka demographic method was 0.11 ± 0.02 year for C. limbatus, compared with 0.17 ± 0.02 and 0.20 ± 0.03 year for two C. tilstoni stocks. Despite their similar appearance, these species differed in both their biological productivity and susceptibility to fishing activities. Monitoring of relative abundance should be a priority given they are likely to have divergent responses to fishing

Detection of interspecies hybridisation in Chondrichthyes: hybrids and hybrid offspring between Australian (Carcharhinus tilstoni) and common (C. limbatus) blacktip shark found in an Australian fishery

Abstract Interspecies hybridisation in nature is a wellstudied phenomenon, but it has not been analysed using genetic markers in the class Chondrichthyes (sharks, rays and chimeras). Two black-tip whaler shark species (Australian, Carcharhinus tilstoni; Common, C. limbatus) have overlapping distributions in Australia, distinct mitochondrial DNA sequence (ND4, COI, control region) and distinct morphological features such as length at sexual maturity, length at birth and number of vertebrae. A mismatch was observed between species identification using mtDNA sequence and species identification using morphological characters. To test whether hybridisation between the two species was responsible, a nuclear gene with species-specific mutations was sequenced. Extensive interspecies hybridisation was found to be occurring. Hybrids were found from five locations on the eastern Australian coastline, spanning 2,000 km. If hybrid fitness is low and hybrids are common, then fisheries recruitment may be overestimated and the productivity of the black-tip shark fishery may be well below that required to support commercial exploitation. To guard against identification errors, the likelihood of hybridisation and subsequent introgression should be assessed prior to using mtDNA (e.g. barcoding) to identify shark species. The C. limbatus-C. tilstoni species complex provides a unique opportunity to investigate the ability of sharks to adapt to environmental change, in particular, the impact of hybridization on species distributions which favour C. tilstoni along the north and C. limbatus along the south eastern Australian coastline