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 region.

Laboratory investigation on the effects of overburden pressure, water, and time on slaking induced material property degradation of coal mine spoil

In open-cut strip mining, waste material is placed in-pit to minimise operational mine costs. Slope failures in these spoil piles pose a significant safety risk to personnel, along with a financial risk from loss of equipment and scheduling delays. It has been observed that most spoil pile failures occur when the pit has been previously filled with water and then subsequently dewatered. The failures are often initiated at the base of spoil piles where the material can undergo significant slaking (disintegration) over time due to overburden pressure and water saturation. It is important to understand how the mechanical properties of base spoil material are affected by slaking when designing safe spoil pile slope angles, heights, and dewatering rates. In this study, fresh spoil material collected from a coal mine in Brown Basin Coalfield of Queensland, Australia was subjected to high overburden pressure (0 – 900 kPa) under saturated condition and maintained over a period of time (0 – 6 months) allowing the material to slake. To create the above conditions, laboratory designed pressure chambers were used. Once a spoil sample was slaked under certain overburden pressure over a period of time, it was tested for classification, permeability, and strength properties. Results of this testing program suggested that the slaking of saturated coal mine spoil increase with overburden pressure and the time duration over which the overburden pressure was maintained. Further, it was observed that shear strength and permeability of spoil decreased with increase in spoil slaking.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Who is the South African retail giant behind the David Jones bid?

Yesterday morning came the news South African retailer Woolworths had offered $4 a share to acquire David Jones, a proposal that has the approval of the department store’s board. This offer, worth an estimated A$2.15 billion, represents a 25% premium over the current share price value. An earlier offer, from rival Myer, was rejected earlier this year. But who is Woolworths? Not to be confused with Australia’s largest supermarket, Woolworths SA is one of South Africa’s largest retailers.

David Jones seeks to exploit top end gap in Australian grocery

While Australia’s supermarkets continue to battle on price, the South African owner of David Jones, Woolworths Holdings, has found a gap in the Australian grocery market and is preparing to exploit it. Reports that the group has appointed Pieter de Wet to overhaul the David Jones food business signals once again the ever-changing face of the Australian food and grocery landscape. A re-energised David Jones food offer will provide positive outcomes for both shoppers and suppliers, while potentially becoming another headache for Coles and Woolworths.

Cost-effectiveness of a nonpharmacological intervention in pediatric burn care

OBJECTIVE To report the cost-effectiveness of a tailored handheld computerized procedural preparation and distraction intervention (Ditto) used during pediatric burn wound care in comparison to standard practice. METHODS An economic evaluation was performed alongside a randomized controlled trial of 75 children aged 4 to 13 years who presented with a burn to the Royal Children's Hospital, Brisbane, Australia. Participants were randomized to either the Ditto intervention (n = 35) or standard practice (n = 40) to measure the effect of the intervention on days taken for burns to re-epithelialize. Direct medical, direct nonmedical, and indirect cost data during burn re-epithelialization were extracted from the randomized controlled trial data and combined with scar management cost data obtained retrospectively from medical charts. Nonparametric bootstrapping was used to estimate statistical uncertainty in cost and effect differences and cost-effectiveness ratios. RESULTS On average, the Ditto intervention reduced the time to re-epithelialize by 3 days at AU$194 less cost for each patient compared with standard practice. The incremental cost-effectiveness plane showed that 78% of the simulated results were within the more effective and less costly quadrant and 22% were in the more effective and more costly quadrant, suggesting a 78% probability that the Ditto intervention dominates standard practice (i.e., cost-saving). At a willingness-to-pay threshold of AU$120, there is a 95% probability that the Ditto intervention is cost-effective (or cost-saving) against standard care. CONCLUSIONS This economic evaluation showed the Ditto intervention to be highly cost-effective against standard practice at a minimal cost for the significant benefits gained, supporting the implementation of the Ditto intervention during burn wound care.