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

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Lifestyle segmentation in tourism and leisure: Imposing order or finding it?

This article examines three different approaches to lifestyle segmentation in improving the quality of tourism and leisure marketing decisions in three separate cases. Tourism and leisure products are prototypical lifestyle purchase yet in many tourism research studies visitors are described by demographics or tourism behaviour only. These cases illustrate different approaches to lifestyle segmentation. Firstly, there are segmentation schemes based on external logic that can be broadly applied across a range of markets, including tourism and leisure. Alternatively, there are schemes that are based on a 'conversation' with the data and which rely on an internal logic within that data that may not transfer to other market contexts. Between these two lie schemes that apply external paradigms to specific datasets. The cases selected illustrate points along this spectrum. The first case study examines the use by government tourism organizations of lifestyle segmentation 'bought in' from an external source. Here lifestyle segmentation data is collected from a representative sample of the Australian population as part of a commercial “single source” data set. The second case is based on a regional tourism study, which has utilized prior theory to develop its own lifestyle segmentation and at the same time related this to boarder characteristics of tourists in Tropical North Queensland. The third case examines the development of tailored lifestyle segmentation among 'event' spectators based on purely internal criteria unrelated to the broader population. These cases provide insight into the appropriate development and application of lifestyle segmentation and the use of the data by tourism and leisure managers. Managers may think about the type of lifestyle segmentation approach required based on how the segmentation scheme results need to be related to the wider market or population

Sensitivity to interaural time difference with bilateral cochlear implants: Development over time and effect of interaural electrode spacing

Sensitivity to interaural time difference (ITD) in constant-amplitude pulse trains was measured in four sequentially implanted bilateral cochlear implant (CI) subjects. The sensitivity measurements were made as a function of time beginning directly after the second ear was implanted, continued for periods of months before subjects began wearing bilateral sound processors, and extended for months while the subjects used bilateral sound processors in day-to-day listening. Measurements were also made as a function of the relative position of the left∕right electrodes. The two subjects with the shortest duration of binaural deprivation before implantation demonstrated ITD sensitivity soon after second-ear implantation (before receiving the second sound processor), while the other two did not demonstrate sensitivity until after months of daily experience using bilateral processors. The interaural mismatch in electrode position required to decrease ITD sensitivity by a factor of 2 (half-width) for CI subjects was five times greater than the half-width for interaural carrier-frequency disparity in normal-hearing subjects listening to sinusoidally amplitude-modulated high-frequency tones. This large half-width is likely to contribute to poor binaural performance in CI users, especially in environments with multiple broadband sound sources

Discussion of \u27Modern statistics for spatial point processes\u27

The paper \u27Modern statistics for spatial point processes\u27 by Jesper Møller and Rasmus P. Waagepetersen is based on a special invited lecture given by the authors at the 21st Nordic Conference on Mathematical Statistics, held at Rebild, Denmark, in June 2006. At the conference, Antti Penttinen and Eva B. Vedel Jensen were invited to discuss the paper. We here present the comments from the two invited discussants and from a number of other scholars, as well as the authors\u27 responses to these comments. Below Figure 1, Figure 2, etc., refer to figures in the paper under discussion, while Figure A, Figure B, etc., refer to figures in the current discussion. All numbered sections and formulas refer to the paper. The Editors © 2007 Board of the Foundation of the Scandinavian Journal of Statistics