Association between prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data

Background: Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease. Objectives: We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. Methods and Data Sources: Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study. Results: Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p, 0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7610 24). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells. Conclusions: Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes.

A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall survival in ovarian cancer. Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs) and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival. Results In silico analysis was performed to identify KLK15 regulatory elements and to classify potentially functional SNPs in these regions. After SNP validation and identification by DNA sequencing of ovarian cancer cell lines and aggressive ovarian cancer patients, 9 SNPs were shortlisted and genotyped using the Sequenom iPLEX Mass Array platform in a cohort of Australian ovarian cancer patients (N = 319). In the Australian dataset we observed significantly worse survival for the KLK15 rs266851 SNP in a dominant model (Hazard Ratio (HR) 1.42, 95% CI 1.02-1.96). This association was observed in the same direction in two independent datasets, with a combined HR for the three studies of 1.16 (1.00-1.34). This SNP lies 15bp downstream of a novel exon and is predicted to be involved in mRNA splicing. The mutant allele is also predicted to abrogate an HSF-2 binding site. Conclusions We provide evidence of association for the SNP rs266851 with ovarian cancer survival. Our results provide the impetus for downstream functional assays and additional independent validation studies to assess the role of KLK15 regulatory SNPs and KLK15 isoforms with alternative intracellular functional roles in ovarian cancer survival.

Exeter short stems compared with standard length Exeter stems : experience from the Australian Orthopaedic Association National Joint Replacement Registry

The standard Exeter stem has a length of 150mm with offsets 37.5mm to 56mm. Shorter stems of lengths 95mm, 115mm and 125mm with offsets 35.5mm or less are available for patients with smaller femurs. Concern has been raised regarding the behaviour of the smaller implants. This paper analysed data from the Australian Orthopaedic Association National Joint Replacement Registry comparing survivorship of stems of offset 35.5mm or less with the standard stems of 37.5mm offset or greater. At seven years there was no significant difference in the Cumulative Percent Revision Rate in the short stems (3.4%, 95% CI 2.4-4.8%) compared with the standard length stems (3.5%, 95% CI 3.3-3.8%) despite its use in a greater proportion of potentially more difficult developmental dysplasia of the hip cases.

Compass points : the locations, landscapes and coordinates of identities in contemporary performance making : proceedings of the Australasian Association for Theatre, Drama & Performance Studies (ADSA) Conference 2012

Compass Points: The Locations, Landscapes and Coordinates of Identities' the Australasian Association for Theatre, Drama and Performance Studies (ADSA) Conference 2012 was held at Queensland University of Technology, July 3-6 2012. The Conference was sponsored by the Australasian Association for Theatre, Drama and Performance Studies (ADSA), Queensland University of Technology (QUT), Ian Potter Foundation, Arts Queensland, La Boite Theatre Company and Queensland Theatre Company. The papers selected for this collection represent a small sample of the scope, depth and diversity of scholarship presented at the conference - they cover a range of genres, cultures and contexts in contemporary performance making from autobiography, to playwrighting, to public space performance and beyond. The papers collected have been peer-reviewed to Australia’s Department of Education, Science and Training (DEST) standards - each has been subject to two blind reviews, followed by acceptance, rejection or revision, and editing of accepted papers - by colleagues from Australasia and overseas. The review process for the conference publication was separate from the review process for acceptance of abstracts for the actual conference presentations. The conference convenors, Bree Hadley and Caroline Heim, edited the collection, and would like to thank all those who gave their time to advise on the peer review process and act as reviewers - Tom Burvill, Christine Comans, Sean Edgecomb, Angela Campbell, Natalie Lazaroo, Jo Loth, Meg Mumford, Ulrike Garde, Laura Ginters, Andre Bastian, Sam Trubridge, Delyse Ryan, Georgia Seffrin, Gillian Arrighi, Rand Hazou, Rob Pensalfini, Sue Fenty-Studham, Mark Radvan, Rob Conkie, Kris Plummer, Lisa Warrington, Kate Flaherty, Bryoni Tresize, Janys Hayes, Lisa Warrington, Teresa Izzard, Kim Durban, Veronica Kelly, Adrian Keirnander, James Davenport, Julie Robson and others. We, and the authors, appreciate the rigour and care with which peers have approached the scholarship presented here. This collection was published in final form on July 3rd 2012, the first day of the ADSA Conference 2012.

Smoking status as a moderator of the association between food insecurity and decreased fruit and vegetable consumption

Food insecurity is the inadequate access to, or availability of, sufficient amounts of nutritious, culturally-appropriate and safe foods, or the inability to acquire such foods by socially acceptable means. Food insecurity has been shown to be associated with poor dietary intakes and poor health status. Recently, evidence has emerged suggesting increased rates of food insecurity among those with substance abuse problems, including those who smoke. This cross-sectional study investigates the potential moderating effect of smoking on the association between food insecurity and fruit and vegetable intakes among the Australian population, using regression analyses. Participants were adults 18 years and older participating in the 2004/05 National Health Survey (n = 19,500). Those from food insecure households were up to two-times more likely to report inadequate fruit and vegetable intakes compared to those who were food secure. Those who smoked were nearly six times more likely to report being food insecure, and up to three-times more likely to report inadequate fruit and vegetable intakes, compared to their non-smoking counterparts. Further analyses revealed a marked decline in the strength of the association between food insecurity and fruit consumption with the addition of smoking status into a regression model. These findings have important implications for the development of policy and interventions to address food insecurity, suggesting that those from food insecure households are less likely to comply with national dietary recommendations, and that this may in part be moderated by smoking status.

Factors affecting technical efficiency of rice farmers in village reservoir irrigation systems of Sri Lanka

Given the importance of water for rice production, this study examines the factors affecting the technical efficiency (TE) of irrigated rice farmers in village irrigation systems (VIS) in Sri Lanka. Primary data were collected from 460 rice farmers in the Kurunagala District, Sri Lanka, to estimate a stochastic translog production frontier for rice production. The mean TE of rice farming in village irrigation was found to be 0.72, although 63% of rice farmers exceeded this average. The most influential factors of TE are membership of Farmer Organisations (FOs) and the participatory rate in collective actions organised by FOs. The results suggest that enhancement of co-operative arrangements of farmers by strengthening the membership of FOs is considered important for increasing TE in rice farming in VIS.