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.

Leg Clubs - Beyond the ulcers : case studies based on participatory action research

Based on Participatory Action Research (PAR), the case studies in this paper examine the psychosocial benefits and outcomes for clients of community based Leg Clubs. The Leg Club model was developed in the United Kingdom (UK) to address the issue of social isolation and non-compliance to leg ulcer treatment. Principles underpinning the Leg Club are based on the Participatory Action Framework (PAR) where the input and involvement of participants is central. This study identifies the strengths of the Leg Club in enabling and empowering people to improve the social context in which they function. In addition it highlights the potential of expanding operations that are normally clinically based (particularly in relation to chronic conditions) but transferable to community settings in order that that they become “agents of change” for addressing such issues as social isolation and the accompanying challenges that these present, including no-compliance to treatment.

Australian journalism studies after ‘Journalism’: breaking down the disciplinary boundaries (for good)

This paper argues that if journalism is to remain a relevant and dynamic academic discipline, it must urgently reconsider the constrained, heavily-policed boundaries traditionally placed around it (particularly in Australia). A simple way of achieving this is to redefine its primary object of study: away from specific, rigid, professional inputs, towards an ever-growing range of media outputs. Such a shift may allow the discipline to freely re-assess its pedagogical and epistemological relationships to contemporary newsmaking practices (or, the ‘new’ news).

Association between ambient ultraviolet radiation and risk of esophageal cancer

OBJECTIVES: Ecological studies have suggested an inverse relationship between latitude and risks of some cancers. However, associations between solar ultraviolet radiation (UVR) exposure and esophageal cancer risk have not been fully explored. We therefore investigated the association between nevi, freckles, and measures of ambient UVR over the life-course with risks of esophageal cancers. METHODS: We compared estimated lifetime residential ambient UVR among Australian patients with esophageal cancer (330 esophageal adenocarcinoma (EAC), 386 esophago-gastric junction adenocarcinoma (EGJAC), and 279 esophageal squamous cell carcinoma (ESCC)), and 1471 population controls. We asked people where they had lived at different periods of their life, and assigned ambient UVR to each location based on measurements from NASA's Total Ozone Mapping Spectrometer database. Freckling and nevus burden were self-reported. We used multivariable logistic regression models to estimate the magnitude of associations between phenotype, ambient UVR, and esophageal cancer risk. RESULTS: Compared with population controls, patients with EAC and EGJAC were less likely to have high levels of estimated cumulative lifetime ambient UVR (EAC odds ratio (OR) 0.59, 95% confidence interval (CI) 0.35-0.99, EGJAC OR 0.55, 0.34-0.90). We found no association between UVR and risk of ESCC (OR 0.91, 0.51-1.64). The associations were independent of age, sex, body mass index, education, state of recruitment, frequency of reflux, smoking status, alcohol consumption, and H. pylori serostatus. Cases with EAC were also significantly less likely to report high levels of nevi than controls. CONCLUSIONS: These data show an inverse association between ambient solar UVR at residential locations and risk of EAC and EGJAC, but not ESCC.

Words and Silences : The journal of the International Oral History Association

Words and Silences is the official on-line journal of the International Oral History Association. It is an internationally peer reviewed, high quality forum for oral historians from a wide range of disciplines and a means for the professional community to share projects and current trends of oral history from around the world. We are extremely pleased to release the first online issue of Word &Silences. This e-journal is the result of long standing discussion and debate about the best way to publish a quality bilingual oral history journal (including a blind peer reviewed section) as a viable solution to mounting difficulties associated with publishing in print. We have discovered that an online version is also not without its challenges and requires tremendous labor intensive dedication. We strongly encourage members to assist us with small review process tasks in the future, so that we can ensure the sustainability of an annual W&S publication for our members and beyond.

Genetic association of the KLK4 locus with risk of prostate cancer

The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

Multilevel determinants of breast cancer survival : association with geographic remoteness and area-level socioeconomic disadvantage

A major priority for cancer control agencies is to reduce geographical inequalities in cancer outcomes. While the poorer breast cancer survival among socioeconomically disadvantaged women is well established, few studies have looked at the independent contribution that area- and individual-level factors make to breast cancer survival. Here we examine relationships between geographic remoteness, area-level socioeconomic disadvantage and breast cancer survival after adjustment for patients’ socio- demographic characteristics and stage at diagnosis. Multilevel logistic regression and Markov chain Monte Carlo simulation were used to analyze 18 568 breast cancer cases extracted from the Queensland Cancer Registry for women aged 30 to 70 years diagnosed between 1997 and 2006 from 478 Statistical Local Areas in Queensland, Australia. Independent of individual-level factors, area-level disadvantage was associated with breast-cancer survival (p=0.032). Compared to women in the least disadvantaged quintile (Quintile 5), women diagnosed while resident in one of the remaining four quintiles had significantly worse survival (OR 1.23, 1.27, 1.30, 1.37 for Quintiles 4, 3, 2 and 1 respectively).) Geographic remoteness was not related to lower survival after multivariable adjustment. There was no evidence that the impact of area-level disadvantage varied by geographic remoteness. At the individual level, Indigenous status, blue collar occupations and advanced disease were important predictors of poorer survival. A woman’s survival after a diagnosis of breast cancer depends on the socio-economic characteristics of the area where she lives, independently of her individual-level characteristics. It is crucial that the underlying reasons for these inequalities be identified to appropriately target policies, resources and effective intervention strategies.

Power of QTL detection using association tests with family controls

The power of testing for a population-wide association between a biallelic quantitative trait locus and a linked biallelic marker locus is predicted both empirically and deterministically for several tests. The tests were based on the analysis of variance (ANOVA) and on a number of transmission disequilibrium tests (TDT). Deterministic power predictions made use of family information, and were functions of population parameters including linkage disequilibrium, allele frequencies, and recombination rate. Deterministic power predictions were very close to the empirical power from simulations in all scenarios considered in this study. The different TDTs had very similar power, intermediate between one-way and nested ANOVAs. One-way ANOVA was the only test that was not robust against spurious disequilibrium. Our general framework for predicting power deterministically can be used to predict power in other association tests. Deterministic power calculations are a powerful tool for researchers to plan and evaluate experiments and obviate the need for elaborate simulation studies.

Work integrated research higher degree studies : experiences, benefits, barriers and coping strategies

Attributed to the changing social, political and economic landscape of the ‘knowledge economy’, Australian universities are under pressure to produce researchers that have a variety of skills which meet the demands of an increasingly diverse job market. As a consequence, the Australian PhD now includes a range of doctoral degrees. This paper reports on the experiences of two PhD students engaged in an informally managed research higher degree program described in this paper as a Work Integrated Research Higher Degree (WIRHD). Their learning process shares the attributes from both the traditional PhD program and professional doctorates. However, because of the blended nature of the learning contexts, what students need to manage within the WIRHD is much more complicated than the established RHD programs. An exploratory case study approach exploring experiences, benefits, barriers and coping strategies was conducted with the view to develop a preliminary integrative framework that attempts to explain the various contexts that influence the learning experience of WIRHD candidates. The paper concludes with some recommended strategies for helping WIRHD candidates to manage the challenges associated with their learning process.

Non-contact ACL injuries : association with clegg soil impact test values for sports fields, soil moisture and prevailing weather

Introduction: There is a recognised relationship between dry weather conditions and increased risk of anterior cruciate ligament (ACL) injury. Previous studies have identified 28 day evaporation as an important weather-based predictor of non-contact ACL injuries in professional Australian Football League matches. The mechanism of non-contact injury to the ACL is believed to increased traction and impact forces between footwear and playing surface. Ground hardness and the amount and quality of grass are factors that would most likely influence this and are inturn, related to the soil moisture content and prevailing weather conditions. This paper explores the relationship between soil moisture content, preceding weather conditions and the Clegg Soil Impact Test (CSIT) which is an internationally recognised standard measure of ground hardness for sports fields. Methodology: The 2.25 kg Clegg Soil Impact Test and a pair of 12 cm soil moisture probes were used to measure ground hardness and percentage moisture content. Five football fields were surveyed at 13 prescribed sites just before seven football matches from October 2008 to January 2009 (an FC Women’s WLeague team). Weather conditions recorded at the nearest weather station were obtained from the Bureau of Meteorology website and total rainfall less evaporation was calculated for 7 and 28 days prior to each match. All non-contact injuries occurring during match play and their location on the field were recorded. Results/conclusions: Ground hardness varied between CSIT 5 and 17 (x10G) (8 is considered a good value for sports fields). Variations within fields were typically greatest in the centre and goal areas. Soil moisture ranged from 3 to 40% with some fields requiring twice the moisture content of others to maintain similar CSIT values. There was a non-linear, negative relationship for ground hardness versus moisture content and a linear relationship with weather (R2, of 0.30 and 0.34, respectively). Three non-contact ACL injuries occurred during the season. Two of these were associated with hard and variable ground conditions.

Improving statistical analysis of matched case-control studies

Matched case–control research designs can be useful because matching can increase power due to reduced variability between subjects. However, inappropriate statistical analysis of matched data could result in a change in the strength of association between the dependent and independent variables or a change in the significance of the findings. We sought to ascertain whether matched case–control studies published in the nursing literature utilized appropriate statistical analyses. Of 41 articles identified that met the inclusion criteria, 31 (76%) used an inappropriate statistical test for comparing data derived from case subjects and their matched controls. In response to this finding, we developed an algorithm to support decision-making regarding statistical tests for matched case–control studies.

The association between pterygium and conjunctival ultraviolet autofluorescence : The Norfolk Island Eye Study

Purpose: To investigate the association between conjunctival ultraviolet autofluorescence (UVAF), a biomarker of ocular ultraviolet radiation (UVR) exposure, and prevalent pterygium. Methods: We conducted a cross-sectional study on Norfolk Island, South Pacific. All permanent residents aged ‡15 were invited to participate. Participants completed a sun exposure questionnaire and underwent autorefraction and slit lamp biomicroscope examination. Area of conjunctival UVAF (sum of temporal ⁄ nasal area in right and left eyes) was determined using computerized methods. Multivariate logistic and linear regression models were used to estimate the associations with pterygia and UVAF, respectively. Results: Of 641 participants, 70 people (10.9%) had pterygium in one or both eyes, and prevalence was higher in males (15.0% versus 7.7%, p = 0.003). Significant independent associations with pterygium in any eye were UVAF (per 10 mm2) [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.16–1.28, p = 0.002], tanning skin phenotype (OR 2.17,1.20–3.92, p = 0.010) and spending more than three-quarters of the day outside (OR 2.22, 1.20–4.09, p = 0.011). Increasing quartile of UVAF was associated with increased risk of pterygium following adjustment of age, sex and time outdoors (pTrend = 0.002). Independent associations with increasing UVAF (per 10 mm2) were decreasing age, time outdoors, skin type and male gender (all p < 0.001). UVAF area correlated well with the duration of outdoor activity (pTrend < 0.001). Conclusion: Pterygium occurs in approximately one-tenth of Norfolk Islanders. Increasing conjunctival UVAF is associated with prevalent pterygia, confirming earlier epidemiological, laboratory and ray-tracing studies that pterygia are associated with UVR. Protection from the sun should be encouraged to reduce the prevalence of pterygium in the community.

An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12

Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci. An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1×10−5) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92×10−4), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65×10−4). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women’s Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05). Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63×10−5) is located within the 5′UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.