A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

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.

NELR Editorial Federal Updates Issue 2012:3

Despite opposition from environmentalists, farmers and parts of the fishing industry, on 23 August 2012, the $6.4bn Alpha Coal mine and rail project in Queensland was approved under the EPBC Act, subject to 19 conditions.1 The approval relates to the proposed construction and operation of an open-cut coal mine and 495km railway line to Abbott Point...

The association between objectively measured neighbourhood features and walking for transport in mid-aged adults

The aim of this paper is to examine the association between a range of objectively measured neighbourhood features and the likelihood of mid-aged adults walking for transport. Increased walking for transport would bring multiple benefits, including improved population and environmental health. As part of the baseline HABITAT study, 10,745 residents of Brisbane, Australia, aged 40–65 years, from 200 neighbourhoods were asked about the time they spent walking for transport. Walking data were collected by mail survey and the physical environmental features of neighbourhoods were compiled using a geographic information systems database. Walking for transport was categorised into four levels and the association between walking and each neighbourhood characteristic was examined using multilevel multinomial models. A number of threshold trends were evident; for example, off-road bikeways were consistently associated with walking between 60 and 150 min per week. Living within 500 m of public transit was also an important predictor but only for those who walked for less than 150 min per week. Interventions targeting these neighbourhood characteristics may lead to improved environmental quality, lower rates of overweight and obesity and associated chromic disease.

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.

The association between motivation in school physical education and self-reported physical activity during Finnish junior high school : a self-determination theory approach

The main purpose of this longitudinal study was to investigate the role of motivational climates, perceived competence and motivational regulations as antecedents of self-reported physical activity during junior high school years. The participants included 237 Finnish students (101 girls, 136 boys) that were 13 years old at the first stage of the study. Students completed the motivational climate and perceived competence questionnaires at Grade 7, motivation towards physical education questionnaire at Grade 8, and self-reported physical activity questionnaire at Grade 9. A path analysis revealed a path from task-involving motivational climate via perceived competence and intrinsic motivation to self-reported physical activity. Perceived competence and intrinsic motivation were statistically significant mediators between task-involving motivational climate and self-reported physical activity. This finding supports the four-stage causal sequence model of motivation.

A note on the ‘Linsanity’ of measuring the relative efficiency of National Basketball Association guards

This note examines the productive efficiency of 62 starting guards during the 2011/12 National Basketball Association (NBA) season. This period coincides with the phenomenal and largely unanticipated performance of New York Knicks’ starting point guard Jeremy Lin and the attendant public and media hype known as Linsanity. We employ a data envelopment analysis (DEA) approach that includes allowance for an undesirable output, here turnovers per game, with the desirable outputs of points, rebounds, assists, steals and blocks per game and an input of minutes per game. The results indicate that depending upon the specification, between 29% and 42% of NBA guards are fully efficient, including Jeremy Lin, with a mean inefficiency of 3.7% and 19.2%. However, while Jeremy Lin is technically efficient, he seldom serves as a benchmark for inefficient players, at least when compared with established players such as Chris Paul and Dwayne Wade. This suggests the uniqueness of Jeremy Lin's productive solution and may explain why his unique style of play, encompassing individual brilliance, unselfish play and team leadership, is of such broad public appeal.

Ureaplasma parvum multiple banded antigen (MBA) size variation - association with fetal inflammation in a sheep model (Published abstract)

Background: Ureaplasma species are the most prevalent isolates from women who deliver preterm. The MBA, a surface exposed lipoprotein, is a key virulence factor of ureaplasmas. We investigated MBA variation after chronic and acute intra-amniotic (IA) ureaplasma infections. Method: U. parvum serovar 3 (2x104 colony-forming-units) was injected IA into pregnant ewes at: 55 days gestation (d, term = 145d) (n=8); 117d (n=8) and 121d (n=8). Fetuses were delivered surgically (124d) and ureaplasmas cultured from amniotic fluid (AF), chorioamnion, fetal lung (FL) and umbilical cord were tested by western blot and PCR assays to demonstrate MBA and mba gene variation respectively. Tissue sections were sectioned and stained by haemotoxylin and eosin and inflammatory cell counts and pathology were reported (blinded to outcome). Results: Numerous MBA/mba variants were generated in vivo after chronic exposure to ureaplasma infection but after acute infection no variants (3d) or very few variants (7d) were generated. Identical MBA variants were detected within the AF and FL but different ureaplasma variants were detected within chorioamnion specimens. The severity of inflammation within chronically infected tissues varied between animals ranging from no inflammation to severe inflammation with/without fibrosis. Chorioamnion, FL and cord from the same animal demonstrated the same degree of inflammation. Conclusions: MBA/mba variation in vivo occurred after the initiation of the host immune response and we propose that ureaplasmas vary the MBA antigen to evade the host immune response. In some animals there was no inflammation despite colonisation with high numbers of ureaplasmas.

Summarization of association rules in multi-tier granule mining

It is a big challenge to find useful associations in databases for user specific needs. The essential issue is how to provide efficient methods for describing meaningful associations and pruning false discoveries or meaningless ones. One major obstacle is the overwhelmingly large volume of discovered patterns. This paper discusses an alternative approach called multi-tier granule mining to improve frequent association mining. Rather than using patterns, it uses granules to represent knowledge implicitly contained in databases. It also uses multi-tier structures and association mappings to represent association rules in terms of granules. Consequently, association rules can be quickly accessed and meaningless association rules can be justified according to the association mappings. Moreover, the proposed structure is also an precise compression of patterns which can restore the original supports. The experimental results shows that the proposed approach is promising.

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.