Evidence-based recommendations for the monitoring and treatment of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64-100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies.

Twelve not so angry men: Masculinities and the perceptions of the 'off-field' violence involved in Australian body contact sports

Recently, media 'scandals' have pervaded a number of Australian body contact sports, in particular rugby league, rugby union and Australian rules football. Utilising the theoretical framework of masculinities, this research interviews footballers to gauge their perceptions of this media attention and how it compares to their own perspectives regarding off-field violence. Drawing inspiration from James Messerschmidt's (2000) 'Nine Lives' study and R.W. Connell's (1995) theoretical masculinities framework, in-depth, semi-structured interviews—known as life histories—were conducted with 12 footballers. Twelve life histories were completed with four men from each of the three major Australian football codes, namely Australian rules football, rugby union and rugby league. The research explores linkages between masculinity, body contact sport and engagement (or lack thereof) in violence 'off field'.

A genetic variant of MDM4 influences regulation by multiple microRNAs in prostate cancer

The oncogene MDM4, also known as MDMX or HDMX, contributes to cancer susceptibility and progression through its capacity to negatively regulate a range of genes with tumour-suppressive functions. As part of a recent genome-wide association study it was determined that the A-allele of the rs4245739 SNP (A>C), located in the 3'-UTR of MDM4, is associated with an increased risk of prostate cancer. Computational predictions revealed that the rs4245739 SNP is located within a predicted binding site for three microRNAs (miRNAs): miR-191-5p, miR-887 and miR-3669. Herein, we show using reporter gene assays and endogenous MDM4 expression analyses that miR-191-5p and miR-887 have a specific affinity for the rs4245739 SNP C-allele in prostate cancer. These miRNAs do not affect MDM4 mRNA levels, rather they inhibit its translation in C-allele-containing PC3 cells but not in LNCaP cells homozygous for the A-allele. By analysing gene expression datasets from patient cohorts, we found that MDM4 is associated with metastasis and prostate cancer progression and that targeting this gene with miR-191-5p or miR-887 decreases in PC3 cell viability. This study is the first, to our knowledge, to demonstrate regulation of the MDM4 rs4245739 SNP C-allele by two miRNAs in prostate cancer, and thereby to identify a mechanism by which the MDM4 rs4245739 SNP A-allele may be associated with an increased risk for prostate cancer.

Estimating equations for parameters in stochastic growth models from tag-recapture data

James (1991, Biometrics 47, 1519-1530) constructed unbiased estimating functions for estimating the two parameters in the von Bertalanffy growth curve from tag-recapture data. This paper provides unbiased estimating functions for a class of growth models that incorporate stochastic components and explanatory variables. a simulation study using seasonal growth models indicates that the proposed method works well while the least-squares methods that are commonly used in the literature may produce substantially biased estimates. The proposed model and method are also applied to real data from tagged rack lobsters to assess the possible seasonal effect on growth.

Growth curves with explanatory variables and estimation of the effect of tagging

The von Bertalanffy growth model is extended to incorporate explanatory variables. The generalized model includes the switched growth model and the seasonal growth model as special cases, and can also be used to assess the tagging effect on growth. Distribution-free and consistent estimating functions are constructed for estimation of growth parameters from tag-recapture data in which age at release is unknown. This generalizes the work of James (1991, Biometrics 47 1519-1530) who considered the classical model and allowed for individual variability in growth. A real dataset from barramundi (Lates calcarifer) is analysed to estimate the growth parameters and possible effect of tagging on growth.

Exercise improves quality of life in ADT-treated prostate cancer: Systematic review of RCTs

Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December, 2014 in English. Eligible study designs included randomised controlled trials with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure, lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety, bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort.

Muscle morphometry of the individual hamstring muscles in semi-elite AFL Players: Preliminary findings from a longitudinal study

Hamstring strains in the Australian Football League (AFL) have a high incidence (15%) and recurrence rate (34%) with lateral hamstring injuries most common (83%). Retrospective studies have found significant muscle volume asymmetries ≤23 months post hamstring injury; however examination of the association between hamstring strains and muscle asymmetry has not been investigated prospectively. This study presents baseline data from a longitudinal study focusing on individual hamstring morphometry in uninjured and injured semi-elite AFL players.

CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer

Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10(-11)). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4x10(-8)). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.

Media accounts of school performance: Reinforcing dominant practices of accountability

Media reportage often act as interpretations of accountability policies thereby making the news media a part of the policy enactment process. Within such a process, their role is that of policy reinforcement rather than policy construction or contestation. This paper draws on the experiences of school leaders in regional Queensland, Australia, and their perceptions of the media frames that are used to report on accountability using school performance. The notion of accountability is theorised in terms of media understandings of ‘holding power to account’, and forms the theoretical framework for this study. The methodological considerations both contextualise aspects of the schools involved in the study, and outline how ‘framing theory’ was used to analyse the data. The paper draws on a number of participant experiences and newspaper accounts of schools to identify the frames that are used by the press when reporting on school performance. Three frames referring to school performance are discussed in this paper: those that rank performance such as league tables; frames that decontextualise performance isolating it from school circumstances and levels of funding; and frames that residualise government schools.

ERAP2 functional knockout in humans does not alter surface heavy chains or HLA-B27, inflammatory cytokines or endoplasmic reticulum stress markers

Introduction Single nucleotide polymorphisms in ERAP2 are strongly associated with ankylosing spondylitis (AS). One AS-associated single nucleotide polymorphism, rs2248374, causes a truncated ERAP2 protein that is degraded by nonsense-mediated decay. Approximately 25% of the populations of European ancestry are therefore natural ERAP2 knockouts. We investigated the effect of this associated variant on HLA class I allele presentation, surface heavy chains, endoplasmic reticulum (ER) stress markers and cytokine gene transcription in AS. Methods Patients with AS and healthy controls with either AA or GG homozygous status for rs2248374 were studied. Antibodies to CD14, CD19-ECD, HLA-A-B-C, Valpha7.2, CD161, anti-HC10 and anti-HLA-B27 were used to analyse peripheral blood mononuclear cells. Expression levels of ER stress markers (GRP78 and CHOP) and proinflammatory genes (tumour necrosis factor (TNF), IL6, IL17 and IL22) were assessed by qPCR. Results There was no significant difference in HLAclass I allele presentation or major histocompatibility class I heavy chains or ER stress markers GRP78 and CHOP or proinflammatory gene expression between genotypes for rs2248374 either between cases, between cases and controls, and between controls. Discussion Large differences were not seen in HLAB27 expression or cytokine levels between subjects with and without ERAP2 in AS cases and controls. This suggests that ERAP2 is more likely to influence AS risk through other mechanisms.

The ghost in the city industrial complex: Le Corbusier and the fascist theory of Urbanisme

Le Corbusier participated in an urban dialogue with the first group in France to call itself fascist: the journalist Georges Valois’s militant Faisceau des Combattants et Producteurs (1925-1927), the “Blue Shirts,” inspired by the Italian “Fasci” of Mussolini. Le Corbusier’s portrait photograph materialised on the front cover of the January 1927 issue of the Faisceau League’s newspaper Le Nouveau Siècle edited by the former anarcho-syndicalist journalist Georges Valois, its leader, who fashioned himself as the French Mussolini. Le Corbusier was described in the Revue as one of les animateurs (the “organisers”) of the Party1 – meaning a member of the technical elite who would drive the Faisceau’s plans. On 1 May 1927, the Nouveau Siècle printed a full-page feature “Le Plan Voisin” on Le Corbusier’s 1922 redesign of Paris : the architect’s single-point perspective sketch appeared below an extract lifted from the architect’s original polemic Le Centre de Paris on the pages of Le Corbusier’s second book Urbanisme published two years earlier, a treatise on urbanism.2 Three weeks later, Le Corbusier presented a slide show of his urban plans at a fascist rally for the inauguration of the Faisceau’s new headquarters on the rue du faubourg Poissonniere, thereby crystalising the architect’s hallowed status in the league...

Factors associated with self-reported driver sleepiness and incidents in city bus drivers

Driver fatigue has received increased attention during recent years and is now considered to be a major contributor to approximately 15–30% of all crashes. However, little is known about fatigue in city bus drivers. It is hypothesized that city bus drivers suffer from sleepiness, which is due to a combination of working conditions, lack of health and reduced sleep quantity and quality. The overall aim with the current study is to investigate if severe driver sleepiness, as indicated by subjective reports of having to fight sleep while driving, is a problem for city based bus drivers in Sweden and if so, to identify the determinants related to working conditions, health and sleep which contribute towards this. The results indicate that driver sleepiness is a problem for city bus drivers, with 19% having to fight to stay awake while driving the bus 2–3 times each week or more and nearly half experiencing this at least 2–4 times per month. In conclusion, severe sleepiness, as indicated by having to fight sleep during driving, was common among the city bus drivers. Severe sleepiness correlated with fatigue related safety risks, such as near crashes.