Genome-wide meta-analysis of common variant differences between men and women

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 x 10(-8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ~115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.

Metacognitions mediate HIV stigma and depression/anxiety in men who have sex with men living with HIV

The study examined whether the relationships between HIV stigma and depression and anxiety would be mediated by metacognitive beliefs and thought control strategies in men who have sex with men living with HIV. Men who have sex with men living with HIV completed an online survey that measured 30-item Metacognitions Questionnaire, thought control strategies (Thought Control Questionnaire), as well as symptoms of depression (Patient Health Questionnaire-9) and anxiety (generalized anxiety disorder-7). The relationships between internalised and anticipated HIV stigma with depressive symptoms were mediated by Negative Metacognitive Beliefs and the use of Worry and Social thought control strategies. Negative Metacognitive Beliefs mediated the association between internalised HIV stigma and anxiety symptoms.

Running Men

In this multi-screen installation, iconic male characters from Hollywood films are reconfigured to create infinitely looping scenes of running; trapping the characters in a kind of Nietchzen eternal recurrence. Stemming primarily from my investigation into anxiety as a shared social experience, the carefully edited, looped, and rotoscoped characters become avatars or surrogates for myself, and for the viewer. Through this editing, they are caught in a space of relentless confusion and paranoia – they run with, and from, anxiety. They are never caught by any unseen pursuers, but are equally unable to catch up to any unseen goal. These figures act as models of masculinity, they are objects of identification and emulation. Simultaneously, as celebrities, they are also fictions of the media sphere, both real and ethereal, they are impossible to grasp. In this duality, the work also references cinema’s tangled conflation of character and celebrity identity. It examines the subjective and intersubjective engagements we can have with popular culture, and the way that these engagements can as strategies to ‘make sense’ of social experiences. The work was exhibited in the Carriageworks space of ‘You Imagine What You Desire’, the 19th Biennale of Sydney.

Running men: The precarious, paranoid body in screen culture

This paper discusses my video installation Running Men as an example of how an artist’s appropriative engagements with screen images of the perilous body can reflect the technological zeitgeist of the last hundred years but also create a space of meditative and mediated reflection in Slavoj Žižek’s “endlessness” of the present-future. In this artwork, iconic male characters from Hollywood films are recontextualised to create infinitely looping scenes of running; trapping the characters in a kind of Nietchzen eternal recurrence that suspends them between impending violence and uncertain futures. Stemming primarily from my investigation into anxiety as a shared social experience, one perhaps primed by the increasing intensity of visual culture in the 21st century, these digitally reconfigured bodies become avatars or surrogates for myself, and for the viewer. Through selective editing, these emblematic figures are caught in a space of relentless confusion and paranoia – they run with, and from anxiety. They are never caught by any unseen pursuers, but are equally unable to catch up to any unseen goal. These figures map an historical trajectory of violence and masculinity as it has been projected through various iterations of screen culture Simultaneously, as celebrities, they are also fictions of the media sphere, both real and ethereal, they are impossible to grasp but paradoxically are objects of identification and emulation. In this duality, the work also references cinema’s tangled conflation of character and celebrity identity. This discussion will address the two distinct but connected sites and activities of body/image engagement. Firstly, the artistic process and conceptual ramifications of this activity, and secondly in the artwork’s potential as an installation to provide an opportunity for the viewer (like the artist) to reflect on the constructed-ness and complicated power structures at play in the representation of a gendered body.

Analysis of body composition in individuals with high bone mass reveals a marked increase in fat mass in women but not men

Context: High bone mass (HBM), detected in 0.2% of dual-energy x-ray absorptiometry (DXA) scans, is characterized by raised body mass index, the basis for which is unclear. Objective: To investigate why body mass index is elevated in individuals with HBM, we characterized body composition and examined whether differences could be explained by bone phenotypes, eg, bone mass and/or bone turnover. Design, Setting, and Participants: We conducted a case-control study of 153 cases with unexplained HBM recruited from 4 UK centers by screening 219 088 DXA scans. Atotal of 138 first-degree relatives (of whom 51 had HBM) and 39 spouses were also recruited. Unaffected individuals served as controls. Main Outcome Measures: We measured fat mass, by DXA, and bone turnover markers. Results: Amongwomen, fat mass was inversely related to age in controls (P<.01), but not in HBM cases (P<.96) in whom mean fat mass was 8.9 [95% CI 4.7, 13.0] kg higher compared with controls (fully adjusted mean difference, P<.001). Increased fat mass in male HBM cases was less marked (gender interaction P = .03). Compared with controls, lean mass was also increased in female HBM cases (by 3.3 [1.2, 5.4] kg; P<.002); however, lean mass increases wereless marked than fat mass increases, resulting in 4.5% lower percentage lean mass in HBM cases (P<.001). Osteocalcin was also lower in female HBM cases compared with controls (by 2.8 [0.1, 5.5]μg/L; P = .04). Differences in fat mass were fully attenuated after hip bone mineral density (BMD) adjustment (P = .52) but unchanged after adjustment for bone turnover (P < .001), whereas the greater hip BMD in female HBM cases was minimally attenuated by fat mass adjustment (P<.001). Conclusions: HBM is characterized by a marked increase in fat mass in females, statistically explained by their greater BMD, but not by markers of bone turnover. Copyright © 2013 by The Endocrine Society.

Clinical application of biomarkers in prostate cancer in men with metabolic syndrome project: Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in diagnosing localised prostate cancer

Localised prostate cancer is a heterogenous disease and a multi-modal approach is required to accurately diagnose and stage the disease. Whilst the use of magnetic resonance imaging (MRI) has become more common, small volume and multi-focal disease are oft en diffi cult to characterise. Prostate specifi c membrane antigen is a cell surface protein, which is expressed in nearly all prostate cancer cells. Its expression is signifi cantly higher in high grade prostate cancer cells. In this study, we compare multi-parametric magnetic resonance imaging and 68-Gallinium-PSMA PET with whole-mount pathology of the prostate to evaluate the applicability of multiparameteric (MP) MRI and 68Ga-PSMA PET in detecting and locating tumour foci in patients with localised prostate cancer.