Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Desk-based workers' perspectives on using sit-stand workstations: a qualitative analysis of the Stand@Work study

Background: Prolonged sitting time has been identified as a health risk factor. Sit-stand workstations allow desk workers to alternate between sitting and standing throughout the working day, but not much is known about their acceptability and feasibility. Hence, the aim of this study was to qualitatively evaluate the acceptability, feasibility and perceptions of using sit-stand workstations in a group of desk-based office workers. Methods. This article describes the qualitative evaluation of the randomized controlled cross-over Stand@Work pilot trial. Participants were adult employees recruited from a non-government health agency in Sydney, Australia. The intervention involved using an Ergotron Workfit S sit-stand workstation for four weeks. After the four week intervention, participants shared their perceptions and experiences of using the sit-stand workstation in focus group interviews with 4-5 participants. Topics covered in the focus groups included patterns of workstation use, barriers and facilitators to standing while working, effects on work performance, physical impacts, and feasibility in the office. Focus group field notes and transcripts were analysed in an iterative process during and after the data collection period to identify the main concepts and themes. Results: During nine 45-min focus groups, a total of 42 participants were interviewed. Participants were largely intrinsically motivated to try the sit-stand workstation, mostly because of curiosity to try something new, interest in potential health benefits, and the relevance to the participant's own and organisation's work. Most participants used the sit-stand workstation and three common usage patterns were identified: task-based routine, time-based routine, and no particular routine. Common barriers to sit-stand workstation use were working in an open plan office, and issues with sit-stand workstation design. Common facilitators of sit-stand workstation use were a supportive work environment conducive to standing, perceived physical health benefits, and perceived work benefits. When prompted, most participants indicated they were interested in using a sit-stand workstation in the future. Conclusions: The use of a sit-stand workstation in this group of desk-based office workers was generally perceived as acceptable and feasible. Future studies are needed to explore this in different desk-based work populations and settings

The effectiveness of sit-stand workstations for changing office workers' sitting time: results from the Stand@Work randomized controlled trial pilot

Prolonged sitting time is detrimental for health. Individuals with desk-based occupations tend to sit a great deal and sit-stand workstations have been identified as a potential strategy to reduce sitting time. Hence, the objective of the current study was to examine the effects of using sit-stand workstations on office workers' sitting time at work and over the whole day.Methods: We conducted a randomized controlled trial pilot with crossover design and waiting list control in Sydney, Australia from September 2011 to July 2012 (n = 42; 86% female; mean age 38 ± 11 years). Participants used a sit-stand workstation for four weeks in the intervention condition. In the time-matched control condition, participants received nothing and crossed over to the intervention condition after four weeks. The primary outcomes, sitting, standing and walking time at work, were assessed before and after using the workstations with ActivPALs and self-report questionnaires. Secondary outcomes, domain-specific sitting over the whole day, were assessed by self-report. Linear mixed models estimated changes in outcomes adjusting for measurement time, study grouping and covariates.Results: Intervention participants significantly reduced objectively assessed time spent sitting at work by 73 min/workday (95% CI: -106,-39) and increased standing time at work by 65 min/workday (95% CI: 47, 83); these changes were significant relative to controls (p = 0.004 and p < 0.001, respectively). Total sitting time significantly declined in intervention participants (-80 min/workday; 95% CI: -155, -4).Conclusions: This study shows that introducing sit-stand workstations in the office can reduce desk-based workers' sitting time at work in the short term. Larger scale studies on more representative samples are needed to determine the public health impact of sit-stand workstations.Trial registration: ACTRN12612000072819

The cross-section of equity returns and assets’ fundamental cash-flow risk

Return decomposition, Cash-flow news, Discount-rate news, Consumption growth, E21, G11, G12,

Detection of intracellular iron by its regulatory effect

Intracellular iron regulates gene expression by inhibiting the interaction of iron regulatory proteins (IRPs) with RNA motifs called iron-responsive elements (IREs). To assay this interaction in living cells we have developed two fluorescent IRE-based reporters that rapidly, reversibly, and specifically respond to changes in cellular iron status as well as signaling that modifies IRP activity. The reporters were also sufficiently sensitive to distinguish apo- from holotransferrin in the medium, to detect the effect of modifiers of the transferrin pathway such as HFE, and to detect the donation or chelation of iron by siderophores bound to the lipocalin neutrophil gelatinase-associated lipocalin (Ngal). In addition, alternative configurations of the IRE motif either enhanced or repressed fluorescence, permitting a ratio analysis of the iron-dependent response. These characteristics make it possible to visualize iron-IRP-IRE interactions in vivo