Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias

Union decline and renewal in Australia and Britain: Lessons from Closed Shops

Declining union density in Australia and Britain has focused attention on the need for union reorganization. This article examines how the development of closed shops in the two countries influenced member exit rates and the internal union relations now affecting union renewal. Findings show that legislative support for the Australian closed shop tended to foster more union dependency on state and employers, union bureaucratization, less active stewards and more dissatisfied members than in Britain. The subsequent outlawing of the Australian closed shop and increasing employer hostility resulted in higher levels of density decline than in Britain. While the greater resilience of British density supports the case for developing strong workplace unionism, the relative bureaucratization of Australian unions within an increasingly antagonistic context, against the British situation of relatively indifferent employers and steward independence, limits the transferability of strategies designed to achieve union renewal

Observations of Photospheric Dynamics and Magnetic Fields: From Large-Scale to Small-Scale Flows

International audienceThis paper reviews solar flows and magnetic fields observed at the photospheric level. We first present the context in which these observations are performed. We describe the various temporal and spatial scales involved, and the coupling between them. Then we present small-scale flows, mainly supergranulation and flows around active regions. Flows at the global scale are then reviewed, again with emphasis on the flows, i.e. differential rotation, torsional oscillation and meridional circulation. In both small- and global-scale we discuss the coupling between flow fields and magnetic field and give an overview of observational techniques. Finally, the possible connection between studies of solar activity and stellar activity is briefly discussed