New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Inclusive practice in WIL [Work integrated learning in the curriculum, HERDSA Guide: Ferns S (Ed)]

Work integrated learning (WIL) connects students with industry, business, government and community with the intention of creating authentic learning experiences that strengthen students’ capacity to develop work-ready skills. WIL has emerged as a key strategy for educational institutions in response to changes in tertiary education and the demand for graduates with work related capabilities. This HERDSA Guide highlights the uniqueness of WIL and the opportunities and challenges it affords. The Guide provides insights into curriculum design, performance-based assessment, academic standards, risk management, institutional leadership, building staff capacity and evaluation strategies for WIL. The Guide offers a range of existing, new and emergent perspectives about WIL in a global context and provides useful information for practitioners and institutional leaders

Inclusive practice in WIL

Work integrated learning (WIL) connects students with industry, business, government and community with the intention of creating authentic learning experiences that strengthen students’ capacity to develop work-ready skills. WIL has emerged as a key strategy for educational institutions in response to changes in tertiary education and the demand for graduates with work related capabilities. This HERDSA Guide highlights the uniqueness of WIL and the opportunities and challenges it affords. The Guide provides insights into curriculum design, performance-based assessment, academic standards, risk management, institutional leadership, building staff capacity and evaluation strategies for WIL. The Guide offers a range of existing, new and emergent perspectives about WIL in a global context and provides useful information for practitioners and institutional leaders

Alternating hemiplegia of childhood: evolution over time and mouse model corroboration

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder caused by ATP1A3 mutations. Some evidence for disease progression exists, but there are few systematic analyses. Here, we evaluate alternating hemiplegia of childhood progression in humans and in the D801N knock-in alternating hemiplegia of childhood mouse, Mashlool, model. This study performed an ambidirectional (prospective and retrospective data) analysis of an alternating hemiplegia of childhood patient cohort (n = 42, age 10.24 +/- 1.48 years) seen at one US centre. To investigate potential disease progression, we used linear mixed effects models incorporating early and subsequent visits, and Wilcoxon Signed Rank test comparing first and last visits. Potential early-life clinical predictors were determined via multivariable regression. We also compared EEG background at first encounter and at last follow-up. We then performed a retrospective confirmation study on a multicentre cohort of alternating hemiplegia of childhood patients from France (n = 52). To investigate disease progression in the Mashlool mouse, we performed behavioural testing on a cohort of Mashlool' mice at prepubescent and adult ages (n =11). Results: US patients, over time, demonstrated mild worsening of non-paroxysmal disability index scores, but not of paroxysmal disability index scores. Increasing age was a predictor of worse scores: P&lt; 0.0001 for the non-paroxysmal disability index, intellectual disability scale and gross motor scores. Earliest non-paroxysmal disability index score was a predictor of last visit non-paroxysmal disability index score (P= 0.022), and earliest intellectual disability score was a predictor of last intellectual disability score (P= 0.035). More patients with EEG background slowing were noted at last follow-up as compared to initial (P=0.015). Similar worsening of disease with age was also noted in the French cohort: age was a significant predictor of non-paroxysmal disability index score (P= 0.001) and first and last non-paroxysmal disability index score scores significantly differed (P=0.002). In animal studies, adult Mashlool mice had, as compared to younger Mashlool mice, (i) worse balance beam performance; (ii) wider base of support; (iii) higher severity of seizures and resultant mortality; and (iv) no increased predisposition to hemiplegic or dystonic spells. In conclusion, (i) non-paroxysmal alternating hemiplegia of childhood manifestations show, on average over time, progression associated with severity of early-life non-paroxysmal disability and age. (ii) Progression also occurs in Mashlool mice, confirming that ATP1A3 disease can lead to age-related worsening. (iii) Clinical findings provide a basis for counselling patients and for designing therapeutic trials. Animal findings confirm a mouse model for investigation of underlying mechanisms of disease progression, and are also consistent with known mechanisms of ATP1A3-related neurodegeneration