Methodological considerations when translating "burnout"

No study has systematically examined how researchers address cross-cultural adaptation of burnout. We conducted an integrative review to examine how researchers had adapted the instruments to the different contexts. We reviewed the Content Validity Indexing scores for the Maslach Burnout Inventory-Human Services Survey from the 12-country comparative nursing workforce study, RN4CAST. In the integrative review, multiple issues related to translation were found in existing studies. In the cross-cultural instrument analysis, 7 out of 22 items on the instrument received an extremely low kappa score. Investigators may need to employ more rigorous cross-cultural adaptation methods when attempting to measure burnout

Maintenance of active chromatin states by HMGN2 is required for stem cell identity in a pluripotent stem cell model

Background: Members of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 and HMGN2 are highly expressed during early development and in the neural stem/progenitor cells of the developing and adult brain. Here, we investigate whether HMGN proteins contribute to the chromatin plasticity and epigenetic regulation that is essential for maintaining pluripotency in stem cells. Results: We show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers Nanog and Ssea1, and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of HMGN2 leads to a global reduction in H3K9 acetylation, and disrupts the profile of H3K4me3, H3K9ac, H3K27ac and H3K122ac at the Nanog and Oct4 loci. At endodermal/mesodermal genes, Hmgn2-knockout cells show a switch from a bivalent to a repressive chromatin configuration. However, at neuronal lineage genes whose expression is increased, no epigenetic changes are observed and their bivalent states are retained following the loss of HMGN2. Conclusions: We conclude that HMGN1 and HMGN2 maintain the identity of pluripotent embryonal carcinoma cells by optimising the pluripotency transcription factor network and protecting the cells from precocious differentiation. Our evidence suggests that HMGN2 regulates active and bivalent genes by promoting an epigenetic landscape of active histone modifications at promoters and enhancers

Exploring the ingredients required to successfully model the placement, generation, and evolution of ice streams in the British-Irish Ice Sheet

Ice stream evolution is a major uncertainty in projections of the future of the Greenland and Antarctic Ice sheets. Accurate simulation of ice stream evolution requires an understanding of a number of “ingredients” that control the location and behaviour of ice stream flow. Here, we test the influence of geothermal heat flux, grid resolution, and bed hydrology on simulated ice streaming. The palaeo-record provides snapshots of ice stream evolution, with a particularly well constrained ice sheet being the British-Irish Ice Sheet (BIIS). We implement a new basal sliding scheme coupled with thermo-mechanics into the BISICLES ice sheet model, to simulate the evolution of the BIIS ice streams. We find that the simulated location and spacing of ice streams matches well with the empirical reconstructions of ice stream flow in terms of position and direction when simple bed hydrology is included. We show that the new basal sliding scheme allows the accurate simulation for the majority of BIIS ice streams. The extensive empirical record of the BIIS has allowed the testing of model inputs, and has helped demonstrate the skill of the ice sheet model in simulating the evolution of the location, spacing, and migration of ice streams through millennia. Simulated ice streams also prompt new empirical mapping of features indicative of streaming in the North Channel region. Ice sheet model development has allowed accurate simulation of the palaeo record, and allows for improved modelling of future ice stream behaviour

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Earth’s mantle composition revealed by mantle plumes

International audienceEarth's mantle is integral to many processes that shape our planet, including convection, crustal formation, crustal recycling, and global heat and volatile budgets. Still, many questions remain unresolved about mantle composition and its influence on geodynamics today and throughout geologic time. Because they originate at depths that can extend to the core-mantle boundary, mantle plumes provide invaluable information about the composition of the deep mantle. In this review, we discuss the effectiveness and challenges of using isotopic analyses of plume-derived rocks to document the origin and composition of mantle heterogeneities, earlyformed mantle reservoirs, crustal recycling processes, core-mantle interactions, and mantle evolution. We discuss isotopic methods and improvements to existing isotopic systems to characterize plume-derived ocean island basalts. Nevertheless, because mantle plumes vary in many properties, including magmatic flux, temperature, tectonic environment, and compositions, geochemical observations on plume-generated systems must be considered carefully before making interpretations about Earth's interior. Consequently, plumes and their melts should be evaluated along a spectrum that acknowledges and contextualizes their differences, particularly mantle flux. Ultimately, the most important advancements in mantle geochemistry, architecture, and dynamics will emerge from cross-disciplinary studies in diverse fields such as experimental petrology, mineral physics, numerical geodynamics, seismology, and geochemistry