Testing eccentricity pumping mechanisms to model eccentric long period sdB binaries with MESA

Hot subdwarf-B stars in long-period binaries are found to be on eccentric orbits, even though current binary-evolution theory predicts those objects to be circularised before the onset of Roche-lobe overflow (RLOF). We aim to find binary-evolution mechanisms that can explain these eccentric long-period orbits, and reproduce the currently observed period-eccentricity diagram. Three different processes are considered; tidally-enhanced wind mass-loss, phase-dependent RLOF on eccentric orbits and the interaction between a circumbinary disk and the binary. The binary module of the stellar-evolution code MESA (Modules for Experiments in Stellar Astrophysics) is extended to include the eccentricity-pumping processes. The effects of different input parameters on the final period and eccentricity of a binary-evolution model are tested with MESA. The end products of models with only tidally-enhanced wind mass-loss can indeed be eccentric, but these models need to lose too much mass, and invariably end up with a helium white dwarf that is too light to ignite helium. Within the tested parameter space, no sdBs in eccentric systems are formed. Phase-dependent RLOF can reintroduce eccentricity during RLOF, and could help to populate the short-period part of the period-eccentricity diagram. When phase-dependent RLOF is combined with eccentricity pumping via a circumbinary disk, the higher eccentricities can be reached as well. A remaining problem is that these models favour a distribution of higher eccentricities at lower periods, while the observed systems show the opposite. The models presented here are potentially capable of explaining the period-eccentricity distribution of long-period sdB binaries, but further theoretical work on the physical mechanisms is necessary.Comment: 18 pages, 9 figures, accepted for publication in A&

Ensemble Asteroseismology of the Young Open Cluster NGC 2244

Our goal is to perform in-depth ensemble asteroseismology of the young open cluster NGC2244 with the 2-wheel Kepler mission. While the nominal Kepler mission already implied a revolution in stellar physics for solar-type stars and red giants, it was not possible to perform asteroseismic studies of massive OB stars because such targets were carefully avoided in the FoV in order not to disturb the exoplanet hunting. Now is an excellent time to fill this hole in mission capacity and to focus on the metal factories of the Universe, for which stellar evolution theory is least adequate. Our white paper aims to remedy major shortcomings in the theory of stellar structure and evolution of the most massive stars by focusing on a large ensemble of stars in a carefully selected young open cluster. Cluster asteroseismology of very young stars such as those of NGC2244 has the major advantage that all cluster stars have similar age, distance and initial chemical composition, implying drastic restrictions for the stellar modeling compared to asteroseismology of single isolated stars with very different ages and metallicities. Our study requires long-term photometric measurements of stars with visual magnitude ranging from 6.5 to 15 in a large FoV with a precision better than 30 ppm for the brightest cluster members (magnitude below 9) up to 500 ppm for the fainter ones, which is well achievable with 2-Wheel Kepler, in combination with high-precision high-resolution spectroscopy and spectro-polarimetry of the brightest pulsating cluster members. These ground-based spectroscopic data will be assembled with the HERMES and CORALIE spectrographs (twin 1.2m Mercator and Euler telescopes, La Palma, Canary Islands and La Silla, Chile), as well as with the spectro-polarimetric NARVAL instrument (2m BLT at the Pic du Midi, French Pyrenees), to which we have guaranteed access.Comment: 10 pages, 3 figures, white paper submitted in response to the NASA call for community input for science investigations the Kepler 2-Wheel spacecraf

Ancient and modern DNA reveal dynamics of domestication and cross-continental dispersal of the dromedary

Dromedaries have been fundamental to the development of human societies in arid landscapes and for long-distance trade across hostile hot terrains for 3,000 y. Today they continue to be an important livestock resource in marginal agro-ecological zones. However, the history of dromedary domestication and the influence of ancient trading networks on their genetic structure have remained elusive. We combined ancient DNA sequences of wild and early-domesticated dromedary samples from arid regions with nuclear microsatellite and mitochondrial genotype information from 1,083 extant animals collected across the species’ range. We observe little phylogeographic signal in the modern population, indicative of extensive gene flow and virtually affecting all regions except East Africa, where dromedary populations have remained relatively isolated. In agreement with archaeological findings, we identify wild dromedaries from the southeast Arabian Peninsula among the founders of the domestic dromedary gene pool. Approximate Bayesian computations further support the “restocking from the wild” hypothesis, with an initial domestication followed by introgression from individuals from wild, now-extinct populations. Compared with other livestock, which show a long history of gene flow with their wild ancestors, we find a high initial diversity relative to the native distribution of the wild ancestor on the Arabian Peninsula and to the brief coexistence of early-domesticated and wild individuals. This study also demonstrates the potential to retrieve ancient DNA sequences from osseous remains excavated in hot and dry desert environments

Asymmetric Excitatory Synaptic Dynamics Underlie Interaural Time Difference Processing in the Auditory System

In order to localize sounds in the environment, the auditory system detects and encodes differences in signals between each ear. The exquisite sensitivity of auditory brain stem neurons to the differences in rise time of the excitation signals from the two ears allows for neuronal encoding of microsecond interaural time differences

Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits

INTRODUCTION: Despite increasing evidence of a role of rare genetic variation in the risk of Alzheimer's disease (AD), limited attention has been paid to its contribution to AD-related biomarker traits indicative of AD-relevant pathophysiological processes. METHODS: We performed whole-exome gene-based rare-variant association studies (RVASs) of 17 AD-related traits on whole-exome sequencing (WES) data generated in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study (n = 450) and whole-genome sequencing (WGS) data from ADNI (n = 808). RESULTS: Mutation screening revealed a novel probably pathogenic mutation (PSEN1 p.Leu232Phe). Gene-based RVAS revealed the exome-wide significant contribution of rare coding variation in RBKS and OR7A10 to cognitive performance and protection against left hippocampal atrophy, respectively. DISCUSSION: The identification of these novel gene-trait associations offers new perspectives into the role of rare coding variation in the distinct pathophysiological processes culminating in AD, which may lead to identification of novel therapeutic and diagnostic targets

Modelling and optimisation in European Kidney Exchange Programmes

The complex multi-criteria optimisation problems arising in Kidney Exchange Programmes have received considerable attention both in practice and in the scientific literature. Whereas theoretical advancements are well reviewed and synthesised, this is not the case for practice. We present a synthesis of models and methods applied in present European Kidney Exchange Programmes, which is based on detailed descriptions we created for this purpose. Most descriptions address national programmes, yet we also present findings on emerging cross-national programmes. The synthesis provides a systematic and detailed description of the models and methods the programmes use, revealing important commonalities as well as considerable variation among them. Rather than distilling a single best practice from these results, we find that the variation in models and methods arises because of variation in country characteristics, policies, and ethics. The synthesised state of the art may benefit future national and cross-national initiatives and direct future theoretical contributions within and across the boundaries of the Operations Research discipline

Modelling and optimisation in European Kidney Exchange Programmes

The complex multi-criteria optimisation problems arising in Kidney Exchange Programmes have received considerable attention both in practice and in the scientific literature. Whereas theoretical advancements are well reviewed and synthesised, this is not the case for practice. We present a synthesis of models and methods applied in present European Kidney Exchange Programmes, which is based on detailed descriptions we created for this purpose. Most descriptions address national programmes, yet we also present findings on emerging cross-national programmes. The synthesis provides a systematic and detailed description of the mo

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe