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Satellite-based earth observation sensors are increasingly able to monitor geophysical signals related to natural hazards, and many groups are working on rapid data acquisition, processing, and dissemination to data users with a wide range of expertise and goals. A particular challenge in the meaningful dissemination of Interferometric Synthetic Aperture Radar (InSAR) data to non-expert users is its unique differential data structure and sometimes low signal-to-noise ratio. In this study, we evaluate the online dissemination of ground deformation measurements from InSAR through Twitter, alongside the provision of open-access InSAR data from the Centre for Observation and Modelling of Earthquakes, Volcanoes and Tectonics (COMET) Looking Into Continents from Space with Synthetic Aperture Radar (LiCSAR) processing system. Our aim is to evaluate (1) who interacts with disseminated InSAR data, (2) how the data are used, and (3) to discuss strategies for meaningful communication and dissemination of open InSAR data. We found that the InSAR Twitter community was primarily composed of non-scientists (62 %), although this grouping included earth observation experts in applications such as commercial industries. Twitter activity was primarily associated with natural hazard response, specifically following earthquakes and volcanic activity, where users disseminated InSAR measurements of ground deformation, often using wrapped and unwrapped interferograms. For earthquake events, Sentinel-1 data were acquired, processed, and tweeted within 4.7±2.8 d (the shortest was 1 d). Open-access Sentinel-1 data dominated the InSAR tweets and were applied to volcanic and earthquake events in the most engaged-with (retweeted) content. Open-access InSAR data provided by LiCSAR were widely accessed, including automatically processed and tweeted interferograms and interactive event pages revealing ground deformation following earthquake events. The further work required to integrate dissemination of InSAR data into longer-term disaster risk-reduction strategies is highly specific, to both hazard type and international community of practice, as well as to local political setting and civil protection mandates. Notably, communication of uncertainties and processing methodologies are still lacking. We conclude by outlining the future direction of COMET LiCSAR products to maximize their useability.

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.

A summary ofrelocation of a 60+ year old soil pH gradient trial (pH 4.5, 5.0, 5.5 ...... 7.5) into a new design layout with paired plots of legacy treatment soils and new treatments soils, encompassing a range of permanent and rotational crops.

The Empirical Canadian High Arctic Ionospheric Model (E-CHAIM) is a 3D empirical model of the high latitude electron density designed as an alternative to the use of the International Reference Ionosphere (IRI) at high latitudes. The model was initially developed through Themens et al. [2017, 2018, and 2019] with climatological representations of the F2 peak, topside, and bottomside ionosphere, respectively. The model also includes a storm peak density model to accommodate the high latitude negative ionospheric response to storm-driven changes in thermospheric composition. Since the initial release of the model, auroral electron precipitation was added in v3.1 to account for enhancements in the auroral E-Region [Watson et al., 2021] and a climatological D-Region was added in v3.2 through the integration of the Faraday IRI-2018 [Friedrich and Torkar, 2018]. Here we will discuss the inclusion of solar energetic proton precipitation in the model and compare the resulting electron density enhancements with corresponding increases in riometer absorption and the electron density structures observed through Incoherent Scatter Radar (ISR). We will also conduct validations of the performance of the auroral electron precipitation module.ReferencesFriedrich, M., C. Pock, and K. Torkar (2018). doi:10.1029/2018JA025437Themens, D.R., P.T. Jayachandran, A.M. McCaffrey, B. Reid, and R.H. Varney (2019). doi:10.1029/2018RS006748Themens, D.R., et al. (2018). doi:10.1002/2017JA024817Themens, D.R., P.T. Jayachandran, I. Galkin, and C. Hall (2017). doi:10.1002/2017JA024398Watson, C., D.R. Themens, and P.T. Jayachandran (2021), doi:10.1029/2021SW002779, The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

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Formal deliberations for the new collective quantified goal on climate finance began at COP26 in Glasgow. This Perspectives article aims to inform this process by discussing the potential size and nature of is post-2025 target. We argue that the climate finance system around the current target to mobilise US$100 billion per year to support developing countries has been fraught with difficulties, and that it would be ineffective to simply increase the climate finance target without addressing these difficulties. Therefore, we identify and discuss five priority elements for negotiations: the relation to Article 2.1(c) of the Paris Agreement; the adaptation-mitigation balance; financial instruments; mobilising private finance; and new and additional finance. To increase transparency, accountability, and trust in climate finance under the UNFCCC and to simultaneously allow for the mobilisation of finance at scale, we suggest setting a sub-target for grants. In combination with additional (sub)target(s), this could define an overall new collective quantified goal that is better suited to serve the challenging dual role of mobilising finance at scale and transferring resources to developing countries. Key policy insights Ambiguous definitions of climate finance and the US$100 billion target allow for multiple interpretations, reducing transparency and trust between countries. Climate finance targets can be interpreted in a dual and sometimes contrasting way: mobilising investment at scale and transferring resources from developed to developing countries. Recognising this duality may help to find common ground for a post-2025 climate finance target. Increasing the climate finance target may prove ineffective without further clarity on private finance mobilisation, the relation to Art. 2.1(c), and other priority elements. More detailed assessments of needs, priorities, costs, and support are needed to inform the post-2025 target and assess climate finance provision effectiveness. A sub-target for grants could increase accountability, trust, and transparency, and target the needs of the most vulnerable developing countries. Negotiations on the post-2025 climate finance target could also consider additional aspects such as access to and prioritisation of finance, and loss and damage. Funding Agencies|German Federal Ministry of Economic Cooperation and Development (BMZ)

Take a journey into the Everest region of Nepal. This book tells the story of a dynamic landscape shaped by glaciers, inhabited by people and wildlife, and visited by tens of thousands of tourists each year. The landscape, flora, and fauna, are illustrated using photographs taken throughout Sagarmatha National Park and we present the current state of scientific understanding on the park’s thinning glaciers.

The human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV).

To examine longitudinal neurocognitive decline among Latino, non-Latino Black, and non-Latino White people with HIV (PWH) and factors that may explain ethnic/racial disparities in neurocognitive decline.Four hundred ninety nine PWH (13.8% Latino, 42.7% Black, 43.5% White; baseline age: M = 43.5) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed neurocognitive, neuromedical, and laboratory assessments every 6-12 months with up to 5 years of follow-up. Longitudinal neurocognitive change was determined via published regression-based norms. Survival analyses investigated the relationship between ethnicity/race and neurocognitive change, and baseline and time-dependent variables that may explain ethnic/racial disparities in neurocognitive decline, including socio-demographic, HIV-disease, medical, psychiatric, and substance use characteristics.In Cox proportional hazard models, hazard ratios for neurocognitive decline were increased for Latino compared with White PWH (HR = 2.25, 95% CI = 1.35 to 3.73, P = 0.002), and Latino compared with Black PWH (HR = 1.86, 95% CI = 1.14 to 3.04, P = 0.013), with no significant differences between Black and White PWH (P = 0.40). Comorbidities, including cardiometabolic factors and more severe neurocognitive comorbidity classification, accounted for 33.6% of the excess hazard for Latino compared with White PWH, decreasing the hazard ratio associated with Latino ethnicity (HR = 1.83, 95% CI = 1.06 to 3.16, P = 0.03), but did not fully account for elevated risk of decline.Latino PWH may be at higher risk of early neurocognitive decline compared with Black and White PWH. Comorbidities accounted for some, but not all, of this increased risk among Latino PWH. Future research examining institutional, sociocultural, and biomedical factors, including structural discrimination and age-related biomarkers, may further explain the observed disparities.

Diabetic cardiomyopathy (CM), occurring in the absence of hypertension, coronary artery disease, and valvular or congenital heart disease, is now recognized as a distinct, multifactorial disease leading to ventricular hypertrophy and abnormal myocardial contractility that correlates with an array of complex molecular and cellular changes. Animal models provide the unique opportunity to investigate mechanistic aspects of diabetic CM, but important caveats exist when extrapolating findings obtained from preclinical models of diabetes to humans. Indeed, animal models do not recapitulate the complexity of environmental factors, most notably the duration of the exposure to insulin resistance that may play a crucial role in the development of diabetic CM. Moreover, most preclinical studies are performed in animals with uncontrolled or poorly controlled diabetes, whereas patients tend to undergo therapeutic intervention. Finally, whilst type 2 diabetes mellitus prevalence trajectory mainly increases at 40- < 75 years (with a currently alarming increase at younger ages, however), it is a legitimate concern how closely rodent models employing young animals recapitulate the disease developing in old people. The aim of this review is to identify the current limitations of rodent models and to discuss how future mechanistic and preclinical studies should integrate key confounding factors to better mimic the diabetic CM phenotype.

Funding Information: We thank two autonomous reviewers and the team of Climate Policy editors for their excellent comments and suggestions. We are thankful for the financial support of the German Federal Ministry of Economic Cooperation and Development (BMZ) for this research. The research was done independently, BMZ had no role in the preparation, analysis or writing of this article or its outcomes. Publisher Copyright: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Formal deliberations for the new collective quantified goal on climate finance began at COP26 in Glasgow. This Perspectives article aims to inform this process by discussing the potential size and nature of is post-2025 target. We argue that the climate finance system around the current target to mobilise US$100 billion per year to support developing countries has been fraught with difficulties, and that it would be ineffective to simply increase the climate finance target without addressing these difficulties. Therefore, we identify and discuss five priority elements for negotiations: the relation to Article 2.1(c) of the Paris Agreement; the adaptation-mitigation balance; financial instruments; mobilising private finance; and ‘new and additional’ finance. To increase transparency, accountability, and trust in climate finance under the UNFCCC and to simultaneously allow for the mobilisation of finance at scale, we suggest setting a sub-target for grants. In combination with additional (sub)target(s), this could define an overall new collective quantified goal that is better suited to serve the challenging dual role of mobilising finance at scale and transferring resources to developing countries. Key policy insights: Ambiguous definitions of climate finance and the US$100 billion target allow for multiple interpretations, reducing transparency and trust between countries. Climate finance targets can be interpreted in a dual and sometimes contrasting way: mobilising investment at scale and transferring resources from developed to developing countries. Recognising this duality may help to find common ground for a post-2025 climate finance target. Increasing the climate finance target may prove ineffective without further clarity on private finance mobilisation, the relation to Art. 2.1(c), and other priority elements. More detailed assessments of needs, priorities, costs, and support are needed to inform the post-2025 target and assess climate finance provision effectiveness. A sub-target for grants could increase accountability, trust, and transparency, and target the needs of the most vulnerable developing countries. Negotiations on the post-2025 climate finance target could also consider additional aspects such as access to and prioritisation of finance, and loss and damage. publishersversion published

Decades of neuroscientific findings have elucidated the highly specialized brain areas involved in reading, especially along the ventral occipitotemporal stream where the critical step of recognizing words occurs. We report on a14-year-oldfemale with temporary dyslexia after aleft ventral occipitotemporal ischemic stroke. Our longitudinal multimodal findings show that the resolution of the reading impairment was associated with heightened activity in the left posterior superior and inferior temporal gyri. Our findings highlight the role of the left inferior temporal gyrus in reading and the importance of perilesional and ipsilateral cortical areas for functional recovery after childhood stroke.

A short review of scalar curvature invariants in gravity theories is presented. We introduce how these invariants are constructed and discuss the minimal number of invariants required for a given spacetime. We then discuss applications of these invariants and focus on three topics that are of particular interest in modern gravity theories., Essay written for the Gravity Research Foundation 2021 Awards for Essays on Gravitation

BackgroundPatient-reported outcomes (PROs) are an essential part of health outcome measurement and vital to patient-centricity and valued-based care. Several international consortia have developed core outcome sets and many of them include PROs. PROs are measured by patient-reported outcome measures (PROMs). PROs and PROMs can be generic or specific to certain diseases or conditions. While the characteristics of generic PROs and PROMs are well recognised as widely relevant and applicable across different domains, diseases and conditions, there is a lack of knowledge on the types of PROs measured by generic PROMs. We also do not know in which disease areas generic PROs and PROMs are commonly used. To date, there has been no systematic review solely focusing on generic PROMs, what they measure and their areas of application.ObjectivesThis systematic review will identify core PROs measured by generic PROMs used in adult populations and the areas in which they are applied.MethodsWe will conduct a systematic review of reviews. The screening process and the reporting will comply with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) 2020 Statement. We will use four databases, Medline [PubMed], CINHAL [Ebsco], Cochrane [Cochrane Library], and PsycINFO [Ovid], and reports from international consortia. Inclusion criteria are systematic reviews, meta-analysis or patient-reported outcome sets developed by international consortia reporting on generic PROMs in adult populations. Articles primarily focusing on patient-reported experience measures (PREMs), children or adolescents, or those not written in English will be excluded. Risk of bias will be assessed by checking if the included articles comply with established guidelines for systematic reviews such as the PRISMA statement. We will extract generic PROMs and PROs measured by these PROMs, and the areas applied from the selected articles and reports. Extracted data and information will be quantitatively and qualitatively synthesised without statistical interference. The quality of the synthesised evidences will be assessed by clarifying the strengths, limitations and possible biases in our review.

Comprehensive evidence‐based guidelines for the practice of pancreas transplantation are yet to be established. The First World Consensus Conference on Pancreas Transplantation was convened for this purpose. A steering committee selected the participants and defined the questions to be addressed. A group of literature reviewers identified 597 studies to be included in summaries for guidelines production. Expert groups formulated the first draft of recommendations. Two rounds of discussion and voting occurred online, using the Delphi method (agreement rate ≥85%). After each round, critical responses of experts were reviewed, and recommendations were amended accordingly. Recommendations were finalized after live discussions. Each session was preceded by expert presentations and a summary of results of systematic literature review. Up to three voting rounds were allowed for each recommendation. To avoid potential conflicts of interest, deliberations on issues regarding the impact of pancreas transplantation on the management of diabetes were conducted by an independent jury. Recommendations on technical issues were determined by experts and validated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Quality of evidence was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology. Each recommendation received a GRADE rating (Grading of Recommendations, Assessment, Development and Evaluations)., This article presents the results of literature search and the methods used to provide evidence‐based guidelines for the practice of pancreas transplantation at the First World Consensus Conference on Pancreas Transplantation.

Value based healthcare (VBHC) aims at improving patient outcomes while optimizing the use of hospitals’ resources among medical personnel, administrations and support services through an evidence-based, collaborative approach.In this paper, we present a blueprint for the implementation of VBHC in hospitals, based on our experience as members of the European University Hospital Alliance (EUHA). The EUHA is a consortium of nine large hospitals in Europe and aims at increasing quality and efficiency of care to ultimately drive better outcomes for patients. The blueprint describes how to prepare hospitals for VBHC implementation, analyses gaps, barriers and facilitators and explores the most effective ways to turn patient pathways to a process that results in high value care. Using a patient centric approach, we identified four core minimum components that must be established as cornerstones and seven organisational enablers to waive the barriers to implementation and ensure sustainability. The blueprint guides through pathway implementation and establishment of key performance indicators in six phases, which hospitals can tailor to their current status on their way to implement VBHC.

This item was presented at the 5th International Clinical Trials Methodology Conference (ICTMC 2019), Brighton, UK, September 2019.

Rock debris covers ~30% of glacier ablation areas in the Central Himalaya and modifies the impact of atmospheric conditions on mass balance. The thermal properties of supraglacial debris are diurnally variable but remain poorly constrained for monsoon-influenced glaciers over the timescale of the ablation season. We measured vertical debris profile temperatures at 12 sites on four glaciers in the Everest region with debris thickness ranging from 0.08 to 2.8 m. Typically, the length of the ice ablation season beneath supraglacial debris was 160 days (15 May to 22 October)—a month longer than the monsoon season. Debris temperature gradients were approximately linear (r2 > 0.83), measured as −40°C m–1 where debris was up to 0.1 m thick, −20°C m–1 for debris 0.1–0.5 m thick, and −4°C m–1 for debris greater than 0.5 m thick. Our results demonstrate that the influence of supraglacial debris on the temperature of the underlying ice surface, and therefore melt, is stable at a seasonal timescale and can be estimated from near-surface temperature. These results have the potential to greatly improve the representation of ablation in calculations of debris-covered glacier mass balance and projections of their response to climate change.

We investigate the sources, scope, and implications of landowner market power. We show how zoning regulations generate spillovers through increased markups and derive conditions under which restricting landownership concentration reduces rents. Using newbuilding-level data from New York City, we find that a 10% increase in ownership concentration in a Census tract is correlated with a 1% increase in rent. Market power is substantial: on average, markups account for nearly a third of rents in Manhattan. Furthermore, pecuniary spillovers between zoning constraints and markups at other buildings are appreciable. Up-zoning that results in 417 additional housing units at zoning-constrained buildings reduces markups on policy-unconstrained units and generates between 5 and 19 additional units through increased competition.

We present a compilation of 2131 high-fidelity mechanisms and centroid depths of moderate-magnitude earthquakes derived using synthetic body-waveform modeling (the Global Waveform-Modelled Earthquake Catalog v1.0—gWFM), which can be visualized and downloaded online (see Data and Resources). In this article, we describe the methods used to construct the gWFM and present a comparison between the earthquake depths and focal mechanisms in the gWFM with those derived by the International Seismological Centre, Global Centroid Moment Tensor (Global CMT) project, and the U.S. Geological Survey (USGS) W-phase, as well as 60 events studied using geodesy. We find that 20%–30% of the earthquakes in routine global catalogs have depths that differ by more than 10 km from those in the gWFM. Shallow-crustal earthquakes of Mw 5–6 are typically the worst located in depth by routine catalogs. Over 90% of the earthquakes in the gWFM are within ±15° in strike, ±5° in dip, and ±15° in rake of the Global CMT and USGS W-phase best double-couple moment tensor solutions. However, the mechanisms of shallow Mw 5–6 earthquakes in the routine catalogs can be inaccurate, due to the well-known insensitivity of long-period surface waves to the vertical dip-slip components of the moment tensor. The gWFM is an archive of well-constrained earthquake source parameters, though it will continue to update as new earthquake mechanisms and depths are published, thereby remaining an up-to-date research tool.

While transgender and gender non-binary (trans/nb) individuals are disproportionately affected by HIV, pre-exposure prophylaxis (PrEP) uptake remains low in this underserved population. We conducted four focus groups with 37 trans/nb individuals in San Diego and Los Angeles to assess barriers and facilitators of PrEP usage. Transcripts were coded for qualitative themes. Although overall PrEP awareness was high, participants reported limited knowledge and misinformation about PrEP. Barriers to PrEP use included: structural access (e.g., discrimination from health care providers, lack of trans-inclusive services, financial barriers), mental health struggles limiting ability to access PrEP, and concerns about potential side effects, drug-drug interactions with hormone therapy, and lack of other STI protection. Facilitators of PrEP usage included: increased PrEP availability, prior experience taking daily medications, and motivation to have active and healthy lives without fear of contracting HIV. Addressing both structural and psychosocial/behavioral factors in trans-affirming health care environments is crucial to designing inclusive, effective PrEP interventions.

International audience; Solar Orbiter is the first space mission observing the solar plasma both in situ and remotely, from a close distance, in and out of the ecliptic. The ultimate goal is to understand how the Sun produces and controls the heliosphere, filling the Solar System and driving the planetary environments. With six remote-sensing and four in-situ instrument suites, the coordination and planning of the operations are essential to address the following four top-level science questions: (1) What drives the solar wind and where does the coronal magnetic field originate?; (2) How do solar transients drive heliospheric variability?; (3) How do solar eruptions produce energetic particle radiation that fills the heliosphere?; (4) How does the solar dynamo work and drive connections between the Sun and the heliosphere? Maximising the mission's science return requires considering the characteristics of each orbit, including the relative position of the spacecraft to Earth (affecting downlink rates), trajectory events (such as gravitational assist manoeuvres), and the phase of the solar activity cycle. Furthermore, since each orbit's science telemetry will be downloaded over the course of the following orbit, science operations must be planned at mission level, rather than at the level of individual orbits. It is important to explore the way in which those science questions are translated into an actual plan of observations that fits into the mission, thus ensuring that no opportunities are missed. First, the overarching goals are broken down into specific, answerable questions along with the required observations and the so-called Science Activity Plan (SAP) is developed to achieve this. The SAP groups objectives that require similar observations into Solar Orbiter Observing Plans, resulting in a strategic, top-level view of the optimal opportunities for science observations during the mission lifetime. This allows for all four mission goals to be addressed. In this paper, we introduce Solar Orbiter's SAP through a series of examples and the strategy being followed.

The 2020 Covid19 pandemic has caused significant disruption to medical education across the world. At the University of Sheffield final year medical students undertook a virtual OSCE via technology in order to graduate however for our Physician Associate course this was more problematic as following completion of the assessments at the university students are also required to pass a national examination with a formal Objective Structured Clinical Examination (OSCE). Due to this it was felt that it was crucial to run an OSCE examination for our students on a face to face basis but within the context of managing the potential safety and risks inherent in doing so. \ud \ud \ud \ud This piece of work describes the process of running the examination including detail which we feel will be useful to others who may seek to undertake examinations for the same reason within the current health emergency or any future such events. It is important to note that some innovations we put in place with respect to technology enhancing safety will remain for future OSCE examinations in any circumstances.

Radial velocity (RV) searches for Earth-mass exoplanets in the habitable zone around Sun-like stars are limited by the effects of stellar variability on the host star. In particular, suppression of convective blueshift and brightness inhomogeneities due to photospheric faculae/plage and starspots are the dominant contribution to the variability of such stellar RVs. Gaussian process (GP) regression is a powerful tool for statistically modeling these quasi-periodic variations. We investigate the limits of this technique using 800 days of RVs from the solar telescope on the High Accuracy Radial velocity Planet Searcher for the Northern hemisphere (HARPS-N) spectrograph. These data provide a well-sampled time series of stellar RV variations. Into this data set, we inject Keplerian signals with periods between 100 and 500 days and amplitudes between 0.6 and 2.4 m s$^{-1}$. We use GP regression to fit the resulting RVs and determine the statistical significance of recovered periods and amplitudes. We then generate synthetic RVs with the same covariance properties as the solar data to determine a lower bound on the observational baseline necessary to detect low-mass planets in Venus-like orbits around a Sun-like star. Our simulations show that discovering planets with a larger mass ($\sim$ 0.5 m s$^{-1}$) using current-generation spectrographs and GP regression will require more than 12 yr of densely sampled RV observations. Furthermore, even with a perfect model of stellar variability, discovering a true exo-Venus ($\sim$ 0.1 m s$^{-1}$) with current instruments would take over 15 yr. Therefore, next-generation spectrographs and better models of stellar variability are required for detection of such planets., 12 pages, 4 figures, 1 table, accepted in AJ

Background Shared decision making (SDM) implementation remains challenging. The factors that promote or hinder implementation of SDM tools for use during the consultation, including contextual factors such as clinician burnout and organizational support, remain unclear. We explored these factors in the context of a practical multicenter randomized trial evaluating the effectiveness of an SDM conversation tool for patients with atrial fibrillation considering anticoagulation therapy. Methods In this cross-sectional study, we recruited clinicians who were regularly involved in conversations with patients regarding anticoagulation for atrial fibrillation. Clinicians reported their characteristics and burnout symptoms using the two-item Maslach Burnout Inventory. Clinicians were trained in using the SDM tool, and they recorded their perceptions of the tool’s normalization potential using the Normalization MeAsure Development (NoMAD) survey instrument and verbally reflected on their answers to these survey questions. When possible, the training sessions and clinicians’ verbal responses to the conversation tool were recorded. Results Our study comprised 183 clinicians recruited into the trial (168 with survey responses and 112 with recordings). Overall, clinicians gave high scores to the normalization potential of the intervention; they endorsed all domains of normalization to the same extent, regardless of site, clinician characteristics, or burnout ratings. In interviews, clinicians paid significant attention to making sense of the tool. Tool buy-in seemed to depend heavily on their ability to see the tool as accurate and “evidence-based” and their perceptions of having time in the consultation to use it. Conclusions While time in the consultation remains a barrier, we did not find a significant association between burnout symptoms and normalization of an SDM conversation tool. Possible areas for improving the normalization of SDM conversation tools in clinical practice include enabling collaboration among clinicians to implement the tool and reporting how clinicians elsewhere use the tool. Direct measures of normalization (i.e., observing how often clinicians access the tool in practice outside of the clinical trial) may further elucidate the role that contextual factors, such as clinician burnout, play in the implementation of SDM. Trial registration ClinicalTrials.gov, NCT02905032. Registered on 9 September 2016.

Chao Chen,1 Ning Wu,2 Crystal Watson2 1Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA; 2Value and Access, Biogen, Cambridge, MA,USA Background: Real-world outcomes from staying on an interferon beta (IFNβ) vs switching to another IFNβ could help guide treatment decisions. This study’s objective was to compare outcomes of stable multiple sclerosis (MS) patients on an IFNβ who stayed on therapy vs those who switched to anotherIFNβ.Methods: MS patients were identified from the Optum Insights Clinformatics Data Mart Multi-Plan who were 18–64 years old and relapse-free (stable) over 1 year while continuously being treated with an IFNβ. Patients were propensity score matched 3:1 using age, gender, initial IFNβ, adherence, and month and year for patients who stayed on the initial IFNβ (No Switch) to patients who switched to another IFNβ (Switch). Patients had to be continuously enrolled for 1 year prior to and 1 year after the index date (date of the first claim of the switched-to IFNβ or the match date when continuing on initial IFNβ treatment). Patients were enrolled with index dates between January 1, 2005 and September 30, 2014. Relapses were recorded during the 1-year follow-up period after index date.Results: After matching, there were 381 patients in the Switch group and 1,143 in the No Switch group. Baseline characteristics were well matched between groups (average age 46 years, 72% female). The percentage of patients experiencing a relapse during the follow-up was significantly higher in the Switch group than in the No Switch group (21% vs 12%, P

Barry Hendin,1 Robert T Naismith,2 Sibyl E Wray,3 Deren Huang,4 Qunming Dong,5 Terrie Livingston,6 Daniel L Jones,6 Crystal Watson,7 Mehul Jhaveri6 1Phoenix Neurological Associates, Phoenix, AZ, USA; 2Department of Neurology, Washington University School of Medicine, St Louis, MO, USA; 3Hope Neurology MS Center, Knoxville, TN, USA; 4Mount Carmel Neuroscience and MDH Research, Westerville, OH, USA; 5Biostatistics, Biogen, Cambridge, MA, USA; 6US Medical, Biogen, Cambridge, MA, USA; 7Global Value and Access, Biogen, Cambridge, MA, USA Objectives: Posthoc analysis of treatment satisfaction in patients switching to subcutaneous (SC) peginterferon beta-1a in the ALLOW study.Patients and methods: Patients with relapsing multiple sclerosis treated with intramuscular interferon (IFN) beta-1a or SC IFN beta-1a or beta-1b remained on their current therapy for a 4-week run-in period, followed by a switch to SC peginterferon beta-1a 125 mcg every 2 weeks for 48 weeks. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM), which covers effectiveness, side effects, convenience, and global satisfaction. Patients completed the TSQM at baseline (prior to starting the 4-week run-in period) and 4, 12, 24, 36, and 48 weeks after switching, and scores were analyzed for the overall population and compared to baseline. Patients reported the severity of flu-like symptoms (FLS) at baseline and with each peginterferon beta-1a injection; clinicians evaluated the occurrence of injection-site reactions (ISRs) after the first dose of peginterferon beta-1a and every 12 weeks thereafter. TSQM scores were stratified by the presence of FLS or ISRs during the study period and by prior IFN therapy use.Results: For the overall population (n=194), convenience and global satisfaction scores significantly improved from baseline at all time points, and side effect satisfaction scores significantly improved up to week 36. Convenience scores significantly improved regardless of FLS, ISRs, or prior IFN therapy. Patients without FLS during the study period showed significant improvements in global satisfaction, but not side effect satisfaction, versus those with FLS. Patients switching from SC IFN therapies achieved greater improvements in treatment satisfaction than patients who switched from intramuscular IFN beta-1a.Conclusions: Switching relapsing multiple sclerosis patients to SC peginterferon beta-1a from other IFN therapies significantly improved treatment satisfaction and convenience. Keywords: interferon beta-1a, interferon beta-1b, peginterferon beta-1a, relapsing multiple sclerosis, treatmentsatisfaction, Treatment Satisfaction Questionnaire for Medication, TSQM, quality of life, patient-reported outcomes

Betsy Sleath,1,2 Delesha M Carpenter,1 Imelda Coyne,3 Scott A Davis,1 Claire Hayes Watson,1 Ceila E Loughlin,4 Nacire Garcia,1 Daniel S Reuland,5 Gail E Tudor6 1Division of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 3School of Nursing and Midwifery, Trinity College, Dublin, Ireland; 4Department of Pediatric Pulmonology, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 5Division of General Internal Medicine and Clinical Epidemiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 6Department of Science and Mathematics, Husson University, Bangor, ME, USA Background: We conducted a randomized controlled trial to test the effectiveness of an asthma question prompt list with video intervention to engage the youth during clinic visits. We examined whether the intervention was associated with 1) providers including youth and caregiver inputs more into asthma treatment regimens, 2) youth and caregivers rating providers as using more of a participatory decision-making style, and 3) youth and caregivers being more satisfied with visits.Methods: English- or Spanish-speaking youth aged 11–17 years with persistent asthma and their caregivers were recruited from four pediatric clinics and randomized to the intervention or usual care groups. The youth in the intervention group watched the video with their caregivers on an iPad and completed a one-page asthma question prompt list before their clinic visits. All visits were audiotaped. Generalized estimating equations were used to analyze the data.Results: Forty providers and their patients (n=359) participated in this study. Providers included youth input into the asthma management treatment regimens during 2.5% of visits and caregiver input during 3.3% of visits. The youth in the intervention group were significantly more likely to rate their providers as using more of a participatory decision-making style (odds ratio=1.7, 95% confidence interval=1.1, 2.5). White caregivers were significantly more likely to rate the providers as more participatory (odds ratio=2.3, 95% confidence interval=1.2, 4.4). Youth (beta=4.9, 95% confidence interval=3.3, 6.5) and caregivers (beta=7.5, 95% confidence interval=3.1, 12.0) who rated their providers as being more participatory were significantly more satisfied with their visits. Youth (beta=–1.9, 95% confidence interval=–3.4, –0.4) and caregivers (beta=–8.8, 95% confidence interval=–16.2, –1.3) who spoke Spanish at home were less satisfied with visits. Conclusion: The intervention did not increase the inclusion of youth and caregiver inputs into asthma treatment regimens. However, it did increase the youth’s perception of participatory decision-making style of the providers, and this in turn was associated with greater satisfaction. Keywords: shared decision-making, patient–provider, question prompt list, video intervention, communication, intervention

John F Foley,1 Kavita V Nair,2 Timothy Vollmer,3 Judith J Stephenson,4 Timothy Niecko,5 Sonalee S Agarwal,6 Crystal Watson6 1Rocky Mountain Multiple Sclerosis Clinic, Salt Lake City, UT, USA; 2Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA; 3Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; 4HealthCore, Inc., Wilmington, DE, USA; 5Niecko Health Economics, Tierra Verde, FL, USA; 6Biogen, Cambridge, MA, USA Background: Multiple sclerosis (MS) patients experience lower health-related quality of life (HRQoL) than the general population. In clinical trials, natalizumab significantly improved HRQoL and reduced relapse rates and disability progression in patients with relapsing MS. In a 1-year analysis of patients included in the current study, HRQoL improvement occurred within 3 months of natalizumab initiation and continued for 1 year thereafter. However, natalizumab’s long-term efficacy in improving HRQoL has not been studied.Methods: In this longitudinal, observational, single-arm US study, HRQoL and treatment satisfaction were evaluated in MS patients receiving intravenous natalizumab 300mg every 4 weeks in clinical settings. Patients completed surveys at baseline and every 6 months for 3 years and reported the following measures: Short Form-12 Version 2 (SF-12v2), Multiple Sclerosis Impact Scale (MSIS-29), and Treatment Satisfaction Questionnaire for Medication.Results: In this study, 120 patients completed ≥3 years of natalizumab treatment. Significant HRQoL improvements were evident from baseline to year 3 by increases in SF-12v2 Physical Component Summary (PCS) and Mental Component Summary scores (P

Hillary J Gross,1,* Crystal Watson2,* 1Health Outcomes Practice, Kantar Health, Princeton, NJ, 2Health Economics and Outcomes Research, Biogen, Cambridge, MA, USA *These authors contributed equally to this work Background: Although most patients with relapsing-remitting multiple sclerosis (RRMS) will develop secondary progressive multiple sclerosis (SPMS), little is known about the burden of multiple sclerosis by disease subtype. This study describes the burden of disease in terms of demographics, disease severity, symptoms, health care resource and disease-modifying therapy (DMT) utilization, work and activity impairment, and physical functioning of SPMS and RRMS patients.Methods: SPMS and RRMS patient responses from the 2012 and 2013 waves of the US National Health and Wellness Survey were evaluated to detect differences in demographics, disease severity, symptoms, and health care resource and DMT utilization. In addition, data from the Work Productivity and Activity Impairment and Short Form-36 questionnaires were analyzed.Results: SPMS patients were older than RRMS patients (mean age 55.7 vs 48.9 years; P

Aims: Cardiovascular (CV) disease is a major cause of reduced life expectancy in type 1 diabetes (T1D). Intensive insulin therapy prevents CV complications but is constrained by hypoglycaemia and weight gain. Adjunct metformin reduces insulin dose requirement and stabilizes weight but there are no data on its cardiovascular effects. We have therefore initiated an international double-blind, randomized, placebo-controlled trial (REMOVAL: REducing with MetfOrmin Vascular Adverse Lesions in type 1 diabetes) to examine whether metformin reduces progression of atherosclerosis in adults with T1D. Individuals >= 40 years of age with T1D for >= 5 years are eligible if they have >= 3 of 10 specified CV risk factors. The enrolment target is 500 participants in 17 international centres.Materials and methods: After 12 weeks of single-blind placebo-controlled run-in, participants with >= 70% adherence are randomized to metformin or matching placebo for 3 years with insulin titrated towards HbA1c 7.0% (53 mmol/mol). The primary endpoint is progression of averaged mean far wall common carotid intima-media thickness (cIMT) measured by ultrasonography at baseline, 12, 24 and 36 months. This design provides 90% power to detect a mean difference of 0.0167 mm in cIMT progression between treatment arms (alpha = 0.05), assuming that up to 20% withdraw or discontinue treatment. Other endpoints include HbA1c, weight, LDL cholesterol, insulin requirement, progression of retinopathy, endothelial function and frequency of hypoglycaemia.Conclusion: REMOVAL is the largest clinical trial of adjunct metformin therapy in T1D to date and will provide clinically meaningful information on its potential to impact CV disease and other complications.

Crystal Watson,1 Christine Prosser,2 Sebastian Braun,2 Pamela B Landsman-Blumberg,3 Erika Gleissner,4 Sarah Naoshy1 1Health Economics and Outcomes Research, Global Market Access, Biogen, Cambridge, MA, USA; 2Real World Evidence, Xcenda GmbH, Hanover, Germany; 3Applied Data Analytics, Xcenda LLC, Palm Harbor, FL, USA; 4Market Access, Biogen, Ismaning, Germany Background: Multiple sclerosis (MS), a progressive neurodegenerative disease, greatly impacts the quality of life and economic status of people affected by this disease. In Germany, the total annual cost of MS is estimated at €40,000 per person with MS. Natalizumab has shown to slow MS disease progression, reduce relapses, and improve the quality of life of people with MS.Objective: To evaluate MS-related and all-cause health care resource utilization and costs among German MS patients during the 12 months before and after initiation of natalizumab in a real-world setting.Methods: The current analysis was conducted using the Health Risk Institute research database. Identified patients were aged ≥18 years with ≥1 diagnosis of MS and had initiated natalizumab therapy (index), with 12-month pre– and post–index-period data. Patients were stratified by prior disease-modifying therapy (DMT) usage or no DMT usage in the pre-index period. Outcome measures included corticosteroid use and number of sick/disability days, inpatient stays, and outpatient visits. Health care costs were calculated separately for pre- and post-index periods on a per-patient basis and adjusted for inflation.Results: In a final sample of 193 natalizumab-treated patients, per-patient MS-related corticosteroid use was reduced by 62.3%, MS-related sick days by 27.6%, and inpatient costs by 78.3% from the pre- to post-index period. Furthermore, the proportion of patients with MS-related hospitalizations decreased from 49.7% to 14.0% (P

Legumes Translated is a new thematic network in Horizon 2020. It supports the Agricultural European Innovation Partnership (EIP Agri) by linking research- and practice-based knowledge to support legume cropping and use. It is therefore in line with the recently announced European Protein Plan (European Commission 2018) that mentions a knowledge platform for protein crops. The overall goal is to support the production and use of grain legume crops in Europe as part of an overall change in protein sourcing and use (Donau Soja, 2017). The challenges that legumes crops can help address are well-documented: the need for more diversity in cropping with more crops that support pollinators; yield stagnation in cereal-dominated systems (e.g. Brisson et al., 2010; Watson et al., 2017); and a 29% deficit in tradable plant protein that is met by about 35 million tonnes of soybean equivalent imported from the Americas (Murphy-Bokern et al., 2017). This is a fundamental challenge to the resilience, acceptance and performance of our agri-food systems. There are indications that Europe is now on the cusp of a significant change manifest in the positive political response to the Donau Soja European Soya Declaration and the European Commission’s work on Europe’s protein balance. Thematic networks are a key element of the EIP Agri. funded from Horizon 2020. They complement both operational groups and Horizon 2020 research and innovation projects by compiling and validating existing knowledge and best practices and providing wider access to this knowledge with particular emphasis on trans-national border knowledge interaction. Legumes Translated has three underlying principles: empowerment of innovators through understanding; practice- and research-based sources of knowledge are mutually supportive; and cropping and farming system innovation must go hand-in-hand with corresponding value chain developments (especially in livestock).

No Abstract

Background The WHO definition of trachomatous trichiasis (TT) is “at least one eyelash touching the globe, or evidence of recent epilation of in-turned eyelashes”, reflecting the fact that epilation is used as a self-management tool for TT. In Fiji’s Western Division, a high TT prevalence (8.7% in those aged ≥15 years) was reported in a 2012 survey, yet a 2013 survey found no TT and Fijian ophthalmologists rarely see TT cases. Local anecdote suggests that eyelash epilation is a common behaviour, even in the absence of trichiasis. Epilators may have been identified as TT cases in previous surveys. Methods We used a preliminary focus group to design an interview questionnaire, and subsequently conducted a population-based prevalence survey to estimate the prevalence of epilation in the absence of trichiasis, and factors associated with this behaviour, in the Western Division of Fiji. Results We sampled 695 individuals aged ≥15 years from a total of 457 households in 23 villages. 125 participants (18%) reported epilating their eyelashes at least once within the past year. Photographs were obtained of the eyes of 121/125 (97%) individuals who epilated, and subsequent analysis by an experienced trachoma grader found no cases of trachomatous conjunctival scarring or trichiasis. The age- and sex- adjusted prevalence of epilation in those aged ≥15 years was 8.6% (95% CI 5.7–11.3%). iTaukei ethnicity, female gender, and a higher frequency of drinking kava root were independently associated with epilation. Conclusion Epilation occurs in this population in the absence of trichiasis, with sufficient frequency to have markedly inflated previous estimates of local TT prevalence. Individuals with epilated eyelashes should be confirmed as having epilated in-turned eyelashes in an eye with scarring of the conjunctiva before being counted as cases of TT., Author Summary Trachoma, caused by infection with ocular strains of Chlamydia trachomatis, represents a major public health issue, and is targeted for global elimination as a public health problem by the year 2020. Until recently, data on trachoma in the Pacific Island states have been sparse, with marked variability in the findings of surveys. The most recent studies in Fiji’s Western Division were conflicted in their estimates of the prevalence of the advanced, blinding, stage of the disease known as trachomatous trichiasis or “TT”. TT results from repeated bouts of infection and resolution, leading to scarring of the eyelid tissue, which causes in-turning of the eyelashes in some individuals so that they grow to touch the globe of the eye. In populations without ready access to healthcare services, individuals may try to self-manage TT by epilating their eyelashes, so that the classical trichiasis sign of contact between eyelashes and eyeball is not seen in surveys. Therefore, the World Health Organization (WHO) definition of TT includes “evidence of recent epilation of in-turned eyelashes”. In the Western Division of Fiji, we carried out a population-based prevalence survey to estimate the prevalence of this behaviour, and to examine associated risk factors. The estimated population prevalence of epilation was 8.6% of those aged ≥15 years, consistent with previously reported estimates of TT in this population, and, importantly, was not associated with any other evidence of advanced trachoma. These data suggest that eyelash epilation is common here, and could inflate estimates of TT wherever such a custom is common. In trachoma surveys, trachomatous scarring should be confirmed to be present when reporting the presence of TT.

State of the art radial-velocity (RV) exoplanet searches are currently limited by RV signals arising from stellar magnetic activity. We analyze solar observations acquired over a 3-year period during the decline of Carrington Cycle 24 to test models of RV variation of Sun-like stars. A purpose-built solar telescope at the High Accuracy Radial velocity Planet Searcher for the Northern hemisphere (HARPS-N) provides disk-integrated solar spectra, from which we extract RVs and $\log{R'_{\rm HK}}$. The Solar Dynamics Observatory (SDO) provides disk-resolved images of magnetic activity. The Solar Radiation and Climate Experiment (SORCE) provides near-continuous solar photometry, analogous to a Kepler light curve. We verify that the SORCE photometry and HARPS-N $\log{R'_{\rm HK}}$ correlate strongly with the SDO-derived magnetic filling factor, while the HARPS-N RV variations do not. To explain this discrepancy, we test existing models of RV variations. We estimate the contributions of the suppression of convective blueshift and the rotational imbalance due to brightness inhomogeneities to the observed HARPS-N RVs. We investigate the time variation of these contributions over several rotation periods, and how these contributions depend on the area of active regions. We find that magnetic active regions smaller than $60 \ \rm Mm^2$ do not significantly suppress convective blueshift. Our area-dependent model reduces the amplitude of activity-induced RV variations by a factor of two. The present study highlights the need to identify a proxy that correlates specifically with large, bright magnetic regions on the surfaces of exoplanet-hosting stars., Comment: 16 pages, 7 figures, accepted by ApJ

IntroductionRandomized clinical trials have demonstrated the efficacy of antiretroviral pre-exposure prophylaxis (PrEP) in preventing HIV acquisition among men who have sex with men (MSM). However, limited research has examined initiation and adherence to PrEP among Black MSM (BMSM) in the United States (US) who are disproportionately represented among newly HIV infected and late to care individuals. This research reports on the HIV Prevention Trials Network 073 (HPTN 073) study aimed to examine PrEP initiation, utilization and adherence among Black MSM utilizing the theoretically principled, culturally informed and client-centered care coordination (C4) model.MethodsThe HPTN 073 study enrolled and followed 226 HIV-uninfected Black MSM in three US cities (Los Angeles, CA; Washington DC; and Chapel Hill, NC) from February 2013 through September 2015. Study participants were offered once daily oral emtricitabine/tenofovir (FTC/TDF) PrEP combined with C4 and followed up for 52weeks. Participants received HIV testing, risk reduction education and clinical monitoring.ResultsOf the 226 men enrolled, 178 participants initiated PrEP (79%), and of these 64% demonstrated PrEP utilization at week 26 (mid-point of the study) based on pharmacokinetic testing. Condomless anal sex with an HIV-infected or unknown status casual male partner was statistically significantly associated with a greater likelihood of PrEP initiation (adjusted odds ratio (OR) 4.4, 95% confidence interval (CI) 1.7, 11.7). Greater age (≥25 vs.

John Willan,1 Toby A Eyre,1,2 Faye Sharpley,1 Caroline Watson,1 Andrew J King,1,3 Karthik Ramasamy1,4 1Department of Hematology, 2Early Phase Clinical Trial Unit, Oxford University Hospitals National Health Service (NHS) Foundation Trust, Churchill Hospital, Oxford, UK; 3Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK; 4National Institute for Health Research(NIHR) Biomedical Research Center Blood Theme, Oxford, UK Abstract: Diagnosis and management of myeloma in the very elderly patient is challenging. Treatment options have vastly improved for elderly myeloma patients but still require the clinician to personalize therapy. In this paper, we offer evidence-based, pragmatic advice on how to overcome six of the main challenges likely to arise: 1) diagnosis of myeloma in this age group, 2) assessment of the need for treatment, and the fitness for combination chemotherapy, 3) provision of the best quality of supportive care, 4) choice of combination chemotherapy in those fit enough for it, 5) treatment of relapsed myeloma, and 6) provision of end of life care. With an increased burden of comorbidities and a reduced resilience to treatment and its associated toxicities, the management of myeloma in this age group requires a different approach to that in younger patients to maximize both quality and length of life.Keywords: myeloma, elderly, diagnosis, treatment&nbsp

Barbara H Johnson,1 Machaon M Bonafede,1 Crystal Watson2 1Outcomes Research, Truven Health Analytics, Cambridge, MA, USA; 2Health Economics and Outcomes Research, Biogen, Cambridge, MA, USA Objectives: The mean lifetime cost of ischemic stroke is approximately $140,048 in the United States, placing stroke among the top 10 most costly conditions among Medicare beneficiaries. The objective of this study was to describe the health-care resource utilization and costs in the year following hospitalization for acute ischemic stroke (AIS).Methods: This retrospective claims analysis quantifies utilization and costs following inpatient admission for AIS among the commercially insured and Medicare beneficiaries in the Truven Health databases. Patients who were 18 years or older and continuously enrolled for 12 months before and after an AIS event occurring (index) between January 2009 and December 2012 were identified. Patients with AIS in the year preindex were excluded. Demographic and clinical characteristics were evaluated at admission and in the preindex, respectively. Direct costs, readmissions, and inpatient length of stay (LOS) were described in the year postindex.Results: The eligible populations comprised 20,314 commercially insured patients and 31,037 Medicare beneficiaries. Average all-cause costs were $61,354 and $44,929 (commercial and Medicare, respectively) in the first year after the AIS. Approximately 50%–55% of total 12-month costs were incurred between day 31 and day 365 following the incident AIS. One quarter (24.6%) of commercially insured patients and 38.8% of Medicare beneficiaries were readmitted within 30 days with 16.6% and 71.7% (commercial and Medicare, respectively) of those having a principal diagnosis of AIS. The average AIS-related readmission length of stay was nearly three times that of the initial hospitalization for both commercially insured patients (3.8 vs 10.8 days) and Medicare beneficiaries (4.0 vs 10.8 days).Conclusion: In addition to the substantial costs of the initial hospitalization of an AIS, these costs double within the year following this event. Given the high cost associated with AIS, new interventions reducing either the acute or longer-term burden of AIS are needed. Keywords: acute ischemic stroke, health-care resource utilization, health-care costs, readmissions

Transiting extrasolar planets are key objects in the study of the formation, migration, and evolution of planetary systems. In particular, the exploration of the atmospheres of giant planets, through transmission spectroscopy or direct imaging, has revealed a large diversity in their chemical composition and physical properties. Studying these giant planets allows one to test the global climate models that are used for the Earth and other solar system planets. However, these studies are mostly limited either to highly-irradiated transiting giant planets or directly-imaged giant planets at large separations. Here we report the physical characterisation of the planets in a bright multi-planetary system (HIP41378) in which the outer planet, HIP41378 f is a Saturn-sized planet (9.2 $\pm$ 0.1 R$_\oplus$) with an anomalously low density of 0.09 $\pm$ 0.02 g cm$^{-3}$ that is not yet understood. Its equilibrium temperature is about 300 K. Therefore, it represents a planet with a mild temperature, in between the hot Jupiters and the colder giant planets of the Solar System. It opens a new window for atmospheric characterisation of giant exoplanets with a moderate irradiation, with the next-generation space telescopes such as JWST and ARIEL as well as the extremely-large ground-based telescopes. HIP41378 f is thus an important laboratory to understand the effect of the irradiation on the physical properties and chemical composition of the atmosphere of planets., Comment: Preprint submitted to Nature Astronomy. The results have not been peer-reviewed yet. Supplementary informations available as ancillary file

KELT-9b is a recently discovered exoplanet with a 1.49 day orbit around a B9.5/A0-type star. The unparalleled levels of ultraviolet irradiation that it receives from its host star put KELT-9b in its own unique class of ultra-hot Jupiters, with an equilibrium temperature >4000 K. The high quantities of dissociated hydrogen and atomic metals present in the dayside atmosphere of KELT-9b bear more resemblance to a K-type star than a gas giant. We present a single observation of KELT-9b during its secondary eclipse, taken with the Wide Field Camera on the Isaac Newton Telescope (INT). This observation was taken in the U-band, a window particularly sensitive to Rayleigh scattering. We do not detect a secondary eclipse signal, but our 3σ upper limit of 181 ppm on the depth allows us to constrain the dayside temperature of KELT-9b at pressures of ~30 mbar to 4995 K (3σ). Although we can place an observational constraint of A g < 0.14, our models suggest that the actual value is considerably lower than this due to H− opacity. This places KELT-9b squarely in the albedo regime populated by its cooler cousins, almost all of which reflect very small components of the light incident on their daysides. This work demonstrates the ability of ground-based 2 m class telescopes like the INT to perform secondary eclipse studies in the near-ultraviolet, which have previously only been conducted from space-based facilities.

This paper reports on the validation and mass measurement of EPIC211682544 b, a sub-Neptune orbiting a quiet G9V star. Using K2 data from campaigns C5 and C16, we find this planet to have a period of 50.818947 ± 0.000094 days and a radius of 2.41 ± 0.12 R⊕. We followed this system with HARPS-N to obtain 67 precise radial velocities. A combined fit of the transit and radial velocity data reveals that EPIC211682544 b has a mass of 14.8 ± 3.1 M⊕. Its bulk density (5.7+1.6/−1.4 g cm−3) implies that this planet has a significant envelope of water or other volatiles around a rocky core. EPIC211682544 b likely formed in a similar way as the cores of the four giant planets in our own Solar System, but for some reason, did not accrete much gas. The planetary mass was confirmed by an independent Gaussian process-based fit to both the radial velocities and the spectroscopic activity indicators. EPIC211682544 b belongs to only a handful of confirmed K2 exoplanets with periods longer than 40 days. It is among the longest periods for a small planet with a precisely determined mass using radial velocities.

This paper reports on the validation and mass measurement of K2-263b, a sub-Neptune orbiting a quiet G9V star. Using K2 data from campaigns C5 and C16, we find this planet to have a period of $50.818947\pm 0.000094$ days and a radius of $2.41\pm0.12$ R$_{\oplus}$. We followed this system with HARPS-N to obtain 67 precise radial velocities. A combined fit of the transit and radial velocity data reveals that K2-263b has a mass of $14.8\pm3.1$ M$_{\oplus}$. Its bulk density ($5.7_{-1.4}^{+1.6}$ g cm$^{-3}$) implies that this planet has a significant envelope of water or other volatiles around a rocky core. EPIC211682544b likely formed in a similar way as the cores of the four giant planets in our own Solar System, but for some reason, did not accrete much gas. The planetary mass was confirmed by an independent Gaussian process-based fit to both the radial velocities and the spectroscopic activity indicators. K2-263b belongs to only a handful of confirmed K2 exoplanets with periods longer than 40 days. It is among the longest periods for a small planet with a precisely determined mass using radial velocities., Comment: 10 pages, 6 figures, accepted for publication in MNRAS. v2: EPIC ID changed to assigned K2 name

Stellar magnetic activity is an important parameter to study as it can give insights into stellar activity cycles and even how the stellar dynamo operates. However, as cool stars evolve along the main sequence, they lose angular momentum due to magnetic braking. This results in a decrease in both the rotational velocity and magnetic field generation. This has lead to many studies concerning the evolution of stellar rotation and stellar activity with age. The majority of these studies construct a relationship that is only reliable for ages younger than a gigayear due to the difficulty of determining ages for older stars. However, recent observational advancements have made it possible to study ages for a larger sample of stars through asteroseismology; opening up the possibility of stellar age investigations for stars older than a gigayear. In our research, we have considered the X-ray luminosity and Calcium II H&K emission as a function of stellar age using asteroseismic ages.

Arsenic contamination of drinking water affects more than 140 million people worldwide. While toxic to humans, inorganic forms of arsenic (arsenite and arsenate), can be used as energy sources for microbial respiration. AioX and its orthologues (ArxX and ArrX) represent the first members of a new sub-family of periplasmic-binding proteins that serve as the first component of a signal transduction system, that's role is to positively regulate expression of arsenic metabolism enzymes. As determined by X-ray crystallography for AioX, arsenite binding only requires subtle conformational changes in protein structure, providing insights into protein-ligand interactions. The binding pocket of all orthologues is conserved but this alone is not sufficient for oxyanion selectivity, with proteins selectively binding either arsenite or arsenate. Phylogenetic evidence, clearly demonstrates that the regulatory proteins evolved together early in prokaryotic evolution and had a separate origin from the metabolic enzymes whose expression they regulate.

Water sourced from Asian mountains is vital to the survival of an estimated 1.4 billion people, but by 2050 anticipated changes in snow and ice cover may threaten these supplies and, in turn, the food security of tens of millions of people. Despite the severity of this developing environmental hazard, the relative importance of glacier and snow-derived water needs more detailed study so that those communities who will experience the greatest shortages can be identified. Specifically, data showing how the contribution of meltwater varies with increasing distance downstream are lacking for many mountain catchments, as are robust hydrological models to simulate extreme scenarios of glacier loss as well as rainfall runoff events. Imprinted on regional-scale hydroclimatological controls of water availability are local-scale cultural beliefs and practices that have evolved over centuries, which determine who is able to access water supplies, for how long, and for what purpose. Building the resilience of human populations and the environment to future water shortages therefore depends on effective interdisciplinary team working to develop an understanding of the complex interactions between physical, socio-economic, cultural and historical factors. Developing simple and practical methods for water management, storage and societal adaptation that are appropriate to the socio-economic and political conditions of mountain-dwelling communities will only be sustainable if they are built on this integrated knowledge-base.