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PubMed: 31227488, Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ., Bayer Bayer, United Kingdom Université Paris Descartes Li Ka Shing Foundation, LKSF University of Michigan, U-M, 1Department of Rheumatology and the Centre of experimental Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Big Data institute, li Ka shing Centre for Health information and Discovery, nuffield Department of Medicine, University of Oxford, Oxford, UK 4Rheumatology a Department, Paris Descartes University, sorbonne Paris Cité, Cochin Hospital, Paris, France 5Data science and analytics, Bayer plc, Reading, UK 6UCl Division of Medicine, Royal Free Campus, london, UK 7Division of Rheumatology, Department of internal Medicine, University of Michigan scleroderma Program, University of Michigan, ann arbor, Michigan, Usa 8Department of experimental and Clinical Medicine, University of Florence, Florence, italy 9Bayer Us llC, Whippany, new Jersey, Usa 10Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Ontario, Canada Acknowledgements The R-code for the linear Mi-lassO was received from Qixuan Chen.21 Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., Contributors study conception and design, acquisition of data, analysis and interpretation of data and drafting and revising the article: OD and MB; analysis and interpretation of data: OD, MB, Rs and nG. all authors have critically reviewed and approved the final submitted version to be published. Funding This study was supported by a grant from Bayer aG. Bayer employees are coauthors of this paper and supported the study design and interpretation of the data, but otherwise Bayer had no influence on the study., Competing interests MOB declares no conflict of interest. OD has had consultancy relationships with actelion, Bayer, Biogen idec, Boehringer ingelheim, Chemomab, espeRare foundation, Genentech/Roche, GsK, inventiva, italfarmaco, lilly, medac, Medimmune, Mitsubishi Tanabe Pharma, Pharmacyclics, novartis, Pfizer, sanofi, sinoxa and UCB in the area of potential treatments of scleroderma and its complications. OD has received research funding from actelion, Bayer, Boehringer ingelheim, Mitsubishi Tanabe Pharma and Roche in the area of potential treatments of scleroderma and its complications. OD has a patent for mir-29 licensed for the treatment of systemic sclerosis. DK has consultancy relationships and/or has received grant/research support from Bayer, Bristol-Myers squibb, Boehringer ingelheim, Genentech/Roche, niH, Pfizer, sanofi-aventis Pharmaceuticals, actelion Pharmaceuticals Us, Chemomab, Corbus, Covis, Cytori, eicos, eMD serono, Gilead, GlaxosmithKline, and UCB Pharma. He is a shareholder of eicos. CPD has consultancy relationships with and/or has received speakers’ bureau fees from actelion Pharmaceuticals Us, Bayer aG, GlaxosmithKline, Csl Behring, Merck serono, Roche Pharmaceuticals, Genentech and Biogen iDeC inc., inventiva, sanofi-aventis Pharmaceuticals and Boehringer ingelheim. JeP has consultancy relationships with and/or has received grant/research support from actelion, Bayer aG, Bristol-Myers squibb, Merck, Pfizer inc. and Roche. MM-C has consultancy relationships and/ or has received grant/research support from Pfizer, Bristol-Myers squibb, actelion, UCB Pharma, Bayer, Chemomab, Genentech/Roche, inventiva and lilly. Ya has consultancy relationships with and/or has received grant/research support from actelion, Pharmaceuticals Us, Bayer aG, Bristol-Myers squibb, inventiva, Medac, Pfizer inc., Roche Pharmaceuticals, Genentech and Biogen iDeC inc., sanofi-aventis Pharmaceuticals and servier. JdOP and JC are employees of Bayer. nTG has nothing to disclose.

C band backscatter parameters contain information about the upper snowpack/firn in the dry snow zone. The wide incidence angle diversity of the Advanced Scatterometer (ASCAT) gives unprecedented characterisation of backscatter anisotropy, revealing the backscatter response to climatic forcing. TheA(isotropic component) andM2(bi-sinusoidal azimuth anisotropy) parameters are investigated here, in conjunction with data from atmospheric and snowpack models, to identify the backscatter response to surface forcing parameters (wind speed and persistence, precipitation, surface temperature, density and grain size). The long-term meanAparameter is successfully recreated with a regression using these drivers, indicating strong links between theAparameter and precipitation on long timescales. While the ASCAT time series is too short to determine which factors drive observed trends, factors influencing the seasonal and short timescale variability are revealed. On these timescales,Astrongly responds to the propagation of surface temperature cycles/anomalies downward through the firn, via direct modulation of the dielectric constant. The influence of precipitation onAis small at shorter timescales. TheM2parameter is controlled by wind speed and persistence, through modification of monodirectionally-aligned surface roughness. This variability indicates that throughout much of coastal Antarctica, a microwave ‘snapshot’ is generally not representative of longer-term conditions.

We propose a new ice sheet model validation framework – the Cryospheric Model Comparison Tool (CmCt) – that takes advantage of ice sheet altimetry and gravimetry observations collected over the past several decades and is applied here to modeling of the Greenland ice sheet. We use realistic simulations performed with the Community Ice Sheet Model (CISM) along with two idealized, non-dynamic models to demonstrate the framework and its use. Dynamic simulations with CISM are forced from 1991 to 2013, using combinations of reanalysis-based surface mass balance and observations of outlet glacier flux change. We propose and demonstrate qualitative and quantitative metrics for use in evaluating the different model simulations against the observations. We find that the altimetry observations used here are largely ambiguous in terms of their ability to distinguish one simulation from another. Based on basin-scale and whole-ice-sheet-scale metrics, we find that simulations using both idealized conceptual models and dynamic, numerical models provide an equally reasonable representation of the ice sheet surface (mean elevation differences of

We evaluate modelled Antarctic ice sheet (AIS) near-surface climate, surface mass balance (SMB) and surface energy balance (SEB) from the updated polar version of the regional atmospheric climate model, RACMO2 (1979–2016). The updated model, referred to as RACMO2.3p2, incorporates upper-air relaxation, a revised topography, tuned parameters in the cloud scheme to generate more precipitation towards the AIS interior and modified snow properties reducing drifting snow sublimation and increasing surface snowmelt. Comparisons of RACMO2 model output with several independent observational data show that the existing biases in AIS temperature, radiative fluxes and SMB components are further reduced with respect to the previous model version. The model-integrated annual average SMB for the ice sheet including ice shelves (minus the Antarctic Peninsula, AP) now amounts to 2229 Gt y−1, with an interannual variability of 109 Gt y−1. The largest improvement is found in modelled surface snowmelt, which now compares well with satellite and weather station observations. For the high-resolution (∼ 5.5 km) AP simulation, results remain comparable to earlier studies. The updated model provides a new, high-resolution data set of the contemporary near-surface climate and SMB of the AIS; this model version will be used for future climate scenario projections in a forthcoming study.

We evaluate modelled Greenland ice sheet (GrIS) near-surface climate, surface energy balance (SEB) and surface mass balance (SMB) from the updated regional climate model RACMO2 (1958–2016). The new model version, referred to as RACMO2.3p2, incorporates updated glacier outlines, topography and ice albedo fields. Parameters in the cloud scheme governing the conversion of cloud condensate into precipitation have been tuned to correct inland snowfall underestimation: snow properties are modified to reduce drifting snow and melt production in the ice sheet percolation zone. The ice albedo prescribed in the updated model is lower at the ice sheet margins, increasing ice melt locally. RACMO2.3p2 shows good agreement compared to in situ meteorological data and point SEB/SMB measurements, and better resolves the spatial patterns and temporal variability of SMB compared with the previous model version, notably in the north-east, south-east and along the K-transect in south-western Greenland. This new model version provides updated, high-resolution gridded fields of the GrIS present-day climate and SMB, and will be used for projections of the GrIS climate and SMB in response to a future climate scenario in a forthcoming study.

The advice of a dynamic multidisciplinary discussion (MDD) is believed to be important in the diagnosis of interstitial lung diseases (ILD). However, to what extent MDD diagnoses differ from the preliminary diagnoses before formal work-up and MDD (preMDD diagnoses), is still insufficiently studied. ispartof: Chest vol:153 issue:6 pages:1416-1423 ispartof: location:United States status: published

Clouds exert a pivotal control on the mass balance of the Greenland and Antarctic Ice Sheet and therefore their contribution to global sea level. Clouds transport moisture onto the marginal ice sheet, where steep topographic gradients force the air to rise and cool, inducing strong orographic precipitation and leaving the interior ice sheet dry (polar desert). Clouds further regulate the radiation balance at the surface and, consequently, surface melt. Depending on their frequency, phase, and structure, clouds not only mute incoming solar radiation but also enhance longwave radiation at the surface. With the advent of novel observations from space (CloudSat-CALIPSO) and in the field, we now have tools to start evaluating the representation of clouds, precipitation, and ice sheet surface radiation in climate models. Here we evaluate the Community Earth System Model version 1 (CESM1(CAM5)) to represent (1) precipitation frequency and phase, using a CALIPSO cloud simulator; (2) cloud radiative effect comparing to a CloudSat-CALIPSO based product; and (3) snowfall amounts and surface mass balance, comparing to CloudSat, in-situ observations, and regional climate model results. After discussing outstanding cloud biases in CESM1(CAM5), we present our efforts to reduce these in the recently released version 2 (CESM2). We show that clouds are considerably better represented in CESM2, leading to improvements in surface radiation, melt, and surface mass balance, although biases in precipitation phase persist. Our work demonstrates the need for high-quality, long-term observations of clouds and their effect on the ice sheet surface to enable continued climate model improvement.

Mass changes of polar ice sheets have an important societal impact, because they affect global sea level. Estimating the current mass budget of ice sheets is equivalent to determining the balance between surface mass gain through precipitation and outflow across the grounding line. For the Antarctic ice sheet, grounding line outflow is governed by oceanic processes and outlet glacier dynamics. In this study, we compute the mass budget of major outlet glaciers in the eastern Dronning Maud Land sector of the Antarctic ice sheet using the input/output method. Input is given by recent surface accumulation estimates (SMB) of the whole drainage basin. The outflow at the grounding line is determined from the radar data of a recent airborne survey and satellite-based velocities using a flow model of combined plug flow and simple shear. This approach is an improvement on previous studies, as the ice thickness is measured, rather than being estimated from hydrostatic equilibrium. In line with the general thickening of the ice sheet over this sector, we estimate the regional mass balance in this area at 3.15 ± 8.23 Gt a−1 according to the most recent SMB model results.

Latest Maastrichtian climate change caused by Deccan volcanism has been invoked as a cause of mass extinction at the Cretaceous-Paleogene (K-Pg) boundary (~66.0 Ma). Yet late Maastrichtian climate and ecological changes are poorly documented, in particular on the Southern Hemisphere. Here we present upper Maastrichtian-lower Danian climate and biotic records from the Bajada del Jagüel (BJ) shelf site (Neuquén Basin, Argentina), employing the TEX86 paleothermometer, marine palynology (dinoflagellate cysts), and micropaleontology (foraminifera). These records are correlated to the astronomically tuned Ocean Drilling Program Site 1262 (Walvis Ridge). Collectively, we use these records to assess climatic and ecological effects of Deccan volcanism in the Southern Atlantic region. Both the TEX86-based sea surface temperature (SST) record at BJ and the bulk carbonate δ18O-based SST record of Site 1262 show a latest Maastrichtian warming of ~2.5–4°C, at 450 to 150 kyr before the K-Pg boundary, coinciding with the a large Deccan outpouring phase. Benthic foraminiferal and dinocyst assemblage changes indicate that this warming resulted in enhanced runoff and stratification of the water column, likely resulting from more humid climate conditions in the Neuquén Basin. These climate conditions could have been caused by an expanding and strengthening thermal low over the South American continent. Biotic changes in response to late Maastrichtian environmental changes are rather limited, when compared to the major turnovers observed at many K-Pg boundary sites worldwide. This suggests that environmental perturbations during the latest Maastrichtian warming event were less severe than those following the K-Pg boundary impact. Fil: Woelders, Lineke. Katholikie Universiteit Leuven; Bélgica Fil: Vellekoop, Johan. Katholikie Universiteit Leuven; Bélgica Fil: Kroon, D.. University of Edinburgh; Reino Unido Fil: Smit, Jan. University of Amsterdam; Países Bajos Fil: Casadio, Silvio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; Argentina Fil: Pramparo, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentina Fil: Dinarès Turell, Jaume. Istituto Nazionale di Geofisica e Vulcanologia; Italia Fil: Peterse, Francien. University of Utrecht; Países Bajos Fil: Sluijs, Appy. University of Utrecht; Países Bajos Fil: Lenaerts, Jan. University of Utrecht; Países Bajos Fil: Speijer, Robert. Katholikie Universiteit Leuven; Bélgica

Mass loss from the Greenland ice sheet (GrIS) in recent years has been dominated by runoff from surface melt. It is currently being studied extensively, while little interest has been given to the smallest component of surface mass balance (SMB): the vapor flux. Although poorly understood, it is not negligible and could potentially play a larger role in SMB in a warming climate where temperature, relative humidity, and precipitation changes remain uncertain. Here we present an innovative approach to estimate the vapor flux using the Atmospheric Infrared Sounder (AIRS) version 6 data and a modified vapor flux model (BMF13) over the GrIS between 2003 and 2014. One modification to the BMF13 model includes a new Multiangle Imaging SpectroRadiometer surface aerodynamic roughness product, which likely produces more accurate estimates of the drag coefficient on the ice sheet. When comparing AIRS data with GC-Net and Programme for Monitoring of the Greenland Ice Sheet automatic weather station observations of skin temperature, near-surface air temperature, and humidity, they agree within 2 K, 2.68 K, and 0.34 g kg−1. Largest differences occur in the ablation zone where there is significant subgrid heterogeneity. Overall, the average vapor flux from the GrIS between 2003 and 2014 was found to be 14.6 ± 3.6 Gt yr−1. No statistically significant trends were found during the data record. This data set is compared to the Regional Atmospheric Climate Model (RACMO2.3) vapor flux, and BMF13 produced smaller vapor fluxes in the summer (~0.05 Gt d−1) and slightly more deposition in the winter (~9.4 × 10−3 Gt d−1). Annually, differences between BMF13 and RACMO2.3 were only 30 ± 15%.

Mass loss from the Greenland ice sheet (GrIS) in recent years has been dominated by runoff from surface melt. It is currently being studied extensively, while little interest has been given to the smallest component of surface mass balance (SMB): the vapor flux. Although poorly understood, it is not negligible and could potentially play a larger role in SMB in a warming climate where temperature, relative humidity, and precipitation changes remain uncertain. Here we present an innovative approach to estimate the vapor flux using the Atmospheric Infrared Sounder (AIRS) version 6 data and a modified vapor flux model (BMF13) over the GrIS between 2003 and 2014. One modification to the BMF13 model includes a new Multiangle Imaging SpectroRadiometer surface aerodynamic roughness product, which likely produces more accurate estimates of the drag coefficient on the ice sheet. When comparing AIRS data with GC-Net and Programme for Monitoring of the Greenland Ice Sheet automatic weather station observations of skin temperature, near-surface air temperature, and humidity, they agree within 2 K, 2.68 K, and 0.34 g kg−1. Largest differences occur in the ablation zone where there is significant subgrid heterogeneity. Overall, the average vapor flux from the GrIS between 2003 and 2014 was found to be 14.6 ± 3.6 Gt yr−1. No statistically significant trends were found during the data record. This data set is compared to the Regional Atmospheric Climate Model (RACMO2.3) vapor flux, and BMF13 produced smaller vapor fluxes in the summer (~0.05 Gt d−1) and slightly more deposition in the winter (~9.4 × 10−3 Gt d−1). Annually, differences between BMF13 and RACMO2.3 were only 30 ± 15%.