Showing papers by "Université libre de Bruxelles published in 2013"
Cooper University Hospital1, St George's Hospital2, Memorial Hospital of Rhode Island3, Emory University4, University of Colorado Denver5, McMaster University6, Washington University in St. Louis7, University of Chicago8, University of Jena9, Rush University Medical Center10, University of Pittsburgh11, University of Pennsylvania12, Federal University of São Paulo13, University of Toronto14, Royal Perth Hospital15, Guy's and St Thomas' NHS Foundation Trust16, Université libre de Bruxelles17
TL;DR: An update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008 is provided.
Abstract: Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke
9,137 citations
Wellcome Trust Sanger Institute1, Cambridge University Hospitals NHS Foundation Trust2, Wellcome Trust3, University of British Columbia4, University of Cambridge5, Oslo University Hospital6, The Breast Cancer Research Foundation7, University of Oslo8, University of Münster9, Université libre de Bruxelles10, German Cancer Research Center11, University of Iceland12, Erasmus University Rotterdam13, French Institute of Health and Medical Research14, Paris Descartes University15, University of Paris16, Broad Institute17, University of Bergen18, University of Oviedo19, University of Queensland20, University of Glasgow21, Harvard University22, United States Department of Veterans Affairs23, Netherlands Cancer Institute24, University of Kiel25, Radboud University Nijmegen26, King's College London27, Curie Institute28, Bankstown Lidcombe Hospital29, University of New South Wales30, University of Barcelona31
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Abstract: All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
7,904 citations
European Institute of Oncology1, Harvard University2, University of Sydney3, Institut Jules Bordet4, Kantonsspital St. Gallen5, University of St. Gallen6, Loyola University Chicago7, Institut Gustave Roussy8, Karolinska Institutet9, University of Bordeaux10, University of Geneva11, University of Pittsburgh12, University of Copenhagen13, University of Newcastle14, Medical University of Vienna15, University of Toronto16, University of Michigan17, Memorial Sloan Kettering Cancer Center18, Mayo Clinic19, Gdańsk Medical University20, University of Gothenburg21, Baylor College of Medicine22, University of North Carolina at Chapel Hill23, Université libre de Bruxelles24, Netherlands Cancer Institute25, Fudan University26, Kyoto University27, King's College London28, University of Göttingen29, Emory University30
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.
2,831 citations
TL;DR: In this article, the authors highlight the disadvantages of this method and present the median absolute deviation, an alternative and more robust measure of dispersion that is easy to implement, and explain the procedures for calculating this indicator in SPSS and R software.
2,647 citations
Paris Diderot University1, University of Barcelona2, University of Padua3, Autonomous University of Barcelona4, Université libre de Bruxelles5, University of Paris6, University of Bologna7, University of Cambridge8, University of Turin9, Katholieke Universiteit Leuven10, Goethe University Frankfurt11, University of Bonn12
TL;DR: Diagnostic criteria for ACLF was established and showed that it is distinct from AD, based not only on the presence of organ failure(s) and high mortality rate but also on age, precipitating events, and systemic inflammation.
2,110 citations
Yale University1, Université libre de Bruxelles2, University of Hamburg3, Uppsala University4, Wisconsin Department of Natural Resources5, United States Geological Survey6, University of Washington7, Stockholm University8, Finnish Environment Institute9, University of Waterloo10, Pierre-and-Marie-Curie University11, United States Naval Academy12
TL;DR: In this article, the authors report regional variations in global inland water surface area, dissolved CO2 and gas transfer velocity, and obtain global CO2 evasion rates of 1.8(-0.25) and 0.52 Pg C yr(-1) from lakes and reservoirs, where the upper and lower limits are respectively the 5th and 95th confidence interval percentiles.
Abstract: Carbon dioxide (CO2) transfer from inland waters to the atmosphere, known as CO2 evasion, is a component of the global carbon cycle. Global estimates of CO2 evasion have been hampered, however, by the lack of a framework for estimating the inland water surface area and gas transfer velocity and by the absence of a global CO2 database. Here we report regional variations in global inland water surface area, dissolved CO2 and gas transfer velocity. We obtain global CO2 evasion rates of 1.8(-0.25)(+0.25) petagrams of carbon (Pg C) per year from streams and rivers and 0.32(-0.26)(+0.52) Pg C yr(-1) from lakes and reservoirs, where the upper and lower limits are respectively the 5th and 95th confidence interval percentiles. The resulting global evasion rate of 2.1 Pg C yr(-1) is higher than previous estimates owing to a larger stream and river evasion rate. Our analysis predicts global hotspots in stream and river evasion, with about 70 per cent of the flux occurring over just 20 per cent of the land surface. The source of inland water CO2 is still not known with certainty and new studies are needed to research the mechanisms controlling CO2 evasion globally.
1,696 citations
British Antarctic Survey1, University of Bristol2, Columbia University3, National Institute of Geophysics and Volcanology4, University of Aberdeen5, University of Texas at Austin6, Centro de Estudios Científicos7, Université libre de Bruxelles8, University of Washington9, Swansea University10, Institute for Geosciences and Natural Resources11, Technical University of Denmark12, National Institute of Polar Research13, California Institute of Technology14, University of Kansas15, Stockholm University16, St. Olaf College17, Norwegian Polar Institute18, Wallops Flight Facility19, University of Canterbury20, University of Oslo21, University of California, Santa Barbara22, University of California, Irvine23, University of York24, Australian Antarctic Division25, Newcastle University26, Goddard Space Flight Center27, Polar Research Institute of China28
TL;DR: Bedmap2 as discussed by the authors is a suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60° S. In particular, the Bedmap2 ice thickness grid is made from 25 million measurements, over two orders of magnitude more than were used in Bedmap1.
Abstract: We present Bedmap2, a new suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60° S. We derived these products using data from a variety of sources, including many substantial surveys completed since the original Bedmap compilation (Bedmap1) in 2001. In particular, the Bedmap2 ice thickness grid is made from 25 million measurements, over two orders of magnitude more than were used in Bedmap1. In most parts of Antarctica the subglacial landscape is visible in much greater detail than was previously available and the improved data-coverage has in many areas revealed the full scale of mountain ranges, valleys, basins and troughs, only fragments of which were previously indicated in local surveys. The derived statistics for Bedmap2 show that the volume of ice contained in the Antarctic ice sheet (27 million km3) and its potential contribution to sea-level rise (58 m) are similar to those of Bedmap1, but the mean thickness of the ice sheet is 4.6% greater, the mean depth of the bed beneath the grounded ice sheet is 72 m lower and the area of ice sheet grounded on bed below sea level is increased by 10%. The Bedmap2 compilation highlights several areas beneath the ice sheet where the bed elevation is substantially lower than the deepest bed indicated by Bedmap1. These products, along with grids of data coverage and uncertainty, provide new opportunities for detailed modelling of the past and future evolution of the Antarctic ice sheets.
1,678 citations
University of Adelaide1, University of Wisconsin-Madison2, Ghent University3, University of Canterbury4, University of Geneva5, Humboldt University of Berlin6, University of California, Irvine7, University of Mainz8, University of California, Berkeley9, Ohio State University10, Université libre de Bruxelles11, Ruhr University Bochum12, University of Wuppertal13, University of Maryland, College Park14, University of Kansas15, Lawrence Berkeley National Laboratory16, RWTH Aachen University17, Uppsala University18, University of Alberta19, Stockholm University20, Vrije Universiteit Brussel21, University of Bonn22, École Polytechnique Fédérale de Lausanne23, Georgia Institute of Technology24, Pennsylvania State University25, Technical University of Dortmund26, Southern University and A&M College27
TL;DR: The presence of a high-energy neutrino flux containing the most energetic neutrinos ever observed is revealed, including 28 events at energies between 30 and 1200 TeV, although the origin of this flux is unknown and the findings are consistent with expectations for a neutRino population with origins outside the solar system.
Abstract: We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4 sigma level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.
1,490 citations
TL;DR: This paper analyzes the literature from the point of view of swarm engineering and proposes two taxonomies: in the first taxonomy, works that deal with design and analysis methods are classified; in the second, works according to the collective behavior studied are classified.
Abstract: Swarm robotics is an approach to collective robotics that takes inspiration from the self-organized behaviors of social animals. Through simple rules and local interactions, swarm robotics aims at designing robust, scalable, and flexible collective behaviors for the coordination of large numbers of robots. In this paper, we analyze the literature from the point of view of swarm engineering: we focus mainly on ideas and concepts that contribute to the advancement of swarm robotics as an engineering field and that could be relevant to tackle real-world applications. Swarm engineering is an emerging discipline that aims at defining systematic and well founded procedures for modeling, designing, realizing, verifying, validating, operating, and maintaining a swarm robotics system. We propose two taxonomies: in the first taxonomy, we classify works that deal with design and analysis methods; in the second taxonomy, we classify works according to the collective behavior studied. We conclude with a discussion of the current limits of swarm robotics as an engineering discipline and with suggestions for future research directions.
1,405 citations
TL;DR: In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis and the data also support the evaluation of immunotherapeutic approaches in selected BC subtypes.
Abstract: Purpose Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT—in this case, anthracycline-only CT—in selected BC subtypes. Patients and Methods We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years.
1,280 citations
TL;DR: The sources, exchanges and fates of carbon in the coastal ocean and how anthropogenic activities have altered the carbon cycle are discussed.
Abstract: The carbon cycle of the coastal ocean is a dynamic component of the global carbon budget. But the diverse sources and sinks of carbon and their complex interactions in these waters remain poorly understood. Here we discuss the sources, exchanges and fates of carbon in the coastal ocean and how anthropogenic activities have altered the carbon cycle. Recent evidence suggests that the coastal ocean may have become a net sink for atmospheric carbon dioxide during post-industrial times. Continued human pressures in coastal zones will probably have an important impact on the future evolution of the coastal ocean's carbon budget.
Université libre de Bruxelles1, University of Exeter2, ETH Zurich3, University of Antwerp4, University of Hamburg5, University of California, San Diego6, University of Bristol7, University of North Carolina at Chapel Hill8, University of Liège9, Centre national de la recherche scientifique10, Geophysical Institute, University of Bergen11, Bjerknes Centre for Climate Research12, Max Planck Society13, University of Bern14, University of Southern California15, Vrije Universiteit Brussel16, Yale University17, University of East Anglia18, Helmholtz Centre for Environmental Research - UFZ19
TL;DR: This article showed that anthropogenic perturbation may have increased the flux of carbon to inland waters by as much as 1.0 Pg C yr−1 since pre-industrial times, mainly owing to enhanced carbon export from soils.
Abstract: A substantial amount of the atmospheric carbon taken up on land through photosynthesis and chemical weathering is transported laterally along the aquatic continuum from upland terrestrial ecosystems to the ocean. So far, global carbon budget estimates have implicitly assumed that the transformation and lateral transport of carbon along this aquatic continuum has remained unchanged since pre-industrial times. A synthesis of published work reveals the magnitude of present-day lateral carbon fluxes from land to ocean, and the extent to which human activities have altered these fluxes. We show that anthropogenic perturbation may have increased the flux of carbon to inland waters by as much as 1.0 Pg C yr−1 since pre-industrial times, mainly owing to enhanced carbon export from soils. Most of this additional carbon input to upstream rivers is either emitted back to the atmosphere as carbon dioxide (~0.4 Pg C yr−1) or sequestered in sediments (~0.5 Pg C yr−1) along the continuum of freshwater bodies, estuaries and coastal waters, leaving only a perturbation carbon input of ~0.1 Pg C yr−1 to the open ocean. According to our analysis, terrestrial ecosystems store ~0.9 Pg C yr−1 at present, which is in agreement with results from forest inventories but significantly differs from the figure of 1.5 Pg C yr−1 previously estimated when ignoring changes in lateral carbon fluxes. We suggest that carbon fluxes along the land–ocean aquatic continuum need to be included in global carbon dioxide budgets.
TL;DR: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants.
Abstract: Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.
TL;DR: These two neutrino-induced events could be a first indication of an astrophysical neutrinos flux; the moderate significance, however, does not permit a definitive conclusion at this time.
Abstract: We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04 +/- 0.16 and 1.14 +/- 0.17 PeV, respectively, the highest neutrino energies observed so far. These events are consistent with fully contained particle showers induced by neutral-current nu(e,mu,tau) ((nu) over bar (e,mu,tau)) or charged-current nu(e) ((nu) over bar (e)) interactions within the IceCube detector. The events were discovered in a search for ultrahigh energy neutrinos using data corresponding to 615.9 days effective live time. The expected number of atmospheric background is 0.082 +/- 0.004(stat)(-0.057)(+0.041)(syst). The probability of observing two or more candidate events under the atmospheric background-only hypothesis is 2.9 x 10(-3) (2.8 sigma) taking into account the uncertainty on the expected number of background events. These two events could be a first indication of an astrophysical neutrino flux; the moderate significance, however, does not permit a definitive conclusion at this time.
TL;DR: Recent studies on rice (Oryza sativa) and Cd-hyperaccumulating plants that have led to important insights into the processes controlling the passage of Cd from the soil to edible plant organs are reviewed.
TL;DR: In this Opinion article, the different parallels that can be drawn between adult SCs and CSCs in solid tumours are discussed.
Abstract: The maintenance and repair of many adult tissues are ensured by stem cells (SCs), which reside at the top of the cellular hierarchy of these tissues. Functional assays, such as in vitro clonogenic assays, transplantation and in vivo lineage tracing, have been used to assess the renewing and differentiation potential of normal SCs. Similar strategies have suggested that solid tumours may also be hierarchically organized and contain cancer SCs (CSCs) that sustain tumour growth and relapse after therapy. In this Opinion article, we discuss the different parallels that can be drawn between adult SCs and CSCs in solid tumours.
TL;DR: The identification of CD4⁺ Tfh cells in breast cancer suggests that they are an important immune element whose presence in the tumor is a prognostic factor.
Abstract: CD4+ T cells are critical regulators of immune responses, but their functional role in human breast cancer is relatively unknown. The goal of this study was to produce an image of CD4+ T cells infiltrating breast tumors using limited ex vivo manipulation to better understand the in vivo differences associated with patient prognosis. We performed comprehensive molecular profiling of infiltrating CD4+ T cells isolated from untreated invasive primary tumors and found that the infiltrating T cell subpopulations included follicular helper T (Tfh) cells, which have not previously been found in solid tumors, as well as Th1, Th2, and Th17 effector memory cells and Tregs. T cell signaling pathway alterations included a mixture of activation and suppression characterized by restricted cytokine/chemokine production, which inversely paralleled lymphoid infiltration levels and could be reproduced in activated donor CD4+ T cells treated with primary tumor supernatant. A comparison of extensively versus minimally infiltrated tumors showed that CXCL13-producing CD4+ Tfh cells distinguish extensive immune infiltrates, principally located in tertiary lymphoid structure germinal centers. An 8-gene Tfh signature, signifying organized antitumor immunity, robustly predicted survival or preoperative response to chemotherapy. Our identification of CD4+ Tfh cells in breast cancer suggests that they are an important immune element whose presence in the tumor is a prognostic factor.
TL;DR: In this article, a detailed description of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson.
Abstract: A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 inverse femtobarns at sqrt(s) = 7 TeV, and up to 5.3 inverse femtobarns at sqrt(s) = 8 TeV. The results for five Higgs boson decay modes gamma gamma, ZZ, WW, tau tau, and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, gamma gamma and ZZ to 4 ell, gives a mass estimate of 125.3 +/- 0.4 (stat) +/- 0.5 (syst) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.
TL;DR: In this paper, a review of recent developments in the quantitative modeling of organic matter degradation in marine sediments is critically reviewed, including the main chemical, biological and physical factors that control the degradation of benthic organic matter.
Brown University1, Université catholique de Louvain2, Scott & White Hospital3, University of Pittsburgh4, University of Paris5, François Rabelais University6, Tufts University7, Mercy Health Partners8, Charles University in Prague9, München Klinik Bogenhausen10, China Medical University (Taiwan)11, Ghent University12, Keio University13, University of Miami14, University of Nebraska Medical Center15, Eisai16, Memorial Hospital of Rhode Island17, Université libre de Bruxelles18
TL;DR: Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality, and no significant differences were observed in any of the prespecified subgroups.
Abstract: Importance Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response. Objective To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality. Design, Setting, and Participants We performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. Interventions Patients with severe sepsis (n = 1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2:1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo, with n = 1304 and n = 657 patients, respectively. Main Outcome Measures The primary end point was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months after beginning treatment. Results Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P = .59; hazard ratio, 1.05; 95% CI, 0.88-1.26; difference in mortality rate, −1.1; 95% CI, −5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P = .79 (hazard ratio, 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. Conclusions and Relevance Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality. Trial Registration clinicaltrials.gov Identifier: NCT00334828
TL;DR: In this paper, two-particle angular correlations for charged particles emitted in pPb collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV are presented.
TL;DR: The role of infection in the pathogenesis of SIRS has been difficult because sterile inflammation and infection can both elicit similar clinical signs of acute systemic inflammation and several such stressors might be present simultaneously in any patient.
TL;DR: This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory.
Abstract: Purpose This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid tumors. Here, we report the health-related quality-of-life (HRQOL) results. Patients and Methods HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference. Results Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who rece...
Dartmouth College1, Uppsala University2, Nagaoka University of Technology3, University of Copenhagen4, Heidelberg University5, Natural Resources Canada6, Oregon State University7, Centre national de la recherche scientifique8, Korean Ocean Research and Development Institute9, Swansea University10, University of Bern11, British Antarctic Survey12, University of Kansas13, National Institute of Polar Research14, University of Iceland15, Stockholm University16, Vrije Universiteit Brussel17, University of Colorado Boulder18, Alfred Wegener Institute for Polar and Marine Research19, University of Washington20, Arctic and Antarctic Research Institute21, Desert Research Institute22, Hokkaido University23, University of Grenoble24, University of California, San Diego25, Université libre de Bruxelles26, Utrecht University27, Oeschger Centre for Climate Change Research28, Max Planck Society29, Swiss Federal Institute for Forest, Snow and Landscape Research30, ETH Zurich31, United Arab Emirates University32, Paul Scherrer Institute33, École Polytechnique Fédérale de Lausanne34, University of East Anglia35, Geological Survey of Canada36
TL;DR: In this paper, the North Greenland Eemian Ice Drilling (NEEM) ice core was extracted from folded Greenland ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records.
Abstract: Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
Université libre de Bruxelles1, Technion – Israel Institute of Technology2, University of Barcelona3, University of Pittsburgh4, Royal Free Hospital5, Claude Bernard University Lyon 16, University of California, San Francisco7, University of Bologna8, National Institutes of Health9, University of Michigan10, Harvard University11, University of Paris-Sud12, University of Giessen13
TL;DR: In this paper, a change in terminology and a new definition of pulmonary hypertension due to LHD was proposed, and the authors suggest to abandon "out-of-proportion" PH and to distinguish "isolated post-capillary PH" from "post-CAPillary PH with a precapillary component" based on the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure.
TL;DR: In this article, the authors investigate the dynamical mass ejection, r-process nucleosynthesis, and properties of electromagnetic counterparts of neutron-star (NS) mergers in dependence on the uncertain properties of the nuclear equation of state (EOS) by employing 40 representative, high-density EOSs in relativistic, hydrodynamical simulations.
Abstract: We investigate systematically the dynamical mass ejection, r-process nucleosynthesis, and properties of electromagnetic counterparts of neutron-star (NS) mergers in dependence on the uncertain properties of the nuclear equation of state (EOS) by employing 40 representative, microphysical high-density EOSs in relativistic, hydrodynamical simulations. The crucial parameter determining the ejecta mass is the radius R{sub 1.35} of a 1.35 M{sub Sun} NS. NSs with smaller R{sub 1.35} (''soft'' EOS) eject systematically higher masses. These range from {approx}10{sup -3} M{sub Sun} to {approx}10{sup -2} M{sub Sun} for 1.35-1.35 M{sub Sun} binaries and from {approx}5 Multiplication-Sign 10{sup -3} M{sub Sun} to {approx}2 Multiplication-Sign 10{sup -2} M{sub Sun} for 1.2-1.5 M{sub Sun} systems (with kinetic energies between {approx}5 Multiplication-Sign 10{sup 49} erg and 10{sup 51} erg). Correspondingly, the bolometric peak luminosities of the optical transients of symmetric (asymmetric) mergers vary between 3 Multiplication-Sign 10{sup 41} erg s{sup -1} and 14 Multiplication-Sign 10{sup 41} erg s{sup -1} (9 Multiplication-Sign 10{sup 41} erg s{sup -1} and 14.5 Multiplication-Sign 10{sup 41} erg s{sup -1}) on timescales between {approx}2 hr and {approx}12 hr. If these signals with absolute bolometric magnitudes from -15.0 to -16.7 are measured, the tight correlation of their properties with those of the merging NSs mightmore » provide valuable constraints on the high-density EOS. The r-process nucleosynthesis exhibits a remarkable robustness independent of the EOS, producing a nearly solar abundance pattern above mass number 130. By the r-process content of the Galaxy and the average production per event the Galactic merger rate is limited to 4 Multiplication-Sign 10{sup -5} yr{sup -1} (4 Multiplication-Sign 10{sup -4} yr{sup -1}) for a soft (stiff) NS EOS, if NS mergers are the main source of heavy r-nuclei. The production ratio of radioactive {sup 232}Th to {sup 238}U attains a stable value of 1.64-1.67, which does not exclude NS mergers as potential sources of heavy r-material in the most metal-poor stars.« less
University of Giessen1, Max Planck Society2, Technion – Israel Institute of Technology3, University of Barcelona4, Royal Free Hospital5, Claude Bernard University Lyon 16, University of California, San Francisco7, University of Bologna8, National Institutes of Health9, University of Michigan10, Harvard University11, University of Paris-Sud12, Université libre de Bruxelles13
TL;DR: The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity.
TL;DR: The data demonstrate that human cortical neurons generated in vitro from ESC/iPSC can develop complex hodological properties characteristic of the cerebral cortex in vivo, thereby offering unprecedented opportunities for the modeling of human cortex diseases and brain repair.
TL;DR: The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound.
Abstract: New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis, several of which are currently in clinical trials. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis.
European Institute of Oncology1, Harvard University2, Université libre de Bruxelles3, University of Bern4, Western General Hospital5, Hoffmann-La Roche6, The Royal Marsden NHS Foundation Trust7, Vita-Salute San Raffaele University8, Geelong Hospital9, Keele University10, Institute of Cancer Research11, The Breast Cancer Research Foundation12, Memorial Sloan Kettering Cancer Center13
TL;DR: 2 years of adjuvant trastuzumab is not more effective than is 1 year of treatment for patients with HER2-positive early breast cancer, and 1year of treatment provides a significant disease-free and overall survival benefit compared with observation.