Showing papers by "Université libre de Bruxelles published in 2015"
TL;DR: The first global map (228 countries) of antibiotic consumption in livestock is presented and it is projected that antimicrobial consumption will rise by 67% by 2030, and nearly double in Brazil, Russia, India, China, and South Africa.
Abstract: Demand for animal protein for human consumption is rising globally at an unprecedented rate. Modern animal production practices are associated with regular use of antimicrobials, potentially increasing selection pressure on bacteria to become resistant. Despite the significant potential consequences for antimicrobial resistance, there has been no quantitative measurement of global antimicrobial consumption by livestock. We address this gap by using Bayesian statistical models combining maps of livestock densities, economic projections of demand for meat products, and current estimates of antimicrobial consumption in high-income countries to map antimicrobial use in food animals for 2010 and 2030. We estimate that the global average annual consumption of antimicrobials per kilogram of animal produced was 45 mg⋅kg(-1), 148 mg⋅kg(-1), and 172 mg⋅kg(-1) for cattle, chicken, and pigs, respectively. Starting from this baseline, we estimate that between 2010 and 2030, the global consumption of antimicrobials will increase by 67%, from 63,151 ± 1,560 tons to 105,596 ± 3,605 tons. Up to a third of the increase in consumption in livestock between 2010 and 2030 is imputable to shifting production practices in middle-income countries where extensive farming systems will be replaced by large-scale intensive farming operations that routinely use antimicrobials in subtherapeutic doses. For Brazil, Russia, India, China, and South Africa, the increase in antimicrobial consumption will be 99%, up to seven times the projected population growth in this group of countries. Better understanding of the consequences of the uninhibited growth in veterinary antimicrobial consumption is needed to assess its potential effects on animal and human health.
2,371 citations
Université libre de Bruxelles1, Charité2, New York University3, University of Milan4, University of Antwerp5, University of California, San Francisco6, University of Auvergne7, Mayo Clinic8, University of Texas MD Anderson Cancer Center9, Harvard University10, Katholieke Universiteit Leuven11, Yeshiva University12, University of Toronto13, University of British Columbia14, Yale University15, Stanford University16, Memorial Sloan Kettering Cancer Center17, Indiana University – Purdue University Indianapolis18, University of Melbourne19
TL;DR: Current data on the clinical validity and utility of TILs in BC are reviewed in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections.
1,971 citations
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
University of British Columbia1, Cornell University2, Paris Diderot University3, Cedars-Sinai Medical Center4, Ludwig Maximilian University of Munich5, Casa Sollievo della Sofferenza6, The Chinese University of Hong Kong7, Université libre de Bruxelles8, University of Cambridge9, University of Toronto10, Goethe University Frankfurt11
TL;DR: Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis.
Abstract: BackgroundA simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need. MethodsWe conducted a phase 3, double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir–velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. ResultsOf the 624 patients who received treatment with sofosbuvir–velpatasvir, 34% had HCV genotype...
909 citations
TL;DR: In this paper, the quantum Hall effect conductance was measured in ultracold atoms subject to artificial gauge fields, and the Chern number was found to be associated with topological phases.
Abstract: Chern numbers characterize the quantum Hall effect conductance—non-zero values are associated with topological phases. Previously only spotted in electronic systems, they have now been measured in ultracold atoms subject to artificial gauge fields.
874 citations
TL;DR: Investigating the immunogenicity of human epidermal growth factor receptor 2 -positive and triple-negative breast cancers and immunologically relevant genes in the neoadjuvant GeparSixto trial found immunologic factors were highly significant predictors of therapy response in the trial, particularly in patients treated with Cb.
Abstract: Purpose Modulation of immunologic interactions in cancer tissue is a promising therapeutic strategy. To investigate the immunogenicity of human epidermal growth factor receptor 2 (HER2) –positive and triple-negative (TN) breast cancers (BCs), we evaluated tumor-infiltrating lymphocytes (TILs) and immunologically relevant genes in the neoadjuvant GeparSixto trial. Patients and Methods GeparSixto investigated the effect of adding carboplatin (Cb) to an anthracycline-plus-taxane combination (PM) on pathologic complete response (pCR). A total of 580 tumors were evaluated before random assignment for stromal TILs and lymphocyte-predominant BC (LPBC). mRNA expression of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) as well as immunosuppressive factors (IDO1, PD-1, PD-L1, CTLA4, FOXP3) was measured in 481 tumors. Results Increased levels of stromal TILs predicted pCR in univariable (P < .001) and multivariable analyses (P < .001). pCR rate was 59.9% in LPBC and 33.8% for non-LPBC (P < .001). pC...
822 citations
Brighton and Sussex Medical School1, Université libre de Bruxelles2, Sunnybrook Health Sciences Centre3, Federal University of São Paulo4, University of Pittsburgh5, University Hospital of Lausanne6, Brown University7, The Feinstein Institute for Medical Research8, University of Amsterdam9, European Medicines Agency10
TL;DR: The understanding of the clinical epidemiology and management of sepsis is set out and how the present approaches might be challenged to develop a new roadmap for future research is asked.
Abstract: Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research.
774 citations
TL;DR: In this paper, the authors conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
721 citations
Vrije Universiteit Brussel1, Pierre-and-Marie-Curie University2, Université libre de Bruxelles3, University of Arizona4, Université catholique de Louvain5, École Normale Supérieure6, Katholieke Universiteit Leuven7, Spanish National Research Council8, University of Paris9, University of Bremen10, Centre national de la recherche scientifique11, Kyoto University12, University of Western Brittany13, French Alternative Energies and Atomic Energy Commission14
TL;DR: It is found that environmental factors are incomplete predictors of community structure and associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns.
Abstract: Species interaction networks are shaped by abiotic and biotic factors. Here, as part of the Tara Oceans project, we studied the photic zone interactome using environmental factors and organismal abundance profiles and found that environmental factors are incomplete predictors of community structure. We found associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns. We identified interactions among grazers, primary producers, viruses, and (mainly parasitic) symbionts and validated network-generated hypotheses using microscopy to confirm symbiotic relationships. We have thus provided a resource to support further research on ocean food webs and integrating biological components into ocean models.
717 citations
TL;DR: To understand the subclonal structure of primary breast cancer, whole-genome and targeted sequencing was applied to multiple samples from each of 50 patients' tumors, finding thatLandmarks of disease progression arose within detectable subclones of antecedent lesions.
Abstract: The sequencing of cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and late in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer.
695 citations
TL;DR: The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV.
Abstract: The gamma-ray sky can be decomposed into individually detected sources, diffuse emission attributed to the interactions of Galactic cosmic rays with gas and radiation fields, and a residual all-sky emission component commonly called the isotropic diffuse gamma-ray background (IGRB). The IGRB comprises all extragalactic emissions too faint or too diffuse to be resolved in a given survey, as well as any residual Galactic foregrounds that are approximately isotropic. The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV. Improvements in event selection and characterization of cosmic-ray backgrounds, better understanding of the diffuse Galactic emission, and a longer data accumulation of 50 months, allow for a refinement and extension of the IGRB measurement with the LAT, now covering the energy range from 100 MeV to 820 GeV. The IGRB spectrum shows a significant high-energy cutoff feature, and can be well described over nearly four decades in energy by a power law with exponential cutoff having a spectral index of 2.32 plus or minus 0.02 and a break energy of (279 plus or minus 52) GeV using our baseline diffuse Galactic emission model. The total intensity attributed to the IGRB is (7.2 plus or minus 0.6) x 10(exp -6) cm(exp -2) s(exp -1) sr(exp -1) above 100 MeV, with an additional +15%/-30% systematic uncertainty due to the Galactic diffuse foregrounds.
Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam +2134 more•Institutions (142)
TL;DR: The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays, and no significant deviations are found.
Abstract: Properties of the Higgs boson with mass near 125 GeV are measured in proton-proton collisions with the CMS experiment at the LHC. Comprehensive sets of production and decay measurements are combined. The decay channels include gamma gamma, ZZ, WW, tau tau, bb, and mu mu pairs. The data samples were collected in 2011 and 2012 and correspond to integrated luminosities of up to 5.1 inverse femtobarns at 7 TeV and up to 19.7 inverse femtobarns at 8 TeV. From the high-resolution gamma gamma and ZZ channels, the mass of the Higgs boson is determined to be 125.02 +0.26 -0.27 (stat) +0.14 -0.15 (syst) GeV. For this mass value, the event yields obtained in the different analyses tagging specific decay channels and production mechanisms are consistent with those expected for the standard model Higgs boson. The combined best-fit signal relative to the standard model expectation is 1.00 +/- 0.09 (stat) +0.08 -0.07 (theo) +/- 0.07 (syst) at the measured mass. The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays. No significant deviations are found.
TL;DR: This work presents a new semi-automated dasymetric modeling approach that incorporates detailed census and ancillary data in a flexible, “Random Forest” estimation technique, and outlines how this algorithm will be extended to provide freely-available gridded population data sets for Africa, Asia and Latin America.
Abstract: High resolution, contemporary data on human population distributions are vital for measuring impacts of population growth, monitoring human-environment interactions and for planning and policy development. Many methods are used to disaggregate census data and predict population densities for finer scale, gridded population data sets. We present a new semi-automated dasymetric modeling approach that incorporates detailed census and ancillary data in a flexible, “Random Forest” estimation technique. We outline the combination of widely available, remotely-sensed and geospatial data that contribute to the modeled dasymetric weights and then use the Random Forest model to generate a gridded prediction of population density at ~100 m spatial resolution. This prediction layer is then used as the weighting surface to perform dasymetric redistribution of the census counts at a country level. As a case study we compare the new algorithm and its products for three countries (Vietnam, Cambodia, and Kenya) with other common gridded population data production methodologies. We discuss the advantages of the new method and increases over the accuracy and flexibility of those previous approaches. Finally, we outline how this algorithm will be extended to provide freely-available gridded population data sets for Africa, Asia and Latin America.
University of East Anglia1, University of Oslo2, Centre national de la recherche scientifique3, University of Exeter4, National Oceanic and Atmospheric Administration5, Karlsruhe Institute of Technology6, Oak Ridge National Laboratory7, University of Paris8, Commonwealth Scientific and Industrial Research Organisation9, University of Maryland, College Park10, Alfred Wegener Institute for Polar and Marine Research11, Woods Hole Research Center12, University of Bristol13, University of Illinois at Urbana–Champaign14, Geophysical Institute, University of Bergen15, Bjerknes Centre for Climate Research16, National Institute for Environmental Studies17, University of California, San Diego18, Plymouth Marine Laboratory19, Netherlands Environmental Assessment Agency20, Lawrence Berkeley National Laboratory21, ETH Zurich22, Hobart Corporation23, Woods Hole Oceanographic Institution24, Appalachian State University25, Wageningen University and Research Centre26, Montana State University27, Australian National University28, Université libre de Bruxelles29, Max Planck Society30, Japan Meteorological Agency31, University of New Hampshire32, Leibniz Institute of Marine Sciences33, Imperial College London34, Oeschger Centre for Climate Change Research35, Joint Institute for the Study of the Atmosphere and Ocean36, Lamont–Doherty Earth Observatory37, VU University Amsterdam38, Atlantic Oceanographic and Meteorological Laboratory39, Met Office40
TL;DR: In this paper, the authors present a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community.
Abstract: Accurate assessment of anthropogenic carbon dioxide (CO 2 ) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates, consistency within and among components, alongside methodology and data limitations. CO 2 emissions from fossil fuel combustion and cement production (E FF ) are based on energy statistics and cement production data, respectively, while emissions from land-use change (E LUC ), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO 2 concentration is measured directly and its rate of growth (G ATM ) is computed from the annual changes in concentration. The mean ocean CO 2 sink (S OCEAN ) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S OCEAN is evaluated with data products based on surveys of ocean CO 2 measurements. The global residual terrestrial CO 2 sink (S LAND ) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO 2 , and land-cover-change (some including nitrogen–carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2004–2013), E FF was 8.9 ± 0.4 GtC yr −1 , E LUC 0.9 ± 0.5 GtC yr −1 , G ATM 4.3 ± 0.1 GtC yr −1 , S OCEAN 2.6 ± 0.5 GtC yr −1 , and S LAND 2.9 ± 0.8 GtC yr −1 . For year 2013 alone, E FF grew to 9.9 ± 0.5 GtC yr −1 , 2.3% above 2012, continuing the growth trend in these emissions, E LUC was 0.9 ± 0.5 GtC yr −1 , G ATM was 5.4 ± 0.2 GtC yr −1 , S OCEAN was 2.9 ± 0.5 GtC yr −1 and S LAND was 2.5 ± 0.9 GtC yr −1 . G ATM was high in 2013, reflecting a steady increase in E FF and smaller and opposite changes between S OCEAN and S LAND compared to the past decade (2004–2013). The global atmospheric CO 2 concentration reached 395.31 ± 0.10 ppm averaged over 2013. We estimate that E FF will increase by 2.5% (1.3–3.5%) to 10.1 ± 0.6 GtC in 2014 (37.0 ± 2.2 GtCO 2 yr −1 ), 65% above emissions in 1990, based on projections of world gross domestic product and recent changes in the carbon intensity of the global economy. From this projection of E FF and assumed constant E LUC for 2014, cumulative emissions of CO 2 will reach about 545 ± 55 GtC (2000 ± 200 GtCO 2 ) for 1870–2014, about 75% from EF FF and 25% from E LUC . This paper documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this living data set (Le Quere et al., 2013, 2014). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2014).
TL;DR: The ESMO-MCBS is an important first step to the critical public policy issue of value in cancer care, helping to frame the appropriate use of limited public and personal resources to deliver cost-effective and affordable cancer care.
TL;DR: The Jiangmen Underground Neutrino Observatory (JUNO) as mentioned in this paper is a 20 kton multi-purpose underground liquid scintillator detector with the determination of the neutrino mass hierarchy as a primary physics goal.
Abstract: The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purpose underground liquid scintillator detector, was proposed with the determination of the neutrino mass hierarchy as a primary physics goal. It is also capable of observing neutrinos from terrestrial and extra-terrestrial sources, including supernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos, atmospheric neutrinos, solar neutrinos, as well as exotic searches such as nucleon decays, dark matter, sterile neutrinos, etc. We present the physics motivations and the anticipated performance of the JUNO detector for various proposed measurements. By detecting reactor antineutrinos from two power plants at 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4 sigma significance with six years of running. The measurement of antineutrino spectrum will also lead to the precise determination of three out of the six oscillation parameters to an accuracy of better than 1\%. Neutrino burst from a typical core-collapse supernova at 10 kpc would lead to ~5000 inverse-beta-decay events and ~2000 all-flavor neutrino-proton elastic scattering events in JUNO. Detection of DSNB would provide valuable information on the cosmic star-formation rate and the average core-collapsed neutrino energy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400 events per year, significantly improving the statistics of existing geoneutrino samples. The JUNO detector is sensitive to several exotic searches, e.g. proton decay via the $p\to K^++\bar
u$ decay channel. The JUNO detector will provide a unique facility to address many outstanding crucial questions in particle and astrophysics. It holds the great potential for further advancing our quest to understanding the fundamental properties of neutrinos, one of the building blocks of our Universe.
21 Oct 2015-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: The Pierre Auger Observatory as mentioned in this paper, the world's largest cosmic ray observatory, has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km$^2$ sr yr.
Abstract: The Pierre Auger Observatory, located on a vast, high plain in western Argentina, is the world's largest cosmic ray observatory. The objectives of the Observatory are to probe the origin and characteristics of cosmic rays above $10^{17}$ eV and to study the interactions of these, the most energetic particles observed in nature. The Auger design features an array of 1660 water-Cherenkov particle detector stations spread over 3000 km$^2$ overlooked by 24 air fluorescence telescopes. In addition, three high elevation fluorescence telescopes overlook a 23.5 km$^2$, 61 detector infill array. The Observatory has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km$^2$ sr yr. This paper describes the design and performance of the detectors, related subsystems and infrastructure that make up the Auger Observatory.
Stanford University1, University of Turin2, Université libre de Bruxelles3, University of Cambridge4, Austrian Academy of Sciences5, Genentech6, Harvard University7, German Cancer Research Center8, Cornell University9, University of Texas MD Anderson Cancer Center10, Columbia University11, Memorial Sloan Kettering Cancer Center12, National Institutes of Health13, Research Institute of Molecular Pathology14, French Institute of Health and Medical Research15
TL;DR: A meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity and devised potential solutions are presented here.
Abstract: The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here.
TL;DR: In this paper, the authors present the first comprehensive study of r-process element nucleosynthesis in the ejecta of compact binary mergers (CBMs) and their relic black hole (BH)-torus systems.
Abstract: We present the first comprehensive study of r-process element nucleosynthesis in the ejecta of compact binary mergers (CBMs) and their relic black hole (BH)–torus systems. The evolution of the BH–accretion tori is simulated for seconds with a Newtonian hydrodynamics code including viscosity effects, pseudo-Newtonian gravity for rotating BHs, and an energy-dependent two-moment closure scheme for the transport of electron neutrinos and antineutrinos. The investigated cases are guided by relativistic double neutron star (NS–NS) and NS–BH merger models, producing ∼3–6 M_⊙ BHs with rotation parameters of A_BH ∼ 0.8 and tori of 0.03–0.3 M_⊙. Our nucleosynthesis analysis includes the dynamical (prompt) ejecta expelled during the CBM phase and the neutrino and viscously driven outflows of the relic BH–torus systems. While typically ∼20–25 per cent of the initial accretion-torus mass are lost by viscously driven outflows, neutrino-powered winds contribute at most another ∼1 per cent, but neutrino heating enhances the viscous ejecta significantly. Since BH–torus ejecta possess a wide distribution of electron fractions (0.1–0.6) and entropies, they produce heavy elements from A ∼ 80 up to the actinides, with relative contributions of A ≳ 130 nuclei being subdominant and sensitively dependent on BH and torus masses and the exact treatment of shear viscosity. The combined ejecta of CBM and BH–torus phases can reproduce the solar abundances amazingly well for A ≳ 90. Varying contributions of the torus ejecta might account for observed variations of lighter elements with 40 ≤ Z ≤ 56 relative to heavier ones, and a considerable reduction of the prompt ejecta compared to the torus ejecta, e.g. in highly asymmetric NS–BH mergers, might explain the composition of heavy-element deficient stars.
Innlandet Hospital Trust1, University of Giessen2, University of Zaragoza3, Hedmark University College4, Université libre de Bruxelles5, University of Copenhagen6, University of Szeged7, University of Padua8, Leiden University9, University of Oslo10, Stavanger University Hospital11, Wrocław Medical University12, Cardiff University13
TL;DR: The association with depression and anxiety was highest for patients with psoriasis, atopic dermatitis, hand eczema, and leg ulcers, and only patients with Psoriasis had significant association with suicidal ideation.
01 Jul 2015
TL;DR: The recent advances in modern BCG and SCG research are reviewed, including reduced measurement noise, clinically relevant feature extraction, and signal modeling.
Abstract: In the past decade, there has been a resurgence in the field of unobtrusive cardiomechanical assessment, through advancing methods for measuring and interpreting ballistocardiogram (BCG) and seismocardiogram (SCG) signals. Novel instrumentation solutions have enabled BCG and SCG measurement outside of clinical settings, in the home, in the field, and even in microgravity. Customized signal processing algorithms have led to reduced measurement noise, clinically relevant feature extraction, and signal modeling. Finally, human subjects physiology studies have been conducted using these novel instruments and signal processing tools with promising results. This paper reviews the recent advances in these areas of modern BCG and SCG research.
TL;DR: The first experimental realization of a dispersionless state is demonstrated, in a photonic Lieb lattice formed by an array of optical waveguides, which opens an exciting door towards quantum simulation of flat-band models in a highly controllable environment.
Abstract: We demonstrate the first experimental realization of a dispersionless state, in a photonic Lieb lattice formed by an array of optical waveguides. This engineered lattice supports three energy bands, including a perfectly flat middle band with an infinite effective mass. We analyze, both experimentally and theoretically, the evolution of well-prepared flat-band states, and show their remarkable robustness, even in the presence of disorder. The realization of flat-band states in photonic lattices opens an exciting door towards quantum simulation of flat-band models in a highly controllable environment.
TL;DR: It is demonstrated that SGLT2 is expressed in glucagon-secreting alpha cells of the pancreatic islets, and dapagliflozin treatment further promotes glucagon secretion and hepatic gluconeogenesis in healthy mice, thereby limiting the decrease of plasma glucose induced by fasting.
Abstract: Type 2 diabetes (T2D) is characterized by chronic hyperglycemia resulting from a deficiency in insulin signaling, because of insulin resistance and/or defects in insulin secretion; it is also associated with increases in glucagon and endogenous glucose production (EGP). Gliflozins, including dapagliflozin, are a new class of approved oral antidiabetic agents that specifically inhibit sodium-glucose co-transporter 2 (SGLT2) function in the kidney, thus preventing renal glucose reabsorption and increasing glycosuria in diabetic individuals while reducing hyperglycemia. However, gliflozin treatment in subjects with T2D increases both plasma glucagon and EGP by unknown mechanisms. In spite of the rise in EGP, T2D patients treated with gliflozin have lower blood glucose levels than those receiving placebo, possibly because of increased glycosuria; however, the resulting increase in plasma glucagon levels represents a possible concerning side effect, especially in a patient population already affected by hyperglucagonemia. Here we demonstrate that SGLT2 is expressed in glucagon-secreting alpha cells of the pancreatic islets. We further found that expression of SLC5A2 (which encodes SGLT2) was lower and glucagon (GCG) gene expression was higher in islets from T2D individuals and in normal islets exposed to chronic hyperglycemia than in islets from non-diabetics. Moreover, hepatocyte nuclear factor 4-α (HNF4A) is specifically expressed in human alpha cells, in which it controls SLC5A2 expression, and its expression is downregulated by hyperglycemia. In addition, inhibition of either SLC5A2 via siRNA-induced gene silencing or SGLT2 via dapagliflozin treatment in human islets triggered glucagon secretion through KATP channel activation. Finally, we found that dapagliflozin treatment further promotes glucagon secretion and hepatic gluconeogenesis in healthy mice, thereby limiting the decrease of plasma glucose induced by fasting. Collectively, these results identify a heretofore unknown role of SGLT2 and designate dapagliflozin an alpha cell secretagogue.
University of Helsinki1, University College London2, Finnish Institute of Occupational Health3, French Institute of Health and Medical Research4, Stockholm University5, RMIT University6, Karolinska Institutet7, Stockholm County Council8, Federal Institute for Occupational Safety and Health9, Université libre de Bruxelles10, Ghent University11, University of Düsseldorf12, University of Duisburg-Essen13, Mid Sweden University14, Umeå University15, University of Copenhagen16, University of Turku17, University of Skövde18, Turku University Hospital19, Uppsala University20, Queen's University Belfast21, University of Essex22, University of Edinburgh23, University of Bristol24
TL;DR: Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker; these findings suggest that more attention should be paid to the management of vascular risk factors in individuals whoWork long hours.
TL;DR: In this article, the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis are combined, and the combined event sample features high-statistics samples of shower-like and track-like events.
Abstract: Evidence for an extraterrestrial flux of high-energy neutrinos has now been found in multiple searches with the IceCube detector. The first solid evidence was provided by a search for neutrino events with deposited energies greater than or similar to 30 TeV and interaction vertices inside the instrumented volume. Recent analyses suggest that the extraterrestrial flux extends to lower energies and is also visible with throughgoing, nu(mu)-induced tracks from the Northern Hemisphere. Here, we combine the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis. The combined event sample features high-statistics samples of shower-like and track-like events. The data are fit in up to three observables: energy, zenith angle, and event topology. Assuming the astrophysical neutrino flux to be isotropic and to consist of equal flavors at Earth, the all-flavor spectrum with neutrino energies between 25 TeV and 2.8 PeV is well described by an unbroken power law with best-fit spectral index -2.50 +/- 0.09 and a flux at 100 TeV of (6.7(-1.2)(+1.1)) x 10(-18) GeV-1 s(-1) sr(-1) cm(-2). Under the same assumptions, an unbroken power law with index -2 is disfavored with a significance of 3.8 sigma (p = 0.0066%) with respect to the best fit. This significance is reduced to 2.1 sigma (p = 1.7%) if instead we compare the best fit to a spectrum with index -2 that has an exponential cut-off at high energies. Allowing the electron-neutrino flux to deviate from the other two flavors, we find a nu(e) fraction of 0.18 +/- 0.11 at Earth. The sole production of electron neutrinos, which would be characteristic of neutron-decay-dominated sources, is rejected with a significance of 3.6 sigma ( p = 0.014%).
TL;DR: The OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer, and updated results support the use of FOLFOX in Patients with stage III disease, including those with dMMR or BRAF mutation.
Abstract: Purpose The MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) study has demonstrated 3-year disease-free survival (DFS) and 6-year overall survival (OS) benefit of adjuvant oxaliplatin in stage II to III resected colon cancer. This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. Methods Survival actualization after 10-year follow-up was performed in 2,246 patients with resected stage II to III colon cancer. We assessed MMR status and BRAF mutation in 1,008 formalin-fixed paraffin-embedded specimens. Results After a median follow-up of 9.5 years, 10-year OS rates in the bolus/infusional fluorouracil plus leucovorin (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX4) arms were 67.1% versus 71.7% (hazard ratio [HR], 0.85; P = .043) in the whole population, 79.5% versus 78.4% for stage II (HR, 1.00; P = .980), and 59.0% versus 67.1% for stage III (HR, 0.80; P = .016) disease. Ninety-five patients (9...
TL;DR: Literacy acquisition provides a remarkable example of how the brain reorganizes to accommodate a novel cultural skill.
Abstract: The acquisition of literacy transforms the human brain. By reviewing studies of illiterate subjects, we propose specific hypotheses on how the functions of core brain systems are partially reoriented or 'recycled' when learning to read. Literacy acquisition improves early visual processing and reorganizes the ventral occipito-temporal pathway: responses to written characters are increased in the left occipito-temporal sulcus, whereas responses to faces shift towards the right hemisphere. Literacy also modifies phonological coding and strengthens the functional and anatomical link between phonemic and graphemic representations. Literacy acquisition therefore provides a remarkable example of how the brain reorganizes to accommodate a novel cultural skill.
Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam2 +2802 more•Institutions (215)
TL;DR: In this paper, the branching fractions of the B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) were observed.
Abstract: The standard model of particle physics describes the fundamental particles and their interactions via the strong, electromagnetic and weak forces. It provides precise predictions for measurable quantities that can be tested experimentally. The probabilities, or branching fractions, of the strange B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) are especially interesting because of their sensitivity to theories that extend the standard model. The standard model predicts that the B-s(0)->mu(+)mu(-) and B-0 ->mu(+)mu(-) decays are very rare, with about four of the former occurring for every billion B-s(0) mesons produced, and one of the latter occurring for every ten billion B-0 mesons(1). A difference in the observed branching fractions with respect to the predictions of the standard model would provide a direction in which the standard model should be extended. Before the Large Hadron Collider (LHC) at CERN2 started operating, no evidence for either decay mode had been found. Upper limits on the branching fractions were an order of magnitude above the standard model predictions. The CMS (Compact Muon Solenoid) and LHCb(Large Hadron Collider beauty) collaborations have performed a joint analysis of the data from proton-proton collisions that they collected in 2011 at a centre-of-mass energy of seven teraelectronvolts and in 2012 at eight teraelectronvolts. Here we report the first observation of the B-s(0)->mu(+)mu(-) decay, with a statistical significance exceeding six standard deviations, and the best measurement so far of its branching fraction. Furthermore, we obtained evidence for the B-0 ->mu(+)mu(-) decay with a statistical significance of three standard deviations. Both measurements are statistically compatible with standard model predictions and allow stringent constraints to be placed on theories beyond the standard model. The LHC experiments will resume taking data in 2015, recording proton-proton collisions at a centre-of-mass energy of 13 teraelectronvolts, which will approximately double the production rates of B-s(0) and B-0 mesons and lead to further improvements in the precision of these crucial tests of the standard model.
TL;DR: The presence of TILs at diagnosis is an independent, positive, prognostic marker in HER2-positive early breast cancer treated with neoadjuvant anti-HER2 agents and chemotherapy for both pCR and EFS end points.
Abstract: Importance The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved outcomes in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer treated with adjuvant trastuzumab and chemotherapy. The prognostic associations in the neoadjuvant setting of other anti-HER2 agents and combinations are unknown. Objective To determine associations between presence of TILs, pathological complete response (pCR), and event-free survival (EFS) end points in patients with early breast cancer treated with trastuzumab, lapatinib, or the combination. Design, Setting, and Participants The NeoALTTO trial (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization) randomly assigned 455 women with HER2-positive early-stage breast cancer between January 5, 2008, and May 27, 2010, to 1 of 3 neoadjuvant treatment arms: trastuzumab, lapatinib, or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. The primary end point used in this study was pCR in the breast and lymph nodes, with a secondary end point of EFS. We evaluated levels of percentage of TILs using hematoxylin-eosin–stained core biopsy sections taken at diagnosis (prior to treatment) in a prospectively defined retrospective analysis. Main Outcomes and Measures Levels of TILs were examined for their associations with efficacy end points adjusted for prognostic clinicopathological factors including PIK3CA genotype. Results Of the 455 patients, 387 (85.1%) tumor samples were used for the present analysis. The median (interquartile range [IQR]) level of TILs was 12.5% (5.0%-30.0%), with levels lower in hormone receptor–positive (10.0% [5.0%-22.5%]) vs hormone receptor–negative (12.5% [3.0%-35.0%]) samples ( P = .02). For the pCR end point, levels of TILs greater than 5% were associated with higher pCR rates independent of treatment group (adjusted odds ratio, 2.60 [95% CI, 1.26-5.39]; P = .01). With a median (IQR) follow-up time of 3.77 (3.50-4.22) years, every 1% increase in TILs was associated with a 3% decrease in the rate of an event (adjusted hazard ratio, 0.97 [95% CI, 0.95-0.99]; P = .002) across all treatment groups. Conclusions and Relevance The presence of TILs at diagnosis is an independent, positive, prognostic marker in HER2-positive early breast cancer treated with neoadjuvant anti-HER2 agents and chemotherapy for both pCR and EFS end points. Trial Registration clinicaltrials.gov Identifier: NCT00553358
University of Manchester1, George Washington University2, Bradford Royal Infirmary3, Université libre de Bruxelles4, Hospital Italiano de Buenos Aires5, Kaiser Permanente6, Technion – Israel Institute of Technology7, University of Barcelona8, University of Pavia9, Marshfield Clinic10, University of Toronto11, University of Paris12, University Hospitals Coventry and Warwickshire NHS Trust13, University of Angers14, University of Pisa15, University of Liverpool16, McGill University17, French Institute of Health and Medical Research18, University of Oxford19, University of Santiago de Compostela20, St Mary's Hospital21, University of Colorado Boulder22, NHS Ayrshire and Arran23, University of Udine24, University Hospitals of Leicester NHS Trust25, University of Sydney26, Katholieke Universiteit Leuven27, Istituto Giannina Gaslini28, Monash University29, University of Brescia30, Leeds General Infirmary31, Belfast Health and Social Care Trust32, University of Nantes33, Kocaeli University34, Temple University35, Boston Children's Hospital36, University of Paris-Sud37, University of Greifswald38, HealthPartners39, Guy's and St Thomas' NHS Foundation Trust40, University of Helsinki41, Royal Children's Hospital42, University of São Paulo43, Pierre-and-Marie-Curie University44, Princess Margaret Hospital for Children45, Amrita Vishwa Vidyapeetham46, Aarhus University47, University of British Columbia48, Rikshospitalet–Radiumhospitalet49, University of Milan50, University of Liège51, Mater Dei Hospital52, Karolinska Institutet53, Tel Aviv University54, University of Utah55, Nottingham University Hospitals NHS Trust56, University of Basel57, University of Melbourne58, University Hospital of Wales59, Christian Medical College & Hospital60, Casa Sollievo della Sofferenza61, Ghent University62, VU University Amsterdam63, Mount Sinai St. Luke's and Mount Sinai Roosevelt64, University of Nottingham65, McMaster University66, University of Glasgow67
TL;DR: A robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferOn‐stimulated gene transcripts in peripheral blood is observed.
Abstract: Aicardi-Goutieres syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutieres syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.