Showing papers by "Université libre de Bruxelles published in 2017"
TL;DR: The association of GRB 170817A, detected by Fermi-GBM 1.7 s after the coalescence, corroborates the hypothesis of a neutron star merger and provides the first direct evidence of a link between these mergers and short γ-ray bursts.
Abstract: On August 17, 2017 at 12∶41:04 UTC the Advanced LIGO and Advanced Virgo gravitational-wave detectors made their first observation of a binary neutron star inspiral. The signal, GW170817, was detected with a combined signal-to-noise ratio of 32.4 and a false-alarm-rate estimate of less than one per 8.0×10^{4} years. We infer the component masses of the binary to be between 0.86 and 2.26 M_{⊙}, in agreement with masses of known neutron stars. Restricting the component spins to the range inferred in binary neutron stars, we find the component masses to be in the range 1.17-1.60 M_{⊙}, with the total mass of the system 2.74_{-0.01}^{+0.04}M_{⊙}. The source was localized within a sky region of 28 deg^{2} (90% probability) and had a luminosity distance of 40_{-14}^{+8} Mpc, the closest and most precisely localized gravitational-wave signal yet. The association with the γ-ray burst GRB 170817A, detected by Fermi-GBM 1.7 s after the coalescence, corroborates the hypothesis of a neutron star merger and provides the first direct evidence of a link between these mergers and short γ-ray bursts. Subsequent identification of transient counterparts across the electromagnetic spectrum in the same location further supports the interpretation of this event as a neutron star merger. This unprecedented joint gravitational and electromagnetic observation provides insight into astrophysics, dense matter, gravitation, and cosmology.
7,327 citations
TL;DR: In this paper, the authors used the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to constrain the difference between the speed of gravity and speed of light to be between $-3
Abstract: On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is $5.0\times {10}^{-8}$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $-3\times {10}^{-15}$ and $+7\times {10}^{-16}$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1–1.4 per year during the 2018–2019 observing run and 0.3–1.7 per year at design sensitivity.
2,633 citations
TL;DR: The magnitude of modifications to the gravitational-wave dispersion relation is constrain, the graviton mass is bound to m_{g}≤7.7×10^{-23} eV/c^{2} and null tests of general relativity are performed, finding that GW170104 is consistent with general relativity.
Abstract: We describe the observation of GW170104, a gravitational-wave signal produced by the coalescence of a pair of stellar-mass black holes. The signal was measured on January 4, 2017 at 10∶11:58.6 UTC by the twin advanced detectors of the Laser Interferometer Gravitational-Wave Observatory during their second observing run, with a network signal-to-noise ratio of 13 and a false alarm rate less than 1 in 70 000 years. The inferred component black hole masses are 31.2^(8.4) _(−6.0)M_⊙ and 19.4^(5.3)_( −5.9)M_⊙ (at the 90% credible level). The black hole spins are best constrained through measurement of the effective inspiral spin parameter, a mass-weighted combination of the spin components perpendicular to the orbital plane, χ_(eff) = −0.12^(0.21)_( −0.30). This result implies that spin configurations with both component spins positively aligned with the orbital angular momentum are disfavored. The source luminosity distance is 880^(450)_(−390) Mpc corresponding to a redshift of z = 0.18^(0.08)_( −0.07) . We constrain the magnitude of modifications to the gravitational-wave dispersion relation and perform null tests of general relativity. Assuming that gravitons are dispersed in vacuum like massive particles, we bound the graviton mass to m_g ≤ 7.7 × 10^(−23) eV/c^2. In all cases, we find that GW170104 is consistent with general relativity.
2,569 citations
St George’s University Hospitals NHS Foundation Trust1, New York University2, McMaster University3, Brown University4, Catholic University of the Sacred Heart5, Autonomous University of Barcelona6, University of Manitoba7, Emory University8, Hebrew University of Jerusalem9, University of Toronto10, University of Pittsburgh11, St Thomas' Hospital12, University College London13, Vanderbilt University14, Keio University15, Memorial Hospital of South Bend16, Rowan University17, University of Mississippi18, Rush University Medical Center19, University of Ulsan20, Universidade Federal do Rio Grande do Sul21, Federal University of São Paulo22, Regions Hospital23, Washington University in St. Louis24, University of Ottawa25, University of Sydney26, University of New South Wales27, Fujita Health University28, University of Copenhagen29, Sapienza University of Rome30, Christiana Care Health System31, Stanford University32, King Abdullah University of Science and Technology33, University of Kansas34, Harvard University35, California Pacific Medical Center36, University of Amsterdam37, Université libre de Bruxelles38, Houston Methodist Hospital39
TL;DR: A consensus committee of 55 international experts representing 25 international organizations was assembled at key international meetings (forSurviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012 as discussed by the authors ).
Abstract: Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for
2,414 citations
TL;DR: For the first time, the nature of gravitational-wave polarizations from the antenna response of the LIGO-Virgo network is tested, thus enabling a new class of phenomenological tests of gravity.
Abstract: On August 14, 2017 at 10∶30:43 UTC, the Advanced Virgo detector and the two Advanced LIGO detectors coherently observed a transient gravitational-wave signal produced by the coalescence of two stellar mass black holes, with a false-alarm rate of ≲1 in 27 000 years. The signal was observed with a three-detector network matched-filter signal-to-noise ratio of 18. The inferred masses of the initial black holes are 30.5-3.0+5.7M⊙ and 25.3-4.2+2.8M⊙ (at the 90% credible level). The luminosity distance of the source is 540-210+130 Mpc, corresponding to a redshift of z=0.11-0.04+0.03. A network of three detectors improves the sky localization of the source, reducing the area of the 90% credible region from 1160 deg2 using only the two LIGO detectors to 60 deg2 using all three detectors. For the first time, we can test the nature of gravitational-wave polarizations from the antenna response of the LIGO-Virgo network, thus enabling a new class of phenomenological tests of gravity.
1,979 citations
University of Freiburg1, University of Alberta2, University of Milan3, Western General Hospital4, Medical University of Vienna5, Bond University6, Norwegian University of Science and Technology7, Beatson West of Scotland Cancer Centre8, Karlstad University9, Sapienza University of Rome10, University of Basel11, University of Lisbon12, University of St. Gallen13, HAN University of Applied Sciences14, Université libre de Bruxelles15
TL;DR: These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients.
1,740 citations
Gdańsk Medical University1, Institut Gustave Roussy2, Pontifícia Universidade Católica do Rio Grande do Sul3, Karolinska University Hospital4, Fortis Healthcare5, European Institute of Oncology6, Curie Institute7, American University of Beirut8, Brighton and Sussex Medical School9, Peter MacCallum Cancer Centre10, BC Cancer Agency11, Ludwig Maximilian University of Munich12, Memorial Sloan Kettering Cancer Center13, Sheba Medical Center14, Harvard University15, Université libre de Bruxelles16, Paris Descartes University17, University of California, San Francisco18, Johns Hopkins University19, Indiana University20, University of Washington21, Martin Luther University of Halle-Wittenberg22, King's College London23, Peking Union Medical College24
TL;DR: This ESO-ESMO ABC 5 Clinical Practice Guideline provides key recommendations for managing advanced breast cancer patients, and provides updates on managing patients with all breast cancer subtypes, LABC, follow-up, palliative and supportive care.
1,514 citations
TL;DR: The InTBIR Participants and Investigators have provided informed consent for the study to take place in Poland.
Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators
1,354 citations
University of Cambridge1, University of Exeter2, The Chinese University of Hong Kong3, Middlesex University4, Southend University Hospital NHS Foundation Trust5, University of Milan6, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico7, Université libre de Bruxelles8, National and Kapodistrian University of Athens9, Rabin Medical Center10, University of Iceland11, University College London12
TL;DR: Treatment with low‐dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo, and there were no significant between‐group differences in the incidence of neonatal adverse outcomes or other adverse events.
Abstract: BackgroundPreterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. MethodsIn this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. ResultsA total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidenc...
1,299 citations
Uppsala University1, University of Trieste2, University Hospital Southampton NHS Foundation Trust3, University of Oxford4, Winterthur Museum, Garden and Library5, University of Hohenheim6, University of Pennsylvania7, Universidade Federal de Minas Gerais8, Fujita Health University9, Aalborg University10, University of Vermont11, Mount Carmel Health12, Sapienza University of Rome13, Kristianstad University College14, Medical University of Vienna15, University of Nice Sophia Antipolis16, HAN University of Applied Sciences17, VU University Medical Center18, University of Erlangen-Nuremberg19, Peking Union Medical College20, Université libre de Bruxelles21, Rabin Medical Center22
TL;DR: An agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established and may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease.
1,294 citations
TL;DR: In this article, a GW signal from the merger of two stellar-mass black holes was observed by the two Advanced Laser Interferometer Gravitational-Wave Observatory detectors with a network signal-to-noise ratio of 13.5%.
Abstract: On 2017 June 8 at 02:01:16.49 UTC, a gravitational-wave (GW) signal from the merger of two stellar-mass black holes was observed by the two Advanced Laser Interferometer Gravitational-Wave Observatory detectors with a network signal-to-noise ratio of 13. This system is the lightest black hole binary so far observed, with component masses of ${12}_{-2}^{+7}\,{M}_{\odot }$ and ${7}_{-2}^{+2}\,{M}_{\odot }$ (90% credible intervals). These lie in the range of measured black hole masses in low-mass X-ray binaries, thus allowing us to compare black holes detected through GWs with electromagnetic observations. The source's luminosity distance is ${340}_{-140}^{+140}\,\mathrm{Mpc}$, corresponding to redshift ${0.07}_{-0.03}^{+0.03}$. We verify that the signal waveform is consistent with the predictions of general relativity.
TL;DR: Pertuzumab significantly improved the rates of invasive‐disease–free survival among patients with HER2‐positive, operable breast cancer when it was added to adjuvant chemotherapy and chemotherapy.
Abstract: BackgroundPertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. MethodsWe randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease–free survival rate of 91.8% with pertuzumab and 89.2% with placebo. ResultsIn the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% ha...
TL;DR: A fully-fledged particle-flow reconstruction algorithm tuned to the CMS detector was developed and has been consistently used in physics analyses for the first time at a hadron collider as mentioned in this paper.
Abstract: The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer. A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider. For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMS performance for jet and hadronic τ decay reconstruction, missing transverse momentum determination, and electron and muon identification. This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods. The data collected by CMS at a centre-of-mass energy of 8\TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.
Medical University of Vienna1, University of Melbourne2, Queen Alexandra Hospital3, Medical University of Graz4, University of Amsterdam5, Technion – Israel Institute of Technology6, Utrecht University7, Université libre de Bruxelles8, Humanitas University9, Durham University10, University of Sydney11, Westmead Hospital12
TL;DR: ESGE recommends that the goals of endoscopic mucosal resection (EMR) are to achieve a completely snare-resected lesion in the safest minimum number of pieces, with adequate margins and without need for adjunctive ablative techniques.
Abstract: 1 ESGE recommends cold snare polypectomy (CSP) as the preferred technique for removal of diminutive polyps (size ≤ 5 mm). This technique has high rates of complete resection, adequate tissue sampling for histology, and low complication rates. (High quality evidence, strong recommendation.) 2 ESGE suggests CSP for sessile polyps 6 – 9 mm in size because of its superior safety profile, although evidence comparing efficacy with hot snare polypectomy (HSP) is lacking. (Moderate quality evidence, weak recommendation.) 3 ESGE suggests HSP (with or without submucosal injection) for removal of sessile polyps 10 – 19 mm in size. In most cases deep thermal injury is a potential risk and thus submucosal injection prior to HSP should be considered. (Low quality evidence, strong recommendation.) 4 ESGE recommends HSP for pedunculated polyps. To prevent bleeding in pedunculated colorectal polyps with head ≥ 20 mm or a stalk ≥ 10 mm in diameter, ESGE recommends pretreatment of the stalk with injection of dilute adrenaline and/or mechanical hemostasis. (Moderate quality evidence, strong recommendation.) 5 ESGE recommends that the goals of endoscopic mucosal resection (EMR) are to achieve a completely snare-resected lesion in the safest minimum number of pieces, with adequate margins and without need for adjunctive ablative techniques. (Low quality evidence; strong recommendation.) 6 ESGE recommends careful lesion assessment prior to EMR to identify features suggestive of poor outcome. Features associated with incomplete resection or recurrence include lesion size > 40 mm, ileocecal valve location, prior failed attempts at resection, and size, morphology, site, and access (SMSA) level 4. (Moderate quality evidence; strong recommendation.) 7 For intraprocedural bleeding, ESGE recommends endoscopic coagulation (snare-tip soft coagulation or coagulating forceps) or mechanical therapy, with or without the combined use of dilute adrenaline injection. (Low quality evidence, strong recommendation.) An algorithm of polypectomy recommendations according to shape and size of polyps is given ( Fig. 1 ).
Wellcome Trust Sanger Institute1, Guy's and St Thomas' NHS Foundation Trust2, Lund University3, AstraZeneca4, Erasmus University Medical Center5, University of Queensland6, Memorial Sloan Kettering Cancer Center7, University of Iceland8, Hanyang University9, Wellcome Trust10, Radboud University Nijmegen11, University of Amsterdam12, University of Oslo13, Royal Brisbane and Women's Hospital14, Curie Institute15, Université libre de Bruxelles16, King's College London17, University of Antwerp18, Harvard University19, Cambridge University Hospitals NHS Foundation Trust20
TL;DR: In this article, a weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples with 98.7% sensitivity (area under the curve (AUC) = 0.98).
Abstract: Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.
TL;DR: 1 year of adjuvant trastuzumab after chemotherapy for patients with HER2-positive early breast cancer significantly improves long-term disease-free survival, compared with observation.
University of Tehran1, Université de Montréal2, New Mexico State University3, Royal Botanic Gardens4, State University of Feira de Santana5, State University of Campinas6, University of the Western Cape7, Federal University of São Carlos8, University of Melbourne9, Federal University of Bahia10, National Taiwan University11, Australian National University12, Complutense University of Madrid13, National Autonomous University of Mexico14, Cornell University15, Université libre de Bruxelles16, National Museum of Natural History17, University of Oxford18, Sao Paulo State University19, Universidad de Morón20, Federal University of Western Bahia21, Royal Botanic Garden Edinburgh22, University of Reading23, University of Zurich24, Universidade Federal do Rio Grande do Sul25, Kyushu University26, University of South Africa27, Tarbiat Modares University28, Montana State University29, University of Johannesburg30, Pontifical Catholic University of Rio de Janeiro31, University of Angers32, National Science Foundation33, Missouri Botanical Garden34, National University of Rosario35, University of Arizona36, Federal University of Rio Grande do Norte37, Universidade Federal de Goiás38, Empresa Brasileira de Pesquisa Agropecuária39, University of Dundee40, Arizona State University at the Polytechnic campus41, Arizona State University42, University of Cape Town43, New York Botanical Garden44, Naturalis45, Heidelberg University46, Chinese Academy of Sciences47
TL;DR: The classification of the legume family proposed here addresses the long-known non-monophyly of the traditionally recognised subfamily Caesalpinioideae, by recognising six robustly supported monophyletic subfamilies and reflects the phylogenetic structure that is consistently resolved.
Abstract: The classification of the legume family proposed here addresses the long-known non-monophyly of the traditionally recognised subfamily Caesalpinioideae, by recognising six robustly supported monophyletic subfamilies. This new classification uses as its framework the most comprehensive phylogenetic analyses of legumes to date, based on plastid matK gene sequences, and including near-complete sampling of genera (698 of the currently recognised 765 genera) and ca. 20% (3696) of known species. The matK gene region has been the most widely sequenced across the legumes, and in most legume lineages, this gene region is sufficiently variable to yield well-supported clades. This analysis resolves the same major clades as in other phylogenies of whole plastid and nuclear gene sets (with much sparser taxon sampling). Our analysis improves upon previous studies that have used large phylogenies of the Leguminosae for addressing evolutionary questions, because it maximises generic sampling and provides a phylogenetic tree that is based on a fully curated set of sequences that are vouchered and taxonomically validated. The phylogenetic trees obtained and the underlying data are available to browse and download, facilitating subsequent analyses that require evolutionary trees. Here we propose a new community-endorsed classification of the family that reflects the phylogenetic structure that is consistently resolved and recognises six subfamilies in Leguminosae: a recircumscribed Caesalpinioideae DC., Cercidoideae Legume Phylogeny Working Group (stat. nov.), Detarioideae Burmeist., Dialioideae Legume Phylogeny Working Group (stat. nov.), Duparquetioideae Legume Phylogeny Working Group (stat. nov.), and Papilionoideae DC. The traditionally recognised subfamily Mimosoideae is a distinct clade nested within the recircumscribed Caesalpinioideae and is referred to informally as the mimosoid clade pending a forthcoming formal tribal and/or cladebased classification of the new Caesalpinioideae. We provide a key for subfamily identification, descriptions with diagnostic charactertistics for the subfamilies, figures illustrating their floral and fruit diversity, and lists of genera by subfamily. This new classification of Leguminosae represents a consensus view of the international legume systematics community; it invokes both compromise and practicality of use.
U. Bhawandeep1, Vardan Khachatryan, Albert M. Sirunyan, Armen Tumasyan +2289 more•Institutions (147)
TL;DR: In this paper, the trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions.
Abstract: This paper describes the CMS trigger system and its performance during Run 1 of the LHC. The trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions. The first level of the trigger is implemented in hardware, and selects events containing detector signals consistent with an electron, photon, muon, tau lepton, jet, or missing transverse energy. A programmable menu of up to 128 object-based algorithms is used to select events for subsequent processing. The trigger thresholds are adjusted to the LHC instantaneous luminosity during data taking in order to restrict the output rate to 100 kHz, the upper limit imposed by the CMS readout electronics. The second level, implemented in software, further refines the purity of the output stream, selecting an average rate of 400 Hz for offline event storage. The objectives, strategy and performance of the trigger system during the LHC Run 1 are described.
TL;DR: In this paper, an improved jet energy scale corrections, based on a data sample corresponding to an integrated luminosity of 19.7 fb^(-1) collected by the CMS experiment in proton-proton collisions at a center-of-mass energy of 8 TeV, are presented.
Abstract: Improved jet energy scale corrections, based on a data sample corresponding to an integrated luminosity of 19.7 fb^(-1) collected by the CMS experiment in proton-proton collisions at a center-of-mass energy of 8 TeV, are presented. The corrections as a function of pseudorapidity η and transverse momentum p_T are extracted from data and simulated events combining several channels and methods. They account successively for the effects of pileup, uniformity of the detector response, and residual data-simulation jet energy scale differences. Further corrections, depending on the jet flavor and distance parameter (jet size) R, are also presented. The jet energy resolution is measured in data and simulated events and is studied as a function of pileup, jet size, and jet flavor. Typical jet energy resolutions at the central rapidities are 15–20% at 30 GeV, about 10% at 100 GeV, and 5% at 1 TeV. The studies exploit events with dijet topology, as well as photon+jet, Z+jet and multijet events. Several new techniques are used to account for the various sources of jet energy scale corrections, and a full set of uncertainties, and their correlations, are provided. The final uncertainties on the jet energy scale are below 3% across the phase space considered by most analyses (p_T > 30 GeV and 0|η| 30 GeV is reached, when excluding the jet flavor uncertainties, which are provided separately for different jet flavors. A new benchmark for jet energy scale determination at hadron colliders is achieved with 0.32% uncertainty for jets with p_T of the order of 165–330 GeV, and |η| < 0.8.
University of Tartu1, Tartu University Hospital2, McMaster University3, University of Lausanne4, Université catholique de Louvain5, University of Adelaide6, Medical University of Graz7, University of Vienna8, University of Nice Sophia Antipolis9, University of Bern10, Maastricht University11, Université libre de Bruxelles12, Tel Aviv University13, Rabin Medical Center14, Ghent University Hospital15, King's College London16, Karolinska University Hospital17, Queen Elizabeth Hospital Birmingham18, Katholieke Universiteit Leuven19, VU University Medical Center20
TL;DR: EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery, and did not detect any evidence of superiority for early PN or delayed EN over EEN.
Abstract: Purpose
To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.
Wellcome Trust Sanger Institute1, Haukeland University Hospital2, University of Bergen3, University of Oxford4, University of Cambridge5, European Bioinformatics Institute6, Los Alamos National Laboratory7, University of New Mexico8, Francis Crick Institute9, Katholieke Universiteit Leuven10, Memorial Sloan Kettering Cancer Center11, King's College London12, Université libre de Bruxelles13, Erasmus University Medical Center14, Brigham and Women's Hospital15, Harvard University16, Institute of Cancer Research17
TL;DR: Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor.
University of Melbourne1, Université libre de Bruxelles2, Katholieke Universiteit Leuven3, University of Victoria4, St. Vincent's Health System5, La Trobe University6, Royal Melbourne Hospital7, Netherlands Cancer Institute8, University of California, San Diego9, Vanderbilt University10, Peter MacCallum Cancer Centre11, University of Antwerp12, University of Paris13, French Institute of Health and Medical Research14, Medical University of Vienna15, Cornell University16, University of Texas MD Anderson Cancer Center17, Mayo Clinic18, University of Queensland19, Royal Brisbane and Women's Hospital20, Harvard University21, Novartis22, Indiana University – Purdue University Indianapolis23, Fred Hutchinson Cancer Research Center24, University of Milan25, University of Auvergne26, Kansai Medical University27, Yeshiva University28, Yonsei University29, Brown University30, Rhode Island Hospital31, Curie Institute32, Charité33, Yale University34, University of British Columbia35, Garvan Institute of Medical Research36, Université Paris-Saclay37, Autonomous University of Madrid38, University of Ottawa39, National Institutes of Health40, New York University41, University of Adelaide42, Stanford University43, Anschutz Medical Campus44, University of Padua45, European Organisation for Research and Treatment of Cancer46, Medical University of Graz47, Hoffmann-La Roche48, Genentech49, MedImmune50, Merck & Co.51, Memorial Sloan Kettering Cancer Center52
TL;DR: Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
Abstract: Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
TL;DR: The design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and the methodology for drilling and deployment are described, including the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis.
Abstract: The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
TL;DR: Changes in the rRNA modification pattern have been observed in response to environmental changes, during development, and in disease, which suggests that rRNA modifications may contribute to the translational control of gene expression.
Abstract: rRNAs are extensively modified during their transcription and subsequent maturation in the nucleolus, nucleus and cytoplasm. RNA modifications, which are installed either by snoRNA-guided or by stand-alone enzymes, generally stabilize the structure of the ribosome. However, they also cluster at functionally important sites of the ribosome, such as the peptidyltransferase center and the decoding site, where they facilitate efficient and accurate protein synthesis. The recent identification of sites of substoichiometric 2'-O-methylation and pseudouridylation has overturned the notion that all rRNA modifications are constitutively present on ribosomes, highlighting nucleotide modifications as an important source of ribosomal heterogeneity. While the mechanisms regulating partial modification and the functions of specialized ribosomes are largely unknown, changes in the rRNA modification pattern have been observed in response to environmental changes, during development, and in disease. This suggests that rRNA modifications may contribute to the translational control of gene expression.
05 Apr 2017
TL;DR: The authors argue that the assumption of equal variances will seldom hold in psychological research, and choosing between Student's t-test and Welch's T-test based on the outcomes of a test of the equality of variances often fails to provide an appropriate answer.
Abstract: When comparing two independent groups, psychology researchers commonly use Student’s t-tests. Assumptions of normality and homogeneity of variance underlie this test. More often than not, when these conditions are not met, Student’s t-test can be severely biased and lead to invalid statistical inferences. Moreover, we argue that the assumption of equal variances will seldom hold in psychological research, and choosing between Student’s t-test and Welch’s t-test based on the outcomes of a test of the equality of variances often fails to provide an appropriate answer. We show that the Welch’s t-test provides a better control of Type 1 error rates when the assumption of homogeneity of variance is not met, and it loses little robustness compared to Student’s t-test when the assumptions are met. We argue that Welch’s t-test should be used as a default strategy.
University of Melbourne1, Université libre de Bruxelles2, Katholieke Universiteit Leuven3, St. Vincent's Health System4, La Trobe University5, Royal Melbourne Hospital6, Netherlands Cancer Institute7, University of California, San Diego8, Vanderbilt University9, Peter MacCallum Cancer Centre10, French Institute of Health and Medical Research11, University of Paris12, Medical University of Vienna13, Cornell University14, University of Texas MD Anderson Cancer Center15, Mayo Clinic16, University of Queensland17, Royal Brisbane and Women's Hospital18, Harvard University19, Novartis20, Indiana University – Purdue University Indianapolis21, Fred Hutchinson Cancer Research Center22, University of Milan23, University of Auvergne24, Kansai Medical University25, Yeshiva University26, Yonsei University27, Brown University28, Rhode Island Hospital29, Curie Institute30, Charité31, Yale University32, University of British Columbia33, University of Victoria34, Garvan Institute of Medical Research35, Université Paris-Saclay36, Autonomous University of Madrid37, University of Ottawa38, National Institutes of Health39, New York University40, University of Adelaide41, Stanford University42, Anschutz Medical Campus43, University of Padua44, European Organisation for Research and Treatment of Cancer45, Medical University of Graz46, Hoffmann-La Roche47, Genentech48, MedImmune49, Merck & Co.50, Memorial Sloan Kettering Cancer Center51
TL;DR: In this paper, a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, was proposed.
Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.
TL;DR: In this paper, the authors predict the cost of a battery pack in 2030 when considering two aspects: firstly a decade of research will ensure an improvement in material sciences altering a battery's chemical composition.
Abstract: The negative impact of the automotive industry on climate change can be tackled by changing from fossil driven vehicles towards battery electric vehicles with no tailpipe emissions. However their adoption mainly depends on the willingness to pay for the extra cost of the traction battery. The goal of this paper is to predict the cost of a battery pack in 2030 when considering two aspects: firstly a decade of research will ensure an improvement in material sciences altering a battery’s chemical composition. Secondly by considering the price erosion due to the production cost optimization, by maturing of the market and by evolving towards to a mass-manufacturing situation. The cost of a lithium Nickel Manganese Cobalt Oxide (NMC) battery (Cathode: NMC 6:2:2 ; Anode: graphite) as well as silicon based lithium-ion battery (Cathode: NMC 6:2:2 ; Anode: silicon alloy), expected to be on the market in 10 years, will be predicted to tackle the first aspect. The second aspect will be considered by combining process-based cost calculations with learning curves, which takes the increasing battery market into account. The 100 dollar/kWh sales barrier will be reached respectively between 2020-2025 for silicon based lithium-ion batteries and 2025–2030 for NMC batteries, which will give a boost to global electric vehicle adoption.
Memorial Sloan Kettering Cancer Center1, Seoul National University Hospital2, Vanderbilt University3, Ottawa Hospital Research Institute4, Japanese Foundation for Cancer Research5, Université libre de Bruxelles6, BC Cancer Agency7, Taipei Veterans General Hospital8, University of California, Los Angeles9, Université catholique de Louvain10, Novartis11
TL;DR: This phase 3 study assessed the efficacy of the pan-PI3K inhibitor buparlisib plus fulvestrant in patients with advanced breast cancer, including an evaluation of the PI3K pathway activation status as a biomarker for clinical benefit.
Abstract: Summary Background Phosphatidylinositol 3-kinase (PI3K) pathway activation is a hallmark of endocrine therapy-resistant, hormone receptor-positive breast cancer This phase 3 study assessed the efficacy of the pan-PI3K inhibitor buparlisib plus fulvestrant in patients with advanced breast cancer, including an evaluation of the PI3K pathway activation status as a biomarker for clinical benefit Methods The BELLE-2 trial was a randomised, double-blind, placebo-controlled, multicentre study Postmenopausal women aged 18 years or older with histologically confirmed, hormone receptor-positive and human epidermal growth factor (HER2)-negative inoperable locally advanced or metastatic breast cancer whose disease had progressed on or after aromatase inhibitor treatment and had received up to one previous line of chemotherapy for advanced disease were included Eligible patients were randomly assigned (1:1) using interactive voice response technology (block size of 6) on day 15 of cycle 1 to receive oral buparlisib (100 mg/day) or matching placebo, starting on day 15 of cycle 1, plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1, and on day 1 of subsequent 28-day cycles Patients were assigned randomisation numbers with a validated interactive response technology; these numbers were linked to different treatment groups which in turn were linked to treatment numbers PI3K status in tumour tissue was determined via central laboratory during a 14-day run-in phase Randomisation was stratified by PI3K pathway activation status (activated vs non-activated vs and unknown) and visceral disease status (present vs absent) Patients, investigators, local radiologists, study team, and anyone involved in the study were masked to the identity of the treatment until unblinding The primary endpoints were progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 11) in the total population, in patients with known (activated or non-activated) PI3K pathway status, and in PI3K pathway-activated patients Efficacy analyses were done in the intention-to-treat population Safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received This trial is registered with ClinicalTrialsgov, number NCT01610284, and is currently ongoing but not recruiting participants Findings Between Sept 7, 2012, and Sept 10, 2014, 1147 patients from 267 centres in 29 countries were randomly assigned to receive buparlisib (n=576) or placebo plus fulvestrant (n=571) In the total patient population (n=1147), median progression-free survival was 6·9 months (95% CI 6·8–7·8) in the buparlisib group versus 5·0 months (4·0–5·2) in the placebo group (hazard ratio [HR] 0·78 [95% CI 0·67–0·89]; one-sided p=0·00021) In patients with known PI3K status (n=851), median progression-free survival was 6·8 months (95% CI 5·0–7·0) in the buparlisib group vs 4·5 months (3·3–5·0) in the placebo group (HR 0·80 [95% CI 0·68–0·94]; one-sided p=0·0033) In PI3K pathway-activated patients (n=372), median progression-free survival was 6·8 months (95% CI 4·9–7·1) in the buparlisib group versus 4·0 months (3·1–5·2) in the placebo group (HR 0·76 [0·60–0·97], one-sided p=0·014) The most common grade 3–4 adverse events in the buparlisib group versus the placebo group were increased alanine aminotransferase (146 [25%] of 573 patients vs six [1%] of 570), increased aspartate aminotransferase (103 [18%] vs 16 [3%]), hyperglycaemia (88 [15%] vs one [ vs none) Serious adverse events were reported in 134 (23%) of 573 patients in the buparlisib group compared with 90 [16%] of 570 patients in the placebo group; the most common serious adverse events (affecting ≥2% of patients) were increased alanine aminotransferase (17 [3%] of 573 vs one [ vs one [ Interpretation The results from this study show that PI3K inhibition combined with endocrine therapy is effective in postmenopausal women with endocrine-resistant, hormone receptor-positive and HER2-negative advanced breast cancer Use of more selective PI3K inhibitors, such as α-specific PI3K inhibitor, is warranted to further improve safety and benefit in this setting No further studies are being pursued because of the toxicity associated with this combination Funding Novartis Pharmaceuticals Corporation
TL;DR: The ESMO Magnitude of Clinical Benefit Scale version 1.1 incorporates 10 revisions and will allow for scoring of single-arm studies and remains very stable; revisions in v1.1 alter the scores of only 12 out of 118 comparative studies and facilitate scoring for single- arm studies.
Jamia Millia Islamia1, Hanoi University of Science2, Vietnam Academy of Science and Technology3, Saitama University4, Aarhus University5, University of California, Santa Barbara6, Commissariat à l'énergie atomique et aux énergies alternatives7, University of Münster8, University of Connecticut9, University of Manchester10, Indian Institute of Technology Guwahati11, Leiden University12, Northwestern University13, Federal University of Paraíba14, Centre national de la recherche scientifique15, Universidade Federal do ABC16, University of Southampton17, Argonne National Laboratory18, Karlsruhe Institute of Technology19, University of Mainz20, Technische Universität München21, Max Planck Society22, Heidelberg University23, University of Tübingen24, Massachusetts Institute of Technology25, Durham University26, University of California, San Diego27, C. N. Yang Institute for Theoretical Physics28, Moscow Institute of Physics and Technology29, Russian Academy of Sciences30, University of Sydney31, University of Copenhagen32, Université libre de Bruxelles33, Paris Diderot University34, Niels Bohr Institute35, Estácio S.A.36, CERN37, University of California, Santa Cruz38, Institute on Taxation and Economic Policy39, University of Bern40, Institute for Advanced Study41, RWTH Aachen University42, Chinese Academy of Sciences43, East China University of Science and Technology44, University of Chicago45, Autonomous University of Madrid46, King's College London47, INAF48, Lawrence Berkeley National Laboratory49, University of Bari50, Istituto Nazionale di Fisica Nucleare51, University of Geneva52, Petersburg Nuclear Physics Institute53, University of Genoa54, Kapteyn Astronomical Institute55, Fermilab56, Spanish National Research Council57, Oak Ridge National Laboratory58, University of California, Berkeley59, École Polytechnique Fédérale de Lausanne60, University of Paris61, University of Zurich62, Mitchell Institute63, Tohoku University64, Princeton University65, Shimane University66, University of Maryland, College Park67, Dresden University of Technology68
TL;DR: A comprehensive review of keV-scale neutrino Dark Matter can be found in this paper, where the role of active neutrinos in particle physics, astrophysics, and cosmology is reviewed.
Abstract: We present a comprehensive review of keV-scale sterile neutrino Dark Matter, collecting views and insights from all disciplines involved—cosmology, astrophysics, nuclear, and particle physics—in each case viewed from both theoretical and experimental/observational perspectives. After reviewing the role of active neutrinos in particle physics, astrophysics, and cosmology, we focus on sterile neutrinos in the context of the Dark Matter puzzle. Here, we first review the physics motivation for sterile neutrino Dark Matter, based on challenges and tensions in purely cold Dark Matter scenarios. We then round out the discussion by critically summarizing all known constraints on sterile neutrino Dark Matter arising from astrophysical observations, laboratory experiments, and theoretical considerations. In this context, we provide a balanced discourse on the possibly positive signal from X-ray observations. Another focus of the paper concerns the construction of particle physics models, aiming to explain how sterile neutrinos of keV-scale masses could arise in concrete settings beyond the Standard Model of elementary particle physics. The paper ends with an extensive review of current and future astrophysical and laboratory searches, highlighting new ideas and their experimental challenges, as well as future perspectives for the discovery of sterile neutrinos.