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Showing papers by "Université libre de Bruxelles published in 2018"


Journal ArticleDOI
17 Apr 2018-Immunity
TL;DR: An extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA identifies six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis.

3,246 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1235 moreInstitutions (132)
TL;DR: This analysis expands upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation of state and have spins within the range observed in Galactic binary neutron stars.
Abstract: On 17 August 2017, the LIGO and Virgo observatories made the first direct detection of gravitational waves from the coalescence of a neutron star binary system. The detection of this gravitational-wave signal, GW170817, offers a novel opportunity to directly probe the properties of matter at the extreme conditions found in the interior of these stars. The initial, minimal-assumption analysis of the LIGO and Virgo data placed constraints on the tidal effects of the coalescing bodies, which were then translated to constraints on neutron star radii. Here, we expand upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation of state and have spins within the range observed in Galactic binary neutron stars. Our analysis employs two methods: the use of equation-of-state-insensitive relations between various macroscopic properties of the neutron stars and the use of an efficient parametrization of the defining function pðρÞ of the equation of state itself. From the LIGO and Virgo data alone and the first method, we measure the two neutron star radii as R1 ¼ 10.8 þ2.0 −1.7 km for the heavier star and R2 ¼ 10.7 þ2.1 −1.5 km for the lighter star at the 90% credible level. If we additionally require that the equation of state supports neutron stars with masses larger than 1.97 M⊙ as required from electromagnetic observations and employ the equation-of-state parametrization, we further constrain R1 ¼ 11.9 þ1.4 −1.4 km and R2 ¼ 11.9 þ1.4 −1.4 km at the 90% credible level. Finally, we obtain constraints on pðρÞ at supranuclear densities, with pressure at twice nuclear saturation density measured at 3.5 þ2.7 −1.7 × 1034 dyn cm−2 at the 90% level.

1,595 citations


Journal ArticleDOI
22 Jun 2018-Science
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

1,357 citations


Journal ArticleDOI
TL;DR: Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile.
Abstract: PurposeNivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported.Patients and MethodsPatients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR.ResultsOf 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reac...

1,339 citations



Journal ArticleDOI
18 Apr 2018-Nature
TL;DR: A large panel of cell surface markers in skin and mammary primary tumours is screened, and the existence of multiple tumour subpopulations associated with different EMT stages are identified: from epithelial to completely mesenchymal states, passing through intermediate hybrid states.
Abstract: In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumour-propagating cell capacity, they displayed differences in cellular plasticity, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes identify the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulate EMT transition states.

981 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy3  +1135 moreInstitutions (139)
TL;DR: In this article, the authors present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves.
Abstract: We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5– 20 deg2 requires at least three detectors of sensitivity within a factor of ∼2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

804 citations


Journal ArticleDOI
TL;DR: There was an increase in the total number both of surgical and endoluminal bariatric/metabolic procedures performed worldwide in 2016 and the surgical trends from 2008 to 2016.
Abstract: Background and aim The International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), being a Federation of 62 national societies, is the ideal network to monitor the number and type of procedures at a global level. The IFSO survey, enriched with a special section on revisional procedures, aims to report the number and types of bariatric procedures performed worldwide in 2016 and analyzes the surgical trends from 2008 to 2016. Methods The 2016 IFSO Survey form was emailed to all IFSO societies. Each Society was requested to indicate the number and type of bariatric procedures performed in the country. Trend analyses from 2008 to 2016 were also performed. Results The total number of bariatric/metabolic procedures performed in 2016 was 685,874; 634,897 (92.6%) of which were primary and 50,977 were revisional (7.4%). Among the primary interventions, 609,897 (96%) were surgical and 25,359 (4%) were endoluminal. The most performed primary surgical bariatric/metabolic procedure was sleeve gastrectomy (SG) (N = 340,550; 53.6%), followed by Roux-en-Y gastric bypass (N = 191,326; 30.1%), and one-anastomosis gastric bypass (N = 30,563; 4.8%). Conclusions In 2016, there was an increase in the total number both of surgical and endoluminal bariatric/metabolic procedures. Revisional procedures represent about 7% of the total bariatric interventions. SG remains the most performed surgical procedure in the world.

684 citations


Journal ArticleDOI
TL;DR: Recent advances in the field of apoptosis, necroptosis and pyroptosis are discussed, with an emphasis on the mechanisms underlying plasma membrane changes observed on dying cells and their implication in cell death-elicited immunogenicity.
Abstract: Ruptured and intact plasma membranes are classically considered as hallmarks of necrotic and apoptotic cell death, respectively. As such, apoptosis is usually considered a non-inflammatory process while necrosis triggers inflammation. Recent studies on necroptosis and pyroptosis, two types of programmed necrosis, revealed that plasma membrane rupture is mediated by MLKL channels during necroptosis but depends on non-selective gasdermin D (GSDMD) pores during pyroptosis. Importantly, the morphology of dying cells executed by MLKL channels can be distinguished from that executed by GSDMD pores. Interestingly, it was found recently that secondary necrosis of apoptotic cells, a previously believed non-regulated form of cell lysis that occurs after apoptosis, can be programmed and executed by plasma membrane pore formation like that of pyroptosis. In addition, pyroptosis is associated with pyroptotic bodies, which have some similarities to apoptotic bodies. Therefore, different cell death programs induce distinctive reshuffling processes of the plasma membrane. Given the fact that the nature of released intracellular contents plays a crucial role in dying/dead cell-induced immunogenicity, not only membrane rupture or integrity but also the nature of plasma membrane breakdown would determine the fate of a cell as well as its ability to elicit an immune response. In this review, we will discuss recent advances in the field of apoptosis, necroptosis and pyroptosis, with an emphasis on the mechanisms underlying plasma membrane changes observed on dying cells and their implication in cell death-elicited immunogenicity.

590 citations


Journal ArticleDOI
Federica Spoto1, Federica Spoto2, Paolo Tanga1, Francois Mignard1  +498 moreInstitutions (86)
TL;DR: In this paper, the authors describe the processing of the Gaia DR2 data, and describe the criteria used to select the sample published in Gaia DR 2, and explore the data set to assess its quality.
Abstract: Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims. We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods. To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results. The overall astrometric performance is close to the expectations, with an optimal range of brightness G ~ 12 − 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G ~ 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.

584 citations


Journal ArticleDOI
Amina Helmi1, F. van Leeuwen2, Paul J. McMillan3, Davide Massari1  +481 moreInstitutions (82)
TL;DR: In this paper, the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way is demonstrated. But the accuracy of the errors, statistical and systematic, are relatively well understood.
Abstract: Context. Aims: The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds. Methods: Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community. Results: Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (iv) derive a lower limit for the mass of the Milky Way of 9.1-2.6+6.2 × 1011 M⊙ based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (vi) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud. Conclusions: All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.

Journal ArticleDOI
TL;DR: If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.
Abstract: Graves' disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves' hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves' hyperthyroidism are usually medically treated for 12-18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12-18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves' patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves' patients with mild/active orbitopathy receiving RAI.

Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Federico Ambrogi1  +2238 moreInstitutions (159)
TL;DR: In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented.
Abstract: Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The b jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV).

Journal ArticleDOI
TL;DR: Preoperative biliary drainage should be reserved for patients with cholangitis, severe symptomatic jaundice, or delayed surgery, or for before neoadjuvant chemotherapy in jaundiced patients.
Abstract: ESGE recommends against routine preoperative biliary drainage in patients with malignant extrahepatic biliary obstruction; preoperative biliary drainage should be reserved for patients with cholangitis, severe symptomatic jaundice (e. g., intense pruritus), or delayed surgery, or for before neoadjuvant chemotherapy in jaundiced patients. Strong recommendation, moderate quality evidence. ESGE recommends the endoscopic placement of a 10-mm diameter self-expandable metal stent (SEMS) for preoperative biliary drainage of malignant extrahepatic biliary obstruction. Strong recommendation, moderate quality evidence. ESGE recommends SEMS insertion for palliative drainage of of extrahepatic malignant biliary obstruction. Strong recommendation, high quality evidence. ESGE recommends against the insertion of uncovered SEMS for the drainage of extrahepatic biliary obstruction of unconfirmed etiology. Strong recommendation, low quality evidence. ESGE suggests against routine preoperative biliary drainage in patients with malignant hilar obstruction. Weak recommendation, low quality evidence. ESGE recommends uncovered SEMSs for palliative drainage of malignant hilar obstruction. Strong recommendation, moderate quality evidence. ESGE recommends temporary insertion of multiple plastic stents or of a fully covered SEMS for treatment of benign biliary strictures. Strong recommendation, moderate quality evidence. ESGE recommends endoscopic placement of plastic stent(s) to treat bile duct leaks that are not due to transection of the common bile duct or common hepatic duct. Strong recommendation, moderate quality evidence.

Journal ArticleDOI
TL;DR: Current treatment for sepsis aims to limit the development of organ dysfunction by providing rapid control of infection, haemodynamic stabilization and organ support when possible to ensure recovery of organ function.
Abstract: Sepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Knowledge of the pathophysiology of organ failure in sepsis is crucial for optimizing the management and treatment of patients and for the development of potential new therapies. In clinical practice, six major organ systems - the cardiovascular (including the microcirculation), respiratory, renal, neurological, haematological and hepatic systems - can be assessed and monitored, whereas others, such as the gut, are less accessible. Over the past 2 decades, considerable amounts of new data have helped improve our understanding of sepsis pathophysiology, including the regulation of inflammatory pathways and the role played by immune suppression during sepsis. The effects of impaired cellular function, including mitochondrial dysfunction and altered cell death mechanisms, on the development of organ dysfunction are also being unravelled. Insights have been gained into interactions between key organs (such as the kidneys and the gut) and organ-organ crosstalk during sepsis. The important role of the microcirculation in sepsis is increasingly apparent, and new techniques have been developed that make it possible to visualize the microcirculation at the bedside, although these techniques are only research tools at present.

Journal ArticleDOI
TL;DR: This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC and demonstrated clinical activity and was well tolerated in Patients with advanced AR- positive TNBC.
Abstract: PurposeStudies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC.Patients and MethodsTumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining > 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed ≥ 10% nuclear AR (the evaluable subgroup).ResultsOf 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 3...

Journal ArticleDOI
TL;DR: A classification system based on gene expression analysis of formalin-fixed PDA samples identified 5 PDA subtypes, based on features of cancer cells and the tumor microenvironment, which might be used to select therapies and predict patient outcomes.

Journal ArticleDOI
TL;DR: In this paper, the performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016.
Abstract: The CMS muon detector system, muon reconstruction software, and high-level trigger underwent significant changes in 2013–2014 in preparation for running at higher LHC collision energy and instantaneous luminosity. The performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016. The measured performance parameters, including spatial resolution, efficiency, and timing, are found to meet all design specifications and are well reproduced by simulation. Despite the more challenging running conditions, the modified muon system is found to perform as well as, and in many aspects better than, previously. We dedicate this paper to the memory of Prof. Alberto Benvenuti, whose work was fundamental for the CMS muon detector.

Journal ArticleDOI
Christopher D. Whelan1, Christopher D. Whelan2, Andre Altmann3, Juan A. Botía4, Neda Jahanshad2, Derrek P. Hibar2, Julie Absil5, Saud Alhusaini6, Saud Alhusaini1, Marina K. M. Alvim7, Pia Auvinen8, Emanuele Bartolini9, Felipe P. G. Bergo7, Tauana Bernardes7, Karen Blackmon10, Karen Blackmon11, Barbara Braga7, Maria Eugenia Caligiuri12, Anna Calvo, Sarah J. A. Carr13, Jian Chen14, Shuai Chen15, Andrea Cherubini12, Philippe David5, Martin Domin16, Sonya Foley17, Wendy Franca7, Gerrit Haaker18, Dmitry Isaev2, Simon S. Keller19, Raviteja Kotikalapudi20, Magdalena A. Kowalczyk21, Ruben Kuzniecky11, Soenke Langner16, Matteo Lenge9, Kelly M. Leyden22, Min Liu6, Richard Q. Loi22, Pascal Martin20, Mario Mascalchi9, Mario Mascalchi23, Marcia Elisabete Morita7, Jose C. Pariente, Raúl Rodríguez-Cruces24, Christian Rummel25, Taavi Saavalainen8, Mira Semmelroch21, Mariasavina Severino26, Rhys H. Thomas17, Rhys H. Thomas27, Manuela Tondelli28, Domenico Tortora26, Anna Elisabetta Vaudano28, Lucy Vivash29, Lucy Vivash30, Felix von Podewils16, Jan Wagner31, Jan Wagner32, Bernd Weber32, Yi Yao15, Clarissa L. Yasuda7, Guohao Zhang33, Núria Bargalló, Benjamin Bender20, Neda Bernasconi6, Andrea Bernasconi6, Boris C. Bernhardt6, Ingmar Blümcke18, Chad Carlson34, Chad Carlson11, Gianpiero L. Cavalleri1, Fernando Cendes7, Luis Concha24, Norman Delanty35, Norman Delanty1, Chantal Depondt5, Orrin Devinsky11, Colin P. Doherty1, Niels K. Focke20, Antonio Gambardella12, Renzo Guerrini9, Khalid Hamandi17, Khalid Hamandi27, Graeme D. Jackson21, Graeme D. Jackson29, Reetta Kälviäinen8, Peter Kochunov36, Patrick Kwan30, Angelo Labate12, Carrie R. McDonald22, Stefano Meletti28, Terence J. O'Brien29, Terence J. O'Brien30, Sebastien Ourselin3, Mark P. Richardson13, Mark P. Richardson37, Pasquale Striano38, Thomas Thesen10, Thomas Thesen11, Roland Wiest25, Junsong Zhang15, Annamaria Vezzani39, Mina Ryten13, Mina Ryten4, Paul M. Thompson2, Sanjay M. Sisodiya4 
01 Feb 2018-Brain
TL;DR: In the largest neuroimaging study to date, Whelan and colleagues report robust structural alterations across and within epilepsy syndromes, including shared volume loss in the thalamus, and widespread cortical thickness differences.
Abstract: Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 × 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 × 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 × 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 × 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 × 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 × 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 × 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.

Journal ArticleDOI
TL;DR: A new version of the Gridded Livestock of the World (GLW 3) database is presented, reflecting the most recently compiled and harmonized subnational livestock distribution data for 2010.
Abstract: Global data sets on the geographic distribution of livestock are essential for diverse applications in agricultural socio-economics, food security, environmental impact assessment and epidemiology. We present a new version of the Gridded Livestock of the World (GLW 3) database, reflecting the most recently compiled and harmonized subnational livestock distribution data for 2010. GLW 3 provides global population densities of cattle, buffaloes, horses, sheep, goats, pigs, chickens and ducks in each land pixel at a spatial resolution of 0.083333 decimal degrees (approximately 10 km at the equator). They are accompanied by detailed metadata on the year, spatial resolution and source of the input census data. Two versions of each species distribution are produced. In the first version, livestock numbers are disaggregated within census polygons according to weights established by statistical models using high resolution spatial covariates (dasymetric weighting). In the second version, animal numbers are distributed homogeneously with equal densities within their census polygons (areal weighting) to provide spatial data layers free of any assumptions linking them to other spatial variables. Machine-accessible metadata file describing the reported data (ISA-Tab format)

Journal ArticleDOI
05 Dec 2018-Nature
TL;DR: This work identifies, categorize and quantify the world’s ammonia emission hotspots using a high-resolution map of atmospheric ammonia obtained from almost a decade of daily IASI satellite observations and suggests that it is necessary to completely revisit the emission inventories of anthropogenic ammonia sources and to account for the rapid evolution of such sources over time.
Abstract: Through its important role in the formation of particulate matter, atmospheric ammonia affects air quality and has implications for human health and life expectancy1,2. Excess ammonia in the environment also contributes to the acidification and eutrophication of ecosystems3,4,5 and to climate change6. Anthropogenic emissions dominate natural ones and mostly originate from agricultural, domestic and industrial activities7. However, the total ammonia budget and the attribution of emissions to specific sources remain highly uncertain across different spatial scales7,8,9. Here we identify, categorize and quantify the world’s ammonia emission hotspots using a high-resolution map of atmospheric ammonia obtained from almost a decade of daily IASI satellite observations. We report 248 hotspots with diameters smaller than 50 kilometres, which we associate with either a single point source or a cluster of agricultural and industrial point sources—with the exception of one hotspot, which can be traced back to a natural source. The state-of-the-art EDGAR emission inventory10 mostly agrees with satellite-derived emission fluxes within a factor of three for larger regions. However, it does not adequately represent the majority of point sources that we identified and underestimates the emissions of two-thirds of them by at least one order of magnitude. Industrial emitters in particular are often found to be displaced or missing. Our results suggest that it is necessary to completely revisit the emission inventories of anthropogenic ammonia sources and to account for the rapid evolution of such sources over time. This will lead to better health and environmental impact assessments of atmospheric ammonia and the implementation of suitable nitrogen management strategies.

Journal ArticleDOI
TL;DR: A formalization of the fraud-detection problem is proposed that realistically describes the operating conditions of FDSs that everyday analyze massive streams of credit card transactions and a novel learning strategy is designed and assessed that effectively addresses class imbalance, concept drift, and verification latency.
Abstract: Detecting frauds in credit card transactions is perhaps one of the best testbeds for computational intelligence algorithms. In fact, this problem involves a number of relevant challenges, namely: concept drift (customers’ habits evolve and fraudsters change their strategies over time), class imbalance (genuine transactions far outnumber frauds), and verification latency (only a small set of transactions are timely checked by investigators). However, the vast majority of learning algorithms that have been proposed for fraud detection rely on assumptions that hardly hold in a real-world fraud-detection system (FDS). This lack of realism concerns two main aspects: 1) the way and timing with which supervised information is provided and 2) the measures used to assess fraud-detection performance. This paper has three major contributions. First, we propose, with the help of our industrial partner, a formalization of the fraud-detection problem that realistically describes the operating conditions of FDSs that everyday analyze massive streams of credit card transactions. We also illustrate the most appropriate performance measures to be used for fraud-detection purposes. Second, we design and assess a novel learning strategy that effectively addresses class imbalance, concept drift, and verification latency. Third, in our experiments, we demonstrate the impact of class unbalance and concept drift in a real-world data stream containing more than 75 million transactions, authorized over a time window of three years.

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TL;DR: ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient, and endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery is to be preferred over open surgery as the next therapeutic step.
Abstract: 1 ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible. Weak recommendation, low quality evidence. 2 ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections. Strong recommendation, moderate quality evidence. FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear. Weak recommendation, low quality evidence. 3 ESGE recommends initial goal-directed intravenous fluid therapy with Ringer’s lactate (e. g. 5 – 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals. Strong recommendation, moderate quality evidence. 4 ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis. Strong recommendation, high quality evidence. 5 ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis. Strong recommendation, low quality evidence. ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient. Weak recommendation, low quality evidence. 6 ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise. Strong recommendation, moderate quality evidence. 7 ESGE suggests that, in the absence of improvement following endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery (if percutaneous drainage has already been performed) is to be preferred over open surgery as the next therapeutic step, taking into account the location of the walled-off necrosis and local expertise. Weak recommendation, low quality evidence. 8 ESGE recommends long-term indwelling of transluminal plastic stents in patients with disconnected pancreatic duct syndrome. Strong recommendation, low quality evidence. Lumen-apposing metal stents should be retrieved within 4 weeks to avoid stent-related adverse effects. Strong recommendation, low quality evidence.

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TL;DR: This consensus aims to provide clinicians with guidelines for practical use and interpretation of the sublingual microcirculation and promote the integration of routine application of HVM microcirculatory monitoring in conventional hemodynamic monitoring of systemic hemodynamic variables.
Abstract: Hand-held vital microscopes (HVMs) were introduced to observe sublingual microcirculatory alterations at the bedside in different shock states in critically ill patients This consensus aims to provide clinicians with guidelines for practical use and interpretation of the sublingual microcirculation Furthermore, it aims to promote the integration of routine application of HVM microcirculatory monitoring in conventional hemodynamic monitoring of systemic hemodynamic variables In accordance with the Delphi method we organized three international expert meetings to discuss the various aspects of the technology, physiology, measurements, and clinical utility of HVM sublingual microcirculatory monitoring to formulate this consensus document A task force from the Cardiovascular Dynamics Section of the European Society of Intensive Care Medicine (with endorsement of its Executive Committee) created this consensus as an update of a previous consensus in 2007 We classified consensus statements as definitions, requirements, and/or recommendations, with a minimum requirement of 80% agreement of all participants In this consensus the nature of microcirculatory alterations is described The nature of variables, which can be extracted from analysis of microcirculatory images, is presented and the needed dataset of variables to identify microcirculatory alterations is defined Practical aspects of sublingual HVM measurements and the nature of artifacts are described Eleven statements were formulated that pertained to image acquisitions and quality statements Fourteen statements addressed the analysis of the images, and 13 statements are related to future developments This consensus describes 25 statements regarding the acquisition and interpretation of microcirculatory images needed to guide the assessment of the microcirculation in critically ill patients

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10 May 2018
TL;DR: The Tropospheric Ozone Assessment Report (TOAR) is an activity of the International Global Atmospheric Chemistry Project as mentioned in this paper, which provides a detailed view of ozone in the lower troposphere across East Asia and Europe.
Abstract: The Tropospheric Ozone Assessment Report (TOAR) is an activity of the International Global Atmospheric Chemistry Project. This paper is a component of the report, focusing on the present-day distribution and trends of tropospheric ozone relevant to climate and global atmospheric chemistry model evaluation. Utilizing the TOAR surface ozone database, several figures present the global distribution and trends of daytime average ozone at 2702 non-urban monitoring sites, highlighting the regions and seasons of the world with the greatest ozone levels. Similarly, ozonesonde and commercial aircraft observations reveal ozone’s distribution throughout the depth of the free troposphere. Long-term surface observations are limited in their global spatial coverage, but data from remote locations indicate that ozone in the 21st century is greater than during the 1970s and 1980s. While some remote sites and many sites in the heavily polluted regions of East Asia show ozone increases since 2000, many others show decreases and there is no clear global pattern for surface ozone changes since 2000. Two new satellite products provide detailed views of ozone in the lower troposphere across East Asia and Europe, revealing the full spatial extent of the spring and summer ozone enhancements across eastern China that cannot be assessed from limited surface observations. Sufficient data are now available (ozonesondes, satellite, aircraft) across the tropics from South America eastwards to the western Pacific Ocean, to indicate a likely tropospheric column ozone increase since the 1990s. The 2014–2016 mean tropospheric ozone burden (TOB) between 60˚N–60˚S from five satellite products is 300 Tg ± 4%. While this agreement is excellent, the products differ in their quantification of TOB trends and further work is required to reconcile the differences. Satellites can now estimate ozone’s global long-wave radiative effect, but evaluation is difficult due to limited in situ observations where the radiative effect is greatest.

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31 May 2018-Cell
TL;DR: This study uncovers a large repertoire of recently evolved genes active during human corticogenesis and reveals how human-specific NOTCH paralogs may have contributed to the expansion of the human cortex.

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TL;DR: In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities, with no increased risk of grade 3 and 4 neuropathy.

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TL;DR: An international group of experts were convened to standardize definitions of New‐Onset Refractory Status Epilepticus (NORSE), Febrile Infection‐Related Epilepsy Syndrome (FIRES), and related conditions to enable improved communication for investigators, physicians, families, patients, and other caregivers.
Abstract: We convened an international group of experts to standardize definitions of New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in-person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.

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05 Apr 2018-Cell
TL;DR: Results from the TCGA PanCancer Atlas project will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing.

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TL;DR: This expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure.
Abstract: Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on "Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease" (Ravenna, October 27-28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.