Showing papers by "University of Barcelona published in 2018"
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4 +1025 more•Institutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).
5,211 citations
Emory University1, University of Pittsburgh2, Riverside Methodist Hospital3, University of Miami4, Autonomous University of Barcelona5, Centre Hospitalier Universitaire de Toulouse6, Baptist Health7, Case Western Reserve University8, University at Buffalo9, Royal Melbourne Hospital10, Rush University Medical Center11, California Pacific Medical Center12, University Health Network13, University Of Tennessee System14, University of Kansas15, University of Barcelona16, Capital District Health Authority17, Kaiser Permanente18, University of California, Los Angeles19, University of California, San Francisco20
TL;DR: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone.
Abstract: BackgroundThe effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. MethodsWe enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, whic...
3,331 citations
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Ilio Vitale3, Stuart A. Aaronson4 +183 more•Institutions (111)
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Abstract: Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.
3,301 citations
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1 +1050 more•Institutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.
2,910 citations
Lund University1, European Space Agency2, Dresden University of Technology3, Heidelberg University4, Telespazio5, University of Barcelona6, University of Edinburgh7, University of Cambridge8, University of Paris9, Serco Group10, INAF11, University of Bern12, University of Bordeaux13, University of Turin14, European Space Research and Technology Centre15, University of Padua16, Centre national de la recherche scientifique17, Max Planck Society18, University of Geneva19, Chinese Academy of Sciences20, Las Cumbres Observatory Global Telescope Network21, Liverpool John Moores University22, Altec Lansing23, Leiden University24
TL;DR: In this article, the authors describe the input data, models, and processing used for the astrometric content of Gaia DR2, and the validation of these results performed within the ASTR task.
Abstract: Context. Gaia Data Release 2 (Gaia DR2) contains results for 1693 million sources in the magnitude range 3 to 21 based on observations collected by the European Space Agency Gaia satellite during the first 22 months of its operational phase.Aims. We describe the input data, models, and processing used for the astrometric content of Gaia DR2, and the validation of these resultsperformed within the astrometry task.Methods. Some 320 billion centroid positions from the pre-processed astrometric CCD observations were used to estimate the five astrometric parameters (positions, parallaxes, and proper motions) for 1332 million sources, and approximate positions at the reference epoch J2015.5 for an additional 361 million mostly faint sources. These data were calculated in two steps. First, the satellite attitude and the astrometric calibration parameters of the CCDs were obtained in an astrometric global iterative solution for 16 million selected sources, using about 1% of the input data. This primary solution was tied to the extragalactic International Celestial Reference System (ICRS) by means of quasars. The resulting attitude and calibration were then used to calculate the astrometric parameters of all the sources. Special validation solutions were used to characterise the random and systematic errors in parallax and proper motion.Results. For the sources with five-parameter astrometric solutions, the median uncertainty in parallax and position at the reference epoch J2015.5 is about 0.04 mas for bright (G = 17 mag, and 0.7 masat G = 20 mag. In the proper motion components the corresponding uncertainties are 0.05, 0.2, and 1.2 mas yr−1 , respectively.The optical reference frame defined by Gaia DR2 is aligned with ICRS and is non-rotating with respect to the quasars to within 0.15 mas yr−1 . From the quasars and validation solutions we estimate that systematics in the parallaxes depending on position, magnitude, and colour are generally below 0.1 mas, but the parallaxes are on the whole too small by about 0.03 mas. Significant spatial correlations of up to 0.04 mas in parallax and 0.07 mas yr−1 in proper motion are seen on small ( DR2 astrometry are given in the appendices.
1,836 citations
National Taiwan University1, Kumamoto University2, Heidelberg University3, University of Münster4, Boston University5, University of Messina6, University of British Columbia7, University of Barcelona8, Columbia University9, Sungkyunkwan University10, Konkuk University11, Istanbul University12, Shinshu University13, University College London14, Harvard University15, Johns Hopkins University16, Mayo Clinic17, Alnylam Pharmaceuticals18, Umeå University19
TL;DR: Patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis with polyneuropathy and showed an effect on gait speed and modified BMI.
Abstract: BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.METHODS: In this phase 3 trial, we randomly assigned patients ...
1,671 citations
National Institutes of Health1, City of Hope National Medical Center2, University of British Columbia3, University of Barcelona4, University of Würzburg5, Bosch6, University of Toronto7, Mayo Clinic8, Alliance for Clinical Trials in Oncology9, Memorial Sloan Kettering Cancer Center10, Cornell University11, Washington University in St. Louis12
TL;DR: Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on “chronic active” B‐cell receptor signaling that is amenable to therapeutic inhibition, and an algorithm was developed and implemented to discover genetic subtypes based on the co‐occurrence of genetic alterations.
Abstract: Background Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell–like [ABC], germinal-center B-cell–like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. Methods We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. Results We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B muta...
1,225 citations
TL;DR: Increased TGFβ in the tumour microenvironment represents a primary mechanism of immune evasion that promotes T-cell exclusion and blocks acquisition of the TH1-effector phenotype, and immunotherapies directed against TGF β signalling may have broad applications in treating patients with advanced colorectal cancer.
Abstract: Most patients with colorectal cancer die as a result of the disease spreading to other organs. However, no prevalent mutations have been associated with metastatic colorectal cancers. Instead, particular features of the tumour microenvironment, such as lack of T-cell infiltration, low type 1 T-helper cell (TH1) activity and reduced immune cytotoxicity or increased TGFβ levels predict adverse outcomes in patients with colorectal cancer. Here we analyse the interplay between genetic alterations and the tumour microenvironment by crossing mice bearing conditional alleles of four main colorectal cancer mutations in intestinal stem cells. Quadruple-mutant mice developed metastatic intestinal tumours that display key hallmarks of human microsatellite-stable colorectal cancers, including low mutational burden, T-cell exclusion and TGFβ-activated stroma. Inhibition of the PD-1-PD-L1 immune checkpoint provoked a limited response in this model system. By contrast, inhibition of TGFβ unleashed a potent and enduring cytotoxic T-cell response against tumour cells that prevented metastasis. In mice with progressive liver metastatic disease, blockade of TGFβ signalling rendered tumours susceptible to anti-PD-1-PD-L1 therapy. Our data show that increased TGFβ in the tumour microenvironment represents a primary mechanism of immune evasion that promotes T-cell exclusion and blocks acquisition of the TH1-effector phenotype. Immunotherapies directed against TGFβ signalling may therefore have broad applications in treating patients with advanced colorectal cancer.
1,176 citations
Christopher Troeger1, Brigette F. Blacker1, Ibrahim A Khalil1, Puja C Rao1 +148 more•Institutions (28)
TL;DR: The findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults.
Abstract: Summary Background Lower respiratory infections are a leading cause of morbidity and mortality around the world The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages Methods We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus We calculated each modelled estimate for each age, sex, year, and location We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years We also did a decomposition analysis of the change in LRI deaths from 2000–16 using the risk factors associated with LRI in GBD 2016 Findings In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475–720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749–1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584–2 512 809) in people of all ages, worldwide Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445–1 770 660) Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7–69·6) Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden Interpretation Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations Funding Bill & Melinda Gates Foundation
1,147 citations
TL;DR: Treatment advances have been made in the past few years, and further advancements are expected in the near future, including biomarker-driven treatments and immunotherapies, as discussed in this Review.
Abstract: The global burden of hepatocellular carcinoma (HCC) is increasing and might soon surpass an annual incidence of 1 million cases Genomic studies have established the landscape of molecular alterations in HCC; however, the most common mutations are not actionable, and only ~25% of tumours harbour potentially targetable drivers Despite the fact that surveillance programmes lead to early diagnosis in 40–50% of patients, at a point when potentially curative treatments are applicable, almost half of all patients with HCC ultimately receive systemic therapies Sorafenib was the first systemic therapy approved for patients with advanced-stage HCC, after a landmark study revealed an improvement in median overall survival from 8 to 11 months New drugs — lenvatinib in the frontline and regorafenib, cabozantinib, and ramucirumab in the second line — have also been demonstrated to improve clinical outcomes, although the median overall survival remains ~1 year; thus, therapeutic breakthroughs are still needed Immune-checkpoint inhibitors are now being incorporated into the HCC treatment armamentarium and combinations of molecularly targeted therapies with immunotherapies are emerging as tools to boost the immune response Research on biomarkers of a response or primary resistance to immunotherapies is also advancing Herein, we summarize the molecular targets and therapies for the management of HCC and discuss the advancements expected in the near future, including biomarker-driven treatments and immunotherapies
1,122 citations
Newcastle University1, Hannover Medical School2, University of Palermo3, Saga University4, University of Würzburg5, Istituto Superiore di Sanità6, RWTH Aachen University7, University of Barcelona8, University of California, San Diego9, Yokohama City University10, French Institute of Health and Medical Research11, VCU Medical Center12, University of Mainz13, Hiroshima University14, Peking University15, Goethe University Frankfurt16
TL;DR: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed, if obesity and DM continue to increase at current and historical rates.
University of British Columbia1, University of Toronto2, University of Michigan3, University of Minnesota4, McMaster University5, University of Western Ontario6, McGill University7, Dalhousie University8, University of Calgary9, Queen's University10, Kyushu University11, University of São Paulo12, Stanford University13, Case Western Reserve University14, University of Barcelona15, University of Sydney16, George Washington University17, Deakin University18
TL;DR: These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments.
Abstract: The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.
University of Cologne1, Georgetown University2, Institute of Cancer Research3, Vita-Salute San Raffaele University4, Pasteur Institute5, University of Ulm6, University of Texas MD Anderson Cancer Center7, University of Barcelona8, The Feinstein Institute for Medical Research9, Ohio State University10, University of California, Irvine11, Medical University of Łódź12, Peter MacCallum Cancer Centre13, University of California, San Diego14
TL;DR: Recommendations include a revised version of the iwCLL response criteria, an update on the use of MRD status for clinical evaluation, and recommendations regarding the assessment and prophylaxis of viral diseases during management of CLL.
Indiana University – Purdue University Indianapolis1, Federal University of Rio de Janeiro2, Boston University3, Johns Hopkins University4, Mayo Clinic5, University of California, Irvine6, University of Pavia7, Columbia University8, University College London9, University of Pennsylvania10, Oregon Health & Science University11, University of Lisbon12, University of Münster13, University of Messina14, University of Barcelona15, Auckland City Hospital16
TL;DR: Inotersen improved the course of neurologic disease and quality of life in patients with hereditary transthyretin amyloidosis and improvements were independent of disease stage, mutation type, or the presence of cardiomyopathy.
Abstract: Background Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin (TTR) that induce transthyretin misfolding and systemi...
TL;DR: The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues, which are the second most targeted group of drug targets, after the G-protein-coupled receptors.
Abstract: The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer. Furthermore, about 150 kinase-targeted drugs are in clinical phase trials, and many kinase-specific inhibitors are in the preclinical stage of drug development. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. This review provides an overview of kinase-targeted drug discovery and development in relation to oncology and highlights the challenges and future potential for kinase-targeted cancer therapies.
University of Cambridge1, University of Barcelona2, INAF3, University of Edinburgh4, Instituto Politécnico Nacional5, Rutherford Appleton Laboratory6, University of Leicester7, Leiden University8, Centre national de la recherche scientifique9, University of Geneva10, Radboud University Nijmegen11, University of Warsaw12
TL;DR: In this paper, the authors describe the photometric content of the second data release of the Gaia project (Gaia DR2) and its validation along with the quality of the data.
Abstract: Aims. We describe the photometric content of the second data release of the Gaia project (Gaia DR2) and its validation along with the quality of the data.Methods. The validation was mainly carried out using an internal analysis of the photometry. External comparisons were also made, but were limited by the precision and systematics that may be present in the external catalogues used.Results. In addition to the photometric quality assessment, we present the best estimates of the three photometric passbands. Various colour-colour transformations are also derived to enable the users to convert between the Gaia and commonly used passbands.Conclusions. The internal analysis of the data shows that the photometric calibrations can reach a precision as low as 2 mmag on individual CCD measurements. Other tests show that systematic effects are present in the data at the 10 mmag level.
Aix-Marseille University1, Spanish National Research Council2, Sciences Po3, University of Paris4, Technical University of Madrid5, The Cyprus Institute6, Central Maine Community College7, University of Salento8, University of Barcelona9, University of Haifa10, City University of Hong Kong11, University of Giessen12
TL;DR: In this paper, a dedicated effort to synthesize existing scientific knowledge across disciplines is underway and aims to provide a better understanding of the combined risks posed in the Mediterranean Basin, where fewer systematic observations schemes and impact models are based.
Abstract: Recent accelerated climate change has exacerbated existing environmental problems in the Mediterranean Basin that are caused by the combination of changes in land use, increasing pollution and declining biodiversity. For five broad and interconnected impact domains (water, ecosystems, food, health and security), current change and future scenarios consistently point to significant and increasing risks during the coming decades. Policies for the sustainable development of Mediterranean countries need to mitigate these risks and consider adaptation options, but currently lack adequate information — particularly for the most vulnerable southern Mediterranean societies, where fewer systematic observations schemes and impact models are based. A dedicated effort to synthesize existing scientific knowledge across disciplines is underway and aims to provide a better understanding of the combined risks posed.
TL;DR: The second Gaia data release (DR2) contains very precise astrometric and photometric properties for more than one billion sources, astrophysical parameters for dozens of millions, radial velocities for millions, variability information for half a million stars from selected variability classes, and orbits for thousands of solar system objects.
Abstract: Context. The second Gaia data release (DR2) contains very precise astrometric and photometric properties for more than one billion sources, astrophysical parameters for dozens of millions, radial velocities for millions, variability information for half a million stars from selected variability classes, and orbits for thousands of solar system objects.Aims. Before the catalogue was published, these data have undergone dedicated validation processes. The goal of this paper is to describe the validation results in terms of completeness, accuracy, and precision of the various Gaia DR2 data.Methods. The validation processes include a systematic analysis of the catalogue content to detect anomalies, either individual errors or statistical properties, using statistical analysis and comparisons to external data or to models.Results. Although the astrometric, photometric, and spectroscopic data are of unprecedented quality and quantity, it is shown that the data cannot be used without dedicated attention to the limitations described here, in the catalogue documentation and in accompanying papers. We place special emphasis on the caveats for the statistical use of the data in scientific exploitation. In particular, we discuss the quality filters and the consideration of the properties, systematics, and uncertainties from astrometry to astrophysical parameters, together with the various selection functions.
TL;DR: In this paper, the authors provide guidelines on how to use parallaxes more efficiently to estimate distances by using Bayesian methods, and provide examples that show more generally how to combine proper motions and paralaxes and the handling of covariances in the uncertainties.
Abstract: Context. The second Gaia data release (Gaia DR2) provides precise five-parameter astrometric data (positions, proper motions, and parallaxes) for an unprecedented number of sources (more than 1.3 billion, mostly stars). This new wealth of data will enable the undertaking of statistical analysis of many astrophysical problems that were previously infeasible for lack of reliable astrometry, and in particular because of the lack of parallaxes. However, the use of this wealth of astrometric data comes with a specific challenge: how can the astrophysical parameters of interest be properly inferred from these data?Aims. The main focus of this paper, but not the only focus, is the issue of the estimation of distances from parallaxes, possibly combined with other information. We start with a critical review of the methods traditionally used to obtain distances from parallaxes and their shortcomings. Then we provide guidelines on how to use parallaxes more efficiently to estimate distances by using Bayesian methods. In particular we also show that negative parallaxes, or parallaxes with relatively large uncertainties still contain valuable information. Finally, we provide examples that show more generally how to use astrometric data for parameter estimation, including the combination of proper motions and parallaxes and the handling of covariances in the uncertainties.Methods. The paper contains examples based on simulated Gaia data to illustrate the problems and the solutions proposed. Furthermore, the developments and methods proposed in the paper are linked to a set of tutorials included in the Gaia archive documentation that provide practical examples and a good starting point for the application of the recommendations to actual problems. In all cases the source code for the analysis methods is provided.Results. Our main recommendation is to always treat the derivation of (astro-)physical parameters from astrometric data, in particular when parallaxes are involved, as an inference problem which should preferably be handled with a full Bayesian approach.Conclusions. Gaia will provide fundamental data for many fields of astronomy. Further data releases will provide more data, and more precise data. Nevertheless, to fully use the potential it will always be necessary to pay careful attention to the statistical treatment of parallaxes and proper motions. The purpose of this paper is to help astronomers find the correct approach.
Alvaro N. Barbeira1, Scott P. Dickinson1, Rodrigo Bonazzola1, Jiamao Zheng1 +260 more•Institutions (43)
TL;DR: A mathematical expression is derived to compute PrediXcan results using summary data, and the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes are investigated.
Abstract: Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease genes are enriched among significant associations for related traits, suggesting that smaller alterations of these genes may cause a spectrum of milder phenotypes.
King's College London1, Policlinico Umberto I2, Zhengzhou University3, University of Bergen4, University of Medicine and Pharmacy of Craiova5, University of Trieste6, University of Pavia7, Ludwig Maximilian University of Munich8, Imperial College London9, University of Verona10, Sapienza University of Rome11, Derriford Hospital12, University Hospital Regensburg13, University of Innsbruck14, Université Paris-Saclay15, University of Barcelona16, University of Copenhagen17, University of Bologna18, University of Virginia19, University of Vienna20, Eindhoven University of Technology21
TL;DR: The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.
Abstract: The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.
TL;DR: In this article, a list of members and cluster parameters for as many clusters as possible was established, making use of Gaia data alone, and an unsupervised membership assignment code, UPMASK, was applied to the Gaia DR2 data contained within the fields of those clusters.
Abstract: Context. Open clusters are convenient probes of the structure and history of the Galactic disk. They are also fundamental to stellar evolution studies. The second Gaia data release contains precise astrometry at the submilliarcsecond level and homogeneous photometry at the mmag level, that can be used to characterise a large number of clusters over the entire sky.Aims. In this study we aim to establish a list of members and derive mean parameters, in particular distances, for as many clusters as possible, making use of Gaia data alone.Methods. We compiled a list of thousands of known or putative clusters from the literature. We then applied an unsupervised membership assignment code, UPMASK, to the Gaia DR2 data contained within the fields of those clusters.Results. We obtained a list of members and cluster parameters for 1229 clusters. As expected, the youngest clusters are seen to be tightly distributed near the Galactic plane and to trace the spiral arms of the Milky Way, while older objects are more uniformly distributed, deviate further from the plane, and tend to be located at larger Galactocentric distances. Thanks to the quality of Gaia DR2 astrometry, the fully homogeneous parameters derived in this study are the most precise to date. Furthermore, we report on the serendipitous discovery of 60 new open clusters in the fields analysed during this study.
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.
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.
TL;DR: For the first time, specific loci that distinguish between BD and SCZ are discovered and polygenic components underlying multiple symptom dimensions are identified that point to the utility of genetics to inform symptomology and potential treatment.
TL;DR: This review, contributed by scientists of complementary disciplines related to carotenoid research, covers recent advances and provides a perspective on future directions on the subjects of carotENoid metabolism, biotechnology, and nutritional and health benefits.
University of Southern California1, University of Oslo2, Oslo University Hospital3, University of Pittsburgh4, Oxford Health NHS Foundation Trust5, University of Cape Town6, University of Texas Health Science Center at Houston7, Heidelberg University8, Neuroscience Research Australia9, Karolinska Institutet10, City University London11, King's College London12, University of Münster13, Icahn School of Medicine at Mount Sinai14, University of Barcelona15, Brown University16, French Institute of Health and Medical Research17, University of Pennsylvania18, Utrecht University19, University of Göttingen20, University of Amsterdam21, Hartford Hospital22, Yale University23, National University of Ireland, Galway24, University of São Paulo25, University of Edinburgh26, West Los Angeles College27, University of California, Los Angeles28, University of California, Irvine29, Medical College of Wisconsin30, McGovern Institute for Brain Research31, Radboud University Nijmegen32, Northumberland, Tyne and Wear NHS Foundation Trust33, National Institutes of Health34, University of California, San Diego35, Dresden University of Technology36, University of Adelaide37, Semel Institute for Neuroscience and Human Behavior38, Pasteur Institute39, University of Birmingham40, VU University Medical Center41, University of Cincinnati Academic Health Center42, University of New South Wales43, Poznan University of Medical Sciences44, Dalhousie University45, Karolinska University Hospital46, University of Gothenburg47, University of Exeter48, Janssen Pharmaceutica49, Cardiff University50
TL;DR: The largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of bipolar disorder patients is performed, revealing previously undetected associations and providing an extensive analysis of potential confounding variables in neuroimaging studies of BD.
Abstract: Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
TL;DR: Prehabilitation enhanced postoperative clinical outcomes in high-risk candidates for elective major abdominal surgery, which can be explained by the increased aerobic capacity.
Abstract: Objective:The aim of this study was to assess the impact of personalized prehabilitation on postoperative complications in high-risk patients undergoing elective major abdominal surgery.Summary Background Data:Prehabilitation, including endurance exercise training and promotion of physical activity,
University Hospital Heidelberg1, Humboldt University of Berlin2, Charité3, University of Düsseldorf4, University of Southern Denmark5, Children's Hospital at Westmead6, Tohoku University7, Walton Centre8, Ruhr University Bochum9, Ludwig Maximilian University of Munich10, Johns Hopkins University11, John Radcliffe Hospital12, University of Barcelona13, Hannover Medical School14, Mayo Clinic15
TL;DR: In this article, the authors proposed indications for MOG-IgG testing based on expert consensus, and gave a list of conditions atypical for MG-EM (red flags) that should prompt physicians to challenge a positive MOG IgG test result, and provided recommendations regarding assay methodology, specimen sampling and data interpretation.
Abstract: Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM (“red flags”) that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation.
TL;DR: In this article, the electrochemical advanced oxidation process electrochemical oxidation is reviewed for its performance over the treatment of actual industrial and urban effluents, and the combination of electrochemical oxide with other water treatment technologies as pre-treatment, post-treatment and integrated treatment is also examined.