scispace - formally typeset
Search or ask a question

Showing papers by "University of Barcelona published in 2016"


Journal ArticleDOI
19 May 2016-Blood
TL;DR: The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies.

5,321 citations


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
TL;DR: Gaia as discussed by the authors is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach.
Abstract: Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.

5,164 citations


Journal ArticleDOI
Theo Vos1, Christine Allen1, Megha Arora1, Ryan M Barber1  +696 moreInstitutions (260)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.

5,050 citations


Journal ArticleDOI
Haidong Wang1, Mohsen Naghavi1, Christine Allen1, Ryan M Barber1  +841 moreInstitutions (293)
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.

4,804 citations


Journal ArticleDOI
Peter Goldstraw1, Kari Chansky, John Crowley, Ramón Rami-Porta2, Hisao Asamura3, Wilfried Ernst Erich Eberhardt4, Andrew G. Nicholson1, Patti A. Groome5, Alan Mitchell, Vanessa Bolejack, David Ball6, David G. Beer7, Ricardo Beyruti8, Frank C. Detterbeck9, Wilfried Eberhardt4, John G. Edwards10, Françoise Galateau-Salle11, Dorothy Giroux12, Fergus V. Gleeson13, James Huang14, Catherine Kennedy15, Jhingook Kim16, Young Tae Kim17, Laura Kingsbury12, Haruhiko Kondo18, Mark Krasnik19, Kaoru Kubota20, Antoon Lerut21, Gustavo Lyons, Mirella Marino, Edith M. Marom22, Jan P. van Meerbeeck23, Takashi Nakano24, Anna K. Nowak25, Michael D Peake26, Thomas W. Rice27, Kenneth E. Rosenzweig28, Enrico Ruffini29, Valerie W. Rusch14, Nagahiro Saijo, Paul Van Schil23, Jean-Paul Sculier30, Lynn Shemanski12, Kelly G. Stratton12, Kenji Suzuki31, Yuji Tachimori32, Charles F. Thomas33, William D. Travis14, Ming-Sound Tsao34, Andrew T. Turrisi35, Johan Vansteenkiste21, Hirokazu Watanabe, Yi-Long Wu, Paul Baas36, Jeremy J. Erasmus22, Seiki Hasegawa24, Kouki Inai37, Kemp H. Kernstine38, Hedy L. Kindler39, Lee M. Krug14, Kristiaan Nackaerts21, Harvey I. Pass40, David C. Rice22, Conrad Falkson5, Pier Luigi Filosso29, Giuseppe Giaccone41, Kazuya Kondo42, Marco Lucchi43, Meinoshin Okumura44, Eugene H. Blackstone27, F. Abad Cavaco, E. Ansótegui Barrera, J. Abal Arca, I. Parente Lamelas, A. Arnau Obrer45, R. Guijarro Jorge45, D. Ball6, G.K. Bascom46, A. I. Blanco Orozco, M. A. González Castro, M.G. Blum, D. Chimondeguy, V. Cvijanovic47, S. Defranchi48, B. de Olaiz Navarro, I. Escobar Campuzano2, I. Macía Vidueira2, E. Fernández Araujo49, F. Andreo García49, Kwun M. Fong, G. Francisco Corral, S. Cerezo González, J. Freixinet Gilart, L. García Arangüena, S. García Barajas50, P. Girard, Tuncay Göksel, M. T. González Budiño51, G. González Casaurrán50, J. A. Gullón Blanco, J. Hernández Hernández, H. Hernández Rodríguez, J. Herrero Collantes, M. Iglesias Heras, J. M. Izquierdo Elena, Erik Jakobsen, S. Kostas52, P. León Atance, A. Núñez Ares, M. Liao, M. Losanovscky, G. Lyons, R. Magaroles53, L. De Esteban Júlvez53, M. Mariñán Gorospe, Brian C. McCaughan15, Catherine J. Kennedy15, R. Melchor Íñiguez54, L. Miravet Sorribes, S. Naranjo Gozalo, C. Álvarez de Arriba, M. Núñez Delgado, J. Padilla Alarcón, J. C. Peñalver Cuesta, Jongsun Park16, H. Pass40, M. J. Pavón Fernández, Mara Rosenberg, Enrico Ruffini29, V. Rusch14, J. Sánchez de Cos Escuín, A. Saura Vinuesa, M. Serra Mitjans, Trond Eirik Strand, Dragan Subotic, S.G. Swisher22, Ricardo Mingarini Terra8, Charles R. Thomas33, Kurt G. Tournoy55, P. Van Schil23, M. Velasquez, Y.L. Wu, K. Yokoi 
Imperial College London1, University of Barcelona2, Keio University3, University of Duisburg-Essen4, Queen's University5, Peter MacCallum Cancer Centre6, University of Michigan7, University of São Paulo8, Yale University9, Northern General Hospital10, University of Caen Lower Normandy11, Fred Hutchinson Cancer Research Center12, University of Oxford13, Memorial Sloan Kettering Cancer Center14, University of Sydney15, Sungkyunkwan University16, Seoul National University17, Kyorin University18, University of Copenhagen19, Nippon Medical School20, Katholieke Universiteit Leuven21, University of Texas MD Anderson Cancer Center22, University of Antwerp23, Hyogo College of Medicine24, University of Western Australia25, Glenfield Hospital26, Cleveland Clinic27, Icahn School of Medicine at Mount Sinai28, University of Turin29, Université libre de Bruxelles30, Juntendo University31, National Cancer Research Institute32, Mayo Clinic33, University of Toronto34, Sinai Grace Hospital35, Netherlands Cancer Institute36, Hiroshima University37, City of Hope National Medical Center38, University of Chicago39, New York University40, Georgetown University41, University of Tokushima42, University of Pisa43, Osaka University44, University of Valencia45, Good Samaritan Hospital46, Military Medical Academy47, Fundación Favaloro48, Autonomous University of Barcelona49, Complutense University of Madrid50, University of Oviedo51, National and Kapodistrian University of Athens52, Rovira i Virgili University53, Autonomous University of Madrid54, Ghent University55
TL;DR: The methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition of the TNM Classification for lung cancer due to be published late 2016 are described.

2,826 citations


Journal ArticleDOI
TL;DR: These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia.
Abstract: It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

2,359 citations


Journal ArticleDOI
TL;DR: The first Gaia data release, Gaia DR1 as discussed by the authors, consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the Hipparcos and Tycho-2 catalogues.
Abstract: Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims: A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods: The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results: Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the Hipparcos and Tycho-2 catalogues - a realisation of the Tycho-Gaia Astrometric Solution (TGAS) - and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of 3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr-1 for the proper motions. A systematic component of 0.3 mas should be added to the parallax uncertainties. For the subset of 94 000 Hipparcos stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr-1. For the secondary astrometric data set, the typical uncertainty of the positions is 10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to0.03 mag over the magnitude range 5 to 20.7. Conclusions: Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.

2,174 citations


Journal ArticleDOI
27 Sep 2016-JAMA
TL;DR: The period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage are characterized are characterized.
Abstract: Importance Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation. Objective To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. Design, Setting, and Patients Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites. Exposures Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment. Main Outcomes and Measures The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation. Results Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, −6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, −5.2% [95% CI, −8.3% to −2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, −0.9% to 4.2%]). Conclusions and Relevance In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.

1,544 citations


Journal ArticleDOI
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2  +679 moreInstitutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.

1,533 citations


Journal ArticleDOI
28 Jul 2016-Cell
TL;DR: It is reported how cancer-driven alterations identified in 11,289 tumors from 29 tissues can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs.

Journal ArticleDOI
TL;DR: Studies now aim to identify molecular markers and imaging techniques that can detect patients with HCC at earlier stages and better predict their survival time and response to treatment.

Journal ArticleDOI
TL;DR: In this randomized trial, cryoballoon ablation was noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation, and there was no significant difference between the two methods with regard to overall safety.
Abstract: BackgroundCurrent guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation. Radiofrequency ablation is the most common method, and cryoballoon ablation is the second most frequently used technology. MethodsWe conducted a multicenter, randomized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillation. The primary efficacy end point in a time-to-event analysis was the first documented clinical failure (recurrence of atrial fibrillation, occurrence of atrial flutter or atrial tachycardia, use of antiarrhythmic drugs, or repeat ablation) following a 90-day period after the index ablation. The noninferiority margin was prespecified as a hazard ratio of 1.43. The primary safety end point was a composite of death, cerebrovascular events, or serious treatment-related adverse events. ResultsA total of 762 patients underwent...

Journal ArticleDOI
TL;DR: The 2009 European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated and 15 recommendations were developed, covering general aspects, such as attaining remission.
Abstract: In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

Journal ArticleDOI
01 Dec 2016-Nature
TL;DR: The HITI method presented here establishes new avenues for basic research and targeted gene therapies and demonstrates the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa.
Abstract: Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

Journal ArticleDOI
TL;DR: The data show an unexpected high rate and pattern of tumor recurrence coinciding with HCV clearance and, although based in a very small cohort of patients, should be taken as a note of caution and prime a large scale assessment that exceeds the individual investigators capacity.


Journal ArticleDOI
TL;DR: In this paper, the authors used pre-clinical testing and appropriate selection of study participants to overcome the barriers to progress in acute ischemic stroke research, and proposed safe and effective treatment strategies that combine neuroprotection reperfusion, better use of advanced brain imaging for patient selection, and wider implementation of pre-hospital conducted clinical trials.
Abstract: Summary Treatments for acute ischaemic stroke continue to evolve after the superior value of endovascular thrombectomy was confirmed over systemic thrombolysis. Unfortunately, numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischaemic stroke, making the search for new treatments imperative. Increased awareness of the relevance of rigorous preclinical testing, and appropriate selection of study participants, might overcome the barriers to progress in stroke research. Relevant areas of interest include the search for safe and effective treatment strategies that combine neuroprotection reperfusion, better use of advanced brain imaging for patient selection, and wider implementation of prehospital conducted clinical trials. Randomised controlled trials of combination treatments completed within the past 5 years have included growth factors, hypothermia, minocycline, natalizumab, fingolimod, and uric acid; the latter two drugs with alteplase produced encouraging results. Blocking of excitotoxicity is also being reassessed in clinical trials with new approaches, such as the postsynaptic density-95 inhibitor NA-1, or peritoneal dialysis to remove excess glutamate. The findings of these randomised trials are anticipated to improve treatment options and clinical outcomes in of patients with acute stroke.

Journal ArticleDOI
TL;DR: Gaia Data Release 1 (Gaia DR1) as discussed by the authors contains a large amount of data collected by the Gaia satellite during the first 14 months of its operational phase, including positions, parallaxes, and proper motions to Hipparcos-type precision or better.
Abstract: Gaia Data Release 1 (Gaia DR1) contains astrometric results for more than 1 billion stars brighter than magnitude 20.7 based on observations collected by the Gaia satellite during the first 14 months of its operational phase. We give a brief overview of the astrometric content of the data release and of the model assumptions, data processing, and validation of the results. For stars in common with the Hipparcos and Tycho-2 catalogues, complete astrometric single-star solutions are obtained by incorporating positional information from the earlier catalogues. For other stars only their positions are obtained by neglecting their proper motions and parallaxes. The results are validated by an analysis of the residuals, through special validation runs, and by comparison with external data. Results. For about two million of the brighter stars (down to magnitude ~11.5) we obtain positions, parallaxes, and proper motions to Hipparcos-type precision or better. For these stars, systematic errors depending e.g. on position and colour are at a level of 0.3 milliarcsecond (mas). For the remaining stars we obtain positions at epoch J2015.0 accurate to ~10 mas. Positions and proper motions are given in a reference frame that is aligned with the International Celestial Reference Frame (ICRF) to better than 0.1 mas at epoch J2015.0, and non-rotating with respect to ICRF to within 0.03 mas/yr. The Hipparcos reference frame is found to rotate with respect to the Gaia DR1 frame at a rate of 0.24 mas/yr. Based on less than a quarter of the nominal mission length and on very provisional and incomplete calibrations, the quality and completeness of the astrometric data in Gaia DR1 are far from what is expected for the final mission products. The results nevertheless represent a huge improvement in the available fundamental stellar data and practical definition of the optical reference frame.

Journal ArticleDOI
TL;DR: In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years.
Abstract: BackgroundPatients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. MethodsWe randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt–chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rat...

Journal ArticleDOI
TL;DR: This Perspective proposes a precision medicine strategy for chronic airway diseases in general, and asthma and COPD in particular, and a discussion of the concept of “treatable traits” as a way towards precision medicine of chronicAirway diseases.
Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway diseases that have a high personal and social impact. They likely represent a continuum of different diseases that may share biological mechanisms (i.e. endotypes), and present similar clinical, functional, imaging and/or biological features that can be observed (i.e. phenotypes) which require individualised treatment. Precision medicine is defined as "treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations". In this Perspective, we propose a precision medicine strategy for chronic airway diseases in general, and asthma and COPD in particular.

Journal ArticleDOI
TL;DR: Parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems and provides high-quality results in diverse systems is presented.
Abstract: We present parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (representing a total simulation time of ~140 μs) covering most of DNA structural space. Parmbsc1 provides high-quality results in diverse systems. Parameters and trajectories are available at http://mmb.irbbarcelona.org/ParmBSC1/.

Journal ArticleDOI
TL;DR: Mental disorders are common among college students, have onsets that mostly occur prior to college entry, and in the case of pre-matriculation disorders are associated with college attrition, and are typically untreated.
Abstract: Background Although mental disorders are significant predictors of educational attainment throughout the entire educational career, most research on mental disorders among students has focused on the primary and secondary school years. Method The World Health Organization World Mental Health Surveys were used to examine the associations of mental disorders with college entry and attrition by comparing college students (n = 1572) and non-students in the same age range (18–22 years; n = 4178), including non-students who recently left college without graduating (n = 702) based on surveys in 21 countries (four low/lower-middle income, five upper-middle-income, one lower-middle or upper-middle at the times of two different surveys, and 11 high income). Lifetime and 12-month prevalence and age-of-onset of DSM-IV anxiety, mood, behavioral and substance disorders were assessed with the Composite International Diagnostic Interview (CIDI). Results One-fifth (20.3%) of college students had 12-month DSM-IV/CIDI disorders; 83.1% of these cases had pre-matriculation onsets. Disorders with pre-matriculation onsets were more important than those with post-matriculation onsets in predicting subsequent college attrition, with substance disorders and, among women, major depression the most important such disorders. Only 16.4% of students with 12-month disorders received any 12-month healthcare treatment for their mental disorders. Conclusions Mental disorders are common among college students, have onsets that mostly occur prior to college entry, in the case of pre-matriculation disorders are associated with college attrition, and are typically untreated. Detection and effective treatment of these disorders early in the college career might reduce attrition and improve educational and psychosocial functioning.

Journal ArticleDOI
TL;DR: In this article, a comprehensive cosmological study of the H0 tension between the direct local measurement and the model-dependent value inferred from the Cosmic Microwave Background is performed.
Abstract: We perform a comprehensive cosmological study of the H0 tension between the direct local measurement and the model-dependent value inferred from the Cosmic Microwave Background. With the recent measurement of H0 this tension has raised to more than 3 σ. We consider changes in the early time physics without modifying the late time cosmology. We also reconstruct the late time expansion history in a model independent way with minimal assumptions using distance measurements from Baryon Acoustic Oscillations and Type Ia Supernovae, finding that at z < 0.6 the recovered shape of the expansion history is less than 5% different than that of a standard ΛCDM model. These probes also provide a model insensitive constraint on the low-redshift standard ruler, measuring directly the combination rsh where H0 = h × 100 Mpc−1km/s and rs is the sound horizon at radiation drag (the standard ruler), traditionally constrained by CMB observations. Thus rs and H0 provide absolute scales for distance measurements (anchors) at opposite ends of the observable Universe. We calibrate the cosmic distance ladder and obtain a model-independent determination of the standard ruler for acoustic scale, rs. The tension in H0 reflects a mismatch between our determination of rs and its standard, CMB-inferred value. Without including high-l Planck CMB polarization data (i.e., only considering the ``recommended baseline" low-l polarisation and temperature and the high l temperature data), a modification of the early-time physics to include a component of dark radiation with an effective number of species around 0.4 would reconcile the CMB-inferred constraints, and the local H0 and standard ruler determinations. The inclusion of the ``preliminary" high-l Planck CMB polarisation data disfavours this solution.

Journal ArticleDOI
University of Utah1, University of Colorado Boulder2, Stanford University3, Oregon Health & Science University4, University of Chicago5, Rush University Medical Center6, University of Barcelona7, Harvard University8, Vanderbilt University9, University of Arizona10, University of Texas Health Science Center at Houston11, University of Pennsylvania12, Emory University13, Université de Montréal14, Samsung Medical Center15, University of Auckland16, University of Pittsburgh17, University of Amsterdam18, University of Ioannina19, University of California, San Francisco20, Eastern Virginia Medical School21, University of New South Wales22, Katholieke Universiteit Leuven23, Guy's and St Thomas' NHS Foundation Trust24, University of Lorraine25, University of British Columbia26, Northwestern University27, Georgia Regents University28, Johns Hopkins University29, New York University30, Korea University31, University of Texas at Austin32, Uniformed Services University of the Health Sciences33, Jikei University School of Medicine34, University of Washington35, University of Siena36, Medical College of Wisconsin37, University of Adelaide38, West Virginia University39, Innsbruck Medical University40, Pusan National University41, University of Calgary42, Medical University of South Carolina43, University of North Carolina at Chapel Hill44, Cleveland Clinic45, Loyola University Chicago46, Cornell University47, Temple University48, University of São Paulo49, National University of Singapore50, San Antonio Military Medical Center51, University of Alabama at Birmingham52, University of Alberta53, Capital Medical University54
TL;DR: This dissertation aims to provide a history of Chinese medical practice in the United States from 1989 to 2002, a period chosen in order to explore its roots as well as specific cases up to and including the year in which descriptions of “modern China” began to circulate.
Abstract: Background The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. Conclusion As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.

Journal ArticleDOI
TL;DR: In this article, the authors quantified maternal mortality throughout the world by underlying cause and age from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories.

Journal ArticleDOI
16 Jun 2016-Blood
TL;DR: Based on data available today, bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival, and overall survival in t(4;14) and del(17/17p), whereas lenalidomide may be associated with improved progression-based survival and progression- free survival int( 4;14), del( 17/17 p), and t(14;16), and gain(1q).

Journal ArticleDOI
TL;DR: The transcatheter pacemaker implanted in patients who had guideline-based indications for ventricular pacing met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds.
Abstract: BackgroundA leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead. MethodsIn a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (≤2.0 V at a pulse width of 0.24 msec and an increase of ≤1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous ...

Journal ArticleDOI
02 Feb 2016-JAMA
TL;DR: Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometAsone alone reduced endoscopic nasal polyp burden after 16 weeks.
Abstract: Importance Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell–mediated diseases. Objective To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis. Design, Setting, and Participants A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up. Interventions Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks. Main Outcomes and Measures Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety. Results Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was −0.3 (95% CI, −1.0 to 0.4) with placebo and −1.9 (95% CI, −2.5 to −1.2) with dupilumab (LS mean difference, −1.6 [95% CI, −2.4 to −0.7]; P P P P Conclusions and Relevance Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications. Trial Registration clinicaltrials.gov Identifier:NCT01920893

Journal ArticleDOI
Haidong Wang1, Zulfiqar A Bhutta2, Zulfiqar A Bhutta3, Matthew M Coates1  +610 moreInstitutions (263)
TL;DR: The Global Burden of Disease 2015 Study provides an analytical framework to comprehensively assess trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time and decomposed the changes in under- 5 mortality to changes in SDI at the global level.