Showing papers by "University of Barcelona published in 2015"
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.
5,792 citations
Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
4,510 citations
University of Helsinki1, Semmelweis University2, University of Szeged3, Hungarian Academy of Sciences4, University of Palermo5, University of Porto6, Institute of Molecular Pathology and Immunology of the University of Porto7, Autonomous University of Barcelona8, Instituto de Biologia Molecular e Celular9, Ikerbasque10, Harvard University11, University of Duisburg-Essen12, Salk Institute for Biological Studies13, Paracelsus Private Medical University of Salzburg14, University of Colorado Denver15, Bilkent University16, Middle East Technical University17, Statens Serum Institut18, University of Southern Denmark19, Ghent University Hospital20, Oslo University Hospital21, University of Belgrade22, University of Ljubljana23, University of Mainz24, Finnish Red Cross25, University of Gothenburg26, Latvian Biomedical Research and Study centre27, University of Applied Sciences and Arts Northwestern Switzerland FHNW28, University of Valencia29, Centro Nacional de Investigaciones Cardiovasculares30, University of Freiburg31, Utrecht University32, Trinity College, Dublin33, University of Barcelona34, Catalan Institution for Research and Advanced Studies35, International University Of Catalonia36, Aarhus University Hospital37
TL;DR: A comprehensive overview of the current understanding of the physiological roles of EVs is provided, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia.
Abstract: In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
3,690 citations
Proceedings Article•
01 Jan 2015TL;DR: This paper extends the idea of a student network that could imitate the soft output of a larger teacher network or ensemble of networks, using not only the outputs but also the intermediate representations learned by the teacher as hints to improve the training process and final performance of the student.
Abstract: While depth tends to improve network performances, it also makes gradient-based training more difficult since deeper networks tend to be more non-linear. The recently proposed knowledge distillation approach is aimed at obtaining small and fast-to-execute models, and it has shown that a student network could imitate the soft output of a larger teacher network or ensemble of networks. In this paper, we extend this idea to allow the training of a student that is deeper and thinner than the teacher, using not only the outputs but also the intermediate representations learned by the teacher as hints to improve the training process and final performance of the student. Because the student intermediate hidden layer will generally be smaller than the teacher's intermediate hidden layer, additional parameters are introduced to map the student hidden layer to the prediction of the teacher hidden layer. This allows one to train deeper students that can generalize better or run faster, a trade-off that is controlled by the chosen student capacity. For example, on CIFAR-10, a deep student network with almost 10.4 times less parameters outperforms a larger, state-of-the-art teacher network.
2,560 citations
Shadab Alam1, Franco D. Albareti2, Carlos Allende Prieto3, Carlos Allende Prieto4 +360 more•Institutions (102)
TL;DR: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrogram, and a novel optical interferometer.
Abstract: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 sq. deg of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-Object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include measured abundances of 15 different elements for each star. In total, SDSS-III added 2350 sq. deg of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 sq. deg; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5,513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra.
2,471 citations
TL;DR: In this article, the first set of parton distribution functions (PDFs) determined with a methodology validated by a closure test is presented, which is based on LO, NLO and NNLO QCD theory and also includes electroweak corrections.
Abstract: We present NNPDF3.0, the first set of parton distribution functions (PDFs) determined with a methodology validated by a closure test. NNPDF3.0 uses a global dataset including HERA-II deep-inelastic inclusive cross-sections, the combined HERA charm data, jet production from ATLAS and CMS, vector boson rapidity and transverse momentum distributions from ATLAS, CMS and LHCb, W+c data from CMS and top quark pair production total cross sections from ATLAS and CMS. Results are based on LO, NLO and NNLO QCD theory and also include electroweak corrections. To validate our methodology, we show that PDFs determined from pseudo-data generated from a known underlying law correctly reproduce the statistical distributions expected on the basis of the assumed experimental uncertainties. This closure test ensures that our methodological uncertainties are negligible in comparison to the generic theoretical and experimental uncertainties of PDF determination. This enables us to determine with confidence PDFs at different perturbative orders and using a variety of experimental datasets ranging from HERA-only up to a global set including the latest LHC results, all using precisely the same validated methodology. We explore some of the phenomenological implications of our results for the upcoming 13 TeV Run of the LHC, in particular for Higgs production cross-sections.
2,028 citations
Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
1,656 citations
Christopher J L Murray1, Ryan M Barber, Kyle J Foreman2, Ayse Abbasoglu Ozgoren +608 more•Institutions (251)
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.
1,609 citations
VU University Amsterdam1, Heidelberg University2, University of Barcelona3, Harvard University4, Complutense University of Madrid5, Lille University of Science and Technology6, Marche Polytechnic University7, Mayo Clinic8, Emory University9, Sapienza University of Rome10, University of Bologna11, University of Arkansas for Medical Sciences12, National and Kapodistrian University of Athens13, Cedars-Sinai Medical Center14, Erasmus University Rotterdam15, University of Navarra16, Centre Hospitalier Universitaire de Nantes17
TL;DR: The R-ISS is a simple and powerful prognostic staging system, and it is recommended for use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
Abstract: Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (l...
TL;DR: In this critical review, some of the most promising electrochemical tools for the treatment of wastewater contaminated by organic pollutants are discussed in detail and the critical assessment of the reactors that can be used to put these technologies into practice is devoted.
Abstract: Traditional physicochemical and biological techniques, as well as advanced oxidation processes (AOPs), are often inadequate, ineffective, or expensive for industrial water reclamation. Within this context, the electrochemical technologies have found a niche where they can become dominant in the near future, especially for the abatement of biorefractory substances. In this critical review, some of the most promising electrochemical tools for the treatment of wastewater contaminated by organic pollutants are discussed in detail with the following goals: (1) to present the fundamental aspects of the selected processes; (2) to discuss the effect of both the main operating parameters and the reactor design on their performance; (3) to critically evaluate their advantages and disadvantages; and (4) to forecast the prospect of their utilization on an applicable scale by identifying the key points to be further investigated. The review is focused on the direct electrochemical oxidation, the indirect electrochemical oxidation mediated by electrogenerated active chlorine, and the coupling between anodic and cathodic processes. The last part of the review is devoted to the critical assessment of the reactors that can be used to put these technologies into practice.
TL;DR: Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples that are dominated by a relatively small number of genes, though few are exclusive to a particular tissue and vary more across tissues than individuals.
Abstract: Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes—which is most clearly seen in blood—though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.
TL;DR: Laroscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery.
Abstract: Background Laparoscopic resection of colorectal cancer is widely used. However, robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking. A trial was designed to compare 3-year rates of cancer recurrence in the pelvic or perineal area (locoregional recurrence) and survival after laparoscopic and open resection of rectal cancer. Methods In this international trial conducted in 30 hospitals, we randomly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge, not invading adjacent tissues, and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio. The primary end point was locoregional recurrence 3 years after the index surgery. Secondary end points included disease-free and overall survival. Results A total of 1044 patients were included (699 in the laparoscopic-surgery group and 345 in the open-surgery group). At 3 years, the locoregional recurrence rate was 5.0% in the ...
TL;DR: In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality.
TL;DR: New metabolic checkpoints for T cell activity are uncovered and it is demonstrated that metabolic reprogramming of tumor-reactive T cells can enhance anti-tumor T cell responses, illuminating new forms of immunotherapy.
Paracelsus Private Medical University of Salzburg1, University of Duisburg-Essen2, Semmelweis University3, University of Turin4, Institut Gustave Roussy5, Brown University6, Pontifical Catholic University of Chile7, University of Barcelona8, Trinity College, Dublin9, Istituto Superiore di Sanità10, Ikerbasque11, Pohang University of Science and Technology12, University of Louisville13, Ghent University Hospital14, La Trobe University15, Harvard University16, National University of Singapore17, Maastricht University18, University of Mainz19, University of Cambridge20, Utrecht University21, Agency for Science, Technology and Research22, University of Gothenburg23, University of Valencia24, University of Freiburg25, Aalborg University26, National Research Council27, Paul Ehrlich Institute28, German Red Cross29, University of Oxford30, Karolinska Institutet31
TL;DR: In this paper, the authors summarize recent developments and the current knowledge of extracellular vesicles (EVs) and discuss safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application.
Abstract: Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
TL;DR: Data from genomic profiling enabled a proposal of HCC in 2 major molecular clusters (proliferation and non Proliferation), with differential enrichment in prognostic signatures, pathway activation and tumor phenotype, which helps define some of the core deregulated pathways in HCC.
TL;DR: In this paper, the performance of the various LHCb sub-detectors and the trigger system are described, using data taken from 2010 to 2012, and it is shown that the design criteria of the experiment have been met.
Abstract: The LHCb detector is a forward spectrometer at the Large Hadron Collider (LHC) at CERN. The experiment is designed for precision measurements of CP violation and rare decays of beauty and charm hadrons. In this paper the performance of the various LHCb sub-detectors and the trigger system are described, using data taken from 2010 to 2012. It is shown that the design criteria of the experiment have been met. The excellent performance of the detector has allowed the LHCb collaboration to publish a wide range of physics results, demonstrating LHCb's unique role, both as a heavy flavour experiment and as a general purpose detector in the forward region.
École Polytechnique Fédérale de Lausanne1, Paris Diderot University2, University of California, Irvine3, Lawrence Berkeley National Laboratory4, Brookhaven National Laboratory5, Max Planck Society6, University of Portsmouth7, New Mexico State University8, University of Utah9, Harvard University10, University of Barcelona11, Aix-Marseille University12, University of Wyoming13, Pierre-and-Marie-Curie University14, Carnegie Mellon University15, Institut d'Astrophysique de Paris16, Drexel University17, Sejong University18, Pennsylvania State University19, Ohio State University20, University of Chicago21
TL;DR: In this paper, a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly forest of high-redshift quasars with a statistical significance of five standard deviations was reported.
Abstract: We report a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly forest of high-redshift quasars with a statistical significance of five standard deviations The study uses 137,562 quasars in the redshift range 2:1 z 3:5 from the Data Release 11 (DR11) of the Baryon Oscillation Spectroscopic Survey (BOSS) of SDSS-III This sample contains three times the number of quasars used in previous studies The measured position of the BAO peak determines the angular distance, DA(z = 2:34) and expansion rate, H(z = 2:34), both on a scale set by the sound horizon at the drag epoch, rd We find DA=rd =
TL;DR: In this article, the pentaquark-charmonium states were observed in the J/ψp channel in Λ0b→J/K−p decays and the significance of these resonances is more than 9 standard deviations.
Abstract: Observations of exotic structures in the J/ψp channel, that we refer to as pentaquark-charmonium states, in Λ0b→J/ψK−p decays are presented. The data sample corresponds to an integrated luminosity of 3/fb acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis is performed on the three-body final-state that reproduces the two-body mass and angular distributions. To obtain a satisfactory fit of the structures seen in the J/ψp mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each describe a resonant state. The significance of each of these resonances is more than 9 standard deviations. One has a mass of 4380±8±29 MeV and a width of 205±18±86 MeV, while the second is narrower, with a mass of 4449.8±1.7±2.5 MeV and a width of 39±5±19 MeV. The preferred JP assignments are of opposite parity, with one state having spin 3/2 and the other 5/2.
University of Barcelona1, Hacettepe University2, Cajal Institute3, European Medicines Agency4, University of Antwerp5, Brighton and Sussex Medical School6, GlaxoSmithKline7, Radboud University Nijmegen8, European Centre for Disease Prevention and Control9, Center for Disease Dynamics, Economics & Policy10, European Food Safety Authority11, University of Seville12, Southmead Hospital13, University College Dublin14, Aix-Marseille University15, Carlos III Health Institute16, University of Tübingen17, University of Warwick18
TL;DR: The views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies are summarized, providing expert recommendations to tackle the global threat of antimacterial resistance.
Abstract: In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.
TL;DR: Stricker et al. as discussed by the authors performed whole-exome sequencing of 86 matched brain metastases, primary tumors, and normal tissue and found potentially clinically informative alterations in the brain metastasis not detected in the matched primary-tumor sample.
Abstract: Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors, and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases.
Significance: Decisions for individualized therapies in patients with brain metastasis are often made from primary-tumor biopsies. We demonstrate that clinically actionable alterations present in brain metastases are frequently not detected in primary biopsies, suggesting that sequencing of primary biopsies alone may miss a substantial number of opportunities for targeted therapy. Cancer Discov; 5(11); 1164–77. ©2015 AACR .
See related commentary by Stricker and Arteaga, [p. 1124][1] .
This article is highlighted in the In This Issue feature, [p. 1111][2]
[1]: /lookup/volpage/5/1124?iss=11
[2]: /lookup/volpage/5/1111?iss=11
University of Barcelona1, Nihon University2, Taipei Veterans General Hospital3, Kindai University4, Peking Union Medical College5, Queen Mary University of London6, Kyungpook National University7, Asan Medical Center8, Tianjin Medical University9, Lenox Hill Hospital10, University of Bologna11, University of Tokyo12, Bayer HealthCare Pharmaceuticals13, Mount Sinai Hospital14
TL;DR: The data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation.
Abstract: Summary Background There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation. Methods We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice-response system. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770. Findings We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12·5 months (IQR 2·6–35·8) and 577 mg per day (SD 212·8) for sorafenib, compared with 22·2 months (8·1–38·8) and 778·0 mg per day (79·8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow-up for recurrence-free survival was 8·5 months (IQR 2·9–19·5) in the sorafenib group and 8·4 months (2·9–19·8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33·3 months in the sorafenib group vs 33·7 months in the placebo group; hazard ratio [HR] 0·940; 95% CI 0·780–1·134; one-sided p=0·26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [ vs five [ Interpretation Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation. Funding Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals.
TL;DR: This paper introduces a novel polyp localization method for colonoscopy videos based on a model of appearance for polyps which defines polyp boundaries in terms of valley information and proves that this method outperforms state-of-the-art computational saliency results.
TL;DR: It is found limited evidence for a causal relationship between surrounding greenness and mental health in adults, whereas the evidence was inadequate in children, and recommendations are provided in order to provide consistent and evidence-based recommendations for policy makers.
Abstract: Many studies conducted during the last decade suggest the mental health benefits of green and blue spaces. We aimed to systematically review the available literature on the long-term mental health benefits of residential green and blue spaces by including studies that used standardized tools or objective measures of both the exposures and the outcomes of interest. We followed the PRISMA statement guidelines for reporting systematic reviews and meta-analysis. In total 28 studies were included in the systematic review. We found limited evidence for a causal relationship between surrounding greenness and mental health in adults, whereas the evidence was inadequate in children. The evidence was also inadequate for the other exposures evaluated (access to green spaces, quality of green spaces, and blue spaces) in both adults and children. The main limitation was the limited number of studies, together with the heterogeneity regarding exposure assessment. Given the increase in mental health problems and the current rapid urbanization worldwide, results of the present systematic review should be taken into account in future urban planning. However, further research is needed to provide more consistent evidence and more detailed information on the mechanisms and the characteristics of the green and blue spaces that promote better mental health. We provide recommendations for future studies in order to provide consistent and evidence-based recommendations for policy makers.
University of Southern Denmark1, Brigham and Women's Hospital2, University of Barcelona3, Autonomous University of Madrid4, University of Arizona5, University of Colorado Denver6, Manchester Academic Health Science Centre7, Autonomous University of Chile8, Harvard University9, Lovelace Respiratory Research Institute10, University of New Mexico11
TL;DR: It is suggested that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline inFEV1 is not an obligate feature of COPd.
Abstract: BackgroundChronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. MethodsWe stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. ResultsAmong 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseli...
Boston Children's Hospital1, NewYork–Presbyterian Hospital2, University of Chicago3, University of Chile4, Ohio State University5, University of Barcelona6, University of Adelaide7, Georgetown University8, Baylor College of Medicine9, American University of Beirut10, University of Pittsburgh11, Sanjay Gandhi Post Graduate Institute of Medical Sciences12
TL;DR: While obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls.
Abstract: Background/Aims: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescence are controversial, primarily because the diagnostic pathological feat
Metropolitan State University of Denver1, University of Catania2, University of California, Berkeley3, Qingdao Agricultural University4, University of Lyon5, United States Department of Agriculture6, University of Minnesota7, Michigan State University8, Hungarian Academy of Sciences9, Hokkaido University10, University of Barcelona11, ENEA12, Corvinus University of Budapest13, Oregon State University14, University of Nice Sophia Antipolis15
TL;DR: It is concluded that particularly fruitful areas of research should include fundamental studies of its overwintering, host-use, and dispersal capabilities; as well as applied studies of alternative, cost-effective management techniques to complement insecticide use within the integrated pest management framework.
Abstract: The Asian vinegar fly Drosophila suzukii (spotted wing Drosophila (SWD)) has emerged as a major invasive insect pest of small and stone fruits in both the Americas and Europe since the late 2000s. While research efforts have rapidly progressed in Asia, North America, and Europe over the past 5 years, important new insights may be gained in comparing and contrasting findings across the regions affected by SWD. In this review, we explore common themes in the invasion biology of SWD by examining (1) its biology and current pest status in endemic and recently invaded regions; (2) current efforts and future research needs for the development of predictive models for its geographic expansion; and (3) prospects for both natural and classical (=importation) biological control of SWD in invaded habitats, with emphasis on the role of hymenopteran parasitoids. We conclude that particularly fruitful areas of research should include fundamental studies of its overwintering, host-use, and dispersal capa- bilities; as well as applied studies of alternative, cost-ef- fective management techniques to complement insecticide use within the integrated pest management framework. Finally, we emphasize that outreach efforts are critical to effective SWD management by highlighting successful
TL;DR: This project reached consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments, and provides an insight into the current worldwide treatment of these conditions.
Abstract: Background Despite extensive knowledge regarding the diagnosis and management of keratoconus and ectatic corneal diseases, many controversies still exist. For that reason, there is a need for current guidelines for the diagnosis and management of these conditions. Purpose This project aimed to reach consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments. Methods The Delphi method was followed with 3 questionnaire rounds and was complemented with a face-to-face meeting. Thirty-six panelists were involved and allocated to 1 of 3 panels: definition/diagnosis, nonsurgical management, or surgical treatment. The level of agreement considered for consensus was two thirds. Results Numerous agreements were generated in definitions, methods of diagnosing, and management of keratoconus and other ectatic diseases. Nonsurgical and surgical treatments for these conditions, including the use of corneal cross-linking and corneal transplantations, were presented in a stepwise approach. A flowchart describing a logical management sequence for keratoconus was created. Conclusions This project resulted in definitions, statements, and recommendations for the diagnosis and management of keratoconus and other ectatic diseases. It also provides an insight into the current worldwide treatment of these conditions.