Showing papers by "Charles University in Prague published in 2017"
Charles University in Prague1, University of Regensburg2, First Faculty of Medicine, Charles University in Prague3, Imperial College London4, University of Hertfordshire5, Pierre-and-Marie-Curie University6, Autonomous University of Barcelona7, Netherlands Cancer Institute8, Medical University of Vienna9, European Association of Urology10, Medical University of Graz11
TL;DR: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice and the stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment.
1,910 citations
Population Health Research Institute1, Centra2, Charles University in Prague3, University of Washington Medical Center4, Brigham and Women's Hospital5, National University of Ireland, Galway6, University College London7, Jagiellonian University8, University of Würzburg9, Semmelweis University10, Karolinska Institutet11, University of the Philippines12, University of La Frontera13, University of Cape Town14, Aalborg University15, Katholieke Universiteit Leuven16, Catholic University of Korea17, Monash University18, Universiti Teknologi MARA19, Paris Diderot University20
TL;DR: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assign to aspirin alone.
Abstract: BackgroundWe evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. MethodsIn this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. ResultsThe primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1....
1,587 citations
TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.
1,573 citations
University of Oldenburg1, University of Vienna2, Zoological Society of London3, University College London4, International Union for Conservation of Nature and Natural Resources5, Lincoln University (New Zealand)6, Leibniz Association7, Free University of Berlin8, University of Auckland9, Academy of Sciences of the Czech Republic10, Stellenbosch University11, Charles University in Prague12, National and Kapodistrian University of Athens13, University of Fribourg14, University of Sassari15, University of Porto16, Sapienza University of Rome17, University of Konstanz18, Durham University19, University of Concepción20, Charles Darwin Foundation21, CABI22, University of Göttingen23, Helmholtz Centre for Environmental Research - UFZ24, Martin Luther University of Halle-Wittenberg25, United States Forest Service26, Bielefeld University27, Botanical Society of Britain and Ireland28, Environment Agency29, National Museum of Natural History30, Institut national de la recherche agronomique31, University of Silesia in Katowice32
TL;DR: In this paper, the authors used a database of 45,813 first records of 16,926 established alien species and showed that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970-2014).
Abstract: Although research on human-mediated exchanges of species has substantially intensified during the last centuries, we know surprisingly little about temporal dynamics of alien species accumulations across regions and taxa. Using a novel database of 45,813 first records of 16,926 established alien species, we show that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970-2014). Inter-continental and inter-taxonomic variation can be largely attributed to the diaspora of European settlers in the nineteenth century and to the acceleration in trade in the twentieth century. For all taxonomic groups, the increase in numbers of alien species does not show any sign of saturation and most taxa even show increases in the rate of first records over time. This highlights that past efforts to mitigate invasions have not been effective enough to keep up with increasing globalization.
1,301 citations
University of South Carolina1, Los Alamos National Laboratory2, Moscow State University3, Delhi Technological University4, University of Paris5, University of California, Davis6, Indian Institute of Technology (BHU) Varanasi7, University of Moratuwa8, University of Illinois at Urbana–Champaign9, California Polytechnic State University10, Sandia National Laboratories11, Max Planck Society12, Indian Institute of Technology Kharagpur13, French Institute for Research in Computer Science and Automation14, University of New Mexico15, Charles University in Prague16, Birla Institute of Technology and Science17, Indian Institute of Technology Bombay18, University of West Bohemia19
TL;DR: The architecture of SymPy is presented, a description of its features, and a discussion of select domain specific submodules are discussed, to become the standard symbolic library for the scientific Python ecosystem.
Abstract: SymPy is an open source computer algebra system written in pure Python. It is built with a focus on extensibility and ease of use, through both interactive and programmatic applications. These characteristics have led SymPy to become a popular symbolic library for the scientific Python ecosystem. This paper presents the architecture of SymPy, a description of its features, and a discussion of select submodules. The supplementary material provide additional examples and further outline details of the architecture and features of SymPy.
1,126 citations
McMaster University1, University of Montpellier2, Transylvania University3, Ghent University Hospital4, University of Sydney5, Humanitas University6, University of South Florida7, Leiden University Medical Center8, RMIT University9, Federal University of Bahia10, Pierre-and-Marie-Curie University11, Saint Louis University12, University of Porto13, Katholieke Universiteit Leuven14, Medical University of Łódź15, University of Tartu16, Oslo University Hospital17, Royal College of Surgeons in Ireland18, University of California, San Diego19, University of Barcelona20, University of Padua21, Monash University22, Charles University in Prague23, University of Manchester24, Ajou University25, University of Genoa26, Nippon Medical School27, University of Aberdeen28, University of Edinburgh29, Kerman Medical University30, Medical University of Warsaw31, National Institutes of Health32, Vilnius University33, University of Turku34, Nova Southeastern University35, Boston Children's Hospital36, Beijing Tongren Hospital37, Charité38
TL;DR: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR, addressing the relative merits of using oral H1‐antihistamines, intranasal H1-antihistsamines, IntranasAL corticosteroids, and leukotriene receptor antagonists either alone or in combination.
Abstract: Background Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. Objective We sought to provide a targeted update of the ARIA guidelines. Methods The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. Results The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. Conclusions Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.
1,098 citations
TL;DR: Different classes of HDAC inhibitors, mechanisms of their actions and novel results of preclinical and clinical studies are summarized, including the combination with other therapeutic modalities are discussed.
Abstract: Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.
815 citations
Karolinska University Hospital1, Karolinska Institutet2, Hospital of the University of Pennsylvania3, Great Ormond Street Hospital4, Brigham and Women's Hospital5, University of Kansas6, Mayo Clinic7, University of Alabama8, University of Pittsburgh9, Central Manchester University Hospitals NHS Foundation Trust10, University of Liverpool11, University of Debrecen12, University of Toronto13, University of Guadalajara14, University of Cambridge15, University of Tsukuba16, United States Department of Health and Human Services17, Tokyo Medical and Dental University18, Oregon State University19, Dalhousie University20, Peking University21, Duke University22, Oslo University Hospital23, New Generation University College24, Charles University in Prague25, National Institutes of Health26
TL;DR: New classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups, and have been partially validated and generally perform better than existing criteria.
Abstract: Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) ‘probable IIM’, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to ‘definite IIM’. A probability of Conclusions The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of ‘definite’, ‘probable’ and ‘possible’ IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.
754 citations
TL;DR: A fully-fledged particle-flow reconstruction algorithm tuned to the CMS detector was developed and has been consistently used in physics analyses for the first time at a hadron collider as mentioned in this paper.
Abstract: The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer. A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider. For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMS performance for jet and hadronic τ decay reconstruction, missing transverse momentum determination, and electron and muon identification. This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods. The data collected by CMS at a centre-of-mass energy of 8\TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.
719 citations
TL;DR: DeepStack is introduced, an algorithm for imperfect-information settings that combines recursive reasoning to handle information asymmetry, decomposition to focus computation on the relevant decision, and a form of intuition that is automatically learned from self-play using deep learning.
Abstract: Artificial intelligence has seen several breakthroughs in recent years, with games often serving as milestones. A common feature of these games is that players have perfect information. Poker, the quintessential game of imperfect information, is a long-standing challenge problem in artificial intelligence. We introduce DeepStack, an algorithm for imperfect-information settings. It combines recursive reasoning to handle information asymmetry, decomposition to focus computation on the relevant decision, and a form of intuition that is automatically learned from self-play using deep learning. In a study involving 44,000 hands of poker, DeepStack defeated, with statistical significance, professional poker players in heads-up no-limit Texas hold’em. The approach is theoretically sound and is shown to produce strategies that are more difficult to exploit than prior approaches.
713 citations
TL;DR: In this article, the authors discuss the building blocks of carbon nitride materials and examine how strategies in synthesis, templating and post-processing translate from the molecular level to macroscopic properties, such as optical and electronic bandgap.
Abstract: In the past decade, research in the field of artificial photosynthesis has shifted from simple, inorganic semiconductors to more abundant, polymeric materials For example, polymeric carbon nitrides have emerged as promising materials for metal-free semiconductors and metal-free photocatalysts Polymeric carbon nitride (melon) and related carbon nitride materials are desirable alternatives to industrially used catalysts because they are easily synthesized from abundant and inexpensive starting materials Furthermore, these materials are chemically benign because they do not contain heavy metal ions, thereby facilitating handling and disposal In this Review, we discuss the building blocks of carbon nitride materials and examine how strategies in synthesis, templating and post-processing translate from the molecular level to macroscopic properties, such as optical and electronic bandgap Applications of carbon nitride materials in bulk heterojunctions, laser-patterned memory devices and energy storage devices indicate that photocatalytic overall water splitting on an industrial scale may be realized in the near future and reveal a new avenue of ‘post-silicon electronics’ Carbon nitrides are potentially cheap and metal-free alternatives for catalysts, semiconductors, battery materials and memory devices In this Review, we discuss the synthesis, design and morphology of these materials, and reflect on the ability of methods such as templating, etching, dye sensitization, heteroatom doping and co-polymerization, as well as the assembly of various heterojunctions, to improve device performance
International Agency for Research on Cancer1, University of Bristol2, University Hospitals Bristol NHS Foundation Trust3, Vanderbilt University Medical Center4, University of Kentucky5, University of Copenhagen6, Lund University7, Technische Universität München8, Fred Hutchinson Cancer Research Center9, Harvard University10, Dartmouth College11, University of Liverpool12, Umeå University13, National Institute of Occupational Health14, New Generation University College15, Radboud University Nijmegen16, BC Cancer Agency17, Washington State University18, University of Hawaii19, Ontario Institute for Cancer Research20, University of Southern California21, Technion – Israel Institute of Technology22, University of Salzburg23, Curie Institute24, Nofer Institute of Occupational Medicine25, University of Ostrava26, Charles University in Prague27, Nanjing Medical University28, University of Oviedo29, University of Sheffield30, University of Texas MD Anderson Cancer Center31, University of Pittsburgh32, Lunenfeld-Tanenbaum Research Institute33
TL;DR: The results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma, and the latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.
Abstract: Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic ...
Icahn School of Medicine at Mount Sinai1, University of Calgary2, Charles University in Prague3, Bezmialem Foundation University4, Medical University of Vienna5, Catholic University of the Sacred Heart6, University of Nice Sophia Antipolis7, University of Oxford8, Humanitas University9, University of California, San Diego10, Katholieke Universiteit Leuven11, University of California, Los Angeles12, AbbVie13, University of Amsterdam14
TL;DR: This trial aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients management with a clinical management algorithm.
U. Bhawandeep1, Vardan Khachatryan, Albert M. Sirunyan, Armen Tumasyan +2289 more•Institutions (147)
TL;DR: In this paper, the trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions.
Abstract: This paper describes the CMS trigger system and its performance during Run 1 of the LHC. The trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions. The first level of the trigger is implemented in hardware, and selects events containing detector signals consistent with an electron, photon, muon, tau lepton, jet, or missing transverse energy. A programmable menu of up to 128 object-based algorithms is used to select events for subsequent processing. The trigger thresholds are adjusted to the LHC instantaneous luminosity during data taking in order to restrict the output rate to 100 kHz, the upper limit imposed by the CMS readout electronics. The second level, implemented in software, further refines the purity of the output stream, selecting an average rate of 400 Hz for offline event storage. The objectives, strategy and performance of the trigger system during the LHC Run 1 are described.
TL;DR: The third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016 is reported.
Abstract: Advances in the management of respiratory distress syndrome (RDS) ensure that clinicians must continue to revise current practice. We report the third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016. Optimizing the outcome for babies with RDS includes consideration of when to use antenatal steroids, and good obstetric practice includes methods of predicting the risk of preterm delivery and also consideration of whether transfer to a perinatal centre is necessary and safe. Methods for optimal delivery room management have become more evidence based, and protocols for lung protection, including initiation of continuous positive airway pressure and titration of oxygen, should be implemented from soon after birth. Surfactant replacement therapy is a crucial part of the management of RDS, and newer protocols for surfactant administration are aimed at avoiding exposure to mechanical ventilation, and there is more evidence of differences among various surfactants in clinical use. Newer methods of maintaining babies on non-invasive respiratory support have been developed and offer potential for greater comfort and less chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease although minimizing the time spent on mechanical ventilation using caffeine and if necessary postnatal steroids are also important considerations. Protocols for optimizing the general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.
University of Erlangen-Nuremberg1, University of Florence2, Utrecht University3, Paris Descartes University4, UCL Institute of Child Health5, Istanbul University6, Charles University in Prague7, University of Bonn8, VU University Amsterdam9, University of Paris10, University College London11, University of Grenoble12, University of Freiburg13, University of Greifswald14, University of Tübingen15, University of Ulm16, University of Lisbon17, University of Barcelona18, HCL Technologies19, Ludwig Maximilian University of Munich20
TL;DR: In patients with drug‐resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the second most common lesion in both groups.
Abstract: BackgroundDetailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. MethodsWe report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). ResultsThe onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of...
Karolinska University Hospital1, Karolinska Institutet2, Hospital of the University of Pennsylvania3, Great Ormond Street Hospital4, Brigham and Women's Hospital5, University of Kansas6, Mayo Clinic7, University of Pittsburgh8, Central Manchester University Hospitals NHS Foundation Trust9, University of Liverpool10, University of Debrecen11, University of Toronto12, University of Guadalajara13, University of Cambridge14, University of Tsukuba15, National Institutes of Health16, Tokyo Medical and Dental University17, Oregon State University18, Dalhousie University19, Peking University20, Duke University21, Oslo University Hospital22, New Generation University College23, Charles University in Prague24
TL;DR: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.
Abstract: Objective
To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.
Methods
Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria.
Results
Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) “probable IIM,” had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to “definite IIM.” A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50–<55% as “possible IIM.”
Conclusion
The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of “definite,” “probable,” and “possible” IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.
TL;DR: In this paper, an improved jet energy scale corrections, based on a data sample corresponding to an integrated luminosity of 19.7 fb^(-1) collected by the CMS experiment in proton-proton collisions at a center-of-mass energy of 8 TeV, are presented.
Abstract: Improved jet energy scale corrections, based on a data sample corresponding to an integrated luminosity of 19.7 fb^(-1) collected by the CMS experiment in proton-proton collisions at a center-of-mass energy of 8 TeV, are presented. The corrections as a function of pseudorapidity η and transverse momentum p_T are extracted from data and simulated events combining several channels and methods. They account successively for the effects of pileup, uniformity of the detector response, and residual data-simulation jet energy scale differences. Further corrections, depending on the jet flavor and distance parameter (jet size) R, are also presented. The jet energy resolution is measured in data and simulated events and is studied as a function of pileup, jet size, and jet flavor. Typical jet energy resolutions at the central rapidities are 15–20% at 30 GeV, about 10% at 100 GeV, and 5% at 1 TeV. The studies exploit events with dijet topology, as well as photon+jet, Z+jet and multijet events. Several new techniques are used to account for the various sources of jet energy scale corrections, and a full set of uncertainties, and their correlations, are provided. The final uncertainties on the jet energy scale are below 3% across the phase space considered by most analyses (p_T > 30 GeV and 0|η| 30 GeV is reached, when excluding the jet flavor uncertainties, which are provided separately for different jet flavors. A new benchmark for jet energy scale determination at hadron colliders is achieved with 0.32% uncertainty for jets with p_T of the order of 165–330 GeV, and |η| < 0.8.
TL;DR: Obinutuzumab‐based immunochemotherapy and maintenance therapy resulted in longer progression‐free survival than rituximab‐ based therapy.
Abstract: BackgroundRituximab-based immunochemotherapy has improved outcomes in patients with follicular lymphoma. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody. We compared rituximab-based chemotherapy with obinutuzumab-based chemotherapy in patients with previously untreated advanced-stage follicular lymphoma. MethodsWe randomly assigned patients to undergo induction treatment with obinutuzumab-based chemotherapy or rituximab-based chemotherapy. Patients with a response received maintenance treatment for up to 2 years with the same antibody that they had received in induction. The primary end point was investigator-assessed progression-free survival. ResultsA total of 1202 patients with follicular lymphoma underwent randomization (601 patients in each group). After a median follow-up of 34.5 months (range, 0 to 54.5), a planned interim analysis showed that obinutuzumab-based chemotherapy resulted in a significantly lower risk of progression, relapse, or death than rituximab-based chemoth...
TL;DR: This paper presents a short overview of the changes to the trigger and data acquisition systems during the first long shutdown of the LHC and shows the performance of the trigger system and its components based on the 2015 proton–proton collision data.
Abstract: During 2015 the ATLAS experiment recorded 3.8 fb(-1) of proton-proton collision data at a centre-of-mass energy of 13 TeV. The ATLAS trigger system is a crucial component of the experiment, respons ...
University of Southern Denmark1, Pfizer2, University of Paris3, University of Zaragoza4, University of East Anglia5, Montreal Heart Institute6, Leiden University Medical Center7, Technische Universität München8, Leiden University9, University of Amsterdam10, University of São Paulo11, University of the Witwatersrand12, Wrocław Medical University13, University of Maryland, Baltimore14, First Faculty of Medicine, Charles University in Prague15, Cleveland Clinic16, University of Manchester17, Auckland City Hospital18, Mayo Clinic19, Charles University in Prague20
TL;DR: In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococzumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower‐risk patients but did have a significant benefit in the Trial involving higher‐risk Patients.
Abstract: BackgroundBococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. MethodsIn two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10...
TL;DR: A rapid search in PubMed shows that using "flow cytometry immunology" as a search term yields more than 68 000 articles, the first of which is not about lymphocytes as mentioned in this paper.
Abstract: The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.
TL;DR: Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS and is exploited to apply a local energy calibration and corrections depending on the nature of the cluster.
Abstract: The reconstruction of the signal from hadrons and jets emerging from the proton–proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals. The resulting topological cell clusters have shape and location information, which is exploited to apply a local energy calibration and corrections depending on the nature of the cluster. Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS.
TL;DR: In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.
Abstract: Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, -4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%; P=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.
University Hospital Southampton NHS Foundation Trust1, University of Padua2, University of Southampton3, University Hospital of Bern4, University of Bern5, University of Western Australia6, Erasmus University Rotterdam7, University of Toronto8, Medical University of Graz9, University of Paris10, Leicester Royal Infirmary11, Imperial College London12, Katholieke Universiteit Leuven13, University of North Carolina at Chapel Hill14, Sapienza University of Rome15, Copenhagen University Hospital16, University of Paris-Sud17, Charles University in Prague18, Cochrane Collaboration19
TL;DR: This guideline focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence, and proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.
Abstract: The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.
International Agency for Research on Cancer1, Lunenfeld-Tanenbaum Research Institute2, Dartmouth College3, Harvard University4, National Institutes of Health5, University of Cambridge6, Copenhagen University Hospital7, University of Copenhagen8, Gentofte Hospital9, University of Texas MD Anderson Cancer Center10, University of Hawaii11, University of Göttingen12, Vanderbilt University Medical Center13, Case Western Reserve University14, University of Oviedo15, Technion – Israel Institute of Technology16, University of Sheffield17, University of Liverpool18, Radboud University Nijmegen19, Washington State University Spokane20, National Institute of Occupational Health21, BC Cancer Agency22, Nanjing Medical University23, New Generation University College24, University of Pittsburgh25, University of Milan26, Princess Margaret Cancer Centre27, University of Southern California28, Sejong University29, Lund University30, Imperial College London31, Aarhus University32, Prevention Institute33, Fred Hutchinson Cancer Research Center34, Technische Universität München35, Ludwig Maximilian University of Munich36, University Hospital Heidelberg37, Umeå University38, University of Kentucky39, Charles University in Prague40, University of Ostrava41, University of Belgrade42, Nofer Institute of Occupational Medicine43, University of Bergen44, National University of Singapore45, Institute of Cancer Research46, American Cancer Society47, Merck & Co.48, University of British Columbia49, University Medical Center Groningen50, National Institute for Health Research51, University of Leicester52, Amgen53, Research Triangle Park54, Washington University in St. Louis55, Baylor College of Medicine56, Anschutz Medical Campus57, University of Washington58, Centre for Addiction and Mental Health59, University of Toronto60, QIMR Berghofer Medical Research Institute61, Laval University62
TL;DR: 18 susceptibility loci achieving genome-wide significance are identified, including 10 new loci linked with lung cancer overall and six loci associated with lung adenocarcinoma, highlighting the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer.
Abstract: Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
TL;DR: The purpose of this CIRSE guideline is to provide a classification system of complications based on combining outcome and severity of sequelae, and the ultimate challenge will be the adoption of this system by practitioners in different countries and health economies within the European Union and beyond.
Abstract: Interventional radiology provides a wide variety of vascular, nonvascular, musculoskeletal, and oncologic minimally invasive techniques aimed at therapy or palliation of a broad spectrum of pathologic conditions. Outcome data for these techniques are globally evaluated by hospitals, insurance companies, and government agencies targeting in a high-quality health care policy, including reimbursement strategies. To analyze effectively the outcome of a technique, accurate reporting of complications is necessary. Throughout the literature, numerous classification systems for complications grading and classification have been reported. Until now, there has been no method for uniform reporting of complications both in terms of definition and grading. The purpose of this CIRSE guideline is to provide a classification system of complications based on combining outcome and severity of sequelae. The ultimate challenge will be the adoption of this system by practitioners in different countries and health economies within the European Union and beyond.
TL;DR: The first measurement of the tau lepton polarization P-tau(D*) in the decay (B) over bar -> D* tau(-) (v) over b (tau) as well as a new measurement of the ratio of the branching fractions was reported in this paper.
Abstract: We report the first measurement of the tau lepton polarization P-tau(D*) in the decay (B) over bar -> D* tau(-) (v) over bar (tau) as well as a newmeasurement of the ratio of the branching fractions R(D*) = B((B) over bar -> D* tau(-) (v) over bar (tau)) / B((B) over bar -> D* l(-) (v) over bar (l)), where l(-) denotes an electron or a muon, and the tau is reconstructed in the modes tau(-) -> pi(-) v(tau) and tau(-) -> rho(-) v(tau). We use the full data sample of 772 x 10(6) B (B) over bar pairs recorded with the Belle detector at the (KEKB) over bar electron-positron collider. Our results, P-tau(D*) = -0.38 +/- 0.51 (stat)(-0.16)(+0.21) (syst) and R(D*) = 0.270 +/- 0.035 (stat)(- 0.025)(+0.028) (syst), are consistent with the theoretical predictions of the standard model.
TL;DR: The Pierre Auger Collaboration reports the observation of thousands of cosmic rays with ultrahigh energies of several exa–electron volts, arriving in a slightly dipolar distribution, showing that they originate outside the Milky Way Galaxy.
Abstract: Cosmic rays are atomic nuclei arriving from outer space that reach the highest energies observed in nature Clues to their origin come from studying the distribution of their arrival directions Using 3 × 10 4 cosmic rays with energies above 8 × 10 18 electron volts, recorded with the Pierre Auger Observatory from a total exposure of 76,800 km 2 sr year, we determined the existence of anisotropy in arrival directions The anisotropy, detected at more than a 52σ level of significance, can be described by a dipole with an amplitude of 65 − 09 + 13 percent toward right ascension α d = 100 ± 10 degrees and declination δ d = − 24 − 13 + 12 degrees That direction indicates an extragalactic origin for these ultrahigh-energy particles
Paris Descartes University1, French Institute of Health and Medical Research2, university of lille3, Rappaport Faculty of Medicine4, University of Lübeck5, University of Padua6, University of Pécs7, University of the Witwatersrand8, University of Giessen9, University of Verona10, University of Zurich11, University of Bari12, Lund University13, Charles University in Prague14, Marche Polytechnic University15, University of Belgrade16, Sapienza University of Rome17, Carol Davila University of Medicine and Pharmacy18, University of Debrecen19, University of Basel20, Ghent University21, Federal University of Paraná22, University of Milan23, Policlinico Umberto I24, Katholieke Universiteit Leuven25, University of Waikato26, University of Otago27, University Hospital Centre Zagreb28, University of Alabama29, James Cook University Hospital30, Technische Universität München31, University of Buenos Aires32, Medical University of Białystok33, University of Florence34
TL;DR: Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality.
Abstract: Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.