Showing papers by "Charles University in Prague published in 2016"
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
TL;DR: In this article, the authors used a Bayesian hierarchical model to estimate trends in diabetes prevalence, defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs in 200 countries and territories in 21 regions, by sex and from 1980 to 2014.
2,782 citations
James Bentham1, Mariachiara Di Cesare2, Mariachiara Di Cesare1, Gretchen A Stevens3 +787 more•Institutions (246)
TL;DR: The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
1,348 citations
University of Turin1, Mayo Clinic2, University of Tübingen3, Emory University4, Semmelweis University5, Ankara University6, Charles University in Prague7, University of Mainz8, Cornell University9, Johnson & Johnson Pharmaceutical Research and Development10, Janssen Pharmaceutica11, Monash University12, Erasmus University Rotterdam13
TL;DR: Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than borteonib and DexamethAsone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia.
Abstract: BackgroundDaratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. MethodsIn this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. ResultsA prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period ...
1,135 citations
Proceedings Article•
01 May 2016
TL;DR: This paper describes v1 of the universal guidelines, the underlying design principles, and the currently available treebanks for 33 languages, as well as highlighting the needs for sound comparative evaluation and cross-lingual learning experiments.
Abstract: Cross-linguistically consistent annotation is necessary for sound comparative evaluation and cross-lingual learning experiments. It is also useful for multilingual system development and comparative linguistic studies. Universal Dependencies is an open community effort to create cross-linguistically consistent treebank annotation for many languages within a dependency-based lexicalist framework. In this paper, we describe v1 of the universal guidelines, the underlying design principles, and the currently available treebanks for 33 languages.
1,111 citations
TL;DR: In this paper, the authors demonstrate room-temperature electrical switching between stable configurations in antiferromagnetic CuMnAs thin-film devices by applied current with magnitudes of order 106 ampere per square centimeter.
Abstract: Antiferromagnets are hard to control by external magnetic fields because of the alternating directions of magnetic moments on individual atoms and the resulting zero net magnetization. However, relativistic quantum mechanics allows for generating current-induced internal fields whose sign alternates with the periodicity of the antiferromagnetic lattice. Using these fields, which couple strongly to the antiferromagnetic order, we demonstrate room-temperature electrical switching between stable configurations in antiferromagnetic CuMnAs thin-film devices by applied current with magnitudes of order 106 ampere per square centimeter. Electrical writing is combined in our solid-state memory with electrical readout and the stored magnetic state is insensitive to and produces no external magnetic field perturbations, which illustrates the unique merits of antiferromagnets for spintronics.
1,008 citations
Norfolk and Norwich University Hospital1, University of East Anglia2, Leiden University Medical Center3, University of Barcelona4, Claude Bernard University Lyon 15, University of Kiel6, Tallaght Hospital7, University of Oxford8, University of Paris9, University of Pennsylvania10, Linköping University11, Charles University in Prague12, Lund University13, Ankara University14
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.
893 citations
National Institutes of Health1, European Society of Cardiology2, Ghent University3, Karolinska Institutet4, Lille University of Science and Technology5, Charles University in Prague6, Hospital Universitario La Paz7, University of Sarajevo8, Shupyk National Medical Academy of Postgraduate Education9, University of Latvia10, Ljubljana University Medical Centre11, University of Ioannina12, University of Würzburg13, Vilnius University14, University Hospital Centre Zagreb15, Nicosia General Hospital16, Jagiellonian University Medical College17, University of Zagreb18, Valve Corporation19, Hacettepe University20, University of Banja Luka21
TL;DR: A large majority of coronary patients do not achieve the guideline standards for secondary prevention with high prevalences of persistent smoking, unhealthy diets, physical inactivity and consequently most patients are overweight or obese with a high prevalence of diabetes.
Abstract: AimsTo determine whether the Joint European Societies guidelines on cardiovascular prevention are being followed in everyday clinical practice of secondary prevention and to describe the lifestyle,...
833 citations
TL;DR: The Jiangmen Underground Neutrino Observatory (JUNO) as mentioned in this paper is a 20kton multi-purpose underground liquid scintillator detector with the determination of neutrino mass hierarchy (MH) as a primary physics goal.
Abstract: The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purpose underground liquid scintillator detector, was proposed with the determination of the neutrino mass hierarchy (MH) as a primary physics goal. The excellent energy resolution and the large fiducial volume anticipated for the JUNO detector offer exciting opportunities for addressing many important topics in neutrino and astro-particle physics. In this document, we present the physics motivations and the anticipated performance of the JUNO detector for various proposed measurements. Following an introduction summarizing the current status and open issues in neutrino physics, we discuss how the detection of antineutrinos generated by a cluster of nuclear power plants allows the determination of the neutrino MH at a 3–4σ significance with six years of running of JUNO. The measurement of antineutrino spectrum with excellent energy resolution will also lead to the precise determination of the neutrino oscillation parameters ${\mathrm{sin}}^{2}{\theta }_{12}$, ${\rm{\Delta }}{m}_{21}^{2}$, and $| {\rm{\Delta }}{m}_{{ee}}^{2}| $ to an accuracy of better than 1%, which will play a crucial role in the future unitarity test of the MNSP matrix. The JUNO detector is capable of observing not only antineutrinos from the power plants, but also neutrinos/antineutrinos from terrestrial and extra-terrestrial sources, including supernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos, atmospheric neutrinos, and solar neutrinos. As a result of JUNO's large size, excellent energy resolution, and vertex reconstruction capability, interesting new data on these topics can be collected. For example, a neutrino burst from a typical core-collapse supernova at a distance of 10 kpc would lead to ∼5000 inverse-beta-decay events and ∼2000 all-flavor neutrino–proton ES events in JUNO, which are of crucial importance for understanding the mechanism of supernova explosion and for exploring novel phenomena such as collective neutrino oscillations. Detection of neutrinos from all past core-collapse supernova explosions in the visible universe with JUNO would further provide valuable information on the cosmic star-formation rate and the average core-collapse neutrino energy spectrum. Antineutrinos originating from the radioactive decay of uranium and thorium in the Earth can be detected in JUNO with a rate of ∼400 events per year, significantly improving the statistics of existing geoneutrino event samples. Atmospheric neutrino events collected in JUNO can provide independent inputs for determining the MH and the octant of the ${\theta }_{23}$ mixing angle. Detection of the (7)Be and (8)B solar neutrino events at JUNO would shed new light on the solar metallicity problem and examine the transition region between the vacuum and matter dominated neutrino oscillations. Regarding light sterile neutrino topics, sterile neutrinos with ${10}^{-5}\,{{\rm{eV}}}^{2}\lt {\rm{\Delta }}{m}_{41}^{2}\lt {10}^{-2}\,{{\rm{eV}}}^{2}$ and a sufficiently large mixing angle ${\theta }_{14}$ could be identified through a precise measurement of the reactor antineutrino energy spectrum. Meanwhile, JUNO can also provide us excellent opportunities to test the eV-scale sterile neutrino hypothesis, using either the radioactive neutrino sources or a cyclotron-produced neutrino beam. The JUNO detector is also sensitive to several other beyondthe-standard-model physics. Examples include the search for proton decay via the $p\to {K}^{+}+\bar{
u }$ decay channel, search for neutrinos resulting from dark-matter annihilation in the Sun, search for violation of Lorentz invariance via the sidereal modulation of the reactor neutrino event rate, and search for the effects of non-standard interactions. The proposed construction of the JUNO detector will provide a unique facility to address many outstanding crucial questions in particle and astrophysics in a timely and cost-effective fashion. It holds the great potential for further advancing our quest to understanding the fundamental properties of neutrinos, one of the building blocks of our Universe.
807 citations
TL;DR: The foundation of a conceptual framework for selecting appropriate indicators for targets from existing sets or formulating new ones is argued for and some recommendations for indicators providers are offered in order to contribute to the tremendous amount of conceptual work needed to lay a strong foundation for the development of the final indicators framework.
803 citations
University of Paris1, Medical University of Vienna2, Leiden University3, Paris Descartes University4, University of Leeds5, Ruhr University Bochum6, Charité7, University College Dublin8, Halmstad University9, Katholieke Universiteit Leuven10, University of Münster11, University of Glasgow12, Charles University in Prague13, University of Erlangen-Nuremberg14, Ghent University Hospital15
TL;DR: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.
Abstract: Background Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. Methods A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. Results The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. Conclusions These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.
TL;DR: This guideline was produced by a multidisciplinary group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to September 2014 and consensus within the guideline group on all recommendations.
Abstract: study question: What is the optimal management of women with premature ovarian insufficiency (POI) based on the best available
evidence in the literature?
summary answer: The guideline development group (GDG) formulated 99 recommendations answering 31 key questions on the
diagnosis and treatment of women with POI.
what is known already: NA.
study design, size, duration: This guideline was produced by a multidisciplinary group of experts in the field using the methodology
of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included
papers up to September 2014 and consensus within the guideline group on all recommendations. The GDG included a patient representative
to ensure input from women with POI. After finalization of the draft, the European Society for Human Reproduction and Embryology
(ESHRE) members and professional organizations were asked to review the guideline.
participants/materials, setting, methods: NA.
main results and the role of chance: The guideline provides 17 recommendations on diagnosis and assessment of POI and 46
recommendations on the different sequelae of POI and their consequences for monitoring and treatment. Furthermore, 24 recommendations
were formulated on hormone replacement therapy in women with POI, and two on alternative and complementary treatment. A chapter on
puberty induction resulted in five recommendations.
limitations, reasons for caution: The main limitation of the guideline is that, due to the lack of data, many of the recommendations
are based on expert opinion or indirect evidence from studies on post-menopausal women or women with Turner Syndrome.
wider implications of the findings: Despite the limitations, the guideline group is confident that this document will be able to
guide health care professionals in providing the best practice for managing women with POI given current evidence. Furthermore, the guideline
grouphas formulated research recommendations on the gaps in knowledge identified in the literature searches, in an attempt to stimulate research
on the key issues in POI.
Carlos III Health Institute1, University of Brescia2, University of Glasgow3, Istanbul University4, Haukeland University Hospital5, University of Erlangen-Nuremberg6, University of Valencia7, Heidelberg University8, Charles University in Prague9, Guy's and St Thomas' NHS Foundation Trust10, Aristotle University of Thessaloniki11, University of Manchester12, University of Milan13
TL;DR: The recommendations of the present document represent the best clinical wisdom upon which physicians, nurses and families should base their decisions and should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.
Abstract: Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.
Memorial Sloan Kettering Cancer Center1, Humanitas University2, Harvard University3, University of Bologna4, University of California, Los Angeles5, Mayo Clinic6, University of Texas MD Anderson Cancer Center7, Princess Margaret Cancer Centre8, Emory University9, Churchill Hospital10, Charles University in Prague11, Bristol-Myers Squibb12, Brigham and Women's Hospital13
TL;DR: Nivolumab resulted in frequent responses with an acceptable safety profile in patients with classical Hodgkin's lymphoma who progressed after autologous stem-cell transplantation and brentuximab vedotin, and might be a new treatment option for a patient population with a high unmet need.
Abstract: Summary Background Malignant cells of classical Hodgkin's lymphoma are characterised by genetic alterations at the 9p24.1 locus, leading to overexpression of PD-1 ligands and evasion of immune surveillance. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed and refractory classical Hodgkin's lymphoma, with an acceptable safety profile. We aimed to assess the clinical benefit and safety of nivolumab monotherapy in patients with classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin. Methods In this ongoing, single-arm phase 2 study, adult patients (aged ≥18 years) with recurrent classical Hodgkin's lymphoma who had failed to respond to autologous stem-cell transplantation and had either relapsed after or failed to respond to brentuximab vedotin, and with an Eastern Cooperative Oncology Group performance status score of 0 or 1, were enrolled from 34 hospitals and academic centres across Europe and North America. Patients were given nivolumab intravenously over 60 min at 3 mg/kg every 2 weeks until progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response following a prespecified minimum follow-up period of 6 months, assessed by an independent radiological review committee (IRRC). All patients who received at least one dose of nivolumab were included in the primary and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02181738. Findings Among 80 treated patients recruited between Aug 26, 2014, and Feb 20, 2015, the median number of previous therapies was four (IQR 4–7). At a median follow-up of 8·9 months (IQR 7·8–9·9), 53 (66·3%, 95% CI 54·8–76·4) of 80 patients achieved an IRRC-assessed objective response. The most common drug-related adverse events (those that occurred in ≥15% of patients) included fatigue (20 [25%] patients), infusion-related reaction (16 [20%]), and rash (13 [16%]). The most common drug-related grade 3 or 4 adverse events were neutropenia (four [5%] patients) and increased lipase concentrations (four [5%]). The most common serious adverse event (any grade) was pyrexia (three [4%] patients). Three patients died during the study; none of these deaths were judged to be treatment related. Interpretation Nivolumab resulted in frequent responses with an acceptable safety profile in patients with classical Hodgkin's lymphoma who progressed after autologous stem-cell transplantation and brentuximab vedotin. Therefore, nivolumab might be a new treatment option for a patient population with a high unmet need. Ongoing follow-up will help to assess the durability of response. Funding Bristol-Myers Squibb.
University of Amsterdam1, University College London2, Sheba Medical Center3, National and Kapodistrian University of Athens4, Paris Descartes University5, Centre Hospitalier Regional et Universitaire de Lille6, Lille University of Science and Technology7, University of Turin8, Maastricht University9, French Institute of Health and Medical Research10, Seconda Università degli Studi di Napoli11, Charles University in Prague12, Odense University Hospital13, University Medical Center Groningen14, University Medical Center15, Freeman Hospital16, University of Padua17
TL;DR: A revised definition of dilated cardiomyopathy (DCM) is proposed in an attempt to bridge the gap between recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures.
Abstract: In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.
Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam +2283 more•Institutions (141)
TL;DR: Combined fits to CMS UE proton–proton data at 7TeV and to UEProton–antiproton data from the CDF experiment at lower s, are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13.
Abstract: New sets of parameters ("tunes") for the underlying-event (UE) modeling of the PYTHIA8, PYTHIA6 and HERWIG++ Monte Carlo event generators are constructed using different parton distribution functions. Combined fits to CMS UE data at sqrt(s) = 7 TeV and to UE data from the CDF experiment at lower sqrt(s), are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13 TeV. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons of the UE tunes to "minimum bias" (MB) events, multijet, and Drell-Yan (q q-bar to Z / gamma* to lepton-antilepton + jets) observables at 7 and 8 TeV are presented, as well as predictions of MB and UE observables at 13 TeV.
12 Aug 2016
TL;DR: The results of the WMT16 shared tasks are presented, which included five machine translation (MT) tasks (standard news, IT-domain, biomedical, multimodal, pronoun), three evaluation tasks (metrics, tuning, run-time estimation of MT quality), and an automatic post-editing task and bilingual document alignment task.
Abstract: This paper presents the results of the WMT16 shared tasks, which included five machine translation (MT) tasks (standard news, IT-domain, biomedical, multimodal, pronoun), three evaluation tasks (metrics, tuning, run-time estimation of MT quality), and an automatic post-editing task and bilingual document alignment task. This year, 102 MT systems from 24 institutions (plus 36 anonymized online systems) were submitted to the 12 translation directions in the news translation task. The IT-domain task received 31 submissions from 12 institutions in 7 directions and the Biomedical task received 15 submissions systems from 5 institutions. Evaluation was both automatic and manual (relative ranking and 100-point scale assessments). The quality estimation task had three subtasks, with a total of 14 teams, submitting 39 entries. The automatic post-editing task had a total of 6 teams, submitting 11 entries.
German Cancer Research Center1, University of Barcelona2, National University of Colombia3, Manchester Royal Infirmary4, Charles University in Prague5, University of Ljubljana6, Universidad Nacional de Asunción7, University of Birmingham8, Université de Montréal9, Pompeu Fabra University10, Mexican Social Security Institute11, Catholic University of Korea12, University of Lagos13, Bangabandhu Sheikh Mujib Medical University14, Hospital General de México15, NewYork–Presbyterian Hospital16, Gomel State Medical University17, Instituto Português de Oncologia Francisco Gentil18, University of the Philippines19, Koç University20, Hacettepe University21, Indian Council of Medical Research22, University of Hawaii23, Cedars-Sinai Medical Center24, Hospital General San Juan de Dios25, Universidad Nacional Autónoma de Honduras26, Bayero University Kano27, Central University of Venezuela28, University of Chile29, Instituto Potosino de Investigación Científica y Tecnológica30
TL;DR: This large international study to estimate fractions of head and neck cancers attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation confirms the important role ofHPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.
Abstract: BACKGROUND:
We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation.
METHODS:
Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results.
RESULTS:
A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America.
CONCLUSIONS:
HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.
Population Health Research Institute1, McMaster University2, Peking Union Medical College3, St. John's University4, University of Cape Town5, University of the Philippines Manila6, Semmelweis University7, University of Amsterdam8, Uppsala University9, UCSI University10, Technion – Israel Institute of Technology11, Charles University in Prague12, National Academy of Sciences of Ukraine13, University of Leicester14, Glenfield Hospital15, Curtin University16, Monash University17, University of Toronto18, University of Caldas19, Laval University20
TL;DR: Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a doses of 12.5mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease.
Abstract: BackgroundAntihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. MethodsIn one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. ResultsThe mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo...
TL;DR: The combination of fludarabine, cyclophosphamide, and rituximab remains the standard front-line therapy in fit patients with chronic lymphocytic leukaemia, but bendamustine and riteximab is associated with less toxic effects.
Abstract: Summary Background Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less toxic combination consisting of bendamustine and rituximab. Methods Treatment-naive fit patients with chronic lymphocytic leukaemia (aged 33–81 years) without del(17p) were enrolled after undergoing a central screening process. Patients were randomly assigned (1:1) with a computer-generated randomisation list using randomly permuted blocks with a block size of eight and were stratified according to participating country and Binet stage. Patients were allocated to receive six cycles of intravenous fludarabine (25 mg/m 2 per day) and cyclophosphamide (250 mg/m 2 per day) for the first 3 days or to intravenous bendamustine (90 mg/m 2 per day) for the first 2 days of each cycle. Rituximab 375 mg/m 2 was given intravenously in both groups on day 0 of cycle 1 and subsequently was given at 500 mg/m 2 during the next five cycles on day 1. The primary endpoint was progression-free survival with the objective to assess non-inferiority of bendamustine and rituximab to the standard therapy. We aimed to show that the 2-year progression-free survival with bendamustine and rituximab was not 67·5% or less with a corresponding non-inferiority margin of 1·388 for the hazard ratio (HR) based on the 90·4% CI. The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. Findings 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included in the intention-to-treat population: 282 patients in the fludarabine, cyclophosphamide, and rituximab group and 279 in the bendamustine and rituximab group. After a median observation time of 37·1 months (IQR 31·0–45·5) median progression-free survival was 41·7 months (95% CI 34·9–45·3) with bendamustine and rituximab and 55·2 months (95% CI not evaluable) with fludarabine, cyclophosphamide, and rituximab (HR 1·643, 90·4% CI 1·308–2·064). As the upper limit of the 90·4% CI was greater than 1·388 the null hypothesis for the corresponding non-inferiority hypothesis was not rejected. Severe neutropenia and infections were more frequently observed with fludarabine, cyclophosphamide, and rituximab (235 [84%] of 279 vs 164 [59%] of 278, and 109 [39%] vs 69 [25%], respectively) during the study. The increased frequency of infectious complications with fludarabine, cyclophosphamide, and rituximab was more pronounced in patients older than 65 years. Interpretation The combination of fludarabine, cyclophosphamide, and rituximab remains the standard front-line therapy in fit patients with chronic lymphocytic leukaemia, but bendamustine and rituximab is associated with less toxic effects. Funding Roche Pharma AG, Mundipharma, German Federal Ministry of Education and Research.
University of Göttingen1, European Society of Cardiology2, University of Warwick3, Athens State University4, University of Ferrara5, Academy for Urban School Leadership6, University of Brescia7, Universidade Nova de Lisboa8, Charles University in Prague9, Bar-Ilan University10, Paris Diderot University11, Linköping University12, Semmelweis University13, Medical University of Łódź14, Cardiovascular Institute of the South15, Alexandria University16, University of Belgrade17, Lithuanian University of Health Sciences18, University of Graz19, University Clinical Hospital Mostar20
TL;DR: The European Society of Cardiology Heart Failure Long‐Term Registry (ESC‐HF‐LT‐R) was set up with the aim of describing the clinical epidemiology and the 1‐year outcomes of patients with heart failure with the added intention of comparing differences between countries.
Abstract: Aims
The European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries.
Methods and results
The ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12 440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1 year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients.
Conclusion
The ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement.
Norwegian University of Science and Technology1, West Chester University of Pennsylvania2, University of British Columbia3, Royal Botanic Gardens4, Southern Illinois University Carbondale5, University of Maryland, College Park6, Ludwig Maximilian University of Munich7, Landcare Research8, American Museum of Natural History9, Schiller International University10, Museu Paraense Emílio Goeldi11, Hiroshima University12, Royal Botanic Garden Edinburgh13, Staatliches Museum für Naturkunde Stuttgart14, Eszterházy Károly College15, University of Valencia16, Spanish National Research Council17, Burapha University18, New York Botanical Garden19, National University of Colombia20, Charles University in Prague21, East China Normal University22
TL;DR: The first-ever worldwide checklist for liverworts and hornworts is presented that includes 7486 species in 398 genera representing 92 families from the two phyla, providing a valuable tool for taxonomists and systematists, analyzing phytogeographic and diversity patterns, aiding in the assessment of floristic and taxonomic knowledge, and identifying geographical gaps.
Abstract: A working checklist of accepted taxa worldwide is vital in achieving the goal of developing an online flora of all known plants by 2020 as part of the Global Strategy for Plant Conservation. We here present the first-ever worldwide checklist for liverworts (Marchantiophyta) and hornworts (Anthocerotophyta) that includes 7486 species in 398 genera representing 92 families from the two phyla. The checklist has far reaching implications and applications, including providing a valuable tool for taxonomists and systematists, analyzing phytogeographic and diversity patterns, aiding in the assessment of floristic and taxonomic knowledge, and identifying geographical gaps in our understanding of the global liverwort and hornwort flora. The checklist is derived from a working data set centralizing nomenclature, taxonomy and geography on a global scale. Prior to this effort a lack of centralization has been a major impediment for the study and analysis of species richness, conservation and systematic research at both regional and global scales. The success of this checklist, initiated in 2008, has been underpinned by its community approach involving taxonomic specialists working towards a consensus on taxonomy, nomenclature and distribution.
TL;DR: The ESCMID Study Group for Infections of the Brain (ESGIB) is a large-scale, randomized, placebo-controlled study that aims to provide real-time information on the safe and effective use of antibiotics in the treatment of central nervous system disorders.
TL;DR: In this article, the performance of the ATLAS muon identification and reconstruction using the first LHC dataset recorded at s√ = 13 TeV in 2015 was evaluated using the Monte Carlo simulations.
Abstract: This article documents the performance of the ATLAS muon identification and reconstruction using the first LHC dataset recorded at s√ = 13 TeV in 2015. Using a large sample of J/ψ→μμ and Z→μμ decays from 3.2 fb−1 of pp collision data, measurements of the reconstruction efficiency, as well as of the momentum scale and resolution, are presented and compared to Monte Carlo simulations. The reconstruction efficiency is measured to be close to 99% over most of the covered phase space (|η| 2.2, the pT resolution for muons from Z→μμ decays is 2.9% while the precision of the momentum scale for low-pT muons from J/ψ→μμ decays is about 0.2%.
TL;DR: a Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid , Spain; b Department of oncology, Haukeland University Hospital, Bergen , Norway; c Institut Gustave Roussy, Villejuif, and d Oncologie Médicale, Hôpitaux Universitaires Paris Nord Val de Seine, Paris , France.
Abstract: a Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid , Spain; b Department of Oncology, Haukeland University Hospital, Bergen , Norway; c Institut Gustave Roussy, Villejuif , and d Oncologie Médicale, Hôpitaux Universitaires Paris Nord Val de Seine, Paris , France; e Department of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Berlin , Germany; f Department of Surgery, Medical University of Vienna, Vienna , Austria; g Department of Oncology, First Faculty of Medicine and General Teaching Hospital, Prague , Czech Republic; h Neuroendocrine Tumour Unit, Royal Free Hospital, London , UK; i Institut für Pathologie und Zytologie, St. Vincenz Krankenhaus, Limburg , Germany; j Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn , Poland; k Neuroendocrine Tumour Unit, Royal Free Hospital, London , UK; l NET Centre, St. Vincent’s University and Department of Clinical Medicine, St. James Hospital and Trinity College, Dublin , Ireland; m Institute of Pathology, University of Bern, Bern , Switzerland
TL;DR: It is shown that the charge transfer per Pt atom is largest for Pt particles of around 50 atoms, and mechanistic and quantitative insights into charge transfer will help to make better use of particle size effects and electronic metal-support interactions in metal/oxide nanomaterials.
Abstract: Electronic interactions between metal nanoparticles and oxide supports control the functionality of nanomaterials, for example, the stability, the activity and the selectivity of catalysts. Such interactions involve electron transfer across the metal/support interface. In this work we quantify this charge transfer on a well-defined platinum/ceria catalyst at particle sizes relevant for heterogeneous catalysis. Combining synchrotron-radiation photoelectron spectroscopy, scanning tunnelling microscopy and density functional calculations we show that the charge transfer per Pt atom is largest for Pt particles of around 50 atoms. Here, approximately one electron is transferred per ten Pt atoms from the nanoparticle to the support. For larger particles, the charge transfer reaches its intrinsic limit set by the support. For smaller particles, charge transfer is partially suppressed by nucleation at defects. These mechanistic and quantitative insights into charge transfer will help to make better use of particle size effects and electronic metal-support interactions in metal/oxide nanomaterials.
Cleveland Clinic1, University of Amsterdam2, Amgen3, Mount Sinai Hospital4, Flinders University5, University of Glasgow6, Clinical Trial Service Unit7, University of Oxford8, Charles University in Prague9, University of California, Los Angeles10, Baylor College of Medicine11, University of Cologne12
TL;DR: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab, two-stage randomized clinical trial was conducted globally.
Abstract: Importance Muscle-related statin intolerance is reported by 5% to 20% of patients. Objective To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. Design, Setting, and Participants Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. Interventions Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). Main Outcome and Measures Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels. Results Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, −16.7% (95% CI, −20.5% to −12.9%), absolute change, −31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, −54.5% (95% CI, −57.2% to −51.8%); absolute change, −106.8 mg/dL ( P P P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). Conclusions and Relevance Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety. Trial Registration clinicaltrials.gov Identifier:NCT01984424
German Cancer Research Center1, University Hospital Heidelberg2, Boston Children's Hospital3, University of Tübingen4, Charles University in Prague5, McGill University6, University of Toronto7, University of Bonn8, Ludwig Maximilian University of Munich9, Augsburg College10, St. Jude Children's Research Hospital11, University of Münster12
TL;DR: Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
University of Coimbra1, University of Aberdeen2, Netherlands Cancer Institute3, University of Rennes4, University of Texas at Austin5, Charles University in Prague6, Hannover Medical School7, Radboud University Nijmegen8, St Bartholomew's Hospital9, Ludwig Maximilian University of Munich10, Umeå University11, University of Eastern Piedmont12
TL;DR: The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes, and it appears to be safe, but better quality studies are required to provide a more definitive answer.
TL;DR: It is shown that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains.
Abstract: Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence.