Showing papers by "University of Zurich published in 2016"
Harvard University1, University of California, San Francisco2, University of Düsseldorf3, Heidelberg University4, Aix-Marseille University5, Ludwig Institute for Cancer Research6, International Agency for Research on Cancer7, German Cancer Research Center8, University of Zurich9, St. Jude Children's Research Hospital10
TL;DR: The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor and is hoped that it will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.
Abstract: The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.
11,197 citations
TL;DR: The Task Force for the management of atrial fibrillation of the European Society of Cardiology has been endorsed by the European Stroke Organisation (ESO).
Abstract: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC)
Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC
Endorsed by the European Stroke Organisation (ESO)
5,255 citations
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: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.
4,804 citations
Mariachiara Di Cesare1, Mariachiara Di Cesare2, James Bentham2, Gretchen A Stevens3 +738 more•Institutions (60)
TL;DR: The posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue, is calculated.
3,766 citations
University of Pittsburgh1, University of Texas MD Anderson Cancer Center2, Stanford University3, University of Duisburg-Essen4, University of Chicago5, Institut Gustave Roussy6, University of Michigan7, Emory University8, Complutense University of Madrid9, Harvard University10, University of Zurich11, Kobe University12, Bristol-Myers Squibb13, Ohio State University14
TL;DR: Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy.
Abstract: BackgroundPatients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. MethodsIn this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. ResultsThe median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to...
3,246 citations
TL;DR: With version 3, the ecoinvent database substantially expands the goals and scopes of LCA studies it can support, and the new system models allow new, different studies to be performed.
Abstract: Purpose
Good background data are an important requirement in LCA. Practitioners generally make use of LCI databases for such data, and the ecoinvent database is the largest transparent unit-process LCI database worldwide. Since its first release in 2003, it has been continuously updated, and version 3 was published in 2013. The release of version 3 introduced several significant methodological and technological improvements, besides a large number of new and updated datasets. The aim was to expand the content of the database, set the foundation for a truly global database, support regionalized LCIA, offer multiple system models, allow for easier integration of data from different regions, and reduce maintenance efforts. This article describes the methodological developments.
2,696 citations
TL;DR: Simultaneous localization and mapping (SLAM) as mentioned in this paper consists in the concurrent construction of a model of the environment (the map), and the estimation of the state of the robot moving within it.
Abstract: Simultaneous localization and mapping (SLAM) consists in the concurrent construction of a model of the environment (the map ), and the estimation of the state of the robot moving within it. The SLAM community has made astonishing progress over the last 30 years, enabling large-scale real-world applications and witnessing a steady transition of this technology to industry. We survey the current state of SLAM and consider future directions. We start by presenting what is now the de-facto standard formulation for SLAM. We then review related work, covering a broad set of topics including robustness and scalability in long-term mapping, metric and semantic representations for mapping, theoretical performance guarantees, active SLAM and exploration, and other new frontiers. This paper simultaneously serves as a position paper and tutorial to those who are users of SLAM. By looking at the published research with a critical eye, we delineate open challenges and new research issues, that still deserve careful scientific investigation. The paper also contains the authors’ take on two questions that often animate discussions during robotics conferences: Do robots need SLAM? and Is SLAM solved?
2,039 citations
TL;DR: This review summarizes the most significant differences between the newly published classification of urogenital tumours and the prior version for renal, penile, and testicular tumours.
2,024 citations
TL;DR: It is concluded that transcript levels by themselves are not sufficient to predict protein levels in many scenarios and to thus explain genotype-phenotype relationships and that high-quality data quantifying different levels of gene expression are indispensable for the complete understanding of biological processes.
TL;DR: In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner, accompanied by a slowing of clinical decline measured by Clinical Dementia Rating—Sum of Boxes and Mini Mental State Examination scores.
Abstract: Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aβ to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating-Sum of Boxes and Mini Mental State Examination scores. The main safety and tolerability findings are amyloid-related imaging abnormalities. These results justify further development of aducanumab for the treatment of AD. Should the slowing of clinical decline be confirmed in ongoing phase 3 clinical trials, it would provide compelling support for the amyloid hypothesis.
TL;DR: The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group, and eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees.
Abstract: eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de.
TL;DR: Powerful mass-spectrometry-based technologies now provide unprecedented insights into the composition, structure, function and control of the proteome, shedding light on complex biological processes and phenotypes.
Abstract: Numerous biological processes are concurrently and coordinately active in every living cell. Each of them encompasses synthetic, catalytic and regulatory functions that are, almost always, carried out by proteins organized further into higher-order structures and networks. For decades, the structures and functions of selected proteins have been studied using biochemical and biophysical methods. However, the properties and behaviour of the proteome as an integrated system have largely remained elusive. Powerful mass-spectrometry-based technologies now provide unprecedented insights into the composition, structure, function and control of the proteome, shedding light on complex biological processes and phenotypes.
TL;DR: Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co- inhibitory receptor expression on T cells dampens effector T-cell responses.
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.
TL;DR: The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation, and may also serve as a basis for local implementation.
Abstract: Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.
TL;DR: Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7.
University College London1, University of Copenhagen2, University of St. Gallen3, University of Hamburg4, Hospital Clínico San Carlos5, University of Liverpool6, Universidad Miguel Hernández de Elche7, University of Victoria8, University of Zurich9, Karolinska University Hospital10, University of Bern11, Medical University of Vienna12, University Hospital of Basel13, Praxis14, Helsinki University Central Hospital15, Warwickshire Hospital16
TL;DR: Evaluating the rate of within-couple HIV transmission among serodifferent heterosexual and MSM couples during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL found no phylogenetically linked transmissions.
Abstract: Importance A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. Objective To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. Design, Setting, and Participants The prospective, observational PARTNER (Partners of People on ART—A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples’ HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. Exposures Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. Main Outcomes and Measures Risk of within-couple HIV transmission to the HIV-negative partner Results Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22 000 condomless sex acts and heterosexuals approximately 36 000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. Conclusions and Relevance Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.
Aix-Marseille University1, University of Zurich2, Memorial Sloan Kettering Cancer Center3, Aarhus University4, French Institute of Health and Medical Research5, Cross Cancer Institute6, University of Siena7, Odense University Hospital8, Broomfield Hospital9, University Hospital Heidelberg10, Harvard University11, Bristol-Myers Squibb12, European Organisation for Research and Treatment of Cancer13
TL;DR: As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence- free survival, overall survival, and distant metastasis-free survival than placebo.
Abstract: BackgroundOn the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. MethodsAfter patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis–free survival, and safety. ResultsAt a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio ...
TL;DR: Sleep appears to have not only a short‐term, use‐dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24‐h cycle.
Abstract: In the last three decades the two-process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time-courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN-lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non-pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short-term, use-dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24-h cycle.
Smithsonian Institution1, Sun Yat-sen University2, University of California, Berkeley3, Naturalis4, Paris-Sorbonne University5, Universidade Federal de Minas Gerais6, University of Vermont7, Federal University of Western Pará8, University of Florida9, James Cook University10, Duke University11, University of Bonn12, University of Neuchâtel13, University of Turku14, University of Alaska Fairbanks15, Missouri Botanical Garden16, National Taiwan University17, Museum of New Zealand Te Papa Tongarewa18, National University of Río Cuarto19, University of Arizona20, Council of Agriculture21, Kaohsiung Medical University22, Chongqing Normal University23, Universidade Federal de Juiz de Fora24, Nanjing Forestry University25, Iowa State University26, Complutense University of Madrid27, University of Kansas28, Denison University29, University of Zurich30
TL;DR: A modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community‐based approach, that uses monophyly as the primary criterion for the recognition of taxa, but also aims to preserve existing taxa and circumscriptions that are both widely accepted and consistent with the understanding of pteridophyte phylogeny.
Abstract: Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predic ...
Sapienza University of Rome1, Marche Polytechnic University2, University of Copenhagen3, University of Milan4, Rikshospitalet–Radiumhospitalet5, University of Oslo6, University of Edinburgh7, University of Würzburg8, Greifswald University Hospital9, University of Zurich10, Medical University of Vienna11, University of Salamanca12
TL;DR: This Consensus Statement aims to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer.
Abstract: Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.
West Virginia University1, Yale University2, Food and Agriculture Organization3, Landcare Research4, University of Udine5, Max Planck Society6, University of Alaska Fairbanks7, Technische Universität München8, Université du Québec à Montréal9, University of the French West Indies and Guiana10, University of Freiburg Faculty of Biology11, Cornell University12, Wageningen University and Research Centre13, University of Sydney14, University of Trás-os-Montes and Alto Douro15, Polytechnic Institute of Viseu16, University of Göttingen17, Russian Academy of Sciences18, Oeschger Centre for Climate Change Research19, Lakehead University20, University of La Frontera21, Seoul National University22, Martin Luther University of Halle-Wittenberg23, University of Cambridge24, James Cook University25, Center for International Forestry Research26, University of Zurich27, University of Yaoundé I28, University of Wisconsin-Madison29, Queensland Government30, Institut national de la recherche agronomique31, Florida International University32, Forest Research Institute33, University of Minnesota34, Polish Academy of Sciences35, Warsaw University of Life Sciences36, Ştefan cel Mare University of Suceava37, University of Florence38, University of Warsaw39, King Juan Carlos University40, Spanish National Research Council41, National Scientific and Technical Research Council42, International Trademark Association43, National University of Austral Patagonia44, Wildlife Conservation Society45, College of African Wildlife Management46, University of York47, Durham University48, Ontario Ministry of Natural Resources49, Pontificia Universidad Católica del Ecuador50, Centre national de la recherche scientifique51, Museu Paraense Emílio Goeldi52, University College London53, University of Leeds54
TL;DR: A consistent positive concave-down effect of biodiversity on forest productivity across the world is revealed, showing that a continued biodiversity loss would result in an accelerating decline in forest productivity worldwide.
Abstract: The biodiversity-productivity relationship (BPR) is foundational to our understanding of the global extinction crisis and its impacts on ecosystem functioning. Understanding BPR is critical for the accurate valuation and effective conservation of biodiversity. Using ground-sourced data from 777,126 permanent plots, spanning 44 countries and most terrestrial biomes, we reveal a globally consistent positive concave-down BPR, showing that continued biodiversity loss would result in an accelerating decline in forest productivity worldwide. The value of biodiversity in maintaining commercial forest productivity alone-US$166 billion to 490 billion per year according to our estimation-is more than twice what it would cost to implement effective global conservation. This highlights the need for a worldwide reassessment of biodiversity values, forest management strategies, and conservation priorities.
TL;DR: It is demonstrated the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence and it is demonstrated that NR delays senescences of neural SCs and melanocyteSCs and increases mouse life span.
Abstract: Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.
TL;DR: In this paper, the membrane potentials of spiking neurons are treated as differentiable signals, where discontinuities at spike times are considered as noise, which enables an error backpropagation mechanism for deep spiking neural networks.
Abstract: Deep spiking neural networks (SNNs) hold the potential for improving the latency and energy efficiency of deep neural networks through data-driven event-based computation. However, training such networks is difficult due to the non-differentiable nature of spike events. In this paper, we introduce a novel technique, which treats the membrane potentials of spiking neurons as differentiable signals, where discontinuities at spike times are considered as noise. This enables an error backpropagation mechanism for deep SNNs that follows the same principles as in conventional deep networks, but works directly on spike signals and membrane potentials. Compared with previous methods relying on indirect training and conversion, our technique has the potential to capture the statistics of spikes more precisely. We evaluate the proposed framework on artificially generated events from the original MNIST handwritten digit benchmark, and also on the N-MNIST benchmark recorded with an event-based dynamic vision sensor, in which the proposed method reduces the error rate by a factor of more than three compared to the best previous SNN, and also achieves a higher accuracy than a conventional convolutional neural network (CNN) trained and tested on the same data. We demonstrate in the context of the MNIST task that thanks to their event-driven operation, deep SNNs (both fully connected and convolutional) trained with our method achieve accuracy equivalent with conventional neural networks. In the N-MNIST example, equivalent accuracy is achieved with about five times fewer computational operations.
TL;DR: It is shown that CHELSA climatological data has a similar accuracy as other products for temperature, but that its predictions of precipitation patterns are better and can increase the accuracy of species range predictions.
Abstract: High resolution information on climatic conditions is essential to many applications in environmental and ecological sciences. Here we present the CHELSA Climatologies at high resolution for the earths land surface areas data of downscaled model output temperature and precipitation estimates of the ERA Interim climatic reanalysis to a high resolution of 30 arc seconds. The temperature algorithm is based on statistical downscaling of atmospheric temperatures. The precipitation algorithm incorporates orographic predictors including wind fields, valley exposition, and boundary layer height with a subsequent bias correction. The resulting data consist of a monthly temperature and precipitation climatology for the years 1979 to 2013. We compare the data derived from the CHELSA algorithm with other standard gridded products and station data from the Global Historical Climate Network. We compare the performance of the new climatologies in species distribution modelling and show that we can increase the accuracy of species range predictions. We further show that CHELSA climatological data has a similar accuracy as other products for temperature but that its predictions of precipitation patterns are better.
National Institutes of Health1, University of Salerno2, Bosch3, St. George's University4, University of Sydney5, Royal North Shore Hospital6, St. Marianna University School of Medicine7, University of Zurich8, National and Kapodistrian University of Athens9, Paris Diderot University10, University of Gothenburg11
TL;DR: Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision‐making by practising clinicians in the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation.
Abstract: Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed.
TL;DR: This work synthesizes the potential of soil organisms to enhance ecosystem service delivery and demonstrates that soil biodiversity promotes multiple ecosystem functions simultaneously (i.e., ecosystem multifunctionality) and applies the concept of ecological intensification to soils.
Abstract: Soil organisms are an integral component of ecosystems, but their activities receive little recognition in agricultural management strategies. Here we synthesize the potential of soil organisms to enhance ecosystem service delivery and demonstrate that soil biodiversity promotes multiple ecosystem functions simultaneously (i.e., ecosystem multifunctionality). We apply the concept of ecological intensification to soils and we develop strategies for targeted exploitation of soil biological traits. We compile promising approaches to enhance agricultural sustainability through the promotion of soil biodiversity and targeted management of soil community composition. We present soil ecological engineering as a concept to generate human land-use systems, which can serve immediate human needs while minimizing environmental impacts.
TL;DR: This paper found that the adjustment in local labor markets is remarkably slow, with wages and labor-force participation rates remaining depressed and unemployment rates remaining elevated for at least a full decade after the China trade shock commences.
Abstract: China's emergence as a great economic power has induced an epochal shift in patterns of world trade. Simultaneously, it has challenged much of the received empirical wisdom about how labor markets adjust to trade shocks. Alongside the heralded consumer benefits of expanded trade are substantial adjustment costs and distributional consequences. These impacts are most visible in the local labor markets in which the industries exposed to foreign competition are concentrated. Adjustment in local labor markets is remarkably slow, with wages and labor-force participation rates remaining depressed and unemployment rates remaining elevated for at least a full decade after the China trade shock commences. Exposed workers experience greater job churning and reduced lifetime income. At the national level, employment has fallen in the US industries more exposed to import competition, as expected, but offsetting employment gains in other industries have yet to materialize. Better understanding when and where trade is ...