Showing papers by "University of Bern published in 2017"
Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
Harvard University1, University of Sheffield2, University of Warwick3, Vita-Salute San Raffaele University4, University of Bern5, St James's University Hospital6, Katholieke Universiteit Leuven7, University of Aberdeen8, Aberdeen Royal Infirmary9, Cardiff University10, Netherlands Cancer Institute11, Erasmus University Rotterdam12
TL;DR: The 2016 EAU-STRO-IOG Prostate Cancer (PCa) Guidelines present updated information on the diagnosis, and treatment of clinically localised prostate cancer and reflect the multidisciplinary nature of PCa management.
2,767 citations
Houston Methodist Hospital1, Erasmus University Rotterdam2, Beth Israel Deaconess Medical Center3, University of Copenhagen4, Pinnacle Financial Partners5, Mount Sinai Hospital6, New York University7, University of Michigan8, University of Pittsburgh9, Spectrum Health10, Mayo Clinic11, McGill University12, University of Bern13, Riverside Methodist Hospital14, Cedars-Sinai Medical Center15, Johns Hopkins University16, Medtronic plc17, Paradigm18
TL;DR: TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure.
Abstract: BackgroundAlthough transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk. MethodsWe evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement. ResultsA total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 7...
2,095 citations
University of Liège1, University of Cambridge2, University of Bern3, University of Washington4, California Institute of Technology5, Massachusetts Institute of Technology6, Université de Namur7, Centre national de la recherche scientifique8, University of Paris9, Cadi Ayyad University10, University of California, San Diego11, University of Leicester12, Liverpool John Moores University13, University of Central Lancashire14, King Abdulaziz University15
TL;DR: The observations reveal that at least seven planets with sizes and masses similar to those of Earth revolve around TRAPPIST-1, and the six inner planets form a near-resonant chain, such that their orbital periods are near-ratios of small integers.
Abstract: One aim of modern astronomy is to detect temperate, Earth-like exoplanets that are well suited for atmospheric characterization. Recently, three Earth-sized planets were detected that transit (that is, pass in front of) a star with a mass just eight per cent that of the Sun, located 12 parsecs away. The transiting configuration of these planets, combined with the Jupiter-like size of their host star—named TRAPPIST-1—makes possible in-depth studies of their atmospheric properties with present-day and future astronomical facilities. Here we report the results of a photometric monitoring campaign of that star from the ground and space. Our observations reveal that at least seven planets with sizes and masses similar to those of Earth revolve around TRAPPIST-1. The six inner planets form a near-resonant chain, such that their orbital periods (1.51, 2.42, 4.04, 6.06, 9.1 and 12.35 days) are near-ratios of small integers. This architecture suggests that the planets formed farther from the star and migrated inwards. Moreover, the seven planets have equilibrium temperatures low enough to make possible the presence of liquid water on their surfaces.
1,476 citations
TL;DR: This guidance provides a data-supported approach to risk stratification, diagnosis, and management of patients with cirrhosis and portal hypertension (PH), varices, and variceal hemorrhage (VH), and statements are based on the following.
1,397 citations
TL;DR: The 2016 EAU-ESTRO-SIOG Guidelines on PCa summarise the most recent findings and advice for use in clinical practice and reflect the multidisciplinary nature of PCa management.
1,271 citations
Paris Descartes University1, Cornell University2, University of Massachusetts Medical School3, Spanish National Research Council4, University of Rome Tor Vergata5, Boston Children's Hospital6, University of Pittsburgh7, National Scientific and Technical Research Council8, National University of Cuyo9, Albert Einstein College of Medicine10, University of California, San Francisco11, University of New Mexico12, University of Split13, Goethe University Frankfurt14, University of Helsinki15, University of Salento16, German Cancer Research Center17, Virginia Commonwealth University18, St. Jude Children's Research Hospital19, Discovery Institute20, Harvard University21, University of Tromsø22, Eötvös Loránd University23, Hungarian Academy of Sciences24, New York University25, University of Vienna26, Babraham Institute27, University of South Australia28, Howard Hughes Medical Institute29, University of Texas Southwestern Medical Center30, University of Oviedo31, University of Graz32, National Institutes of Health33, Queens College34, City University of New York35, University of Tokyo36, University of Zurich37, Novartis38, Austrian Academy of Sciences39, University of Groningen40, University of Cambridge41, University of Padua42, University of Oxford43, University of Bern44, University of Oslo45, University of Crete46, Foundation for Research & Technology – Hellas47, Francis Crick Institute48, Osaka University49, Icahn School of Medicine at Mount Sinai50
TL;DR: A panel of leading experts in the field attempts here to define several autophagy‐related terms based on specific biochemical features to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagic research.
Abstract: Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research.
1,095 citations
TL;DR: Investment in understanding migraine leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.
Abstract: Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.
1,036 citations
TL;DR: Overall, the frequency of MPS varies for each population due to differences in ethnic backgrounds and/or founder effects that affect the birth prevalence of each type of M PS, as seen for other rare genetic diseases.
996 citations
TL;DR: Pertuzumab significantly improved the rates of invasive‐disease–free survival among patients with HER2‐positive, operable breast cancer when it was added to adjuvant chemotherapy and chemotherapy.
Abstract: BackgroundPertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. MethodsWe randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease–free survival rate of 91.8% with pertuzumab and 89.2% with placebo. ResultsIn the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% ha...
933 citations
University of East Anglia1, University of Exeter2, Max Planck Society3, Commonwealth Scientific and Industrial Research Organisation4, Stanford University5, Oak Ridge National Laboratory6, National Oceanic and Atmospheric Administration7, Atlantic Oceanographic and Meteorological Laboratory8, Cooperative Institute for Marine and Atmospheric Studies9, Bjerknes Centre for Climate Research10, Geophysical Institute, University of Bergen11, Met Office12, École Normale Supérieure13, Centre national de la recherche scientifique14, University of Maryland, College Park15, National Institute of Water and Atmospheric Research16, International Institute for Applied Systems Analysis17, Alfred Wegener Institute for Polar and Marine Research18, Woods Hole Oceanographic Institution19, University of New Hampshire20, University of Illinois at Urbana–Champaign21, Karlsruhe Institute of Technology22, University of California, San Diego23, Utrecht University24, Netherlands Environmental Assessment Agency25, Leibniz Institute of Marine Sciences26, University of Paris27, Cooperative Research Centre28, Hobart Corporation29, Oeschger Centre for Climate Change Research30, University of Bern31, National Center for Atmospheric Research32, University of Miami33, Council of Scientific and Industrial Research34, Institute of Arctic and Alpine Research35, National Institute for Environmental Studies36, Spanish National Research Council37, Montana State University38, Goddard Space Flight Center39, Leibniz Institute for Baltic Sea Research40, University of Delaware41, Auburn University42, Food and Agriculture Organization43, Wageningen University and Research Centre44, VU University Amsterdam45, University of Groningen46
TL;DR: In this paper, the authors quantify the five major components of the global carbon budget and their uncertainties, and the resulting carbon budget imbalance (BIM) is a measure of imperfect data and understanding of the contemporary carbon cycle.
Abstract: Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the "global carbon budget" – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on land-cover change data and bookkeeping models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) and terrestrial CO2 sink (SLAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2007–2016), EFF was 9.4 ± 0.5 GtC yr−1, ELUC 1.3 ± 0.7 GtC yr−1, GATM 4.7 ± 0.1 GtC yr−1, SOCEAN 2.4 ± 0.5 GtC yr−1, and SLAND 3.0 ± 0.8 GtC yr−1, with a budget imbalance BIM of 0.6 GtC yr−1 indicating overestimated emissions and/or underestimated sinks. For year 2016 alone, the growth in EFF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr−1. Also for 2016, ELUC was 1.3 ± 0.7 GtC yr−1, GATM was 6.1 ± 0.2 GtC yr−1, SOCEAN was 2.6 ± 0.5 GtC yr−1, and SLAND was 2.7 ± 1.0 GtC yr−1, with a small BIM of −0.3 GtC. GATM continued to be higher in 2016 compared to the past decade (2007–2016), reflecting in part the high fossil emissions and the small SLAND consistent with El Nino conditions. The global atmospheric CO2 concentration reached 402.8 ± 0.1 ppm averaged over 2016. For 2017, preliminary data for the first 6–9 months indicate a renewed growth in EFF of +2.0 % (range of 0.8 to 3.0 %) based on national emissions projections for China, USA, and India, and projections of gross domestic product (GDP) corrected for recent changes in the carbon intensity of the economy for the rest of the world. This living data update documents changes in the methods and data sets used in this new global carbon budget compared with previous publications of this data set (Le Quere et al., 2016, 2015b, a, 2014, 2013). All results presented here can be downloaded from https://doi.org/10.18160/GCP-2017 (GCP, 2017).
University of Mainz1, University of Freiburg2, University of Würzburg3, Federal Institute for Drugs and Medical Devices4, RWTH Aachen University5, University of Regensburg6, University of Göttingen7, University of Tübingen8, Innsbruck Medical University9, University of Bern10, Ludwig Maximilian University of Munich11, Technische Universität München12, Max Planck Society13, University of Lausanne14
TL;DR: Following the new guidelines for therapeutic drug monitoring in psychiatry holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.
Abstract: Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.
TL;DR: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT and can support clinical decision making for treatment duration.
TL;DR: The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.
Zhengzhou University1, The Royal Marsden NHS Foundation Trust2, University of Bern3, Policlinico Umberto I4, University of Paris5, University of Pavia6, Goethe University Frankfurt7, University of Bergen8, University of Erlangen-Nuremberg9, Erasmus University Rotterdam10, University of Bologna11, University of Medicine and Pharmacy of Craiova12, King's College London13, University of Southern Denmark14
TL;DR: The first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography is presented, focused on the assessment of diffuse liver disease.
Abstract: We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.
VU University Medical Center1, University of Southern California2, Max Planck Society3, McMaster University4, University of Adelaide5, University of California, Irvine6, Erasmus University Rotterdam7, Delft University of Technology8, Erasmus University Medical Center9, German Center for Neurodegenerative Diseases10, Greifswald University Hospital11, University of Münster12, University of Marburg13, University of Queensland14, QIMR Berghofer Medical Research Institute15, Queensland University of Technology16, Virginia Commonwealth University17, University of Göttingen18, University Hospital Heidelberg19, University of Sydney20, Trinity College, Dublin21, Otto-von-Guericke University Magdeburg22, University of Regensburg23, University Medical Center Groningen24, Leiden University Medical Center25, University of Melbourne26, University of Texas Health Science Center at Houston27, Charité28, University of Bonn29, University of Lübeck30, University Medical Center Freiburg31, Stanford University32, University of Calgary33, Warneford Hospital34, Royal Edinburgh Hospital35, University of Edinburgh36, University of Bern37, Cardiff University38, Leibniz Institute for Neurobiology39, University of Tübingen40, Tomsk State University41, Mental Health Research Institute42, Siberian State Medical University43
TL;DR: In this article, the authors present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD.
Abstract: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
University of Barcelona1, Katholieke Universiteit Leuven2, Newcastle University3, National University of Ireland, Galway4, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico5, Imperial College London6, Freeman Hospital7, University of Edinburgh8, Papworth Hospital9, Hannover Medical School10, University of Belgrade11, Uppsala University12, Maastricht University13, Queen's University Belfast14, University of Bern15, Cochrane Collaboration16, University of Dundee17
TL;DR: The ERS guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature, using the GRADE approach to define the quality of the evidence and the level of recommendations.
Abstract: Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.
Yukawa Institute for Theoretical Physics1, Nagoya University2, KEK3, Brookhaven National Laboratory4, Université Paris-Saclay5, Washington University in St. Louis6, University of Connecticut7, University of Bern8, Spanish National Research Council9, University of Southern Denmark10, University of Rome Tor Vergata11, Forschungszentrum Jülich12, University of Wuppertal13, Osaka University14, San Francisco State University15, Indiana University16, Graduate University for Advanced Studies17, American Physical Society18, University of Edinburgh19, University of Southampton20, Aix-Marseille University21, National Chiao Tung University22, Roma Tre University23, Columbia University24, Autonomous University of Madrid25, University of Washington26, University of Mainz27
TL;DR: The determination of the light-quark masses, the form factor, and the decay constant ratio arising in the semileptonic $$K \rightarrow \pi $$K→π transition at zero momentum transfer are reported on.
Abstract: We review lattice results related to pion, kaon, D- and B-meson physics with the aim of making them easily accessible to the particle-physics community. More specifically, we report on the determination of the light-quark masses, the form factor [Formula: see text], arising in the semileptonic [Formula: see text] transition at zero momentum transfer, as well as the decay constant ratio [Formula: see text] and its consequences for the CKM matrix elements [Formula: see text] and [Formula: see text]. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of [Formula: see text] and [Formula: see text] Chiral Perturbation Theory. We review the determination of the [Formula: see text] parameter of neutral kaon mixing as well as the additional four B parameters that arise in theories of physics beyond the Standard Model. The latter quantities are an addition compared to the previous review. For the heavy-quark sector, we provide results for [Formula: see text] and [Formula: see text] (also new compared to the previous review), as well as those for D- and B-meson-decay constants, form factors, and mixing parameters. These are the heavy-quark quantities most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. Finally, we review the status of lattice determinations of the strong coupling constant [Formula: see text].
TL;DR: Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30‐day risk of a composite of death or severe renal failure leading to renal‐replacement therapy was lower among those who initially underwent PCI of the culprit lesion only than amongThose who underwent immediate multivessels PCI.
Abstract: BackgroundIn patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial. MethodsIn this multicenter trial, we randomly assigned 706 patients who had multivessel disease, acute myocardial infarction, and cardiogenic shock to one of two initial revascularization strategies: either PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, or immediate multivessel PCI. The primary end point was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Safety end points included bleeding and stroke. ResultsAt 30 days, the composite primary end point of death or renal-replacement therapy had occurred in 1...
TL;DR: The status and tracking capabilities of the IGS monitoring station network are presented and the multi-GNSS products derived from this resource are discussed and the achieved performance is assessed and related to the current level of space segment and user equipment characterization.
University of Bern1, University of Toronto2, Niigata University3, University of Lausanne4, Pierre-and-Marie-Curie University5, Copenhagen University Hospital6, University of Erlangen-Nuremberg7, University of California, San Francisco8, Medical University of Graz9, Radboud University Nijmegen10, Geneva College11, University of Helsinki12, University College Dublin13, Mayo Clinic14, Tokyo Medical and Dental University15, Paris Descartes University16, National Defense Medical College17, St James's University Hospital18
TL;DR: Members of the ITBCC were able to reach strong consensus on a single international, evidence-based method for tumor budding assessment and reporting and it is proposed that this method be incorporated into colorectal cancer guidelines/protocols and staging systems.
University of Bern1, University of British Columbia2, Netherlands Cancer Institute3, University of Washington4, Erasmus University Rotterdam5, Lund University6, University of North Carolina at Chapel Hill7, Baylor College of Medicine8, University of Texas MD Anderson Cancer Center9, University of Alberta10, University of California, Davis11
TL;DR: Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, the results suggest that patients with basal tumors should be prioritized for NAC, and the first single-sample genomic subtyping classifier to subtype MIBC is discovered, which may be suitable for integration into routine clinical practice.
University of Michigan1, Amgen2, University of Florence3, Laval University4, University of Lyon5, University of California, San Francisco6, University of Graz7, University of British Columbia8, University of Bern9, University of Liège10, Paris Descartes University11, Columbia University12, Leiden University Medical Center13
TL;DR: The yearly exposure-adjusted participant incidence of adverse events for all individuals receiving denosumab decreased from 165·3 to 95·9 per 100 participant-years over the course of 10 years, and serious adverse event rates were generally stable over time.
TL;DR: The latest advances in defining the functional contribution of ER stress to brain diseases are discussed, including novel evidence that relates the UPR to synaptic function, which has implications for cognition and memory.
Abstract: The clinical manifestation of neurodegenerative diseases is initiated by the selective alteration in the functionality of distinct neuronal populations. The pathology of many neurodegenerative diseases includes accumulation of misfolded proteins in the brain. In physiological conditions, the proteostasis network maintains normal protein folding, trafficking and degradation; alterations in this network - particularly disturbances to the function of endoplasmic reticulum (ER) - are thought to contribute to abnormal protein aggregation. ER stress triggers a signalling reaction known as the unfolded protein response (UPR), which induces adaptive programmes that improve protein folding and promote quality control mechanisms and degradative pathways or can activate apoptosis when damage is irreversible. In this Review, we discuss the latest advances in defining the functional contribution of ER stress to brain diseases, including novel evidence that relates the UPR to synaptic function, which has implications for cognition and memory. A complex concept is emerging wherein the consequences of ER stress can differ drastically depending on the disease context and the UPR signalling pathway that is altered. Strategies to target specific components of the UPR using small molecules and gene therapy are in development, and promise interesting avenues for future interventions to delay or stop neurodegeneration.
TL;DR: Current knowledge on the cellular and molecular mechanisms involved in immune-cell trafficking and lymphatic drainage from the central nervous system are summarized, and differences in rodent and human CNS anatomy are taken.
Abstract: Discoveries leading to an improved understanding of immune surveillance of the central nervous system (CNS) have repeatedly provoked dismissal of the existence of immune privilege of the CNS. Recent rediscoveries of lymphatic vessels within the dura mater surrounding the brain, made possible by modern live-cell imaging technologies, have revived this discussion. This review emphasizes the fact that understanding immune privilege of the CNS requires intimate knowledge of its unique anatomy. Endothelial, epithelial and glial brain barriers establish compartments in the CNS that differ strikingly with regard to their accessibility to immune-cell subsets. There is a unique system of lymphatic drainage from the CNS to the peripheral lymph nodes. We summarize current knowledge on the cellular and molecular mechanisms involved in immune-cell trafficking and lymphatic drainage from the CNS, and we take into account differences in rodent and human CNS anatomy.
TL;DR: Elevated pre-treatment NLR and PLR are associated with shorter OS and PFS and with lower response rates in patients with metastatic NSCLC treated with nivolumab independently of other prognostic factors.
TL;DR: An overview of electrical microstates in the brain, which are defined as successive short time periods during which the configuration of the scalp potential field remains semi‐stable, suggests quasi‐simultaneity of activity among the nodes of large‐scale networks.
TL;DR: This work sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice, indicating a microbial involvement in the development of Abeta amyloid pathology and suggesting that microbiota may contribute to the developed neurodegenerative diseases.
Abstract: Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.
TL;DR: It is demonstrated that hybridization between two divergent lineages facilitated this process by providing genetic variation that subsequently became recombined and sorted into many new species, indicating rapid and extensive adaptive radiation.
Abstract: Understanding why some evolutionary lineages generate exceptionally high species diversity is an important goal in evolutionary biology. Haplochromine cichlid fishes of Africa’s Lake Victoria region encompass >700 diverse species that all evolved in the last 150,000 years. How this ‘Lake Victoria Region Superflock’ could evolve on such rapid timescales is an enduring question. Here, we demonstrate that hybridization between two divergent lineages facilitated this process by providing genetic variation that subsequently became recombined and sorted into many new species. Notably, the hybridization event generated exceptional allelic variation at an opsin gene known to be involved in adaptation and speciation. More generally, differentiation between new species is accentuated around variants that were fixed differences between the parental lineages, and that now appear in many new combinations in the radiation species. We conclude that hybridization between divergent lineages, when coincident with ecological opportunity, may facilitate rapid and extensive adaptive radiation. Cichlids underwent a rapid diversification in the Lake Victoria region, expanding to more than 700 species within 150,000 years. Here, Meier and colleagues show that an ancient hybridization between two divergent cichlid lineages generated high genetic diversity that facilitated the rapid radiation.
University of Tartu1, Tartu University Hospital2, McMaster University3, University of Lausanne4, Université catholique de Louvain5, University of Adelaide6, Medical University of Graz7, University of Vienna8, University of Nice Sophia Antipolis9, University of Bern10, Maastricht University11, Université libre de Bruxelles12, Tel Aviv University13, Rabin Medical Center14, Ghent University Hospital15, King's College London16, Karolinska University Hospital17, Queen Elizabeth Hospital Birmingham18, Katholieke Universiteit Leuven19, VU University Medical Center20
TL;DR: EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery, and did not detect any evidence of superiority for early PN or delayed EN over EEN.
Abstract: Purpose
To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.