Showing papers by "University of Buenos Aires published in 2019"
University of California, San Francisco1, University of Birmingham2, University of Liège3, Advocate Lutheran General Hospital4, Kantonsspital St. Gallen5, University of Adelaide6, Baylor College of Medicine7, Mayo Clinic8, University of Southern California9, Asahikawa Medical University10, University of Dundee11, Pontifical Catholic University of Chile12, Uppsala University13, University of Hong Kong14, Royal Adelaide Hospital15, University of Hamburg16, Sunnybrook Health Sciences Centre17, University of Minnesota18, Technische Universität München19, University of Cambridge20, University of Bologna21, Washington University in St. Louis22, Greenville Health System23, University of Bristol24, University of Ottawa25, Nagoya University26, University of Texas Southwestern Medical Center27, Shanghai Jiao Tong University28, Icahn School of Medicine at Mount Sinai29, Brigham and Women's Hospital30, Oregon Health & Science University31, University of Buenos Aires32, Duke University33, St. Elizabeth's Medical Center34, Dartmouth College35, University of Massachusetts Amherst36, University of the Witwatersrand37, Ghent University Hospital38, Sun Yat-sen University39
TL;DR: The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP) resulting in three stages of complexity for intervention.
993 citations
TL;DR: Although deficiencies in polyphenol intake do not result in specific deficiency diseases, adequate intake of polyphenols could confer health benefits, especially with regard to chronic diseases, because tea, cocoa, fruits, and berries, as well as vegetables, are rich inpolyphenols.
Abstract: Although deficiencies in polyphenol intake do not result in specific deficiency diseases, adequate intake of polyphenols could confer health benefits, especially with regard to chronic diseases. Tea, cocoa, fruits, and berries, as well as vegetables, are rich in polyphenols. Flavan-3-ols from cocoa have been found to be associated with a reduced risk of stroke, myocardial infarction, and diabetes, as well as improvements in lipids, endothelial-dependent blood flow and blood pressure, insulin resistance, and systemic inflammation. The flavonoid quercetin and the stilbene resveratrol have also been associated with cardiometabolic health. Although polyphenols have been associated with improved cerebral blood flow, evidence of an impact on cognition is more limited. The ability of dietary polyphenols to produce clinical effects may be due, at least in part, to a bi-directional relationship with the gut microbiota. Polyphenols can impact the composition of the gut microbiota (which are independently associated with health benefits), and gut bacteria metabolize polyphenols into bioactive compounds that produce clinical benefits. Another critical interaction is that of polyphenols with other phytochemicals, which could be relevant to interpreting the health parameter effects of polyphenols assayed as purified extracts, whole foods, or whole food extracts.
552 citations
TL;DR: To update evidence‐based medicine recommendations for treating nonmotor symptoms in Parkinson's disease, the World Health Organization (WHO) selected Austria as a preferred destination for research and clinical trials.
Abstract: Objective
To update evidence‐based medicine recommendations for treating nonmotor symptoms in Parkinson's disease (PD).
527 citations
TL;DR: An AI model trained on endoscopic video can differentiate diminutive adenomas from hyperplastic polyps with high accuracy and should be used in a live patient clinical trial setting to address resect and discard.
Abstract: Background In general, academic but not community endoscopists have demonstrated adequate endoscopic differentiation accuracy to make the ‘resect and discard’ paradigm for diminutive colorectal polyps workable. Computer analysis of video could potentially eliminate the obstacle of interobserver variability in endoscopic polyp interpretation and enable widespread acceptance of ‘resect and discard’. Study design and methods We developed an artificial intelligence (AI) model for real-time assessment of endoscopic video images of colorectal polyps. A deep convolutional neural network model was used. Only narrow band imaging video frames were used, split equally between relevant multiclasses. Unaltered videos from routine exams not specifically designed or adapted for AI classification were used to train and validate the model. The model was tested on a separate series of 125 videos of consecutively encountered diminutive polyps that were proven to be adenomas or hyperplastic polyps. Results The AI model works with a confidence mechanism and did not generate sufficient confidence to predict the histology of 19 polyps in the test set, representing 15% of the polyps. For the remaining 106 diminutive polyps, the accuracy of the model was 94% (95% CI 86% to 97%), the sensitivity for identification of adenomas was 98% (95% CI 92% to 100%), specificity was 83% (95% CI 67% to 93%), negative predictive value 97% and positive predictive value 90%. Conclusions An AI model trained on endoscopic video can differentiate diminutive adenomas from hyperplastic polyps with high accuracy. Additional study of this programme in a live patient clinical trial setting to address resect and discard is planned.
437 citations
University of Würzburg1, National University of Comahue2, Spanish National Research Council3, Swedish University of Agricultural Sciences4, University of Lisbon5, Universidade Federal de Goiás6, Stanford University7, Commonwealth Scientific and Industrial Research Organisation8, National University of Río Negro9, ETH Zurich10, Cornell University11, University of California, Davis12, The Nature Conservancy13, Wageningen University and Research Centre14, University of British Columbia15, Great Lakes Bioenergy Research Center16, University of California, Santa Cruz17, University of Padua18, University of New England (Australia)19, Lund University20, University of Göttingen21, University of La Rochelle22, Institut national de la recherche agronomique23, Federal University of Ceará24, University of Freiburg25, Concordia University Wisconsin26, University of Belgrade27, National University of Tucumán28, Michigan State University29, University of Brasília30, University of Greenwich31, University of Reading32, University of Wisconsin-Madison33, National Institute of Amazonian Research34, Boise State University35, University of Texas at Austin36, University of Haifa37, Kansas State University38, University of Hamburg39, Bioversity International40, University of California, Santa Barbara41, Seattle University42, University of Vienna43, University of Florida44, Centro Agronómico Tropical de Investigación y Enseñanza45, National Audubon Society46, University of Buenos Aires47, Virginia Tech48, University of Bordeaux49, University of Auckland50, University of California, Berkeley51, University College Dublin52, Trinity College, Dublin53, University of Tokyo54, Federal University of Bahia55, Lincoln University (New Zealand)56, National Institute for Environmental Studies57, International Food Policy Research Institute58, Xi'an Jiaotong-Liverpool University59
TL;DR: Using a global database from 89 studies (with 1475 locations), the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change is partitioned.
Abstract: Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by a few dominant species or rely on high richness remains unclear. Using a global database from 89 studies (with 1475 locations), we partition the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change. Pollinator and enemy richness directly supported ecosystem services in addition to and independent of abundance and dominance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society.
434 citations
University of Queensland1, University of the West Indies2, University of Florence3, Bournemouth University4, University of Southampton5, University of Buenos Aires6, University of Grenoble7, United Nations University8, University of Washington9, University of the Witwatersrand10, Aix-Marseille University11, National Institute for Environmental Studies12, World Bank13, University of Cambridge14, University of Bristol15, Alfred Wegener Institute for Polar and Marine Research16, ETH Zurich17, College of The Bahamas18, University of East Anglia19
TL;DR: The climate change–impact literature is reviewed, expanding on the recent report of the Intergovernmental Panel on Climate Change, and it is argued that impacts accelerating as a function of distance from the optimal temperature for an organism or an ecosystem process is a consequence of impacts accelerating.
Abstract: Increased concentrations of atmospheric greenhouse gases have led to a global mean surface temperature 1.0°C higher than during the pre-industrial period. We expand on the recent IPCC Special Report on global warming of 1.5°C and review the additional risks associated with higher levels of warming, each having major implications for multiple geographies, climates, and ecosystems. Limiting warming to 1.5°C rather than 2.0°C would be required to maintain substantial proportions of ecosystems and would have clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where the escalation of climate-related risks may prevent the achievement of the United Nations Sustainable Development Goals.
406 citations
French Institute of Health and Medical Research1, University of Liège2, University of Buenos Aires3, Collège de France4, Université Paris-Saclay5, Pompeu Fabra University6, National Scientific and Technical Research Council7, University of Birmingham8, University of Western Ontario9, Columbia University10, Cornell University11
TL;DR: The results establish that consciousness rests on the brain’s ability to sustain rich brain dynamics and pave the way for determining specific and generalizable fingerprints of conscious and unconscious states.
Abstract: Adopting the framework of brain dynamics as a cornerstone of human consciousness, we determined whether dynamic signal coordination provides specific and generalizable patterns pertaining to conscious and unconscious states after brain damage. A dynamic pattern of coordinated and anticoordinated functional magnetic resonance imaging signals characterized healthy individuals and minimally conscious patients. The brains of unresponsive patients showed primarily a pattern of low interareal phase coherence mainly mediated by structural connectivity, and had smaller chances to transition between patterns. The complex pattern was further corroborated in patients with covert cognition, who could perform neuroimaging mental imagery tasks, validating this pattern’s implication in consciousness. Anesthesia increased the probability of the less complex pattern to equal levels, validating its implication in unconsciousness. Our results establish that consciousness rests on the brain’s ability to sustain rich brain dynamics and pave the way for determining specific and generalizable fingerprints of conscious and unconscious states.
288 citations
TL;DR: In this article, a search for high-mass dielectron and dimuon resonances in the mass range of 250 GeV to 6 TeV was performed at the Large Hadron Collider.
248 citations
King's College London1, Imperial College London2, Yale University3, Gazi University4, University of California, San Francisco5, Boston Children's Hospital6, Medical University of Warsaw7, University of Adelaide8, Sichuan University9, MedStar Washington Hospital Center10, Selçuk University11, Lithuanian University of Health Sciences12, Erasmus University Rotterdam13, University of Southern California14, University of Milano-Bicocca15, University of Salamanca16, University of Gothenburg17, University of Amsterdam18, Chongqing Medical University19, University of Buenos Aires20, University of Health Sciences Antigua21, University of Nottingham22
TL;DR: The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more and the association with the concentration of specific biochemical markers is unclear.
237 citations
University of Würzburg1, National University of Comahue2, Spanish National Research Council3, Swedish University of Agricultural Sciences4, University of Lisbon5, Universidade Federal de Goiás6, Stanford University7, Commonwealth Scientific and Industrial Research Organisation8, National University of Río Negro9, ETH Zurich10, Cornell University11, University of California, Davis12, The Nature Conservancy13, Wageningen University and Research Centre14, University of British Columbia15, Great Lakes Bioenergy Research Center16, University of California, Berkeley17, University of Padua18, University of New England (United States)19, Lund University20, University of Göttingen21, Institut national de la recherche agronomique22, University of La Rochelle23, Federal University of Ceará24, Concordia University Wisconsin25, University of Belgrade26, National University of Tucumán27, Michigan State University28, University of Brasília29, University of Greenwich30, University of Reading31, University of Wisconsin-Madison32, Boise State University33, University of Texas at Austin34, University of Haifa35, Kansas State University36, University of Freiburg37, University of Hamburg38, University of California, Santa Barbara39, Seattle University40, University of Vienna41, University of Florida42, Centro Agronómico Tropical de Investigación y Enseñanza43, National Audubon Society44, University of Buenos Aires45, Virginia Tech46, University of Bordeaux47, University of Auckland48, University College Dublin49, Trinity College, Dublin50, University of Tokyo51, Federal University of Bahia52, Lincoln University (Pennsylvania)53, National Institute for Environmental Studies54, International Food Policy Research Institute55, Xi'an Jiaotong-Liverpool University56
TL;DR: Using a global database from 89 crop systems, the relative importance of abundance and species richness for pollination, biological pest control and final yields in the context of on-going land-use change is partitioned.
Abstract: Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by few abundant species or rely on high richness remains unclear. Using a global database from 89 crop systems, we partition the relative importance of abundance and species richness for pollination, biological pest control and final yields in the context of on-going land-use change. Pollinator and enemy richness directly supported ecosystem services independent of abundance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society.
237 citations
TL;DR: An exclusion limit on the H→invisible branching ratio of 0.26(0.17_{-0.05}^{+0.07}) at 95% confidence level is observed (expected) in combination with the results at sqrt[s]=7 and 8 TeV.
Abstract: Dark matter particles, if sufficiently light, may be produced in decays of the Higgs boson. This Letter presents a statistical combination of searches for H→invisible decays where H is produced according to the standard model via vector boson fusion, Z(ll)H, and W/Z(had)H, all performed with the ATLAS detector using 36.1 fb^{-1} of pp collisions at a center-of-mass energy of sqrt[s]=13 TeV at the LHC. In combination with the results at sqrt[s]=7 and 8 TeV, an exclusion limit on the H→invisible branching ratio of 0.26(0.17_{-0.05}^{+0.07}) at 95% confidence level is observed (expected).
TL;DR: In this article, an improved energy clustering algorithm is introduced, and its implications for the measurement and identification of prompt electrons and photons are discussed in detail, including corrections and calibrations that affect performance, including energy calibration, identification and isolation efficiencies.
Abstract: This paper describes the reconstruction of electrons and photons with the ATLAS detector, employed for measurements and searches exploiting the complete LHC Run 2 dataset. An improved energy clustering algorithm is introduced, and its implications for the measurement and identification of prompt electrons and photons are discussed in detail. Corrections and calibrations that affect performance, including energy calibration, identification and isolation efficiencies, and the measurement of the charge of reconstructed electron candidates are determined using up to 81 fb−1 of proton-proton collision data collected at √s=13 TeV between 2015 and 2017.
TL;DR: In this article, the ATLAS Collaboration during Run 2 of the Large Hadron Collider (LHC) was used to identify jets containing b-hadrons, and the performance of the algorithms was evaluated in the s...
Abstract: The algorithms used by the ATLAS Collaboration during Run 2 of the Large Hadron Collider to identify jets containing b-hadrons are presented. The performance of the algorithms is evaluated in the s ...
TL;DR: In this paper, the decays of B0 s! + and B0! + have been studied using 26 : 3 fb of 13TeV LHC proton-proton collision data collected with the ATLAS detector in 2015 and 2016.
Abstract: A study of the decays B0 s ! + and B0 ! + has been performed using 26 : 3 fb of 13TeV LHC proton-proton collision data collected with the ATLAS detector in 2015 and 2016. Since the detector resolut ...
Simon Fraser University1, Medical University of Vienna2, Tehran University of Medical Sciences3, University of Queensland4, Ankara University5, University of Zurich6, University of Buenos Aires7, Nemours Foundation8, Aristotle University of Thessaloniki9, Karolinska University Hospital10, Memorial Sloan Kettering Cancer Center11, University of Sydney12, University of Gothenburg13, Sheba Medical Center14, Lyons15, University of Trieste16
TL;DR: Nets are able to classify dermoscopic and close-up images of nonpigmented lesions as accurately as human experts in an experimental setting as to compare the accuracy of a CNN-based classifier with that of physicians with different levels of experience.
Abstract: Importance Convolutional neural networks (CNNs) achieve expert-level accuracy in the diagnosis of pigmented melanocytic lesions. However, the most common types of skin cancer are nonpigmented and nonmelanocytic, and are more difficult to diagnose. Objective To compare the accuracy of a CNN-based classifier with that of physicians with different levels of experience. Design, Setting, and Participants A CNN-based classification model was trained on 7895 dermoscopic and 5829 close-up images of lesions excised at a primary skin cancer clinic between January 1, 2008, and July 13, 2017, for a combined evaluation of both imaging methods. The combined CNN (cCNN) was tested on a set of 2072 unknown cases and compared with results from 95 human raters who were medical personnel, including 62 board-certified dermatologists, with different experience in dermoscopy. Main Outcomes and Measures The proportions of correct specific diagnoses and the accuracy to differentiate between benign and malignant lesions measured as an area under the receiver operating characteristic curve served as main outcome measures. Results Among 95 human raters (51.6% female; mean age, 43.4 years; 95% CI, 41.0-45.7 years), the participants were divided into 3 groups (according to years of experience with dermoscopy): beginner raters ( 10 years). The area under the receiver operating characteristic curve of the trained cCNN was higher than human ratings (0.742; 95% CI, 0.729-0.755 vs 0.695; 95% CI, 0.676-0.713;P Conclusions and Relevance Neural networks are able to classify dermoscopic and close-up images of nonpigmented lesions as accurately as human experts in an experimental setting.
National University of Comahue1, University of Buenos Aires2, Naturalis3, Leiden University4, National University of Río Negro5, Rocky Mountain Biological Laboratory6, University of Maryland, College Park7, Andong National University8, Princeton University9, University of Chile10, Stellenbosch University11, Martin Luther University of Halle-Wittenberg12, Percy FitzPatrick Institute of African Ornithology13
TL;DR: World regions of particular concern are identified where environmentally damaging practices associated with large‐scale, industrial agriculture threaten key ecosystem services that underlie productivity, in addition to other benefits provided by biodiversity.
Abstract: The global increase in the proportion of land cultivated with pollinator-dependent crops implies increased reliance on pollination services. Yet agricultural practices themselves can profoundly affect pollinator supply and pollination. Extensive monocultures are associated with a limited pollinator supply and reduced pollination, whereas agricultural diversification can enhance both. Therefore, areas where agricultural diversity has increased, or at least been maintained, may better sustain high and more stable productivity of pollinator-dependent crops. Given that >80% of all crops depend, to varying extents, on insect pollination, a global increase in agricultural pollinator dependence over recent decades might have led to a concomitant increase in agricultural diversification. We evaluated whether an increase in the area of pollinator-dependent crops has indeed been associated with an increase in agricultural diversity, measured here as crop diversity, at the global, regional, and country scales for the period 1961-2016. Globally, results show a relatively weak and decelerating rise in agricultural diversity over time that was largely decoupled from the strong and continually increasing trend in agricultural dependency on pollinators. At regional and country levels, there was no consistent relationship between temporal changes in pollinator dependence and crop diversification. Instead, our results show heterogeneous responses in which increasing pollinator dependence for some countries and regions has been associated with either an increase or a decrease in agricultural diversity. Particularly worrisome is a rapid expansion of pollinator-dependent oilseed crops in several countries of the Americas and Asia that has resulted in a decrease in agricultural diversity. In these regions, reliance on pollinators is increasing, yet agricultural practices that undermine pollination services are expanding. Our analysis has thereby identified world regions of particular concern where environmentally damaging practices associated with large-scale, industrial agriculture threaten key ecosystem services that underlie productivity, in addition to other benefits provided by biodiversity.
Hungarian Academy of Sciences1, Eötvös Loránd University2, Clark University3, University of Toronto4, University of Szeged5, Szent István University6, United States Department of Energy7, Landcare Research8, University of Paris9, San Francisco State University10, Naturalis11, University of Tennessee12, Polish Academy of Sciences13, American Museum of Natural History14, Finnish Environment Institute15, University of Buenos Aires16, Royal Botanic Gardens17, University of Oslo18, Utrecht University19, United States Forest Service20, University of Central Oklahoma21, University of Tartu22, University of Helsinki23, Russian Academy of Sciences24, Swedish Museum of Natural History25, Mendel University26, New York Botanical Garden27, University of California, Berkeley28, Institut national de la recherche agronomique29
TL;DR: A phylogenetic tree of 5,284 fungal species is used to infer ages and broad patterns of speciation/extinction, diversification and morphological innovation in mushroom-forming fungi.
Abstract: Mushroom-forming fungi (Agaricomycetes) have the greatest morphological diversity and complexity of any group of fungi. They have radiated into most niches and fulfil diverse roles in the ecosystem, including wood decomposers, pathogens or mycorrhizal mutualists. Despite the importance of mushroom-forming fungi, large-scale patterns of their evolutionary history are poorly known, in part due to the lack of a comprehensive and dated molecular phylogeny. Here, using multigene and genome-based data, we assemble a 5,284-species phylogenetic tree and infer ages and broad patterns of speciation/extinction and morphological innovation in mushroom-forming fungi. Agaricomycetes started a rapid class-wide radiation in the Jurassic, coinciding with the spread of (sub)tropical coniferous forests and a warming climate. A possible mass extinction, several clade-specific adaptive radiations and morphological diversification of fruiting bodies followed during the Cretaceous and the Paleogene, convergently giving rise to the classic toadstool morphology, with a cap, stalk and gills (pileate-stipitate morphology). This morphology is associated with increased rates of lineage diversification, suggesting it represents a key innovation in the evolution of mushroom-forming fungi. The increase in mushroom diversity started during the Mesozoic-Cenozoic radiation event, an era of humid climate when terrestrial communities dominated by gymnosperms and reptiles were also expanding.
San Diego State University1, Charles University in Prague2, Cairo University3, Monash University4, University of Notre Dame5, Delft University of Technology6, University of Liverpool7, Utrecht University8, Kavli Institute of Nanoscience9, Aix-Marseille University10, University of California, Davis11, New York University12, University of Otago13, University of Groningen14, Katholieke Universiteit Leuven15, University of Los Andes16, Norwegian Institute of Public Health17, Universidad Mayor18, Saint Petersburg State University of Information Technologies, Mechanics and Optics19, National Autonomous University of Mexico20, Technical University of Denmark21, University of Jordan22, University of Alicante23, University of Illinois at Urbana–Champaign24, Autonomous University of Barcelona25, Pontifical Catholic University of Chile26, University of Warsaw27, Dartmouth College28, University of Khartoum29, University of Chicago30, University of Barcelona31, Scripps Research Institute32, University College Cork33, University of Tampere34, Northern Illinois University35, University of Sydney36, Columbus Zoo and Aquarium37, McGill University38, University of Western Australia39, University of Colorado Boulder40, Virginia Tech41, Tel Aviv University42, Instituto Superior Técnico43, Makerere University44, University of California, San Diego45, Hawaii Pacific University46, Stockholm University47, University of California, Irvine48, University of Buenos Aires49, Fudan University50, University of Padua51, University of Pittsburgh52, Ebonyi State University53, Andrés Bello National University54, University of Copenhagen55, Radboud University Nijmegen56
TL;DR: It is concluded that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
Abstract: Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
University of Cincinnati1, University of Toronto2, Harvard University3, St George's, University of London4, University of Pittsburgh5, University of Kentucky6, United States Department of Veterans Affairs7, University of California, San Francisco8, McGill University9, University of California, San Diego10, University of Washington11, Van Andel Institute12, University of Alabama at Birmingham13, University of Buenos Aires14, Austral University15, Sanofi S.A.16, Michael J. Fox Foundation17, University of Texas at San Antonio18, Cleveland Clinic19
TL;DR: It is hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress.
Abstract: The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts.
Johns Hopkins University School of Medicine1, Johns Hopkins University2, University of Brescia3, Indian Institute of Chemical Biology4, Cardiff University5, Ohio State University6, University of Virginia7, Ikerbasque8, National Institutes of Health9, Loyola University Chicago10, Southern Medical University11, University of Maryland, College Park12, University of Alabama at Birmingham13, PSL Research University14, University of California, San Diego15, Oslo University Hospital16, Harvard University17, University of Buenos Aires18, Icahn School of Medicine at Mount Sinai19, University of Washington20, Shaw University21, French Institute of Health and Medical Research22, Ghent University23, Flanders Institute for Biotechnology24, Spanish National Research Council25, Utrecht University26, University of Würzburg27, Tsinghua University28, Oxford Brookes University29
TL;DR: It is revealed that while much progress has been made in the field, there are still several concepts that divide opinion and areas with little to no consensus include EV storage and stability, as well as whether and how EVs fuse with target cells.
Abstract: Paracrine and endocrine roles have increasingly been ascribed to extracellular vesicles (EVs) generated by multicellular organisms. Central to the biogenesis, content, and function of EVs are their delimiting lipid bilayer membranes. To evaluate research progress on membranes and EVs, the International Society for Extracellular Vesicles (ISEV) conducted a workshop in March 2018 in Baltimore, Maryland, USA, bringing together key opinion leaders and hands-on researchers who were selected on the basis of submitted applications. The workshop was accompanied by two scientific surveys and covered four broad topics: EV biogenesis and release; EV uptake and fusion; technologies and strategies used to study EV membranes; and EV transfer and functional assays. In this ISEV position paper, we synthesize the results of the workshop and the related surveys to outline important outstanding questions about EV membranes and describe areas of consensus. The workshop discussions and survey responses reveal that while much progress has been made in the field, there are still several concepts that divide opinion. Good consensus exists in some areas, including particular aspects of EV biogenesis, uptake and downstream signalling. Areas with little to no consensus include EV storage and stability, as well as whether and how EVs fuse with target cells. Further research is needed in these key areas, as a better understanding of membrane biology will contribute substantially towards advancing the field of extracellular vesicles.
TL;DR: It is demonstrated that Mott nanodevices retain a memory of previous resistive switching events long after the insulating resistance has recovered, and it is found that the intrinsic metastability of first-order phase transitions is the origin of this phenomenon.
Abstract: Resistive switching, a phenomenon in which the resistance of a device can be modified by applying an electric field1–5, is at the core of emerging technologies such as neuromorphic computing and resistive memories6–9. Among the different types of resistive switching, threshold firing10–14 is one of the most promising, as it may enable the implementation of artificial spiking neurons7,13,14. Threshold firing is observed in Mott insulators featuring an insulator-to-metal transition15,16, which can be triggered by applying an external voltage: the material becomes conducting (‘fires’) if a threshold voltage is exceeded7,10–12. The dynamics of this induced transition have been thoroughly studied, and its underlying mechanism and characteristic time are well documented10,12,17,18. By contrast, there is little knowledge regarding the opposite transition: the process by which the system returns to the insulating state after the voltage is removed. Here we show that Mott nanodevices retain a memory of previous resistive switching events long after the insulating resistance has recovered. We demonstrate that, although the device returns to its insulating state within 50 to 150 nanoseconds, it is possible to re-trigger the insulator-to-metal transition by using subthreshold voltages for a much longer time (up to several milliseconds). We find that the intrinsic metastability of first-order phase transitions is the origin of this phenomenon, and so it is potentially present in all Mott systems. This effect constitutes a new type of volatile memory in Mott-based devices, with potential applications in resistive memories, solid-state frequency discriminators and neuromorphic circuits. Mott materials feature scale-less relaxation dynamics after the insulator-to-metal transition that make its electric triggering dependent on recent switching events.
TL;DR: The Sustainable Development Goals and the New Urban Agenda recognise the role of cities in achieving sustainable development as discussed by the authors, however, these agendas were agreed and signed by national goverment authorities.
Abstract: The Sustainable Development Goals and the New Urban Agenda recognise the role of cities in achieving sustainable development. However, these agendas were agreed and signed by national gover...
TL;DR: Algorithms used for the reconstruction and identification of electrons in the central region of the ATLAS detector at the Large Hadron Collider (LHC) are presented in this article, these algorithms a...
Abstract: Algorithms used for the reconstruction and identification of electrons in the central region of the ATLAS detector at the Large Hadron Collider (LHC) are presented in this paper; these algorithms a ...
University of Buenos Aires1, Boston Children's Hospital2, Northwestern University3, University Kebangsaan Malaysia Medical Centre4, University of Copenhagen5, Moscow State University6, National Academy of Sciences of Belarus7, University of Bremen8, University of California, San Diego9, Federal University of Rio de Janeiro10, Queen's University11, Birla Institute of Technology and Science12, Indian Institute of Toxicology Research13, Baylor College of Medicine14, Harry Perkins Institute of Medical Research15, University of Western Australia16, Tata Institute of Fundamental Research17, Government of India18, Royal Children's Hospital19, Leibniz Institute for Neurobiology20, Jikei University School of Medicine21, Indian Institute of Chemical Biology22, Nencki Institute of Experimental Biology23, University of Minho24, Indira Gandhi National Tribal University25, University of Queensland26, Technische Universität München27, Otto-von-Guericke University Magdeburg28, Tokyo University of Pharmacy and Life Sciences29
TL;DR: This review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity.
Abstract: The past 20 years have resulted in unprecedented progress in understanding brain energy metabolism and its role in health and disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address the basic concepts of brain energy metabolism and approach the question of why the brain has high energy expenditure. Our review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity. Disturbances to the energetic balance, to mitochondria quality control or to glia-neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS. We cover neuronal energy consumption in neural transmission and basic ('housekeeping') cellular processes. Additionally, we describe the most common (glucose) and alternative sources of energy namely glutamate, lactate, ketone bodies, and medium chain fatty acids. We discuss the multifaceted role of non-neuronal cells in the transport of energy substrates from circulation (pericytes and astrocytes) and in the supply (astrocytes and microglia) and usage of different energy fuels. Finally, we address pathological consequences of disrupted energy homeostasis in the CNS.
TL;DR: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared withprednisone alone, and the primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day Prednisone dose from month 0 to month 60.
Abstract: Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.
TL;DR: This paper summarizes the research work resulting from over 25 years' experience in biomaterials, including studies conducted at the laboratory on the local and systemic factors affecting the peri-implant bone healing process, using experimental models developed by the research team.
Abstract: Osseointegration was originally defined as a direct structural and functional connection between ordered living bone and the surface of a load-carrying implant. It is now said that an implant is regarded as osseointegrated when there is no progressive relative movement between the implant and the bone with which it is in direct contact. Although the term osseointegration was initially used with reference to titanium metallic implants, the concept is currently applied to all biomaterials that have the ability to osseointegrate. Biomaterials are closely related to the mechanism of osseointegration; these materials are designed to be implanted or incorporated into the living system with the aims to substitute for, or regenerate, tissues and tissue functions. Objective evaluation of the properties of the different biomaterials and of the factors that influence bone repair in general, and at the bone tissue-implant interface, is essential to the clinical success of an implant. The Biomaterials Laboratory of the Oral Pathology Department of the School of Dentistry at the University of Buenos Aires is devoted to the study and research of the properties and biological effects of biomaterials for dental implants and bone substitutes. This paper summarizes the research work resulting from over 25 years' experience in this field. It includes studies conducted at our laboratory on the local and systemic factors affecting the peri-implant bone healing process, using experimental models developed by our research team. The results of our research on corrosion, focusing on dental implants, as well as our experience in the evaluation of failed dental implants and bone biopsies obtained following maxillary sinus floor augmentation with bone substitutes, are also reported. Research on biomaterials and their interaction with the biological system is a continuing challenge in biomedicine, which aims to achieve optimal biocompatibility and thus contribute to patient health.
Loyola University New Orleans1, Miami University2, Australian National University3, University of Wollongong4, National Center for Atmospheric Research5, Murdoch University6, Aristotle University of Thessaloniki7, Swiss Federal Institute of Aquatic Science and Technology8, North Carolina State University9, National Institute of Water and Atmospheric Research10, Smithsonian Environmental Research Center11, University of Buenos Aires12, University of Guelph13, QIMR Berghofer Medical Research Institute14, University of Edinburgh15, Salford Royal NHS Foundation Trust16, Linnaeus University17, Rensselaer Polytechnic Institute18, University of Michigan19, University of Idaho20, Leiden University21, University of Erlangen-Nuremberg22, Finnish Meteorological Institute23, University College Cork24, University of Helsinki25, Cancer Council Victoria26, University of Gothenburg27, Columbia University28, University of Western Australia29, King's College London30, United States Environmental Protection Agency31
TL;DR: The Montreal Protocol has also played an important role in mitigating climate change as discussed by the authors, and the Montreal Protocol will continue to have far-reaching benefits for human well-being and environmental sustainability.
Abstract: Changes in stratospheric ozone and climate over the past 40-plus years have altered the solar ultraviolet (UV) radiation conditions at the Earth’s surface. Ozone depletion has also contributed to climate change across the Southern Hemisphere. These changes are interacting in complex ways to affect human health, food and water security, and ecosystem services. Many adverse effects of high UV exposure have been avoided thanks to the Montreal Protocol with its Amendments and Adjustments, which have effectively controlled the production and use of ozone-depleting substances. This international treaty has also played an important role in mitigating climate change. Climate change is modifying UV exposure and affecting how people and ecosystems respond to UV; these effects will become more pronounced in the future. The interactions between stratospheric ozone, climate and UV radiation will therefore shift over time; however, the Montreal Protocol will continue to have far-reaching benefits for human well-being and environmental sustainability.
Smithsonian Environmental Research Center1, Johns Hopkins University2, Marquette University3, University of Minnesota4, Eastern Michigan University5, Wichita State University6, University of North Carolina at Greensboro7, Virginia Institute of Marine Science8, University of Wyoming9, Qatar University10, New Mexico State University11, VU University Amsterdam12, Southern Illinois University Carbondale13, University of Maryland, College Park14, United States Department of Agriculture15, University of Bayreuth16, The Wilderness Society17, Kansas State University18, Institut national de la recherche agronomique19, University of Central Florida20, University of Alberta21, Archbold Biological Station22, University of Colorado Boulder23, James Hutton Institute24, University of Buenos Aires25, Stanford University26, Northwest A&F University27, University of New Mexico28, Lanzhou University29, University of Oulu30, Queensland University of Technology31, University of Kansas32, Towson University33, Michigan State University34, University of Oregon35, Chinese Academy of Sciences36, University of Tasmania37, Jönköping University38, Norwegian University of Life Sciences39, Colorado State University40, University of Greifswald41, Northern Arizona University42, University of Kentucky43, University of Texas at El Paso44, La Trobe University45, University of Houston46, Charles Sturt University47, University of Sydney48, University of Manchester49, Arizona State University50, Leiden University51, University of Oklahoma52, University of California, Santa Cruz53, Oregon State University54, University of British Columbia55, Inner Mongolia University56, Utrecht University57, Georgia Institute of Technology58
TL;DR: An unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs shows that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated, and finds that plant communities are fairly resistant to experimentally manipulated G CDs in the short term.
Abstract: Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
TL;DR: Advances in knowledge of stratospheric ozone dynamics and climate change are summarized, and uncertainties and knowledge gaps are identified that limit the ability to fully evaluate the ecological consequences of these environmental changes on terrestrial ecosystems.
Abstract: Exposure of plants and animals to ultraviolet-B radiation (UV-B; 280–315 nm) is modified by stratospheric ozone dynamics and climate change. Even though stabilisation and projected recovery of stratospheric ozone is expected to curtail future increases in UV-B radiation at the Earth's surface, on-going changes in climate are increasingly exposing plants and animals to novel combinations of UV-B radiation and other climate change factors (e.g., ultraviolet-A and visible radiation, water availability, temperature and elevated carbon dioxide). Climate change is also shifting vegetation cover, geographic ranges of species, and seasonal timing of development, which further modifies exposure to UV-B radiation. Since our last assessment, there has been increased understanding of the underlying mechanisms by which plants perceive UV-B radiation, eliciting changes in growth, development and tolerances of abiotic and biotic factors. However, major questions remain on how UV-B radiation is interacting with other climate change factors to modify the production and quality of crops, as well as important ecosystem processes such as plant and animal competition, pest–pathogen interactions, and the decomposition of dead plant matter (litter). In addition, stratospheric ozone depletion is directly contributing to climate change in the southern hemisphere, such that terrestrial ecosystems in this region are being exposed to altered patterns of precipitation, temperature and fire regimes as well as UV-B radiation. These ozone-driven changes in climate have been implicated in both increases and reductions in the growth, survival and reproduction of plants and animals in Antarctica, South America and New Zealand. In this assessment, we summarise advances in our knowledge of these and other linkages and effects, and identify uncertainties and knowledge gaps that limit our ability to fully evaluate the ecological consequences of these environmental changes on terrestrial ecosystems.
University of Buenos Aires1, Leipzig University2, Tel Aviv Sourasky Medical Center3, Tel Aviv University4, Favaloro University5, L V Prasad Eye Institute6, Istanbul University7, University of Sydney8, Chiang Mai University9, University of Paris10, University of Perugia11, Monterrey Institute of Technology and Higher Education12, Macquarie University13, Westmead Hospital14
TL;DR: In this article, the efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment.
Abstract: Purpose:To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment.Methods:This multicenter i