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Showing papers by "University of Wisconsin-Madison published in 2019"


Journal ArticleDOI
TL;DR: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than amongThose who received placebo, regardless of the presence or absence of diabetes.
Abstract: Background In patients with type 2 diabetes, inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-ind...

3,541 citations


Journal ArticleDOI
TL;DR: This article gives an up-to-date and accessible introduction to the CasADi framework, which has undergone numerous design improvements over the last 7 years.
Abstract: We present CasADi, an open-source software framework for numerical optimization. CasADi is a general-purpose tool that can be used to model and solve optimization problems with a large degree of flexibility, larger than what is associated with popular algebraic modeling languages such as AMPL, GAMS, JuMP or Pyomo. Of special interest are problems constrained by differential equations, i.e. optimal control problems. CasADi is written in self-contained C++, but is most conveniently used via full-featured interfaces to Python, MATLAB or Octave. Since its inception in late 2009, it has been used successfully for academic teaching as well as in applications from multiple fields, including process control, robotics and aerospace. This article gives an up-to-date and accessible introduction to the CasADi framework, which has undergone numerous design improvements over the last 7 years.

2,056 citations


Journal ArticleDOI
TL;DR: UNITE is a web-based database and sequence management environment for the molecular identification of fungi that targets the formal fungal barcode—the nuclear ribosomal internal transcribed spacer region—and offers all public fungal ITS sequences for reference.
Abstract: Alfred P. Sloan Foundation [G-2015-14062]; Swedish Research Council of Environment, Agricultural Sciences, and Spatial Planning [FORMAS, 215-2011-498]; European Regional Development Fund (Centre of Excellence EcolChange) [TK131]; Estonian Research Council [IUT20-30]. Funding for open access charge: Swedish Research Council of Environment, Agricultural Sciences and Spatial Planning.

1,674 citations


Journal ArticleDOI
TL;DR: This is the first study to report global prevalence of obstructive sleep apnoea; with almost 1 billion people affected, and with prevalence exceeding 50% in some countries, effective diagnostic and treatment strategies are needed to minimise the negative health impacts and to maximise cost-effectiveness.

1,487 citations


Journal ArticleDOI
TL;DR: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer.
Abstract: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.

1,218 citations


Journal ArticleDOI
01 May 2019-Nature
TL;DR: A comprehensive assessment of the world’s rivers and their connectivity shows that only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length.
Abstract: Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them. A comprehensive assessment of the world’s rivers and their connectivity shows that only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length.

1,071 citations


Journal ArticleDOI
TL;DR: This research aims to provide real-time information about how to improve the quality of life for people with learning disabilities and to provide a roadmap for the sustained support of those with learning difficulties.
Abstract: Carol Mitchell, PhD, ACS, RDMS, RDCS, RVT, RT(R), FASE, Co-Chair, Peter S. Rahko, MD, FASE, Co-Chair, Lori A. Blauwet, MD, FASE, Barry Canaday, RN, MS, RDCS, RCS, FASE, Joshua A. Finstuen, MA, RT(R), RDCS, FASE, Michael C. Foster, BA, RCS, RCCS, RDCS, FASE, Kenneth Horton, ACS, RCS, FASE, Kofo O. Ogunyankin, MD, FASE, Richard A. Palma, BS, RDCS, RCS, ACS, FASE, and Eric J. Velazquez, MD, FASE,Madison, Wisconsin; Rochester, Minnesota; Klamath Falls, Oregon; Durham, North Carolina; Salt Lake City, Utah; Ikoyi, Lagos, Nigeria; and Hartford, Connecticut

1,011 citations


Journal ArticleDOI
Željko Ivezić1, Steven M. Kahn2, J. Anthony Tyson3, Bob Abel4  +332 moreInstitutions (55)
TL;DR: The Large Synoptic Survey Telescope (LSST) as discussed by the authors is a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachon in northern Chile.
Abstract: We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the solar system, exploring the transient optical sky, and mapping the Milky Way. LSST will be a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachon in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2 field of view, a 3.2-gigapixel camera, and six filters (ugrizy) covering the wavelength range 320–1050 nm. The project is in the construction phase and will begin regular survey operations by 2022. About 90% of the observing time will be devoted to a deep-wide-fast survey mode that will uniformly observe a 18,000 deg2 region about 800 times (summed over all six bands) during the anticipated 10 yr of operations and will yield a co-added map to r ~ 27.5. These data will result in databases including about 32 trillion observations of 20 billion galaxies and a similar number of stars, and they will serve the majority of the primary science programs. The remaining 10% of the observing time will be allocated to special projects such as Very Deep and Very Fast time domain surveys, whose details are currently under discussion. We illustrate how the LSST science drivers led to these choices of system parameters, and we describe the expected data products and their characteristics.

921 citations


Journal ArticleDOI
TL;DR: By integrating the catalytic property and inherent nanomaterial nature of nanozyme systems, it is anticipated that stimuli-responsive nanozymes will open up new horizons for diagnosis, treatment, and theranostics.
Abstract: Nanozymes are nanomaterial-based artificial enzymes. By effectively mimicking catalytic sites of natural enzymes or harboring multivalent elements for reactions, nanozyme systems have successfully served as direct surrogates of traditional enzymes for catalysis. With the rapid development and ever-deepening understanding of nanotechnology, nanozymes offer higher catalytic stability, ease of modification and lower manufacturing cost than protein enzymes. Additionally, nanozymes possess inherent nanomaterial properties, providing not only a simple substitute of enzymes but also a multimodal platform interfacing complex biologic environments. Recent extensive research has focused on designing various nanozyme systems that are responsive to one or multiple substrates by tailored means. Catalytic activities of nanozymes can be regulated by pH, H2O2 and glutathione concentrations and levels of oxygenation in different microenvironments. Moreover, nanozymes can be remotely-controlled via different stimuli, including a magnetic field, light, ultrasound, and heat. Collectively, these factors can be adjusted to maximize the diagnostic and therapeutic efficacies of different diseases in biomedical settings. Therefore, by integrating the catalytic property and inherent nanomaterial nature of nanozyme systems, we anticipate that stimuli-responsive nanozymes will open up new horizons for diagnosis, treatment, and theranostics.

860 citations


Journal ArticleDOI
01 Jan 2019-Geoderma
TL;DR: In this paper, the authors identify measurable biotic or abiotic properties that control soil organic carbon (SOC) storage at different spatial scales and could serve as indicators for an efficient quantification of SOC.

784 citations


Journal ArticleDOI
TL;DR: There is an urgent need for research that examines how people actually move their faces to express emotions and other social information in the variety of contexts that make up everyday life, as well as careful study of the mechanisms by which people perceive instances of emotion in one another.
Abstract: It is commonly assumed that a person’s emotional state can be readily inferred from his or her facial movements, typically called emotional expressions or facial expressions. This assumption influences legal judgments, policy decisions, national security protocols, and educational practices; guides the diagnosis and treatment of psychiatric illness, as well as the development of commercial applications; and pervades everyday social interactions as well as research in other scientific fields such as artificial intelligence, neuroscience, and computer vision. In this article, we survey examples of this widespread assumption, which we refer to as the common view, and we then examine the scientific evidence that tests this view, focusing on the six most popular emotion categories used by consumers of emotion research: anger, disgust, fear, happiness, sadness, and surprise. The available scientific evidence suggests that people do sometimes smile when happy, frown when sad, scowl when angry, and so on, as proposed by the common view, more than what would be expected by chance. Yet how people communicate anger, disgust, fear, happiness, sadness, and surprise varies substantially across cultures, situations, and even across people within a single situation. Furthermore, similar configurations of facial movements variably express instances of more than one emotion category. In fact, a given configuration of facial movements, such as a scowl, often communicates something other than an emotional state. Scientists agree that facial movements convey a range of information and are important for social communication, emotional or otherwise. But our review suggests an urgent need for research that examines how people actually move their faces to express emotions and other social information in the variety of contexts that make up everyday life, as well as careful study of the mechanisms by which people perceive instances of emotion in one another. We make specific research recommendations that will yield a more valid picture of how people move their faces to express emotions and how they infer emotional meaning from facial movements in situations of everyday life. This research is crucial to provide consumers of emotion research with the translational information they require.

Journal ArticleDOI
TL;DR: In this paper, a connection between the distance conjecture and a refined version of the de Sitter conjecture in any parametrically controlled regime of string theory by using Bousso's covariant entropy bound was made.

Journal ArticleDOI
TL;DR: This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.
Abstract: Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

Journal ArticleDOI
TL;DR: This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations.
Abstract: Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

Journal ArticleDOI
TL;DR: New insights are discussed into the transcriptional and epigenetic regulation of BGCs and the ecological roles of fungal secondary metabolites in warfare, defence and development and avenues for the discovery of new fungal metabolites and current challenges in their identification are explored.
Abstract: One of the exciting movements in microbial sciences has been a refocusing and revitalization of efforts to mine the fungal secondary metabolome. The magnitude of biosynthetic gene clusters (BGCs) in a single filamentous fungal genome combined with the historic number of sequenced genomes suggests that the secondary metabolite wealth of filamentous fungi is largely untapped. Mining algorithms and scalable expression platforms have greatly expanded access to the chemical repertoire of fungal-derived secondary metabolites. In this Review, I discuss new insights into the transcriptional and epigenetic regulation of BGCs and the ecological roles of fungal secondary metabolites in warfare, defence and development. I also explore avenues for the identification of new fungal metabolites and the challenges in harvesting fungal-derived secondary metabolites. In this Review, Nancy P. Keller describes the classification and genetics of secondary metabolites and biosynthetic gene clusters, cluster regulation and the ecological roles of secondary metabolites, and she explores avenues for the discovery of new fungal metabolites and current challenges in their identification.

Journal ArticleDOI
TL;DR: In this paper, the capabilities of the open-knowledge software instrument Modules for Experiments in Stellar Astrophysics (MESA) have been updated to improve numerical energy conservation capabilities, including during mass changes.
Abstract: We update the capabilities of the open-knowledge software instrument Modules for Experiments in Stellar Astrophysics (MESA). RSP is a new functionality in MESAstar that models the nonlinear radial stellar pulsations that characterize RR Lyrae, Cepheids, and other classes of variable stars. We significantly enhance numerical energy conservation capabilities, including during mass changes. For example, this enables calculations through the He flash that conserve energy to better than 0.001%. To improve the modeling of rotating stars in MESA, we introduce a new approach to modifying the pressure and temperature equations of stellar structure, as well as a formulation of the projection effects of gravity darkening. A new scheme for tracking convective boundaries yields reliable values of the convective core mass and allows the natural emergence of adiabatic semiconvection regions during both core hydrogen- and helium-burning phases. We quantify the parallel performance of MESA on current-generation multicore architectures and demonstrate improvements in the computational efficiency of radiative levitation. We report updates to the equation of state and nuclear reaction physics modules. We briefly discuss the current treatment of fallback in core-collapse supernova models and the thermodynamic evolution of supernova explosions. We close by discussing the new MESA Testhub software infrastructure to enhance source code development.

Journal ArticleDOI
TL;DR: In this article, the authors summarized recent developments in the synthesis and characterization of metal halide perovskite nanostructures with controllable compositions, dimensionality, morphologies and orientations.
Abstract: Nanostructures of inorganic semiconductors have revolutionized many areas of electronics, optoelectronics and photonics. The controlled synthesis of semiconductor nanostructures could lead to novel physical properties, improved optoelectronic device performance and new areas for exploration. Lead halide perovskites have recently excited the photovoltaic research community owing to their high solar-conversion efficiencies and ease of solution processing; they also hold great promise for optoelectronic applications, such as light-emitting diodes and lasers. In this Review, we summarize recent developments in the synthesis and characterization of metal halide perovskite nanostructures with controllable compositions, dimensionality, morphologies and orientations. We examine the advantageous optical properties, improved stability and potential optoelectronic applications of these 1D and 2D single-crystal perovskite nanostructures and compare them with those of bulk perovskites and nanostructures of conventional semiconductors. Studies in which perovskite nanostructures have been used to study the fundamental physical properties of perovskites are also highlighted. Finally, we discuss the challenges in realizing halide perovskite nanostructures for optoelectronic and photonic applications and offer our perspectives on future opportunities and research directions. Metal halide perovskite nanostructures are promising materials for optoelectronic applications. In this Review, we discuss the synthesis and properties of 1D and 2D single-crystal perovskite nanostructures, examine potential optoelectronic applications and highlight recent studies in which these nanostructures have been used to study the fundamental properties of perovskites.

Journal ArticleDOI
A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4  +1491 moreInstitutions (239)
TL;DR: In this article, the authors present the second volume of the Future Circular Collider Conceptual Design Report, devoted to the electron-positron collider FCC-ee, and present the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan.
Abstract: In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.

Journal ArticleDOI
TL;DR: To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.
Abstract: Mental health symptoms and disorders are common among elite athletes, may have sport related manifestations within this population and impair performance. Mental health cannot be separated from physical health, as evidenced by mental health symptoms and disorders increasing the risk of physical injury and delaying subsequent recovery. There are no evidence or consensus based guidelines for diagnosis and management of mental health symptoms and disorders in elite athletes. Diagnosis must differentiate character traits particular to elite athletes from psychosocial maladaptations.Management strategies should address all contributors to mental health symptoms and consider biopsychosocial factors relevant to athletes to maximise benefit and minimise harm. Management must involve both treatment of affected individual athletes and optimising environments in which all elite athletes train and compete. To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.

Journal ArticleDOI
TL;DR: The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) as discussed by the authors address all aspects of management for NSCLC, focusing on recent updates in immunotherapy.
Abstract: The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."

Journal ArticleDOI
TL;DR: The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors and desmoid tumors.
Abstract: The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal cell carcinoma, and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize the NCCN Kidney Cancer Panel discussions for the 2020 update to the guidelines regarding initial management and first-line systemic therapy options for patients with advanced clear cell renal cell carcinoma.

Journal ArticleDOI
TL;DR: It is shown how being misinformed is a function of a person’s ability and motivation to spot falsehoods, but also of other group-level and societal factors that increase the chances of citizens to be exposed to correct(ive) information.
Abstract: Concerns about public misinformation in the United States—ranging from politics to science—are growing. Here, we provide an overview of how and why citizens become (and sometimes remain) misinformed about science. Our discussion focuses specifically on misinformation among individual citizens. However, it is impossible to understand individual information processing and acceptance without taking into account social networks, information ecologies, and other macro-level variables that provide important social context. Specifically, we show how being misinformed is a function of a person’s ability and motivation to spot falsehoods, but also of other group-level and societal factors that increase the chances of citizens to be exposed to correct(ive) information. We conclude by discussing a number of research areas—some of which echo themes of the 2017 National Academies of Sciences, Engineering, and Medicine’s Communicating Science Effectively report—that will be particularly important for our future understanding of misinformation, specifically a systems approach to the problem of misinformation, the need for more systematic analyses of science communication in new media environments, and a (re)focusing on traditionally underserved audiences.

Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Federico Ambrogi1  +2265 moreInstitutions (153)
TL;DR: Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented and constraints are placed on various two Higgs doublet models.
Abstract: Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented. The analysis uses the LHC proton–proton collision data set recorded with the CMS detector in 2016 at $\sqrt{s}=13\,\text {Te}\text {V} $ , corresponding to an integrated luminosity of 35.9 ${\,\text {fb}^{-1}} $ . The combination is based on analyses targeting the five main Higgs boson production mechanisms (gluon fusion, vector boson fusion, and associated production with a $\mathrm {W}$ or $\mathrm {Z}$ boson, or a top quark-antiquark pair) and the following decay modes: $\mathrm {H} \rightarrow \gamma \gamma $ , $\mathrm {Z}\mathrm {Z}$ , $\mathrm {W}\mathrm {W}$ , $\mathrm {\tau }\mathrm {\tau }$ , $\mathrm {b} \mathrm {b} $ , and $\mathrm {\mu }\mathrm {\mu }$ . Searches for invisible Higgs boson decays are also considered. The best-fit ratio of the signal yield to the standard model expectation is measured to be $\mu =1.17\pm 0.10$ , assuming a Higgs boson mass of $125.09\,\text {Ge}\text {V} $ . Additional results are given for various assumptions on the scaling behavior of the production and decay modes, including generic parametrizations based on ratios of cross sections and branching fractions or couplings. The results are compatible with the standard model predictions in all parametrizations considered. In addition, constraints are placed on various two Higgs doublet models.

Journal ArticleDOI
TL;DR: 5 sets of empirical findings are described that fundamentally undermine the gender binary, spanning multiple disciplines, that refute sexual dimorphism of the human brain and psychological findings that highlight the similarities between men and women.
Abstract: The view that humans comprise only two types of beings, women and men, a framework that is sometimes referred to as the "gender binary," played a profound role in shaping the history of psychological science. In recent years, serious challenges to the gender binary have arisen from both academic research and social activism. This review describes 5 sets of empirical findings, spanning multiple disciplines, that fundamentally undermine the gender binary. These sources of evidence include neuroscience findings that refute sexual dimorphism of the human brain; behavioral neuroendocrinology findings that challenge the notion of genetically fixed, nonoverlapping, sexually dimorphic hormonal systems; psychological findings that highlight the similarities between men and women; psychological research on transgender and nonbinary individuals' identities and experiences; and developmental research suggesting that the tendency to view gender/sex as a meaningful, binary category is culturally determined and malleable. Costs associated with reliance on the gender binary and recommendations for future research, as well as clinical practice, are outlined. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Journal ArticleDOI
Matteo Dainese1, Emily A. Martin1, Marcelo A. Aizen2, Matthias Albrecht, Ignasi Bartomeus3, Riccardo Bommarco4, Luísa G. Carvalheiro5, Luísa G. Carvalheiro6, Rebecca Chaplin-Kramer7, Vesna Gagic8, Lucas Alejandro Garibaldi9, Jaboury Ghazoul10, Heather Grab11, Mattias Jonsson4, Daniel S. Karp12, Christina M. Kennedy13, David Kleijn14, Claire Kremen15, Douglas A. Landis16, Deborah K. Letourneau17, Lorenzo Marini18, Katja Poveda11, Romina Rader19, Henrik G. Smith20, Teja Tscharntke21, Georg K.S. Andersson20, Isabelle Badenhausser22, Isabelle Badenhausser23, Svenja Baensch21, Antonio Diego M. Bezerra24, Felix J.J.A. Bianchi14, Virginie Boreux10, Virginie Boreux25, Vincent Bretagnolle23, Berta Caballero-López, Pablo Cavigliasso26, Aleksandar Ćetković27, Natacha P. Chacoff28, Alice Classen1, Sarah Cusser29, Felipe D. da Silva e Silva30, G. Arjen de Groot14, Jan H. Dudenhöffer31, Johan Ekroos20, Thijs P.M. Fijen14, Pierre Franck22, Breno Magalhães Freitas24, Michael P.D. Garratt32, Claudio Gratton33, Juliana Hipólito34, Juliana Hipólito9, Andrea Holzschuh1, Lauren Hunt35, Aaron L. Iverson11, Shalene Jha36, Tamar Keasar37, Tania N. Kim38, Miriam Kishinevsky37, Björn K. Klatt21, Björn K. Klatt20, Alexandra-Maria Klein25, Kristin M. Krewenka39, Smitha Krishnan10, Smitha Krishnan40, Ashley E. Larsen41, Claire Lavigne22, Heidi Liere42, Bea Maas43, Rachel E. Mallinger44, Eliana Martinez Pachon, Alejandra Martínez-Salinas45, Timothy D. Meehan46, Matthew G. E. Mitchell15, Gonzalo Alberto Roman Molina47, Maike Nesper10, Lovisa Nilsson20, Megan E. O'Rourke48, Marcell K. Peters1, Milan Plećaš27, Simon G. Potts33, Davi de L. Ramos, Jay A. Rosenheim12, Maj Rundlöf20, Adrien Rusch49, Agustín Sáez2, Jeroen Scheper14, Matthias Schleuning, Julia Schmack50, Amber R. Sciligo51, Colleen L. Seymour, Dara A. Stanley52, Rebecca Stewart20, Jane C. Stout53, Louis Sutter, Mayura B. Takada54, Hisatomo Taki, Giovanni Tamburini25, Matthias Tschumi, Blandina Felipe Viana55, Catrin Westphal21, Bryony K. Willcox19, Stephen D. Wratten56, Akira Yoshioka57, Carlos Zaragoza-Trello3, Wei Zhang58, Yi Zou59, Ingolf Steffan-Dewenter1 
University of Würzburg1, National University of Comahue2, Spanish National Research Council3, Swedish University of Agricultural Sciences4, Universidade Federal de Goiás5, University of Lisbon6, 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, Institut national de la recherche agronomique22, University of La Rochelle23, 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.

Journal ArticleDOI
A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4  +1496 moreInstitutions (238)
TL;DR: In this paper, the authors describe the detailed design and preparation of a construction project for a post-LHC circular energy frontier collider in collaboration with national institutes, laboratories and universities worldwide, and enhanced by a strong participation of industrial partners.
Abstract: Particle physics has arrived at an important moment of its history. The discovery of the Higgs boson, with a mass of 125 GeV, completes the matrix of particles and interactions that has constituted the “Standard Model” for several decades. This model is a consistent and predictive theory, which has so far proven successful at describing all phenomena accessible to collider experiments. However, several experimental facts do require the extension of the Standard Model and explanations are needed for observations such as the abundance of matter over antimatter, the striking evidence for dark matter and the non-zero neutrino masses. Theoretical issues such as the hierarchy problem, and, more in general, the dynamical origin of the Higgs mechanism, do likewise point to the existence of physics beyond the Standard Model. This report contains the description of a novel research infrastructure based on a highest-energy hadron collider with a centre-of-mass collision energy of 100 TeV and an integrated luminosity of at least a factor of 5 larger than the HL-LHC. It will extend the current energy frontier by almost an order of magnitude. The mass reach for direct discovery will reach several tens of TeV, and allow, for example, to produce new particles whose existence could be indirectly exposed by precision measurements during the earlier preceding e+e– collider phase. This collider will also precisely measure the Higgs self-coupling and thoroughly explore the dynamics of electroweak symmetry breaking at the TeV scale, to elucidate the nature of the electroweak phase transition. WIMPs as thermal dark matter candidates will be discovered, or ruled out. As a single project, this particle collider infrastructure will serve the world-wide physics community for about 25 years and, in combination with a lepton collider (see FCC conceptual design report volume 2), will provide a research tool until the end of the 21st century. Collision energies beyond 100 TeV can be considered when using high-temperature superconductors. The European Strategy for Particle Physics (ESPP) update 2013 stated “To stay at the forefront of particle physics, Europe needs to be in a position to propose an ambitious post-LHC accelerator project at CERN by the time of the next Strategy update”. The FCC study has implemented the ESPP recommendation by developing a long-term vision for an “accelerator project in a global context”. This document describes the detailed design and preparation of a construction project for a post-LHC circular energy frontier collider “in collaboration with national institutes, laboratories and universities worldwide”, and enhanced by a strong participation of industrial partners. Now, a coordinated preparation effort can be based on a core of an ever-growing consortium of already more than 135 institutes worldwide. The technology for constructing a high-energy circular hadron collider can be brought to the technology readiness level required for constructing within the coming ten years through a focused R&D programme. The FCC-hh concept comprises in the baseline scenario a power-saving, low-temperature superconducting magnet system based on an evolution of the Nb3Sn technology pioneered at the HL-LHC, an energy-efficient cryogenic refrigeration infrastructure based on a neon-helium (Nelium) light gas mixture, a high-reliability and low loss cryogen distribution infrastructure based on Invar, high-power distributed beam transfer using superconducting elements and local magnet energy recovery and re-use technologies that are already gradually introduced at other CERN accelerators. On a longer timescale, high-temperature superconductors can be developed together with industrial partners to achieve an even more energy efficient particle collider or to reach even higher collision energies.The re-use of the LHC and its injector chain, which also serve for a concurrently running physics programme, is an essential lever to come to an overall sustainable research infrastructure at the energy frontier. Strategic R&D for FCC-hh aims at minimising construction cost and energy consumption, while maximising the socio-economic impact. It will mitigate technology-related risks and ensure that industry can benefit from an acceptable utility. Concerning the implementation, a preparatory phase of about eight years is both necessary and adequate to establish the project governance and organisation structures, to build the international machine and experiment consortia, to develop a territorial implantation plan in agreement with the host-states’ requirements, to optimise the disposal of land and underground volumes, and to prepare the civil engineering project. Such a large-scale, international fundamental research infrastructure, tightly involving industrial partners and providing training at all education levels, will be a strong motor of economic and societal development in all participating nations. The FCC study has implemented a set of actions towards a coherent vision for the world-wide high-energy and particle physics community, providing a collaborative framework for topically complementary and geographically well-balanced contributions. This conceptual design report lays the foundation for a subsequent infrastructure preparatory and technical design phase.

Journal ArticleDOI
21 Nov 2019-Nature
TL;DR: It is shown that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota, and is linked with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis.
Abstract: Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1–3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin—a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6—as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis. In patients with alcoholic hepatitis, cytolysin-positive Enterococcus faecalis strains are correlated with liver disease severity and increased mortality, and in mouse models these strains can be specifically targeted by bacteriophages.

Journal ArticleDOI
TL;DR: In this Perspective, the authors present a framework, context and guidelines for accelerating the translation of machine-learning-based interventions in health care.
Abstract: Interest in machine-learning applications within medicine has been growing, but few studies have progressed to deployment in patient care. We present a framework, context and ultimately guidelines for accelerating the translation of machine-learning-based interventions in health care. To be successful, translation will require a team of engaged stakeholders and a systematic process from beginning (problem formulation) to end (widespread deployment).

Proceedings Article
01 Jan 2019
TL;DR: The authors showed that over-parameterized neural networks can learn some notable concept classes, including two and three-layer networks with fewer parameters and smooth activations, and that the learning can be simply done by SGD (stochastic gradient descent) or its variants in polynomial time using polynomially many samples.
Abstract: The fundamental learning theory behind neural networks remains largely open. What classes of functions can neural networks actually learn? Why doesn't the trained network overfit when it is overparameterized? In this work, we prove that overparameterized neural networks can learn some notable concept classes, including two and three-layer networks with fewer parameters and smooth activations. Moreover, the learning can be simply done by SGD (stochastic gradient descent) or its variants in polynomial time using polynomially many samples. The sample complexity can also be almost independent of the number of parameters in the network. On the technique side, our analysis goes beyond the so-called NTK (neural tangent kernel) linearization of neural networks in prior works. We establish a new notion of quadratic approximation of the neural network, and connect it to the SGD theory of escaping saddle points.

Journal ArticleDOI
TL;DR: The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.
Abstract: Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.