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Journal ArticleDOI
C. Babusiaux1, F. van Leeuwen1, M. A. Barstow1, Carme Jordi1  +448 moreInstitutions (2)
TL;DR: Gaia Data Release 2 provides high-precision astrometry and three-band photometry for about 1.3 billion sources over the full sky as mentioned in this paper, which is unprecedented in both precision and coverage of the various Milky Way stellar populations and stellar evolutionary phases.
Abstract: Context. Gaia Data Release 2 provides high-precision astrometry and three-band photometry for about 1.3 billion sources over the full sky. The precision, accuracy, and homogeneity of both astrometry and photometry are unprecedented. Aims. We highlight the power of the Gaia DR2 in studying many fine structures of the Hertzsprung-Russell diagram (HRD). Gaia allows us to present many different HRDs, depending in particular on stellar population selections. We do not aim here for completeness in terms of types of stars or stellar evolutionary aspects. Instead, we have chosen several illustrative examples. Methods. We describe some of the selections that can be made in Gaia DR2 to highlight the main structures of the Gaia HRDs. We select both field and cluster (open and globular) stars, compare the observations with previous classifications and with stellar evolutionary tracks, and we present variations of the Gaia HRD with age, metallicity, and kinematics. Late stages of stellar evolution such as hot subdwarfs, post-AGB stars, planetary nebulae, and white dwarfs are also analysed, as well as low-mass brown dwarf objects. Results. The Gaia HRDs are unprecedented in both precision and coverage of the various Milky Way stellar populations and stellar evolutionary phases. Many fine structures of the HRDs are presented. The clear split of the white dwarf sequence into hydrogen and helium white dwarfs is presented for the first time in an HRD. The relation between kinematics and the HRD is nicely illustrated. Two different populations in a classical kinematic selection of the halo are unambiguously identified in the HRD. Membership and mean parameters for a selected list of open clusters are provided. They allow drawing very detailed cluster sequences, highlighting fine structures, and providing extremely precise empirical isochrones that will lead to more insight in stellar physics. Conclusions. Gaia DR2 demonstrates the potential of combining precise astrometry and photometry for large samples for studies in stellar evolution and stellar population and opens an entire new area for HRD-based studies.

733 citations


Posted Content
TL;DR: Tacotron 2 as mentioned in this paper uses a recurrent sequence-to-sequence feature prediction network that maps character embeddings to mel-scale spectrograms, followed by a modified WaveNet model acting as a vocoder to synthesize timedomain waveforms.
Abstract: This paper describes Tacotron 2, a neural network architecture for speech synthesis directly from text. The system is composed of a recurrent sequence-to-sequence feature prediction network that maps character embeddings to mel-scale spectrograms, followed by a modified WaveNet model acting as a vocoder to synthesize timedomain waveforms from those spectrograms. Our model achieves a mean opinion score (MOS) of $4.53$ comparable to a MOS of $4.58$ for professionally recorded speech. To validate our design choices, we present ablation studies of key components of our system and evaluate the impact of using mel spectrograms as the input to WaveNet instead of linguistic, duration, and $F_0$ features. We further demonstrate that using a compact acoustic intermediate representation enables significant simplification of the WaveNet architecture.

733 citations


Posted Content
TL;DR: This paper explores how a rich environment can help to promote the learning of complex behavior, and finds that this encourages the emergence of robust behaviours that perform well across a suite of tasks.
Abstract: The reinforcement learning paradigm allows, in principle, for complex behaviours to be learned directly from simple reward signals. In practice, however, it is common to carefully hand-design the reward function to encourage a particular solution, or to derive it from demonstration data. In this paper explore how a rich environment can help to promote the learning of complex behavior. Specifically, we train agents in diverse environmental contexts, and find that this encourages the emergence of robust behaviours that perform well across a suite of tasks. We demonstrate this principle for locomotion -- behaviours that are known for their sensitivity to the choice of reward. We train several simulated bodies on a diverse set of challenging terrains and obstacles, using a simple reward function based on forward progress. Using a novel scalable variant of policy gradient reinforcement learning, our agents learn to run, jump, crouch and turn as required by the environment without explicit reward-based guidance. A visual depiction of highlights of the learned behavior can be viewed following this https URL .

733 citations


Journal ArticleDOI
TL;DR: A review of one-part AAMs in terms of raw materials, activators, additives, mechanical and physical properties, curing mechanisms, hydration products, and environmental impacts can be found in this paper.

733 citations


Journal ArticleDOI
TL;DR: In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years.
Abstract: BackgroundPatients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. MethodsWe randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt–chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rat...

733 citations


Journal ArticleDOI
TL;DR: A definition of microbiome is proposed based on the compact, clear, and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings.
Abstract: The field of microbiome research has evolved rapidly over the past few decades and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term “microbiome.” Moreover, a consensus on best practices in microbiome research is missing. Recently, a panel of international experts discussed the current gaps in the frame of the European-funded MicrobiomeSupport project. The meeting brought together about 40 leaders from diverse microbiome areas, while more than a hundred experts from all over the world took part in an online survey accompanying the workshop. This article excerpts the outcomes of the workshop and the corresponding online survey embedded in a short historical introduction and future outlook. We propose a definition of microbiome based on the compact, clear, and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings. We clearly separate the terms microbiome and microbiota and provide a comprehensive discussion considering the composition of microbiota, the heterogeneity and dynamics of microbiomes in time and space, the stability and resilience of microbial networks, the definition of core microbiomes, and functionally relevant keystone species as well as co-evolutionary principles of microbe-host and inter-species interactions within the microbiome. These broad definitions together with the suggested unifying concepts will help to improve standardization of microbiome studies in the future, and could be the starting point for an integrated assessment of data resulting in a more rapid transfer of knowledge from basic science into practice. Furthermore, microbiome standards are important for solving new challenges associated with anthropogenic-driven changes in the field of planetary health, for which the understanding of microbiomes might play a key role.

733 citations


Journal ArticleDOI
12 Feb 2019-JAMA
TL;DR: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of more than 140mm Hg did not result in a significant reduction in the risk of probable dementia.
Abstract: Importance There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration ClinicalTrials.gov Identifier:NCT01206062

732 citations


Journal ArticleDOI
TL;DR: This paper found that the adjustment in local labor markets is remarkably slow, with wages and labor-force participation rates remaining depressed and unemployment rates remaining elevated for at least a full decade after the China trade shock commences.
Abstract: China's emergence as a great economic power has induced an epochal shift in patterns of world trade. Simultaneously, it has challenged much of the received empirical wisdom about how labor markets adjust to trade shocks. Alongside the heralded consumer benefits of expanded trade are substantial adjustment costs and distributional consequences. These impacts are most visible in the local labor markets in which the industries exposed to foreign competition are concentrated. Adjustment in local labor markets is remarkably slow, with wages and labor-force participation rates remaining depressed and unemployment rates remaining elevated for at least a full decade after the China trade shock commences. Exposed workers experience greater job churning and reduced lifetime income. At the national level, employment has fallen in the US industries more exposed to import competition, as expected, but offsetting employment gains in other industries have yet to materialize. Better understanding when and where trade is ...

732 citations


Journal ArticleDOI
TL;DR: The fourth update of “European Guidelines for the Management of RDS” by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018 is reported.
Abstract: As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of “European Guidelines for the Management of RDS” by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

732 citations


Journal ArticleDOI
TL;DR: Deep neural networks are used for solving a broad range of problems from computer vision, natural-language processing, and audio analysis where the invariances of these structures are built into networks used to model them.
Abstract: Many scientific fields study data with an underlying structure that is a non-Euclidean space. Some examples include social networks in computational social sciences, sensor networks in communications, functional networks in brain imaging, regulatory networks in genetics, and meshed surfaces in computer graphics. In many applications, such geometric data are large and complex (in the case of social networks, on the scale of billions), and are natural targets for machine learning techniques. In particular, we would like to use deep neural networks, which have recently proven to be powerful tools for a broad range of problems from computer vision, natural language processing, and audio analysis. However, these tools have been most successful on data with an underlying Euclidean or grid-like structure, and in cases where the invariances of these structures are built into networks used to model them. Geometric deep learning is an umbrella term for emerging techniques attempting to generalize (structured) deep neural models to non-Euclidean domains such as graphs and manifolds. The purpose of this paper is to overview different examples of geometric deep learning problems and present available solutions, key difficulties, applications, and future research directions in this nascent field.

732 citations


Journal ArticleDOI
TL;DR: A sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort, and nomenclature and classification criteria for patients with IIP and autoimmune features are provided.
Abstract: Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort. The “European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease” was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity. The task force proposes the term “interstitial pneumonia with autoimmune features” (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra-thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features. A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort. ERS/ATS task force provides nomenclature and classification criteria for patients with IIP and autoimmune features

Journal ArticleDOI
TL;DR: Quantum thermodynamics is an emerging research field aiming to extend standard thermodynamics and non-equilibrium statistical physics to ensembles of sizes well below the thermodynamic limit.
Abstract: Quantum thermodynamics is an emerging research field aiming to extend standard thermodynamics and non-equilibrium statistical physics to ensembles of sizes well below the thermodynamic limit, in non-equilibrium situations, and with the full inclusion of quantum effects Fuelled by experimental advances and the potential of future nanoscale applications this research effort is pursued by scientists with different backgrounds, including statistical physics, many-body theory, mesoscopic physics and quantum information theory, who bring various tools and methods to the field A multitude of theoretical questions are being addressed ranging from issues of thermalisation of quantum systems and various definitions of "work", to the efficiency and power of quantum engines This overview provides a perspective on a selection of these current trends accessible to postgraduate students and researchers alike

Journal ArticleDOI
03 May 2016-JAMA
TL;DR: In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there wasno significant difference with gem citabine compared with gemcitabine plus erlotinib used as maintenance therapy.
Abstract: Importance In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown. Objectives To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival. Design, Setting, and Participants In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013. Interventions In the first randomization, 223 patients received 1000 mg/m 2 weekly of gemcitabine alone and 219 patients received 1000 mg/m 2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine). Main Outcomes and Measures The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects. Results A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea. Conclusions and Relevance In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy. Trial Registration clinicaltrials.gov Identifier:NCT00634725

Journal ArticleDOI
06 Jan 2017-Science
TL;DR: The energy-minimizing electron densities for atomic species, as produced by 128 historical and modern DFT functionals, were found to become closer to the exact ones until the early 2000s, when this trend was reversed by unconstrained functionals sacrificing physical rigor for the flexibility of empirical fitting.
Abstract: The theorems at the core of density functional theory (DFT) state that the energy of a many-electron system in its ground state is fully defined by its electron density distribution. This connection is made via the exact functional for the energy, which minimizes at the exact density. For years, DFT development focused on energies, implicitly assuming that functionals producing better energies become better approximations of the exact functional. We examined the other side of the coin: the energy-minimizing electron densities for atomic species, as produced by 128 historical and modern DFT functionals. We found that these densities became closer to the exact ones, reflecting theoretical advances, until the early 2000s, when this trend was reversed by unconstrained functionals sacrificing physical rigor for the flexibility of empirical fitting.

Journal ArticleDOI
TL;DR: NetWAS is introduced, which combines genes with nominally significant genome-wide association study (GWAS) P values and tissue-specific networks to identify disease-gene associations more accurately than GWAS alone.
Abstract: Tissue and cell-type identity lie at the core of human physiology and disease. Understanding the genetic underpinnings of complex tissues and individual cell lineages is crucial for developing improved diagnostics and therapeutics. We present genome-wide functional interaction networks for 144 human tissues and cell types developed using a data-driven Bayesian methodology that integrates thousands of diverse experiments spanning tissue and disease states. Tissue-specific networks predict lineage-specific responses to perturbation, identify the changing functional roles of genes across tissues and illuminate relationships among diseases. We introduce NetWAS, which combines genes with nominally significant genome-wide association study (GWAS) P values and tissue-specific networks to identify disease-gene associations more accurately than GWAS alone. Our webserver, GIANT, provides an interface to human tissue networks through multi-gene queries, network visualization, analysis tools including NetWAS and downloadable networks. GIANT enables systematic exploration of the landscape of interacting genes that shape specialized cellular functions across more than a hundred human tissues and cell types.

Posted ContentDOI
09 Mar 2020-bioRxiv
TL;DR: TBtools (a Toolkit for Biologists integrating various biological data handling tools), a stand-alone software with a user-friendly interface designed to meet the increasing demand for big-data analyses, ranging from bulk sequence processing to interactive data visualization.
Abstract: The rapid development of high-throughput sequencing (HTS) techniques has led biology into the big-data era. Data analyses using various bioinformatics tools rely on programming and command-line environments, which are challenging and time-consuming for most wet-lab biologists. Here, we present TBtools (a Toolkit for Biologists integrating various biological data handling tools), a stand-alone software with a user-friendly interface. The toolkit incorporates over 100 functions, which are designed to meet the increasing demand for big-data analyses, ranging from bulk sequence processing to interactive data visualization. A wide variety of graphs can be prepared in TBtools, with a new plotting engine (“JIGplot”) developed to maximum their interactive ability, which allows quick point-and-click modification to almost every graphic feature. TBtools is a platform-independent software that can be run under all operating systems with Java Runtime Environment 1.6 or newer. It is freely available to non-commercial users at https://github.com/CJ-Chen/TBtools/releases.

Journal ArticleDOI
TL;DR: During home confinement, sleep timing markedly changed, with people going to bed and waking up later, and spending more time in bed, but, paradoxically, also reporting a lower sleep quality.
Abstract: Italy is one of the major COVID-19 hotspots. To reduce the spread of the infections and the pressure on Italian healthcare systems, since March 10, 2020, Italy has been under a total lockdown, forcing people into home confinement. Here we present data from 1,310 people living in the Italian territory (Mage = 23.91 ± 3.60 years, 880 females, 501 workers, 809 university students), who completed an online survey from March 24 to March 28, 2020. In the survey, we asked participants to think about their use of digital media before going to bed, their sleep pattern and their subjective experience of time in the previous week (March 17-23, which was the second week of the lockdown) and up to the first week of February (February 3-10, before any restriction in any Italian area). During the lockdown, people increased the usage of digital media near bedtime, but this change did not affect sleep habits. Nevertheless, during home confinement, sleep timing markedly changed, with people going to bed and waking up later, and spending more time in bed, but, paradoxically, also reporting a lower sleep quality. The increase in sleep difficulties was stronger for people with a higher level of depression, anxiety and stress symptomatology, and associated with the feeling of elongation of time. Considering that the lockdown is likely to continue for weeks, research data are urgently needed to support decision making, to build public awareness and to provide timely and supportive psychosocial interventions.

Journal ArticleDOI
TL;DR: Perinatal depression appears to impose a higher burden on women in low- and middle-income countries and studies in low income countries were especially scarce in this review, demonstrating a need for more epidemiological research in those regions.

Journal ArticleDOI
TL;DR: This paper aims to provide new ideas for TNBC treatment by summarizing existing treatment regimens, therapeutic drugs, and their efficacy for different TNBC subtypes and reviewing some new preclinical studies and targeted treatment regimen for T NBC.
Abstract: Triple-negative breast cancer (TNBC), a specific subtype of breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2), has clinical features that include high invasiveness, high metastatic potential, proneness to relapse, and poor prognosis. Because TNBC tumors lack ER, PR, and HER2 expression, they are not sensitive to endocrine therapy or HER2 treatment, and standardized TNBC treatment regimens are still lacking. Therefore, development of new TNBC treatment strategies has become an urgent clinical need. By summarizing existing treatment regimens, therapeutic drugs, and their efficacy for different TNBC subtypes and reviewing some new preclinical studies and targeted treatment regimens for TNBC, this paper aims to provide new ideas for TNBC treatment.

Journal ArticleDOI
TL;DR: In this article, the authors quantify trends and attributes of extreme regional ocean warming (marine heatwaves, MHWs) across all ocean basins and examine their biological impacts from species to ecosystems.
Abstract: The global ocean has warmed substantially over the past century, with far-reaching implications for marine ecosystems. Concurrent with long-term persistent warming, discrete periods of extreme regional ocean warming (marine heatwaves, MHWs) have increased in frequency. Here we quantify trends and attributes of MHWs across all ocean basins and examine their biological impacts from species to ecosystems. Multiple regions in the Pacific, Atlantic and Indian Oceans are particularly vulnerable to MHW intensification, due to the co-existence of high levels of biodiversity, a prevalence of species found at their warm range edges or concurrent non-climatic human impacts. The physical attributes of prominent MHWs varied considerably, but all had deleterious impacts across a range of biological processes and taxa, including critical foundation species (corals, seagrasses and kelps). MHWs, which will probably intensify with anthropogenic climate change, are rapidly emerging as forceful agents of disturbance with the capacity to restructure entire ecosystems and disrupt the provision of ecological goods and services in coming decades.

Journal ArticleDOI
01 Jan 2017-Gut
TL;DR: The first metagenomic profiling study of CRC faecal microbiomes is presented to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology.
Abstract: Objective To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes. Design We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls. Results Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei . We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I–II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC. Conclusions We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.


Posted Content
TL;DR: A new architecture designed to overcome the challenges of training very deep networks, inspired by Long Short-Term Memory recurrent networks, which allows unimpeded information flow across many layers on information highways.
Abstract: Theoretical and empirical evidence indicates that the depth of neural networks is crucial for their success. However, training becomes more difficult as depth increases, and training of very deep networks remains an open problem. Here we introduce a new architecture designed to overcome this. Our so-called highway networks allow unimpeded information flow across many layers on information highways. They are inspired by Long Short-Term Memory recurrent networks and use adaptive gating units to regulate the information flow. Even with hundreds of layers, highway networks can be trained directly through simple gradient descent. This enables the study of extremely deep and efficient architectures.

Journal ArticleDOI
TL;DR: The global HCC BRIDGE study was a multiregional, large‐scale, longitudinal cohort study undertaken to improve understanding of real‐life management of patients with HCC, from diagnosis to death.
Abstract: Background & Aims Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. The global HCC BRIDGE study was a multiregional, large-scale, longitudinal cohort study undertaken to improve understanding of real-life management of patients with HCC, from diagnosis to death.

Journal ArticleDOI
TL;DR: In this paper, a combined fit to global neutrino oscillation data available as of fall 2016 in the scenario of three-neutrinos oscillations was performed and the allowed ranges of the six oscillation parameters were presented.
Abstract: We perform a combined fit to global neutrino oscillation data available as of fall 2016 in the scenario of three-neutrino oscillations and present updated allowed ranges of the six oscillation parameters. We discuss the differences arising between the consistent combination of the data samples from accelerator and reactor experiments compared to partial combinations. We quantify the confidence in the determination of the less precisely known parameters θ 23, δ CP, and the neutrino mass ordering by performing a Monte Carlo study of the long baseline accelerator and reactor data. We find that the sensitivity to the mass ordering and the θ 23 octant is below 1σ. Maximal θ 23 mixing is allowed at slightly more than 90% CL. The best fit for the CP violating phase is around 270°, CP conservation is allowed at slightly above 1σ, and values of δ CP ≃ 90° are disfavored at around 99% CL for normal ordering and higher CL for inverted ordering.

Journal ArticleDOI
TL;DR: It is concluded that congenital Zika syndrome is a recognizable pattern of structural anomalies and functional disabilities secondary to central and, perhaps, peripheral nervous system damage that can help determine essential follow-up and ongoing care for affected infants and children.
Abstract: Importance Zika virus infection can be prenatally passed from a pregnant woman to her fetus. There is sufficient evidence to conclude that intrauterine Zika virus infection is a cause of microcephaly and serious brain anomalies, but the full spectrum of anomalies has not been delineated. To inform pediatric clinicians who may be called on to evaluate and treat affected infants and children, we review the most recent evidence to better characterize congenital Zika syndrome. Observations We reviewed published reports of congenital anomalies occurring in fetuses or infants with presumed or laboratory-confirmed intrauterine Zika virus infection. We conducted a comprehensive search of the English literature using Medline and EMBASE forZikafrom inception through September 30, 2016. Congenital anomalies were considered in the context of the presumed pathogenetic mechanism related to the neurotropic properties of the virus. We conclude that congenital Zika syndrome is a recognizable pattern of structural anomalies and functional disabilities secondary to central and, perhaps, peripheral nervous system damage. Although many of the components of this syndrome, such as cognitive, sensory, and motor disabilities, are shared by other congenital infections, there are 5 features that are rarely seen with other congenital infections or are unique to congenital Zika virus infection: (1) severe microcephaly with partially collapsed skull; (2) thin cerebral cortices with subcortical calcifications; (3) macular scarring and focal pigmentary retinal mottling; (4) congenital contractures; and (5) marked early hypertonia and symptoms of extrapyramidal involvement. Conclusions and Relevance Although the full spectrum of adverse reproductive outcomes caused by Zika virus infection is not yet determined, a distinctive phenotype—the congenital Zika syndrome—has emerged. Recognition of this phenotype by clinicians for infants and children can help ensure appropriate etiologic evaluation and comprehensive clinical investigation to define the range of anomalies in an affected infant as well as determine essential follow-up and ongoing care.

Journal ArticleDOI
TL;DR: In this article, the authors study the task of sampling from the output distributions of (pseudo-)random quantum circuits, a natural task for benchmarking quantum computers, and show that this sampling task must take exponential time in a classical computer.
Abstract: A critical question for the field of quantum computing in the near future is whether quantum devices without error correction can perform a well-defined computational task beyond the capabilities of state-of-the-art classical computers, achieving so-called quantum supremacy. We study the task of sampling from the output distributions of (pseudo-)random quantum circuits, a natural task for benchmarking quantum computers. Crucially, sampling this distribution classically requires a direct numerical simulation of the circuit, with computational cost exponential in the number of qubits. This requirement is typical of chaotic systems. We extend previous results in computational complexity to argue more formally that this sampling task must take exponential time in a classical computer. We study the convergence to the chaotic regime using extensive supercomputer simulations, modeling circuits with up to 42 qubits - the largest quantum circuits simulated to date for a computational task that approaches quantum supremacy. We argue that while chaotic states are extremely sensitive to errors, quantum supremacy can be achieved in the near-term with approximately fifty superconducting qubits. We introduce cross entropy as a useful benchmark of quantum circuits which approximates the circuit fidelity. We show that the cross entropy can be efficiently measured when circuit simulations are available. Beyond the classically tractable regime, the cross entropy can be extrapolated and compared with theoretical estimates of circuit fidelity to define a practical quantum supremacy test.

Proceedings ArticleDOI
15 Jun 2019
TL;DR: This study revisits numerous previously proposed self-supervised models, conducts a thorough large scale study and uncovers multiple crucial insights about standard recipes for CNN design that do not always translate to self- supervised representation learning.
Abstract: Unsupervised visual representation learning remains a largely unsolved problem in computer vision research. Among a big body of recently proposed approaches for unsupervised learning of visual representations, a class of self-supervised techniques achieves superior performance on many challenging benchmarks. A large number of the pretext tasks for self-supervised learning have been studied, but other important aspects, such as the choice of convolutional neural networks (CNN), has not received equal attention. Therefore, we revisit numerous previously proposed self-supervised models, conduct a thorough large scale study and, as a result, uncover multiple crucial insights. We challenge a number of common practices in self-supervised visual representation learning and observe that standard recipes for CNN design do not always translate to self-supervised representation learning. As part of our study, we drastically boost the performance of previously proposed techniques and outperform previously published state-of-the-art results by a large margin. We will release the code for reproducing our experiments when the anonymity requirements are lifted.

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TL;DR: In this article, the authors examine a crowdfunding platform that connects artists with funders and find that local and distant funders exhibit different funding patterns, and that local funders appear less responsive to information about the cumulative funds raised by an artist.
Abstract: We examine a crowdfunding platform that connects artists with funders. Although the Internet reduces many distance-related frictions, local and distant funders exhibit different funding patterns. Local funders appear less responsive to information about the cumulative funds raised by an artist. However, this distance effect appears to proxy for a social effect: it is largely explained by funders who likely have an offline social relationship with the artist (“friends and family”). Yet, this social effect does not persist past the first investment, suggesting that it may be driven by an activity like search but not monitoring. Thus, although the platform seems to diminish many distance-sensitive costs, it does not eliminate all of them. These findings provide a deeper understanding of the abilities and limitations of online markets to facilitate transactions and convey information between buyers and sellers with varying degrees of social connectedness.

Journal ArticleDOI
TL;DR: Effects of Intermittent Fasting on Health and Aging evidence is accumulating that eating in a 6-hour period and fasting for 18 hours can trigger a metabolic switch from glucose-based to ketone-base fasting.
Abstract: Effects of Intermittent Fasting on Health and Aging Evidence is accumulating that eating in a 6-hour period and fasting for 18 hours can trigger a metabolic switch from glucose-based to ketone-base...