Showing papers by "Uppsala University published in 2018"
University of Minnesota1, University of Colorado Boulder2, VU University Amsterdam3, Harvard University4, University of Southern California5, University of Tartu6, University of Queensland7, Erasmus University Rotterdam8, Hospital for Special Surgery9, University of Copenhagen10, Statens Serum Institut11, Broad Institute12, University of Essex13, University of Edinburgh14, University of Cambridge15, University Hospital of Lausanne16, Geisinger Health System17, Wenzhou Medical College18, Stanford University19, University of North Carolina at Chapel Hill20, University of Wisconsin-Madison21, Hofstra University22, The Feinstein Institute for Medical Research23, University of Dundee24, University of Toronto25, Princeton University26, National Bureau of Economic Research27, New York University Shanghai28, Queen's University29, Karolinska Institutet30, Uppsala University31, University of Lausanne32, New York University33, Stockholm School of Economics34
TL;DR: A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11–13% of the variance ineducational attainment and 7–10% ofthe variance in cognitive performance, which substantially increases the utility ofpolygenic scores as tools in research.
Abstract: Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
1,658 citations
TL;DR: Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on antICOagulation.
Abstract: The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).
1,499 citations
TL;DR: Five replicable clusters of patients with diabetes were identified, which had significantly different patient characteristics and risk of diabetic complications, which might eventually help to tailor and target early treatment to patients who would benefit most.
1,279 citations
TL;DR: This work demonstrates substantial mitigation of both non-radiative losses and photoinduced ion migration in perovskite films and interfaces by decorating the surfaces and grain boundaries with passivating potassium halide layers, and demonstrates the inhibition of transient photo induced ion-migration processes across a wide range of mixed halide perovSKite bandgaps in materials that exhibit bandgap instabilities when unpassivated.
Abstract: M.A.-J. thanks Nava Technology Limited and Nyak Technology Limited for their funding and technical support. Z.A.-G. acknowledges funding from a Winton Studentship, and ICON Studentship from the Lloyd’s Register Foundation. This project has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement number PIOF-GA-2013-622630, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 756962), and the Royal Society and Tata Group (UF150033). We thank the Engineering and Physical Sciences Research Council (EPSRC) for support. XMaS is a mid-range facility at the European Synchrotron Radiation Facility supported by the EPSRC and we are grateful to the XMaS beamline team staff for their support. We thank Diamond Light Source for access to beamline I09 and staff member T.-L. Lee as well as U. Cappel for assistance during the HAXPES measurements. S.C., C.D. and G.D. acknowledge funding from the ERC under grant number 25961976 PHOTO EM and financial support from the European Union under grant number 77 312483 ESTEEM2. M.A. thanks the president of the UAE’s Distinguished Student Scholarship Program, granted by the Ministry of Presidential Affairs. H.R. and B.P. acknowledge support from the Swedish research council (2014-6019) and the Swedish foundation for strategic research. E.M.H. and T.J.S. were supported by the Netherlands Organization for Scientific Research under the Echo grant number 712.014.007.
1,210 citations
TL;DR: The transcriptional basis of the gradual phenotypic change along the arteriovenous axis is uncovered and unexpected cell type differences are revealed: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells.
Abstract: Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited Here, using vascular sin
1,151 citations
University of Oxford1, University of Michigan2, Wellcome Trust Sanger Institute3, Amgen4, University of Cambridge5, University of Copenhagen6, University of Liverpool7, University of Freiburg8, Boston University9, University of Tartu10, Erasmus University Medical Center11, Leiden University Medical Center12, Pasteur Institute13, Icahn School of Medicine at Mount Sinai14, UCLA Medical Center15, Vanderbilt University Medical Center16, Wake Forest University17, National University of Singapore18, Imperial College London19, London North West Healthcare NHS Trust20, Charité21, Innsbruck Medical University22, Washington University in St. Louis23, Queen Mary University of London24, University of Southern Denmark25, National and Kapodistrian University of Athens26, Robertson Centre for Biostatistics27, University of Exeter28, Uppsala University29, University of Düsseldorf30, Steno Diabetes Center31, Aalborg University32, University of Eastern Finland33, Broad Institute34, Frederiksberg Hospital35, Lund University36, University of Bergen37, Technische Universität München38, University of North Carolina at Chapel Hill39, University of Edinburgh40, Ninewells Hospital41, University of Minnesota42, University of Glasgow43, Ludwig Maximilian University of Munich44, University of Iceland45, Aarhus University46, Stanford University47, Science for Life Laboratory48, University of Helsinki49, National Institutes of Health50, University of Dundee51, Harvard University52
TL;DR: Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
1,136 citations
Swedish University of Agricultural Sciences1, Uppsala University2, University of Tartu3, Max Delbrück Center for Molecular Medicine4, Charité5, Leiden University6, University of Wisconsin-Madison7, Braunschweig University of Technology8, Technical University of Madrid9, Wageningen University and Research Centre10, University of California, Riverside11, University of Oslo12, Lund University13, ETH Zurich14, American Museum of Natural History15, University of Würzburg16
TL;DR: It is shown that bacterial, but not fungal, genetic diversity is highest in temperate habitats and that microbial gene composition varies more strongly with environmental variables than with geographic distance, and that the relative contributions of these microorganisms to global nutrient cycling varies spatially.
Abstract: Soils harbour some of the most diverse microbiomes on Earth and are essential for both nutrient cycling and carbon storage. To understand soil functioning, it is necessary to model the global distribution patterns and functional gene repertoires of soil microorganisms, as well as the biotic and environmental associations between the diversity and structure of both bacterial and fungal soil communities1–4. Here we show, by leveraging metagenomics and metabarcoding of global topsoil samples (189 sites, 7,560 subsamples), that bacterial, but not fungal, genetic diversity is highest in temperate habitats and that microbial gene composition varies more strongly with environmental variables than with geographic distance. We demonstrate that fungi and bacteria show global niche differentiation that is associated with contrasting diversity responses to precipitation and soil pH. Furthermore, we provide evidence for strong bacterial–fungal antagonism, inferred from antibiotic-resistance genes, in topsoil and ocean habitats, indicating the substantial role of biotic interactions in shaping microbial communities. Our results suggest that both competition and environmental filtering affect the abundance, composition and encoded gene functions of bacterial and fungal communities, indicating that the relative contributions of these microorganisms to global nutrient cycling varies spatially.
1,108 citations
TL;DR: Patients with type 2 diabetes who had five risk‐factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population.
Abstract: Background Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular ...
806 citations
Evangelos Evangelou1, Evangelos Evangelou2, Helen R. Warren3, Helen R. Warren4 +338 more•Institutions (93)
TL;DR: In this article, the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry was conducted.
Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future
728 citations
University of Cambridge1, Australian National University2, Norwegian Institute of Public Health3, Utrecht University4, University of Tromsø5, Johns Hopkins University6, The George Institute for Global Health7, University of Oxford8, National Institutes of Health9, University of Copenhagen10, Copenhagen University Hospital11, University of Western Australia12, Harry Perkins Institute of Medical Research13, Fiona Stanley Hospital14, University of London15, Lund University16, University of Pittsburgh17, French Institute of Health and Medical Research18, University College London19, Technische Universität München20, University of Ulm21, University of Padua22, University of Southampton23, German Cancer Research Center24, Erasmus University Medical Center25, Umeå University26, Cardiff University27, Greifswald University Hospital28, Aarhus University29, Portland State University30, University of New South Wales31, Harvard University32, National and Kapodistrian University of Athens33, University of Hawaii34, Columbia University35, University of Iowa36, Duke University37, Yamagata University38, Tuskegee University39, University of Helsinki40, University of Oulu41, Medical University of South Carolina42, Kaiser Permanente43, University of Washington44, University of Groningen45, University of Granada46, Yale University47, Prevention Institute48, University of Edinburgh49, Uppsala University50, Basque Government51, Royal Prince Alfred Hospital52, Kyushu University53, Harokopio University54, University of California, San Diego55, VU University Medical Center56, Aalborg University57, University of Eastern Finland58, Laval University59, University of Vermont60, Wake Forest Baptist Medical Center61, Wake Forest University62, Kanazawa Medical University63, Baker IDI Heart and Diabetes Institute64, Heidelberg University65, Istituto Superiore di Sanità66, Pasteur Institute67, City College of New York68, Howard University69, University of Glasgow70, International Agency for Research on Cancer71, University of Bristol72, University of Auckland73
TL;DR: Current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week, and data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
711 citations
Broad Institute1, Harvard University2, VU University Amsterdam3, University of Minnesota4, Hospital for Special Surgery5, University of Southern California6, University of Colorado Boulder7, Karolinska Institutet8, Uppsala University9, Stockholm School of Economics10, University of Queensland11, National Bureau of Economic Research12, New York University13, Research Institute of Industrial Economics14
TL;DR: Applying MTAG to summary statistics for depressive symptoms, neuroticism and subjective well-being increased discovery of associated loci as compared to single-trait analyses, yielding more informative bioinformatics analyses and increasing the variance explained by polygenic scores by approximately 25%, matching theoretical expectations.
Abstract: We introduce multi-trait analysis of GWAS (MTAG), a method for joint analysis of summary statistics from genome-wide association studies (GWAS) of different traits, possibly from overlapping samples. We apply MTAG to summary statistics for depressive symptoms (N eff = 354,862), neuroticism (N = 168,105), and subjective well-being (N = 388,538). As compared to the 32, 9, and 13 genome-wide significant loci identified in the single-trait GWAS (most of which are themselves novel), MTAG increases the number of associated loci to 64, 37, and 49, respectively. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase the variance explained by polygenic scores by approximately 25%, matching theoretical expectations.
TL;DR: In this article, a review of >30 years of research on alternative poly(ethylene oxide) host materials for Li-ion-conducting solid polymer electrolytes is presented, with a clear focus on Li batteries.
TL;DR: In this article, the authors compute global glacier runoff changes for 56 large-scale glacierized drainage basins to 2100 and analyse the glacial impact on streamflow, concluding that the downstream hydrological effects of continued glacier wastage can be substantial, but the magnitudes vary greatly among basins and throughout the melt season.
Abstract: Worldwide glacier retreat and associated future runoff changes raise major concerns over the sustainability of global water resources1–4, but global-scale assessments of glacier decline and the resulting hydrological consequences are scarce5,6. Here we compute global glacier runoff changes for 56 large-scale glacierized drainage basins to 2100 and analyse the glacial impact on streamflow. In roughly half of the investigated basins, the modelled annual glacier runoff continues to rise until a maximum (‘peak water’) is reached, beyond which runoff steadily declines. In the remaining basins, this tipping point has already been passed. Peak water occurs later in basins with larger glaciers and higher ice-cover fractions. Typically, future glacier runoff increases in early summer but decreases in late summer. Although most of the 56 basins have less than 2% ice coverage, by 2100 one-third of them might experience runoff decreases greater than 10% due to glacier mass loss in at least one month of the melt season, with the largest reductions in central Asia and the Andes. We conclude that, even in large-scale basins with minimal ice-cover fraction, the downstream hydrological effects of continued glacier wastage can be substantial, but the magnitudes vary greatly among basins and throughout the melt season.
Fredrick R. Schumacher1, Ali Amin Al Olama2, Sonja I. Berndt3, Sara Benlloch2 +204 more•Institutions (79)
TL;DR: A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology of PrCa1.
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1. A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.
TL;DR: In this paper, the authors describe the processing of the Gaia DR2 data, and describe the criteria used to select the sample published in Gaia DR 2, and explore the data set to assess its quality.
Abstract: Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims. We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods. To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results. The overall astrometric performance is close to the expectations, with an optimal range of brightness G ~ 12 − 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G ~ 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.
TL;DR: In this paper, the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way is demonstrated. But the accuracy of the errors, statistical and systematic, are relatively well understood.
Abstract: Context. Aims: The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds. Methods: Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community. Results: Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (iv) derive a lower limit for the mass of the Milky Way of 9.1-2.6+6.2 × 1011 M⊙ based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (vi) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud. Conclusions: All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.
[...]
TL;DR: In this article, the authors analyzed the economic impact of industrial robots and found that industrial robots increased both labor productivity and value added, while reducing the hours of both low-skilled and middle-skilled workers.
Abstract: Despite ubiquitous discussions of robots’ potential impact, there is almost no systematic empirical evidence on their economic effects. In this paper we analyze for the first time the economic impact of industrial robots, using new data on a panel of industries in 17 countries from 1993-2007. We find that industrial robots increased both labor productivity and value added. Our panel identification is robust to numerous controls, and we find similar results instrumenting increased robot use with a measure of workers’ replaceability by robots, which is based on the tasks prevalent in industries before robots were widely employed. We calculate that the increased use of robots raised countries’ average growth rates by about 0.37 percentage points. We also find that robots increased both wages and total factor productivity. While robots had no significant effect on total hours worked, there is some evidence that they reduced the hours of both low-skilled and middle-skilled workers.
TL;DR: This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation that are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.
Abstract: Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
TL;DR: An energy-aware offloading scheme, which jointly optimizes communication and computation resource allocation under the limited energy and sensitive latency, and an iterative search algorithm combining interior penalty function with D.C. (the difference of two convex functions/sets) programming to find the optimal solution.
Abstract: Mobile edge computing (MEC) brings computation capacity to the edge of mobile networks in close proximity to smart mobile devices (SMDs) and contributes to energy saving compared with local computing, but resulting in increased network load and transmission latency. To investigate the tradeoff between energy consumption and latency, we present an energy-aware offloading scheme, which jointly optimizes communication and computation resource allocation under the limited energy and sensitive latency. In this paper, single and multicell MEC network scenarios are considered at the same time. The residual energy of smart devices’ battery is introduced into the definition of the weighting factor of energy consumption and latency. In terms of the mixed integer nonlinear problem for computation offloading and resource allocation, we propose an iterative search algorithm combining interior penalty function with D.C. (the difference of two convex functions/sets) programming to find the optimal solution. Numerical results show that the proposed algorithm can obtain lower total cost (i.e., the weighted sum of energy consumption and execution latency) comparing with the baseline algorithms, and the energy-aware weighting factor is of great significance to maintain the lifetime of SMDs.
The Heart Research Institute1, Saint Louis University2, Wake Forest University3, University of Maryland, Baltimore4, Heidelberg University5, University of Florida6, University of Milan7, University of Miami8, University of Erlangen-Nuremberg9, Université du Québec à Montréal10, University of Otago11, University of Adelaide12, Agostino Gemelli University Polyclinic13, United States Department of Veterans Affairs14, Tufts University15, Kyung Hee University16, Dalhousie University17, King's College London18, Sichuan University19, The Chinese University of Hong Kong20, University of Western Australia21, National Institutes of Health22, National University of Singapore23, Uppsala University24, University of São Paulo25, Memorial Hospital of South Bend26, Vrije Universiteit Brussel27, Maastricht University28, Universidad Pública de Navarra29, Centre Hospitalier Universitaire de Toulouse30
TL;DR: Evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR) are presented.
Abstract: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefitharm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
TL;DR: This paper shows how to modify the backpropagation algorithm to compute the partial derivatives of the network output with respect to the space variables which is needed to approximate the differential operator.
TL;DR: The results suggest that state-of-the-art deep learning techniques can extract more prognostic information from the tissue morphology of colorectal cancer than an experienced human observer.
Abstract: Image-based machine learning and deep learning in particular has recently shown expert-level accuracy in medical image classification. In this study, we combine convolutional and recurrent architectures to train a deep network to predict colorectal cancer outcome based on images of tumour tissue samples. The novelty of our approach is that we directly predict patient outcome, without any intermediate tissue classification. We evaluate a set of digitized haematoxylin-eosin-stained tumour tissue microarray (TMA) samples from 420 colorectal cancer patients with clinicopathological and outcome data available. The results show that deep learning-based outcome prediction with only small tissue areas as input outperforms (hazard ratio 2.3; CI 95% 1.79-3.03; AUC 0.69) visual histological assessment performed by human experts on both TMA spot (HR 1.67; CI 95% 1.28-2.19; AUC 0.58) and whole-slide level (HR 1.65; CI 95% 1.30-2.15; AUC 0.57) in the stratification into low- and high-risk patients. Our results suggest that state-of-the-art deep learning techniques can extract more prognostic information from the tissue morphology of colorectal cancer than an experienced human observer.
Book•
26 Dec 2018TL;DR: The paper gives a survey of errors-in-variables methods in system identification, and a number of approaches for parameter estimation of errors invariables models are presented.
Abstract: The paper gives a survey of errors-in-variables methods in system identification. Background and motivation are given, and examples illustrate why the identification problem can be difficult. Under general weak assumptions, the systems are not identifiable, but can be parameterized using one degree-of-freedom. Examples where identifiability is achieved under additional assumptions are also provided. A number of approaches for parameter estimation of errors-in-variables models are presented. The underlying assumptions and principles for each approach are highlighted.
University of Geneva1, University of Helsinki2, Katholieke Universiteit Leuven3, University of Washington4, University of Wisconsin-Madison5, German Cancer Research Center6, Heidelberg University7, University of Nottingham8, VU University Amsterdam9, University of California, Irvine10, University of California, San Francisco11, French Institute of Health and Medical Research12, Harvard University13, Maine Medical Center14, University of Turin15, National Institutes of Health16, University of Texas Southwestern Medical Center17, University of Lausanne18, University of Missouri19, École Polytechnique Fédérale de Lausanne20, Uppsala University21, University of Arkansas for Medical Sciences22, University of Bern23, University of Virginia24, Imperial College London25, University of California, San Diego26, University College London27, Flanders Institute for Biotechnology28, University of Oxford29, University of California, Los Angeles30, University of Texas MD Anderson Cancer Center31, University of Toronto32, University of Illinois at Chicago33, University of Amsterdam34, George Washington University35, University of Liège36, University of Eastern Finland37, Ludwig Institute for Cancer Research38, Indiana University39, University of Edinburgh40, Maastricht University41, Loyola University Medical Center42, National Scientific and Technical Research Council43, University of Bari44, University of Fribourg45, Ohio State University46, University of Melbourne47, University of Antwerp48, University of Münster49
TL;DR: In vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis are described and critical aspects that are relevant for their execution and proper interpretation are highlighted.
Abstract: The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
TL;DR: Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time, to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization.
Abstract: The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time.
TL;DR: The second Gaia data release (Gaia DR2) contains, beyond the astrometry, three-band photometry for 1.38 billion sources as discussed by the authors, which is used to infer stellar effective temperatures, T eff, for all sources brighter than G = 17 mag with T eff in the range 3000-10 000 K (some 161 million sources).
Abstract: The second Gaia data release (Gaia DR2) contains, beyond the astrometry, three-band photometry for 1.38 billion sources. One band is the G band, the other two were obtained by integrating the Gaia prism spectra (BP and RP). We have used these three broad photometric bands to infer stellar effective temperatures, T eff , for all sources brighter than G = 17 mag with T eff in the range 3000–10 000 K (some 161 million sources). Using in addition the parallaxes, we infer the line-of-sight extinction, A G , and the reddening, E (BP − RP), for 88 million sources. Together with a bolometric correction we derive luminosity and radius for 77 million sources. These quantities as well as their estimated uncertainties are part of Gaia DR2. Here we describe the procedures by which these quantities were obtained, including the underlying assumptions, comparison with literature estimates, and the limitations of our results. Typical accuracies are of order 324 K (T eff ), 0.46 mag (A G ), 0.23 mag (E (BP − RP)), 15% (luminosity), and 10% (radius). Being based on only a small number of observable quantities and limited training data, our results are necessarily subject to some extreme assumptions that can lead to strong systematics in some cases (not included in the aforementioned accuracy estimates). One aspect is the non-negativity contraint of our estimates, in particular extinction, which we discuss. Yet in several regions of parameter space our results show very good performance, for example for red clump stars and solar analogues. Large uncertainties render the extinctions less useful at the individual star level, but they show good performance for ensemble estimates. We identify regimes in which our parameters should and should not be used and we define a “clean” sample. Despite the limitations, this is the largest catalogue of uniformly-inferred stellar parameters to date. More precise and detailed astrophysical parameters based on the full BP/RP spectrophotometry are planned as part of the third Gaia data release.
TL;DR: A brief overview of attempts to construct de Sitter vacua in string theory can be found in this paper, where the results of this 20-year endeavor could point to the fact that string theory harbors no de Satter vacua.
Abstract: We present a brief overview of attempts to construct de Sitter vacua in string theory and explain how the results of this 20-year endeavor could point to the fact that string theory harbors no de S...
TL;DR: An updated phylum- and class-level fungal classification accounting for monophyly and divergence time so that the main taxonomic ranks are more informative and an example of testing evolutionary ecological hypotheses based on a global soil fungal data set is provided.
Abstract: High-throughput sequencing studies generate vast amounts of taxonomic data. Evolutionary ecological hypotheses of the recovered taxa and Species Hypotheses are difficult to test due to problems with alignments and the lack of a phylogenetic backbone. We propose an updated phylum- and class-level fungal classification accounting for monophyly and divergence time so that the main taxonomic ranks are more informative. Based on phylogenies and divergence time estimates, we adopt phylum rank to Aphelidiomycota, Basidiobolomycota, Calcarisporiellomycota, Glomeromycota, Entomophthoromycota, Entorrhizomycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota and Olpidiomycota. We accept nine subkingdoms to accommodate these 18 phyla. We consider the kingdom Nucleariae (phyla Nuclearida and Fonticulida) as a sister group to the Fungi. We also introduce a perl script and a newick-formatted classification backbone for assigning Species Hypotheses into a hierarchical taxonomic framework, using this or any other classification system. We provide an example of testing evolutionary ecological hypotheses based on a global soil fungal data set.
Proceedings Article•
01 Jan 2018
TL;DR: This overview paper defines the task and the updated evaluation methodology, describes data preparation, report and analyze the main results, and provides a brief categorization of the different approaches of the participating systems.
Abstract: Every year, the Conference on Computational Natural Language Learning (CoNLL) features a shared task, in which participants train and test their learning systems on the same data sets. In 2018, one of two tasks was devoted to learning dependency parsers for a large number of languages, in a real-world setting without any gold-standard annotation on test input. All test sets followed a unified annotation scheme, namely that of Universal Dependencies. This shared task constitutes a 2nd edition—the first one took place in 2017 (Zeman et al., 2017); the main metric from 2017 has been kept, allowing for easy comparison, also in 2018, and two new main metrics have been used. New datasets added to the Universal Dependencies collection between mid-2017 and the spring of 2018 have contributed to increased difficulty of the task this year. In this overview paper, we define the task and the updated evaluation methodology, describe data preparation, report and analyze the main results, and provide a brief categorization of the different approaches of the participating systems.
TL;DR: Findings suggest that comprehensive risk assessments and the aim of reaching a low-risk profile are valid in PAH.
Abstract: Aims: Guidelines recommend a goal-oriented treatment approach in pulmonary arterial hypertension (PAH). The aim is to reach a low-risk profile, as determined by a risk assessment instrument. This s ...