Showing papers by "University of Paris published in 2011"
Memorial Sloan Kettering Cancer Center1, University of Kiel2, Institut Gustave Roussy3, Netherlands Cancer Institute4, The Royal Marsden NHS Foundation Trust5, University of Zurich6, University of Tübingen7, University of Manchester8, University of Paris9, University of Duisburg-Essen10, University of California, Los Angeles11, Vanderbilt University12, University of Pittsburgh13, University of Nantes14, Plexxikon15, Hoffmann-La Roche16, Genentech17, Harvard University18, Peter MacCallum Cancer Centre19
TL;DR: Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation in a phase 3 randomized clinical trial.
Abstract: At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Conclusions Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann–La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.)
6,773 citations
Institut Gustave Roussy1, University of South Florida2, University of Tübingen3, University of Paris4, Université catholique de Louvain5, Aix-Marseille University6, National Health Service7, University of Kiel8, McGill University9, University of Barcelona10, MedImmune11, Bristol-Myers Squibb12, Memorial Sloan Kettering Cancer Center13
TL;DR: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dACarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma.
Abstract: A B S T R AC T Background Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. Methods We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no doselimiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival. Results Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab–dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab–dacarbazine group. Conclusions Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00324155.)
4,069 citations
01 Jan 2011
TL;DR: The basic properties of proximity operators which are relevant to signal processing and optimization methods based on these operators are reviewed and proximal splitting methods are shown to capture and extend several well-known algorithms in a unifying framework.
Abstract: The proximity operator of a convex function is a natural extension of the notion of a projection operator onto a convex set. This tool, which plays a central role in the analysis and the numerical solution of convex optimization problems, has recently been introduced in the arena of inverse problems and, especially, in signal processing, where it has become increasingly important. In this paper, we review the basic properties of proximity operators which are relevant to signal processing and present optimization methods based on these operators. These proximal splitting methods are shown to capture and extend several well-known algorithms in a unifying framework. Applications of proximal methods in signal recovery and synthesis are discussed.
1,942 citations
Seattle Children's1, National Health Service2, Beaumont Hospital3, University of Toronto4, University of Queensland5, Charles University in Prague6, Ludwig Maximilian University of Munich7, University College Dublin8, Case Western Reserve University9, Stanford University10, University of Paris11, University of Alabama at Birmingham12, Vertex Pharmaceuticals13, Queen's University Belfast14
TL;DR: Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks and substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride.
Abstract: Background Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis. Methods We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV1). Results The change from baseline through week 24 in the percent of predicted FEV1 was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P<0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained...
1,835 citations
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
1,829 citations
TL;DR: Meta-analyses of all data provided compelling evidence that ABCA7 and the MS4A gene cluster are new Alzheimer's disease susceptibility loci and independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance.
Abstract: We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10).
1,771 citations
TL;DR: The lower rate of local vascular complications may be a reason to use the radial approach in patients with acute coronary syndromes who were undergoing coronary angiography with possible intervention.
1,739 citations
Stephan Ripke1, Alan R. Sanders2, Kenneth S. Kendler3, Douglas F. Levinson4 +207 more•Institutions (71)
TL;DR: The authors examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects.
Abstract: We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).
1,671 citations
TL;DR: The theoretical and experimental status quo of this very active field of quantum repeater protocols is reviewed, and the potentials of different approaches are compared quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons.
Abstract: The distribution of quantum states over long distances is limited by photon loss. Straightforward amplification as in classical telecommunications is not an option in quantum communication because of the no-cloning theorem. This problem could be overcome by implementing quantum repeater protocols, which create long-distance entanglement from shorter-distance entanglement via entanglement swapping. Such protocols require the capacity to create entanglement in a heralded fashion, to store it in quantum memories, and to swap it. One attractive general strategy for realizing quantum repeaters is based on the use of atomic ensembles as quantum memories, in combination with linear optical techniques and photon counting to perform all required operations. Here the theoretical and experimental status quo of this very active field are reviewed. The potentials of different approaches are compared quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons.
1,603 citations
TL;DR: A rapid and reliable PCR-based technique was developed for detection of genes encoding carbapenemases belonging to different classes using optimized conditions, with PCR giving distinct amplicon sizes corresponding to the different genes for each mixture.
1,438 citations
TL;DR: The T2K experiment observes indications of ν (μ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target, and under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance.
Abstract: The T2K experiment observes indications of nu(mu) -> nu(mu) e appearance in data accumulated with 1.43 x 10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Delta m(23)(2)| = 2.4 x 10(-3) eV(2), sin(2)2 theta(23) = 1 and sin(2)2 theta(13) = 0, the expected number of such events is 1.5 +/- 0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7 x 10(-3), equivalent to 2.5 sigma significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2 theta(13) < 0.28(0.34) for delta(CP) = 0 and a normal (inverted) hierarchy.
TL;DR: The findings suggest that contacts predicted by DCA can be used as a reliable guide to facilitate computational predictions of alternative protein conformations, protein complex formation, and even the de novo prediction of protein domain structures, contingent on the existence of a large number of homologous sequences which are being rapidly made available due to advances in genome sequencing.
Abstract: The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. It has long been suggested that the resulting correlations among amino acid compositions at different sequence positions can be exploited to infer spatial contacts within the tertiary protein structure. Crucial to this inference is the ability to disentangle direct and indirect correlations, as accomplished by the recently introduced direct-coupling analysis (DCA). Here we develop a computationally efficient implementation of DCA, which allows us to evaluate the accuracy of contact prediction by DCA for a large number of protein domains, based purely on sequence information. DCA is shown to yield a large number of correctly predicted contacts, recapitulating the global structure of the contact map for the majority of the protein domains examined. Furthermore, our analysis captures clear signals beyond intradomain residue contacts, arising, e.g., from alternative protein conformations, ligand-mediated residue couplings, and interdomain interactions in protein oligomers. Our findings suggest that contacts predicted by DCA can be used as a reliable guide to facilitate computational predictions of alternative protein conformations, protein complex formation, and even the de novo prediction of protein domain structures, contingent on the existence of a large number of homologous sequences which are being rapidly made available due to advances in genome sequencing.
Wellcome Trust Sanger Institute1, Université de Montréal2, University of Edinburgh3, University of Kiel4, Karolinska Institutet5, Cedars-Sinai Medical Center6, University of Cambridge7, University of Pennsylvania8, Casa Sollievo della Sofferenza9, University of Pittsburgh10, Université libre de Bruxelles11, University of Otago12, Johns Hopkins University13, Ludwig Maximilian University of Munich14, Charité15, Lille University of Science and Technology16, Cincinnati Children's Hospital Medical Center17, Ghent University18, Torbay Hospital19, University of Groningen20, Mater Health Services21, University of Liège22, University of Washington23, University of Utah24, QIMR Berghofer Medical Research Institute25, University of Paris26, University of Western Australia27, Tel Aviv University28, University of Dundee29, Harvard University30, University of Manchester31, Utrecht University32, University of Florence33, King's College London34, Yale University35, Royal Hospital for Sick Children36, Katholieke Universiteit Leuven37, Guy's and St Thomas' NHS Foundation Trust38, University of Barcelona39, University of Chicago40, University of Bern41, Agency for Science, Technology and Research42, University of California, San Francisco43, University of Toronto44, University of Oslo45, Leiden University46, University of Amsterdam47, Aarhus University48, National and Kapodistrian University of Athens49, Lithuanian University of Health Sciences50, Newcastle University51, Emory University52, Örebro University53, French Institute of Health and Medical Research54, Center for Applied Genomics55
TL;DR: A meta-analysis of six ulcerative colitis genome-wide association study datasets found many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1.
Abstract: Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.
TL;DR: The use and reporting of the Delphi method for quality indicators selection need to be improved and some guidance is provided to improve the using and reported of the method in future surveys.
Abstract: Objective
Delphi technique is a structured process commonly used to developed healthcare quality indicators, but there is a little recommendation for researchers who wish to use it. This study aimed 1) to describe reporting of the Delphi method to develop quality indicators, 2) to discuss specific methodological skills for quality indicators selection 3) to give guidance about this practice.
University of Manchester1, Boston University2, Medical University of Vienna3, University of Ottawa4, VU University Amsterdam5, Leiden University6, Columbia University7, Johns Hopkins University8, University of Pisa9, University of Melbourne10, University of York11, University of Florence12, University of Paris13, University of Leeds14, University of California, Los Angeles15, University of Santiago de Compostela16, University of Toronto17, University of Bristol18, Maastricht University19, University of Nebraska Medical Center20, Autonomous University of Madrid21, New York University22, Genentech23, Food and Drug Administration24, Stanford University25, University of Basel26, MedImmune27, University of Kansas28
TL;DR: It is proposed that a patient's RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint counts, CRP level, and patient global assessment are all ≤1, or (2) when the score on the Simplified Disease Activity Index is ≤3.
Abstract: Objective Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used defi nition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a defi nition. Methods A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecifi ed analyses from RA clinical trials. The committee requested a stringent defi nition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to defi ne remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate defi nitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as defi nitions using disease activity indexes. To select a defi nition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Results Survey results for the defi nition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0–10 scale). Analyses suggested the need to include a patientreported measure. Examination of 2-year follow-up data suggested that many candidate defi nitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score–based measures of remission did not
TL;DR: In this article, the authors synthesize literature concerning the sources, composition, mechanisms of stabilisation and destabilization of soil organic matter (SOM) stored in subsoil horizons.
Abstract: Despite their low carbon (C) content, most subsoil horizons contribute to more than half of the total soil C stocks, and therefore need to be considered in the global C cycle. Until recently, the properties and dynamics of C in deep soils was largely ignored. The aim of this review is to synthesize literature concerning the sources, composition, mechanisms of stabilisation and destabilization of soil organic matter (SOM) stored in subsoil horizons. Organic C input into subsoils occurs in dissolved form (DOC) following preferential flow pathways, as aboveground or root litter and exudates along root channels and/or through bioturbation. The relative importance of these inputs for subsoil C distribution and dynamics still needs to be evaluated. Generally, C in deep soil horizons is characterized by high mean residence times of up to several thousand years. With few exceptions, the carbon-to-nitrogen (C/N) ratio is decreasing with soil depth, while the stable C and N isotope ratios of SOM are increasing, indicating that organic matter (OM) in deep soil horizons is highly processed. Several studies suggest that SOM in subsoils is enriched in microbial-derived C compounds and depleted in energy-rich plant material compared to topsoil SOM. However, the chemical composition of SOM in subsoils is soil-type specific and greatly influenced by pedological processes. Interaction with the mineral phase, in particular amorphous iron (Fe) and aluminum (Al) oxides was reported to be the main stabilization mechanism in acid and near neutral soils. In addition, occlusion within soil aggregates has been identified to account for a great proportion of SOM preserved in subsoils. Laboratory studies have shown that the decomposition of subsoil C with high residence times could be stimulated by addition of labile C. Other mechanisms leading to destabilisation of SOM in subsoils include disruption of the physical structure and nutrient supply to soil microorganisms. One of the most important factors leading to protection of SOM in subsoils may be the spatial separation of SOM, microorganisms and extracellular enzyme activity possibly related to the heterogeneity of C input. As a result of the different processes, stabilized SOM in subsoils is horizontally stratified. In order to better understand deep SOM dynamics and to include them into soil C models, quantitative information about C fluxes resulting from C input, stabilization and destabilization processes at the field scale are necessary.
Mayo Clinic1, New York University2, University of Hamburg3, Children's National Medical Center4, University of Girona5, Johns Hopkins University6, St George's, University of London7, Harvard University8, University of Ottawa9, University of Toronto10, University of Miami11, University of Paris12, University College London13, University of Münster14, University of Sydney15, Cincinnati Children's Hospital Medical Center16, University of Oxford17, University of Amsterdam18, Indiana University19
TL;DR: This dissertation aims to provide a history of modern medicine and some of the techniques and practices used in modern medicine, as well as some new approaches, that were introduced in the field of medicine more than 40 years ago.
Marcos Daniel Actis1, G. Agnetta2, Felix Aharonian3, A. G. Akhperjanian +682 more•Institutions (109)
TL;DR: The ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes as mentioned in this paper, which is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100GeV and above 100 TeV.
Abstract: Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
University of Bologna1, University of Copenhagen2, Imperial College London3, University of Bergen4, University of Trieste5, Ludwig Maximilian University of Munich6, University of Paris7, University of Verona8, Sapienza University of Rome9, University of Regensburg10, Innsbruck Medical University11, Institut Gustave Roussy12, Hai phong University Of Medicine and Pharmacy13, University of Cambridge14, The Royal Marsden NHS Foundation Trust15, Katholieke Universiteit Leuven16
TL;DR: Authors F. Piscaglia, C. Nolsøe, M. M. Gilja, and H. P. Weskott review the manuscript and suggest ways in which the manuscript could have been improved.
Abstract: Authors F. Piscaglia1, C. Nolsøe2, C. F. Dietrich3, D. O. Cosgrove4, O. H. Gilja5, M. Bachmann Nielsen6, T. Albrecht7, L. Barozzi8, M. Bertolotto9, O. Catalano10, M. Claudon11, D. A. Clevert12, J. M. Correas13, M. D’Onofrio14, F. M. Drudi15, J. Eyding16, M. Giovannini17, M. Hocke18, A. Ignee19, E. M. Jung20, A. S. Klauser21, N. Lassau22, E. Leen23, G. Mathis24, A. Saftoiu25, G. Seidel26, P. S. Sidhu27, G. ter. Haar28, D. Timmerman29, H. P. Weskott30
TL;DR: Evaluated the performance of ten high dimensional classification methods proposed to automatically discriminate between patients with Alzheimer's disease or mild cognitive impairment and elderly controls using 509 subjects from the ADNI database, finding whole-brain methods achieved high accuracies and the use of feature selection did not improve the performance but substantially increased the computation times.
University of Colorado Boulder1, University of Toronto2, Pierre-and-Marie-Curie University3, University of Oxford4, University of Paris5, Centre national de la recherche scientifique6, Aix-Marseille University7, INAF8, University of California, Santa Barbara9, Las Cumbres Observatory Global Telescope Network10, Defence Research and Development Canada11, University of Victoria12, California Institute of Technology13, Centra14, Lawrence Berkeley National Laboratory15, University of Waterloo16, Australian Astronomical Observatory17, University of California, Berkeley18
TL;DR: In this article, the authors combine high redshift Type Ia supernovae from the first 3 years of the Supernova Legacy Survey (SNLS) with other supernova (SN) samples, primarily at lower redshifts, to form a high-quality joint sample of 472 SNe (123 low-$z, 93 SDSS, 242 SNLS, and 14 {\it Hubble Space Telescope}).
Abstract: We combine high redshift Type Ia supernovae from the first 3 years of the Supernova Legacy Survey (SNLS) with other supernova (SN) samples, primarily at lower redshifts, to form a high-quality joint sample of 472 SNe (123 low-$z$, 93 SDSS, 242 SNLS, and 14 {\it Hubble Space Telescope}). SN data alone require cosmic acceleration at >99.9% confidence, including systematic effects. For the dark energy equation of state parameter (assumed constant out to at least $z=1.4$) in a flat universe, we find $w = -0.91^{+0.16}_{-0.20}(\mathrm{stat}) ^{+0.07}_{-0.14} (\mathrm{sys})$ from SNe only, consistent with a cosmological constant. Our fits include a correction for the recently discovered relationship between host-galaxy mass and SN absolute brightness. We pay particular attention to systematic uncertainties, characterizing them using a systematics covariance matrix that incorporates the redshift dependence of these effects, as well as the shape-luminosity and color-luminosity relationships. Unlike previous work, we include the effects of systematic terms on the empirical light-curve models. The total systematic uncertainty is dominated by calibration terms. We describe how the systematic uncertainties can be reduced with soon to be available improved nearby and intermediate-redshift samples, particularly those calibrated onto USNO/SDSS-like systems.
University of Southampton1, University of Paris2, Nestlé3, French Institute of Health and Medical Research4, The Coca-Cola Company5, University of Naples Federico II6, University of Düsseldorf7, Spanish National Research Council8, University of Crete9, Kraft Foods10, Sapienza University of Rome11, Maastricht University12, University of Helsinki13, University of Graz14
TL;DR: Potential mechanisms are described and research gaps, which limit the understanding of the interaction between diet and postprandial and chronic low-grade inflammation, are identified.
Abstract: Low-grade inflammation is a characteristic of the obese state, and adipose tissue releases many inflammatory mediators. The source of these mediators within adipose tissue is not clear, but infiltrating macrophages seem to be especially important, although adipocytes themselves play a role. Obese people have higher circulating concentrations of many inflammatory markers than lean people do, and these are believed to play a role in causing insulin resistance and other metabolic disturbances. Blood concentrations of inflammatory markers are lowered following weight loss. In the hours following the consumption of a meal, there is an elevation in the concentrations of inflammatory mediators in the bloodstream, which is exaggerated in obese subjects and in type 2 diabetics. Both high-glucose and high-fat meals may induce postprandial inflammation, and this is exaggerated by a high meal content of advanced glycation end products (AGE) and partly ablated by inclusion of certain antioxidants or antioxidant-containing foods within the meal. Healthy eating patterns are associated with lower circulating concentrations of inflammatory markers. Among the components of a healthy diet, whole grains, vegetables and fruits, and fish are all associated with lower inflammation. AGE are associated with enhanced oxidative stress and inflammation. SFA and trans-MUFA are pro-inflammatory, while PUFA, especially long-chain n-3 PUFA, are anti-inflammatory. Hyperglycaemia induces both postprandial and chronic low-grade inflammation. Vitamin C, vitamin E and carotenoids decrease the circulating concentrations of inflammatory markers. Potential mechanisms are described and research gaps, which limit our understanding of the interaction between diet and postprandial and chronic low-grade inflammation, are identified.
TL;DR: In this article, the authors carried out a detailed environmental evaluation of geopolymer concrete production using the Life Cycle Assessment methodology and found that the production of most standard types of OPC concrete has a slightly lower impact on global warming than standard Ordinary Portland Cement.
16 Jul 2011
TL;DR: This work proposes a strongly performing method that scales to image annotation datasets by simultaneously learning to optimize precision at the top of the ranked list of annotations for a given image and learning a low-dimensional joint embedding space for both images and annotations.
Abstract: Image annotation datasets are becoming larger and larger, with tens of millions of images and tens of thousands of possible annotations. We propose a strongly performing method that scales to such datasets by simultaneously learning to optimize precision at the top of the ranked list of annotations for a given image and learning a low-dimensional joint embedding space for both images and annotations. Our method, called WSABIE, both outperforms several baseline methods and is faster and consumes less memory.
TL;DR: Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment, and the outcome was death in 9 cases, but no predictive factors for serious cases were found.
TL;DR: It is reported that inactivation of Tet2 in mouse perturbs both early and late steps of hematopoiesis including myeloid and lymphoid differentiation in a cell-autonomous manner, endows the cells with competitive advantage, and eventually leads to the development of malignancies.
TL;DR: It is shown that RAN translation across human spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1) CAG expansion transcripts results in the accumulation of SCA8 polyalanine and DM1 polyglutamine expansion proteins in previously established mouse models and human tissue.
Abstract: Trinucleotide expansions cause disease by both protein- and RNA-mediated mechanisms. Unexpectedly, we discovered that CAG expansion constructs express homopolymeric polyglutamine, polyalanine, and polyserine proteins in the absence of an ATG start codon. This repeat-associated non-ATG translation (RAN translation) occurs across long, hairpin-forming repeats in transfected cells or when expansion constructs are integrated into the genome in lentiviral-transduced cells and brains. Additionally, we show that RAN translation across human spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1) CAG expansion transcripts results in the accumulation of SCA8 polyalanine and DM1 polyglutamine expansion proteins in previously established SCA8 and DM1 mouse models and human tissue. These results have implications for understanding fundamental mechanisms of gene expression. Moreover, these toxic, unexpected, homopolymeric proteins now should be considered in pathogenic models of microsatellite disorders.
TL;DR: After 2 years of follow-up, laparoscopic Heller's myotomy, as compared with pneumatic dilation, was not associated with superior rates of therapeutic success.
Abstract: BACKGROUND Many experts consider laparoscopic Heller's myotomy (LHM) to be superior to pneumatic dilation for the treatment of achalasia, and LHM is increasingly considered to be the treatment of choice for this disorder. METHODS We randomly assigned patients with newly diagnosed achalasia to pneumatic dilation or LHM with Dor's fundoplication. Symptoms, including weight loss, dysphagia, retrosternal pain, and regurgitation, were assessed with the use of the Eckardt score (which ranges from 0 to 12, with higher scores indicating more pronounced symptoms). The primary outcome was therapeutic success (a drop in the Eckardt score to ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for retreatment, pressure at the lower esophageal sphincter, esophageal emptying on a timed barium esophagogram, quality of life, and the rate of complications. RESULTS A total of 201 patients were randomly assigned to pneumatic dilation (95 patients) or LHM (106). The mean follow-up time was 43 months (95% confidence interval [CI], 40 to 47). In an intention-to-treat analysis, there was no significant difference between the two groups in the primary outcome; the rate of therapeutic success with pneumatic dilation was 90% after 1 year of follow-up and 86% after 2 years, as compared with a rate with LHM of 93% after 1 year and 90% after 2 years (P=0.46). After 2 years of follow-up, there was no significant between-group difference in the pressure at the lower esophageal sphincter (LHM, 10 mm Hg [95% CI, 8.7 to 12]; pneumatic dilation, 12 mm Hg [95% CI, 9.7 to 14]; P=0.27); esophageal emptying, as assessed by the height of barium-contrast column (LHM, 1.9 cm [95% CI, 0 to 6.8]; pneumatic dilation, 3.7 cm [95% CI, 0 to 8.8]; P=0.21); or quality of life. Similar results were obtained in the per-protocol analysis. Perforation of the esophagus occurred in 4% of the patients during pneumatic dilation, whereas mucosal tears occurred in 12% during LHM. Abnormal exposure to esophageal acid was observed in 15% and 23% of the patients in the pneumatic-dilation and LHM groups, respectively (P=0.28). CONCLUSIONS After 2 years of follow-up, LHM, as compared with pneumatic dilation, was not associated with superior rates of therapeutic success. (European Achalasia Trial Netherlands Trial Register number, NTR37, and Current Controlled Trials number, ISRCTN56304564.).
TL;DR: Clay minerals, recently discovered to be widespread in Mars’s Noachian terrains, indicate long-duration interaction between water and rock over 3.7 billion years ago, and available data indicate substantial Martian clay formation by hydrothermal groundwater circulation and a Noachia rock record dominated by evidence of subsurface waters.
Abstract: Clay minerals, recently discovered to be widespread in Mars’s Noachian terrains, indicate long-duration interaction between water and rock over 3.7 billion years ago. Analysis of how they formed should indicate what environmental conditions prevailed on early Mars. If clays formed near the surface by weathering, as is common on Earth, their presence would indicate past surface conditions warmer and wetter than at present. However, available data instead indicate substantial Martian clay formation by hydrothermal groundwater circulation and a Noachian rock record dominated by evidence of subsurface waters. Cold, arid conditions with only transient surface water may have characterized Mars’s surface for over 4 billion years, since the early-Noachian period, and the longest-duration aqueous, potentially habitable environments may have been in the subsurface.
[...]
11 Dec 2011-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: The T2K experiment as discussed by the authors is a long-baseline neutrino oscillation experiment whose main goal is to measure the last unknown lepton sector mixing angle by observing its appearance in a particle beam generated by the J-PARC accelerator.
Abstract: The T2K experiment is a long-baseline neutrino oscillation experiment Its main goal is to measure the last unknown lepton sector mixing angle {\theta}_{13} by observing {
u}_e appearance in a {
u}_{\mu} beam It also aims to make a precision measurement of the known oscillation parameters, {\Delta}m^{2}_{23} and sin^{2} 2{\theta}_{23}, via {
u}_{\mu} disappearance studies Other goals of the experiment include various neutrino cross section measurements and sterile neutrino searches The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem