Showing papers by "University of Toronto published in 2011"
TL;DR: In this article, a combination of seven-year data from WMAP and improved astrophysical data rigorously tests the standard cosmological model and places new constraints on its basic parameters and extensions.
Abstract: The combination of seven-year data from WMAP and improved astrophysical data rigorously tests the standard cosmological model and places new constraints on its basic parameters and extensions. By combining the WMAP data with the latest distance measurements from the baryon acoustic oscillations (BAO) in the distribution of galaxies and the Hubble constant (H0) measurement, we determine the parameters of the simplest six-parameter ΛCDM model. The power-law index of the primordial power spectrum is ns = 0.968 ± 0.012 (68% CL) for this data combination, a measurement that excludes the Harrison–Zel’dovich–Peebles spectrum by 99.5% CL. The other parameters, including those beyond the minimal set, are also consistent with, and improved from, the five-year results. We find no convincing deviations from the minimal model. The seven-year temperature power spectrum gives a better determination of the third acoustic peak, which results in a better determination of the redshift of the matter-radiation equality epoch. Notable examples of improved parameters are the total mass of neutrinos, � mν < 0.58 eV (95% CL), and the effective number of neutrino species, Neff = 4.34 +0.86 −0.88 (68% CL), which benefit from better determinations of the third peak and H0. The limit on a constant dark energy equation of state parameter from WMAP+BAO+H0, without high-redshift Type Ia supernovae, is w =− 1.10 ± 0.14 (68% CL). We detect the effect of primordial helium on the temperature power spectrum and provide a new test of big bang nucleosynthesis by measuring Yp = 0.326 ± 0.075 (68% CL). We detect, and show on the map for the first time, the tangential and radial polarization patterns around hot and cold spots of temperature fluctuations, an important test of physical processes at z = 1090 and the dominance of adiabatic scalar fluctuations. The seven-year polarization data have significantly improved: we now detect the temperature–E-mode polarization cross power spectrum at 21σ , compared with 13σ from the five-year data. With the seven-year temperature–B-mode cross power spectrum, the limit on a rotation of the polarization plane due to potential parity-violating effects has improved by 38% to Δα =− 1. 1 ± 1. 4(statistical) ± 1. 5(systematic) (68% CL). We report significant detections of the Sunyaev–Zel’dovich (SZ) effect at the locations of known clusters of galaxies. The measured SZ signal agrees well with the expected signal from the X-ray data on a cluster-by-cluster basis. However, it is a factor of 0.5–0.7 times the predictions from “universal profile” of Arnaud et al., analytical models, and hydrodynamical simulations. We find, for the first time in the SZ effect, a significant difference between the cooling-flow and non-cooling-flow clusters (or relaxed and non-relaxed clusters), which can explain some of the discrepancy. This lower amplitude is consistent with the lower-than-theoretically expected SZ power spectrum recently measured by the South Pole Telescope Collaboration.
11,309 citations
University of Amsterdam1, University of Toronto2, Centre Hospitalier Universitaire de Toulouse3, Cleveland Clinic4, Tohoku University5, Charles University in Prague6, University College Dublin7, University of Basel8, Icahn School of Medicine at Mount Sinai9, Lund University10, University College London11, University of California, San Francisco12, Mayo Clinic13, University of Texas Health Science Center at Houston14
TL;DR: These revisions simplify the McDonald Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
Abstract: New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
8,883 citations
TL;DR: The propensity score is a balancing score: conditional on the propensity score, the distribution of observed baseline covariates will be similar between treated and untreated subjects, and different causal average treatment effects and their relationship with propensity score analyses are described.
Abstract: The propensity score is the probability of treatment assignment conditional on observed baseline characteristics. The propensity score allows one to design and analyze an observational (nonrandomized) study so that it mimics some of the particular characteristics of a randomized controlled trial. In particular, the propensity score is a balancing score: conditional on the propensity score, the distribution of observed baseline covariates will be similar between treated and untreated subjects. I describe 4 different propensity score methods: matching on the propensity score, stratification on the propensity score, inverse probability of treatment weighting using the propensity score, and covariate adjustment using the propensity score. I describe balance diagnostics for examining whether the propensity score model has been adequately specified. Furthermore, I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data. I describe different causal average treatment effects and their relationship with propensity score analyses.
7,895 citations
National Institutes of Health1, Cardiff University2, Erasmus University Rotterdam3, VU University Amsterdam4, University of Manchester5, University College London6, University of Helsinki7, University of Oulu8, Johns Hopkins University9, Georgetown University10, Illumina11, University Hospital of Wales12, University of Eastern Finland13, University of Miami14, University of Turin15, University of Cagliari16, The Catholic University of America17, Microsoft18, University of Toronto19, University of Würzburg20, University of Washington21, Aneurin Bevan University Health Board22
TL;DR: The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases, and a large hexanucleotide repeat expansion in the first intron of C9ORF72 is shown.
3,784 citations
Katholieke Universiteit Leuven1, Oslo University Hospital2, University of Pennsylvania3, University of Rochester4, Medical College of Wisconsin5, Roswell Park Cancer Institute6, Massachusetts Institute of Technology7, Harvard University8, Wayne State University9, University of British Columbia10, University of Oslo11, Medical University of Warsaw12, University of Liège13, University of Toronto14, Polish Academy of Sciences15
TL;DR: The photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells as discussed by the authors, which can prolong survival in patients with inoperable cancers and significantly improve quality of life.
Abstract: Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. CA Cancer J Clin 2011;61:250-281. V C
3,770 citations
University of Pennsylvania1, University of New South Wales2, Mayo Clinic3, University of California, Los Angeles4, University of California, San Francisco5, Erasmus University Rotterdam6, Johns Hopkins University7, University of Western Ontario8, University Hospital Southampton NHS Foundation Trust9, University of Southampton10, University College London11, University of California, San Diego12, University of Toronto13, Northwestern University14, Harvard University15, Technische Universität München16, Lille University of Science and Technology17, VU University Amsterdam18, Favaloro University19, Kessler Foundation20, Vita-Salute San Raffaele University21
TL;DR: The revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotmporal lobar degeneration and reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations.
Abstract: Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.
3,706 citations
University of Trento1, University of California, San Francisco2, Johns Hopkins University3, Northwestern University4, University of Western Ontario5, University of California, Los Angeles6, Vita-Salute San Raffaele University7, University College London8, University of Toronto9, Mayo Clinic10, University of California, Davis11, Katholieke Universiteit Leuven12, University of Cambridge13, University of New South Wales14, University of Pennsylvania15
TL;DR: This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results.
Abstract: This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA—nonfluent/agrammatic, semantic, and logopenic—were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as “imaging-supported” if the expected pattern of atrophy is found and “with definite pathology” if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.
3,635 citations
3,322 citations
2,819 citations
TL;DR: The Semantic Orientation CALculator (SO-CAL) uses dictionaries of words annotated with their semantic orientation (polarity and strength), and incorporates intensification and negation, and is applied to the polarity classification task.
Abstract: We present a lexicon-based approach to extracting sentiment from text. The Semantic Orientation CALculator (SO-CAL) uses dictionaries of words annotated with their semantic orientation (polarity and strength), and incorporates intensification and negation. SO-CAL is applied to the polarity classification task, the process of assigning a positive or negative label to a text that captures the text's opinion towards its main subject matter. We show that SO-CAL's performance is consistent across domains and in completely unseen data. Additionally, we describe the process of dictionary creation, and our use of Mechanical Turk to check dictionaries for consistency and reliability.
2,798 citations
16 Oct 2011
TL;DR: Novel extensions to the core GPU pipeline demonstrate object segmentation and user interaction directly in front of the sensor, without degrading camera tracking or reconstruction, to enable real-time multi-touch interactions anywhere.
Abstract: KinectFusion enables a user holding and moving a standard Kinect camera to rapidly create detailed 3D reconstructions of an indoor scene. Only the depth data from Kinect is used to track the 3D pose of the sensor and reconstruct, geometrically precise, 3D models of the physical scene in real-time. The capabilities of KinectFusion, as well as the novel GPU-based pipeline are described in full. Uses of the core system for low-cost handheld scanning, and geometry-aware augmented reality and physics-based interactions are shown. Novel extensions to the core GPU pipeline demonstrate object segmentation and user interaction directly in front of the sensor, without degrading camera tracking or reconstruction. These extensions are used to enable real-time multi-touch interactions anywhere, allowing any planar or non-planar reconstructed physical surface to be appropriated for touch.
TL;DR: An overview of PFASs detected in the environment, wildlife, and humans, and recommend clear, specific, and descriptive terminology, names, and acronyms for PFAS, can be found in this article.
Abstract: The primary aim of this article is to provide an overview of perfluoroalkyl and polyfluoroalkyl substances (PFASs) detected in the environment, wildlife, and humans, and recommend clear, specific, and descriptive terminology, names, and acronyms for PFASs. The overarching objective is to unify and harmonize communication on PFASs by offering terminology for use by the global scientific, regulatory, and industrial communities. A particular emphasis is placed on long-chain perfluoroalkyl acids, substances related to the long-chain perfluoroalkyl acids, and substances intended as alternatives to the use of the long-chain perfluoroalkyl acids or their precursors. First, we define PFASs, classify them into various families, and recommend a pragmatic set of common names and acronyms for both the families and their individual members. Terminology related to fluorinated polymers is an important aspect of our classification. Second, we provide a brief description of the 2 main production processes, electrochemical fluorination and telomerization, used for introducing perfluoroalkyl moieties into organic compounds, and we specify the types of byproducts (isomers and homologues) likely to arise in these processes. Third, we show how the principal families of PFASs are interrelated as industrial, environmental, or metabolic precursors or transformation products of one another. We pay particular attention to those PFASs that have the potential to be converted, by abiotic or biotic environmental processes or by human metabolism, into long-chain perfluoroalkyl carboxylic or sulfonic acids, which are currently the focus of regulatory action. The Supplemental Data lists 42 families and subfamilies of PFASs and 268 selected individual compounds, providing recommended names and acronyms, and structural formulas, as well as Chemical Abstracts Service registry numbers. Integr Environ Assess Manag 2011;7:513–541. © 2011 SETAC
Daniel J. Eisenstein1, Daniel J. Eisenstein2, David H. Weinberg3, Eric Agol4 +260 more•Institutions (62)
TL;DR: SDSS-III as mentioned in this paper is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars.
Abstract: Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z 100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)
TL;DR: Single-cell “mass cytometry” analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention.
Abstract: Flow cytometry is an essential tool for dissecting the functional complexity of hematopoiesis. We used single-cell "mass cytometry" to examine healthy human bone marrow, measuring 34 parameters simultaneously in single cells (binding of 31 antibodies, viability, DNA content, and relative cell size). The signaling behavior of cell subsets spanning a defined hematopoietic hierarchy was monitored with 18 simultaneous markers of functional signaling states perturbed by a set of ex vivo stimuli and inhibitors. The data set allowed for an algorithmically driven assembly of related cell types defined by surface antigen expression, providing a superimposable map of cell signaling responses in combination with drug inhibition. Visualized in this manner, the analysis revealed previously unappreciated instances of both precise signaling responses that were bounded within conventionally defined cell subsets and more continuous phosphorylation responses that crossed cell population boundaries in unexpected manners yet tracked closely with cellular phenotype. Collectively, such single-cell analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention.
TL;DR: In this paper, the evolutionary relationship between CRISPR-Cas and Cas proteins is analyzed and a unified classification of these systems is proposed based on multiple criteria. But, the classification is based on the phylogenies of the most common cas genes, the sequence and organization of the CRISpr repeats and the architecture of the Cas loci.
Abstract: The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR-Cas systems and Cas proteins. Three major types of CRISPR-Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR-Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a 'polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR-cas loci.
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TL;DR: In this article, the authors proposed a framework for fair classification comprising a task-specific metric for determining the degree to which individuals are similar with respect to the classification task at hand, and an algorithm for maximizing utility subject to the fairness constraint that similar individuals are treated similarly.
Abstract: We study fairness in classification, where individuals are classified, e.g., admitted to a university, and the goal is to prevent discrimination against individuals based on their membership in some group, while maintaining utility for the classifier (the university). The main conceptual contribution of this paper is a framework for fair classification comprising (1) a (hypothetical) task-specific metric for determining the degree to which individuals are similar with respect to the classification task at hand; (2) an algorithm for maximizing utility subject to the fairness constraint, that similar individuals are treated similarly. We also present an adaptation of our approach to achieve the complementary goal of "fair affirmative action," which guarantees statistical parity (i.e., the demographics of the set of individuals receiving any classification are the same as the demographics of the underlying population), while treating similar individuals as similarly as possible. Finally, we discuss the relationship of fairness to privacy: when fairness implies privacy, and how tools developed in the context of differential privacy may be applied to fairness.
TL;DR: The use of silica-rich SCMs influences the amount and kind of hydrates formed and thus the volume, the porosity and finally the durability of these materials.
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...
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.
TL;DR: The Alzheimer Disease Genetics Consortium performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1), two replication stages (stages 2 and 3), and both joint analysis and meta-analysis approaches were used.
Abstract: The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.
Wellcome Trust1, University of London2, Dana Corporation3, University of Toronto4, Federal University of São Paulo5, Duke University6, University of Wisconsin-Madison7, University of Oxford8, John E. Fogarty International Center9, University of Queensland10, Chinese Center for Disease Control and Prevention11, Harvard University12, Johns Hopkins University13, Muhimbili University of Health and Allied Sciences14, King's College London15, University of Ibadan16, Cayetano Heredia University17, University of California, Berkeley18, Indian Institute of Science19, University of Cambridge20, World Health Organization21, Health Canada22, University of Cape Town23, National Health and Medical Research Council24, Medical Research Council25, Canadian Institutes of Health Research26, National Institutes of Health27
TL;DR: A consortium of researchers, advocates and clinicians announces here research priorities for improving the lives of people with mental illness around the world, and calls for urgent action and investment.
Abstract: A consortium of researchers, advocates and clinicians announces here research priorities for improving the lives of people with mental illness around the world, and calls for urgent action and investment.
TL;DR: The results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.
Abstract: Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.
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)).
TL;DR: In this paper, the authors developed guidelines for reporting reliability and agreement studies in interrater and intra-arater reliability and agreements, and proposed 15 issues that should be addressed when reporting such studies.
TL;DR: FD measures can explain variation in ecosystem function even when richness does not, and should be incorporated into conservation and restoration decision-making, especially for those efforts attempting to reconstruct or preserve healthy, functioning ecosystems.
Abstract: Summary 1. The goal of conservation and restoration activities is to maintain biological diversity and the ecosystem services that this diversity provides. These activities traditionally focus on the measures of species diversity that include only information on the presence and abundance of species. Yet how diversity influences ecosystem function depends on the traits and niches filled by species. 2. Biological diversity can be quantified in ways that account for functional and phenotypic differences. A number of such measures of functional diversity (FD) have been created, quantifying the distribution of traits in a community or the relative magnitude of species similarities and differences. We review FD measures and why they are intuitively useful for understanding ecological patterns and are important for management. 3. In order for FD to be meaningful and worth measuring, it must be correlated with ecosystem function, and it should provide information above and beyond what species richness or diversity can explain. We review these two propositions, examining whether the strength of the correlation between FD and species richness varies across differing environmental gradients and whether FD offers greater explanatory power of ecosystem function than species richness. 4. Previous research shows that the relationship between FD and richness is complex and context dependent. Different functional traits can show individual responses to different gradients, meaning that important changes in diversity can occur with minimal change in richness. Further, FD can explain variation in ecosystem function even when richness does not. 5. Synthesis and applications. FD measures those aspects of diversity that potentially affect community assembly and function. Given this explanatory power, FD should be incorporated into conservation and restoration decision-making, especially for those efforts attempting to reconstruct or preserve healthy, functioning ecosystems.
Hiroaki Aihara1, Carlos Allende Prieto2, Carlos Allende Prieto3, Deokkeun An4 +191 more•Institutions (58)
TL;DR: The first data release of SDSS-III is described in this article, which includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the Sloan Digital Sky Survey imaging to 14,555 deg2, or over a third of the Celestial Sphere.
Abstract: The Sloan Digital Sky Survey (SDSS) started a new phase in 2008 August, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Lyα forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the SDSS imaging to 14,555 deg2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Exploration (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameter pipeline, which has better determination of metallicity for high-metallicity stars.
TL;DR: The principles learned from studies of various natural antenna complexes are described and how to elucidate strategies for designing light-harvesting systems are suggested to be used for solar fuel production, to direct and regulate excitation energy flow using molecular organizations that facilitate feedback and control, or to transfer excitons over long distances.
Abstract: Solar fuel production often starts with the energy from light being absorbed by an assembly of molecules; this electronic excitation is subsequently transferred to a suitable acceptor. For example, in photosynthesis, antenna complexes capture sunlight and direct the energy to reaction centres that then carry out the associated chemistry. In this Review, we describe the principles learned from studies of various natural antenna complexes and suggest how to elucidate strategies for designing light-harvesting systems. We envisage that such systems will be used for solar fuel production, to direct and regulate excitation energy flow using molecular organizations that facilitate feedback and control, or to transfer excitons over long distances. Also described are the notable properties of light-harvesting chromophores, spatial-energetic landscapes, the roles of excitonic states and quantum coherence, as well as how antennas are regulated and photoprotected.
TL;DR: Three large-scale neural system models of primate neocortex that emphasize the key contributions of local dynamics, signal transmission delays and noise to the emerging RSNs are reviewed.
Abstract: A broad body of experimental work has demonstrated that apparently spontaneous brain activity is not random. At the level of large-scale neural systems, as measured with functional MRI (fMRI), this ongoing activity reflects the organization of a series of highly coherent functional networks. These so-called resting-state networks (RSNs) closely relate to the underlying anatomical connectivity but cannot be understood in those terms alone. Here we review three large-scale neural system models of primate neocortex that emphasize the key contributions of local dynamics, signal transmission delays and noise to the emerging RSNs. We propose that the formation and dissolution of resting-state patterns reflects the exploration of possible functional network configurations around a stable anatomical skeleton.
22 Oct 2011
TL;DR: In this article, a fully homomorphic encryption scheme based solely on the (standard) learning with errors (LWE) assumption is presented. But the security of their scheme is based on the worst-case hardness of ''short vector problems'' on arbitrary lattices.
Abstract: We present a fully homomorphic encryption scheme that is based solely on the(standard) learning with errors (LWE) assumption. Applying known results on LWE, the security of our scheme is based on the worst-case hardness of ``short vector problems'' on arbitrary lattices. Our construction improves on previous works in two aspects:\begin{enumerate}\item We show that ``somewhat homomorphic'' encryption can be based on LWE, using a new {\em re-linearization} technique. In contrast, all previous schemes relied on complexity assumptions related to ideals in various rings. \item We deviate from the "squashing paradigm'' used in all previous works. We introduce a new {\em dimension-modulus reduction} technique, which shortens the cipher texts and reduces the decryption complexity of our scheme, {\em without introducing additional assumptions}. \end{enumerate}Our scheme has very short cipher texts and we therefore use it to construct an asymptotically efficient LWE-based single-server private information retrieval (PIR) protocol. The communication complexity of our protocol (in the public-key model) is $k \cdot \polylog(k)+\log \dbs$ bits per single-bit query (here, $k$ is a security parameter).
TL;DR: In this paper, the angular power spectra derived from the seven-year maps and discuss the cosmological conclusions that can be inferred from WMAP data alone are presented. But the results are limited to the case of L 2.
Abstract: The WMAP mission has produced sky maps from seven years of observations at L2. We present the angular power spectra derived from the seven-year maps and discuss the cosmological conclusions that can be inferred from WMAP data alone. With the seven-year data, the temperature (TT) spectrum measurement has a signal-to-noise ratio per multipole that exceeds unity for l 2.7(95%CL). Also, using WMAP data alone, the primordial helium mass fraction is found to be Y He = 0.28+0.14 ?0.15, and with data from higher-resolution cosmic microwave background experiments included, we now establish the existence of pre-stellar helium at >3?. These new WMAP measurements provide important tests of big bang cosmology.