Showing papers by "University of Toronto published in 2010"
Proceedings Article•
21 Jun 2010TL;DR: Restricted Boltzmann machines were developed using binary stochastic hidden units that learn features that are better for object recognition on the NORB dataset and face verification on the Labeled Faces in the Wild dataset.
Abstract: Restricted Boltzmann machines were developed using binary stochastic hidden units. These can be generalized by replacing each binary unit by an infinite number of copies that all have the same weights but have progressively more negative biases. The learning and inference rules for these "Stepped Sigmoid Units" are unchanged. They can be approximated efficiently by noisy, rectified linear units. Compared with binary units, these units learn features that are better for object recognition on the NORB dataset and face verification on the Labeled Faces in the Wild dataset. Unlike binary units, rectified linear units preserve information about relative intensities as information travels through multiple layers of feature detectors.
14,799 citations
TL;DR: Specific recommendations to clarify and enhance this methodology are outlined for each stage of the Arksey and O'Malley framework, to support the advancement, application and relevance of scoping studies in health research.
Abstract: Scoping studies are an increasingly popular approach to reviewing health research evidence. In 2005, Arksey and O'Malley published the first methodological framework for conducting scoping studies. While this framework provides an excellent foundation for scoping study methodology, further clarifying and enhancing this framework will help support the consistency with which authors undertake and report scoping studies and may encourage researchers and clinicians to engage in this process. We build upon our experiences conducting three scoping studies using the Arksey and O'Malley methodology to propose recommendations that clarify and enhance each stage of the framework. Recommendations include: clarifying and linking the purpose and research question (stage one); balancing feasibility with breadth and comprehensiveness of the scoping process (stage two); using an iterative team approach to selecting studies (stage three) and extracting data (stage four); incorporating a numerical summary and qualitative thematic analysis, reporting results, and considering the implications of study findings to policy, practice, or research (stage five); and incorporating consultation with stakeholders as a required knowledge translation component of scoping study methodology (stage six). Lastly, we propose additional considerations for scoping study methodology in order to support the advancement, application and relevance of scoping studies in health research. Specific recommendations to clarify and enhance this methodology are outlined for each stage of the Arksey and O'Malley framework. Continued debate and development about scoping study methodology will help to maximize the usefulness and rigor of scoping study findings within healthcare research and practice.
7,536 citations
Medical University of Vienna1, Boston University2, Arthritis Research UK3, Johns Hopkins University4, University of California, San Francisco5, Humboldt University of Berlin6, University of Toronto7, National Jewish Health8, Brigham and Women's Hospital9, Paris Descartes University10, University of Leeds11, Catholic University of the Sacred Heart12, Erasmus University Rotterdam13, University of Colorado Denver14, Leiden University15, University of California, San Diego16, University of Massachusetts Medical School17, University of Michigan18, University of Washington19, McGill University Health Centre20, University of Pittsburgh21, Ministry of Health (New Zealand)22, New York University23, University of Manchester24, University of Amsterdam25, University of Kansas26, Women's College Hospital27
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classifi cation criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classifi cation criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated infl ammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/ or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classifi cation as ‘defi nite RA’ is based on the confi rmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classifi cation system redefi nes the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defi ning the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.
7,120 citations
TL;DR: Principal component analysis (PCA) as discussed by the authors is a multivariate technique that analyzes a data table in which observations are described by several inter-correlated quantitative dependent variables, and its goal is to extract the important information from the table, to represent it as a set of new orthogonal variables called principal components, and display the pattern of similarity of the observations and of the variables as points in maps.
Abstract: Principal component analysis PCA is a multivariate technique that analyzes a data table in which observations are described by several inter-correlated quantitative dependent variables. Its goal is to extract the important information from the table, to represent it as a set of new orthogonal variables called principal components, and to display the pattern of similarity of the observations and of the variables as points in maps. The quality of the PCA model can be evaluated using cross-validation techniques such as the bootstrap and the jackknife. PCA can be generalized as correspondence analysis CA in order to handle qualitative variables and as multiple factor analysis MFA in order to handle heterogeneous sets of variables. Mathematically, PCA depends upon the eigen-decomposition of positive semi-definite matrices and upon the singular value decomposition SVD of rectangular matrices. Copyright © 2010 John Wiley & Sons, Inc.
6,398 citations
Medical University of Vienna1, Boston University2, Arthritis Research UK3, Johns Hopkins University4, University of California, San Francisco5, Charité6, University of Toronto7, National Jewish Health8, Harvard University9, University of Paris10, University of Leeds11, Catholic University of the Sacred Heart12, Erasmus University Rotterdam13, University of Colorado Denver14, Leiden University15, University of California, San Diego16, University of Massachusetts Medical School17, University of Michigan18, University of Washington19, McGill University20, University of Pittsburgh21, Ministry of Health (New Zealand)22, New York University23, University of Manchester24, University of Amsterdam25
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classification as ‘definite RA’ is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.
5,964 citations
Harvard University1, China Medical Board2, Aga Khan University3, Washington University in St. Louis4, Cayetano Heredia University5, Peking University6, National Health Laboratory Service7, University of Pennsylvania8, University of Toronto9, Rockefeller Foundation10, Public Health Foundation of India11, The Sage Colleges12, Bill & Melinda Gates Foundation13, Makerere University14, American University of Beirut15
TL;DR: In this article, the authors present a comprehensive framework that considers the connections between education and health systems, centred on people as co-producers and as drivers of needs and demands in both systems.
4,215 citations
University of Utah1, University of Michigan2, The Royal Marsden NHS Foundation Trust3, Ohio State University4, Indiana University5, St. Jude Medical Center6, University of Queensland7, Beaumont Hospital8, BC Cancer Agency9, University of Rochester10, Harvard University11, American Society of Clinical Oncology12, National Institutes of Health13, Baylor College of Medicine14, Sungkyunkwan University15, University of the West of England16, Tohoku University17, Radboud University Nijmegen18, University of Toronto19, Saint Joseph Mercy Health System20, Mayo Clinic21, University of Washington22, Memorial Hospital of South Bend23, University of Texas at Austin24, Johns Hopkins University25
TL;DR: An international Expert Panel that conducted a systematic review and evaluation of the literature and developed recommendations for optimal IHC ER/PgR testing performance recommended that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences.
Abstract: Purpose To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. Methods The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. Results Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria. Recommendations The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.
3,902 citations
TL;DR: A meta-analysis of studies measuring cytokine concentration in patients with major depression reports significantly higher concentrations of the proinflammatory cytokines TNF-alpha and IL-6 in depressed subjects compared with control subjects, strengthening evidence that depression is accompanied by activation of the IRS.
3,800 citations
TL;DR: The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make Gene MANIA a useful tool for any biologist.
Abstract: GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist.
3,211 citations
TL;DR: New estimates for 2008 of the major causes of death in children younger than 5 years in 193 countries are reported to help to focus national programmes and donor assistance.
2,898 citations
TL;DR: This paper presents an autonomous and distributed demand-side energy management system among users that takes advantage of a two-way digital communication infrastructure which is envisioned in the future smart grid.
Abstract: Most of the existing demand-side management programs focus primarily on the interactions between a utility company and its customers/users. In this paper, we present an autonomous and distributed demand-side energy management system among users that takes advantage of a two-way digital communication infrastructure which is envisioned in the future smart grid. We use game theory and formulate an energy consumption scheduling game, where the players are the users and their strategies are the daily schedules of their household appliances and loads. It is assumed that the utility company can adopt adequate pricing tariffs that differentiate the energy usage in time and level. We show that for a common scenario, with a single utility company serving multiple customers, the global optimal performance in terms of minimizing the energy costs is achieved at the Nash equilibrium of the formulated energy consumption scheduling game. The proposed distributed demand-side energy management strategy requires each user to simply apply its best response strategy to the current total load and tariffs in the power distribution system. The users can maintain privacy and do not need to reveal the details on their energy consumption schedules to other users. We also show that users will have the incentives to participate in the energy consumption scheduling game and subscribing to such services. Simulation results confirm that the proposed approach can reduce the peak-to-average ratio of the total energy demand, the total energy costs, as well as each user's individual daily electricity charges.
Mayo Clinic1, Rutgers University2, University of Alabama at Birmingham3, Lenox Hill Hospital4, Oregon Health & Science University5, Laval University6, University of Calgary7, University of California, Los Angeles8, University at Buffalo9, Harvard University10, MetroHealth11, University of Toronto12, Columbia University13, University of Maryland, Baltimore14
TL;DR: Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotids-artery stenting and the group undergoes carOTid endarterectomy.
Abstract: For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P = 0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P = 0.84) or sex (P = 0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P = 0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P = 0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P = 0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P = 0.18), for stroke (4.1% vs. 2.3%, P = 0.01), and for myocardial infarction (1.1% vs. 2.3%, P = 0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P = 0.85). CONCLUSIONS Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)
University of Kiel1, Cedars-Sinai Medical Center2, Wellcome Trust Sanger Institute3, University of Pennsylvania4, QIMR Berghofer Medical Research Institute5, Peninsula College of Medicine and Dentistry6, University of Edinburgh7, University of Cambridge8, University of Otago9, University of Washington10, University of Groningen11, University of Liège12, Harvard University13, Casa Sollievo della Sofferenza14, King's College London15, University of Chicago16, Yale University17, Johns Hopkins University18, Ludwig Maximilian University of Munich19, Charité20, McGill University21, Lille University of Science and Technology22, Cincinnati Children's Hospital Medical Center23, Ghent University24, Torbay Hospital25, Mater Health Services26, Université libre de Bruxelles27, RWTH Aachen University28, University of Utah29, Örebro University30, Leiden University31, University of Paris32, Technion – Israel Institute of Technology33, University of Western Australia34, Tel Aviv University35, University of Dundee36, University of Manchester37, University of Pittsburgh38, Royal Hospital for Sick Children39, Katholieke Universiteit Leuven40, Guy's and St Thomas' NHS Foundation Trust41, University of Bern42, University of Toronto43, University of Amsterdam44, Karolinska Institutet45, University of Zurich46, Université de Montréal47, Emory University48, Newcastle University49
TL;DR: A meta-analysis of six Crohn's disease genome-wide association studies and a series of in silico analyses highlighted particular genes within these loci implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.
Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
TL;DR: The routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes does not support the routine use.
Abstract: Methods We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. Results The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P = 0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P = 0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P = 0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P = 0.057 for interaction). Conclusions The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)
TL;DR: A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function.
Abstract: A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic genetic interactions, generating quantitative genetic interaction profiles for ~75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function. The global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification.
TL;DR: This Review highlights recent advances in the synthesis, bioconjugation, and cellular uses of gold nanoconjugates.
Abstract: Gold colloids have fascinated scientists for over a century and are now heavily utilized in chemistry, biology, engineering, and medicine. Today these materials can be synthesized reproducibly, modified with seemingly limitless chemical functional groups, and, in certain cases, characterized with atomic-level precision. This Review highlights recent advances in the synthesis, bioconjugation, and cellular uses of gold nanoconjugates. There are now many examples of highly sensitive and selective assays based upon gold nanoconjugates. In recent years, focus has turned to therapeutic possibilities for such materials. Structures which behave as gene-regulating agents, drug carriers, imaging agents, and photoresponsive therapeutics have been developed and studied in the context of cells and many debilitating diseases. These structures are not simply chosen as alternatives to molecule-based systems, but rather for their new physical and chemical properties, which confer substantive advantages in cellular and medical applications.
15 Apr 2010
TL;DR: Systematic studies of more than 25,000 cancer genomes will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
Abstract: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
TL;DR: System-wide analyses of protein and mRNA expression in individual cells with single-molecule sensitivity using a newly constructed yellow fluorescent protein fusion library for Escherichia coli found that almost all protein number distributions can be described by the gamma distribution with two fitting parameters which, at low expression levels, have clear physical interpretations as the transcription rate and protein burst size.
Abstract: Protein and messenger RNA (mRNA) copy numbers vary from cell to cell in isogenic bacterial populations. However, these molecules often exist in low copy numbers and are difficult to detect in single cells. We carried out quantitative system-wide analyses of protein and mRNA expression in individual cells with single-molecule sensitivity using a newly constructed yellow fluorescent protein fusion library for Escherichia coli. We found that almost all protein number distributions can be described by the gamma distribution with two fitting parameters which, at low expression levels, have clear physical interpretations as the transcription rate and protein burst size. At high expression levels, the distributions are dominated by extrinsic noise. We found that a single cell's protein and mRNA copy numbers for any given gene are uncorrelated.
TL;DR: The genome-wide characteristics of rare (<1% frequency) copy number variation in ASD are analysed using dense genotyping arrays to reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Abstract: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
TL;DR: An overview of the theory and currently known techniques for multi-cell MIMO (multiple input multiple output) cooperation in wireless networks is presented and a few promising and quite fundamental research avenues are also suggested.
Abstract: This paper presents an overview of the theory and currently known techniques for multi-cell MIMO (multiple input multiple output) cooperation in wireless networks. In dense networks where interference emerges as the key capacity-limiting factor, multi-cell cooperation can dramatically improve the system performance. Remarkably, such techniques literally exploit inter-cell interference by allowing the user data to be jointly processed by several interfering base stations, thus mimicking the benefits of a large virtual MIMO array. Multi-cell MIMO cooperation concepts are examined from different perspectives, including an examination of the fundamental information-theoretic limits, a review of the coding and signal processing algorithmic developments, and, going beyond that, consideration of very practical issues related to scalability and system-level integration. A few promising and quite fundamental research avenues are also suggested.
Queen Mary University of London1, National Health Service2, University of Toronto3, Manchester Royal Infirmary4, NewYork–Presbyterian Hospital5, University of New South Wales6, Hospital of the University of Pennsylvania7, University of Washington8, Boston Children's Hospital9, Hull York Medical School10, King's College London11, St James's University Hospital12, Scripps Research Institute13, Harvard University14
TL;DR: This consensus document aims to report on new data and provide consensus-based recommendations relating to diagnosis and treatment of ITP in adults, in children, and during pregnancy.
TL;DR: Evidence is provided for a role for the long nuclear-retained regulatory RNA, MALAT1 in AS regulation and for the role for an nrRNA in the regulation of gene expression, which suggests that MALat1 regulates AS by modulating the levels of active SR proteins.
TL;DR: It is concluded that the heritability void left by genome-wide association studies will not be accounted for by common CNVs, and 30 loci with CNVs that are candidates for influencing disease susceptibility are identified.
Abstract: Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.
TL;DR: This work developed “Enrichment Map”, a network-based visualization method for gene-set enrichment results that is implemented as a freely available and user friendly plug-in for the Cytoscape network visualization software and is a significant advance in the interpretation of enrichment analysis.
Abstract: Background: Gene-set enrichment analysis is a useful technique to help functionally characterize large gene lists, such as the results of gene expression experiments. This technique finds functionally coherent gene-sets, such as pathways, that are statistically over-represented in a given gene list. Ideally, the number of resulting sets is smaller than the number of genes in the list, thus simplifying interpretation. However, the increasing number and redundancy of gene-sets used by many current enrichment analysis software works against this ideal. Principal Findings: To overcome gene-set redundancy and help in the interpretation of large gene lists, we developed ‘‘Enrichment Map’’, a network-based visualization method for gene-set enrichment results. Gene-sets are organized in a network, where each set is a node and edges represent gene overlap between sets. Automated network layout groups related gene-sets into network clusters, enabling the user to quickly identify the major enriched functional themes and more easily interpret the enrichment results. Conclusions: Enrichment Map is a significant advance in the interpretation of enrichment analysis. Any research project that generates a list of genes can take advantage of this visualization framework. Enrichment Map is implemented as a freely available and user friendly plug-in for the Cytoscape network visualization software (http://baderlab.org/Software/ EnrichmentMap/).
TL;DR: A consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning the association between diabetes and cancer incidence or prognosis and whether diabetes treatments influence risk of cancer or cancer prognosis.
Abstract: Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis, 2) risk factors common to both diabetes and cancer, 3) possible biologic links between diabetes and cancer risk, and 4) whether diabetes treatments influence risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.
TL;DR: Simulation results show that the combination of the proposed energy consumption scheduling design and the price predictor filter leads to significant reduction not only in users' payments but also in the resulting peak-to-average ratio in load demand for various load scenarios.
Abstract: Real-time electricity pricing models can potentially lead to economic and environmental advantages compared to the current common flat rates. In particular, they can provide end users with the opportunity to reduce their electricity expenditures by responding to pricing that varies with different times of the day. However, recent studies have revealed that the lack of knowledge among users about how to respond to time-varying prices as well as the lack of effective building automation systems are two major barriers for fully utilizing the potential benefits of real-time pricing tariffs. We tackle these problems by proposing an optimal and automatic residential energy consumption scheduling framework which attempts to achieve a desired trade-off between minimizing the electricity payment and minimizing the waiting time for the operation of each appliance in household in presence of a real-time pricing tariff combined with inclining block rates. Our design requires minimum effort from the users and is based on simple linear programming computations. Moreover, we argue that any residential load control strategy in real-time electricity pricing environments requires price prediction capabilities. This is particularly true if the utility companies provide price information only one or two hours ahead of time. By applying a simple and efficient weighted average price prediction filter to the actual hourly-based price values used by the Illinois Power Company from January 2007 to December 2009, we obtain the optimal choices of the coefficients for each day of the week to be used by the price predictor filter. Simulation results show that the combination of the proposed energy consumption scheduling design and the price predictor filter leads to significant reduction not only in users' payments but also in the resulting peak-to-average ratio in load demand for various load scenarios. Therefore, the deployment of the proposed optimal energy consumption scheduling schemes is beneficial for both end users and utility companies.
Book•
25 Feb 2010
TL;DR: This book describes recent advances in alcohol research which have direct relevance for the development of effective alcohol policies at the local, national and international levels.
Abstract: From a public health perspective, alcohol is a major contributor to morbidity and mortality. This book describes recent advances in alcohol research which have direct relevance for the development of effective alcohol policies at the local, national and international levels. The central purpose of the book is to empower those responsible for public health and social welfare.
McGill University1, University of Groningen2, Uniformed Services University of the Health Sciences3, Accreditation Council for Graduate Medical Education4, University of New South Wales5, Australian National University6, Royal College of Physicians and Surgeons of Canada7, McMaster University8, University of Dundee9, American Board of Internal Medicine10, Johns Hopkins University11, University of Toronto12, University of Sheffield13, University of Ottawa14, University of Western Ontario15
TL;DR: The evolution of CBME from the outcomes movement in the 20th century to a renewed approach that, focused on accountability and curricular outcomes and organized around competencies, promotes greater learner-centredness and de-emphasizes time-based curricular design is described.
Abstract: Although competency-based medical education (CBME) has attracted renewed interest in recent years among educators and policy-makers in the health care professions, there is little agreement on many aspects of this paradigm. We convened a unique partnership – the International CBME Collaborators – to examine conceptual issues and current debates in CBME. We engaged in a multi-stage group process and held a consensus conference with the aim of reviewing the scholarly literature of competency-based medical education, identifying controversies in need of clarification, proposing definitions and concepts that could be useful to educators across many jurisdictions, and exploring future directions for this approach to preparing health professionals. In this paper, we describe the evolution of CBME from the outcomes movement in the 20th century to a renewed approach that, focused on accountability and curricular outcomes and organized around competencies, promotes greater learner-centredness and de-emphasizes time-based curricular design. In this paradigm, competence and related terms are redefined to emphasize their multi-dimensional, dynamic, developmental, and contextual nature. CBME therefore has significant implications for the planning of medical curricula and will have an important impact in reshaping the enterprise of medical education. We elaborate on this emerging CBME approach and its related concepts, and invite medical educators everywhere to enter into further dialogue about the promise and the potential perils of competency-based medical curricula for the 21st century.
Utrecht University1, Leiden University2, University of Crete3, Humboldt University of Berlin4, University of Genoa5, University of Paris6, University of Leeds7, Hospital for Special Surgery8, University of Santiago de Compostela9, University of Erlangen-Nuremberg10, University of Toronto11, University of Glasgow12, Autonomous University of Madrid13
TL;DR: The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion.
Abstract: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA).
TL;DR: Sterically encumbered Lewis acid and Lewis base combinations do not undergo the ubiquitous neutralization reaction to form "classical" Lewis acid/Lewis base adducts, but both the unquenched Lewis acidity and basicity of such sterically "frustrated Lewis pairs (FLPs)" is available to carry out unusual reactions.
Abstract: Sterically encumbered Lewis acid and Lewis base combinations do not undergo the ubiquitous neutralization reaction to form "classical" Lewis acid/Lewis base adducts. Rather, both the unquenched Lewis acidity and basicity of such sterically "frustrated Lewis pairs (FLPs)" is available to carry out unusual reactions. Typical examples of frustrated Lewis pairs are inter- or intramolecular combinations of bulky phosphines or amines with strongly electrophilic RB(C(6)F(5))(2) components. Many examples of such frustrated Lewis pairs are able to cleave dihydrogen heterolytically. The resulting H(+)/H(-) pairs (stabilized for example, in the form of the respective phosphonium cation/hydridoborate anion salts) serve as active metal-free catalysts for the hydrogenation of, for example, bulky imines, enamines, or enol ethers. Frustrated Lewis pairs also react with alkenes, aldehydes, and a variety of other small molecules, including carbon dioxide, in cooperative three-component reactions, offering new strategies for synthetic chemistry.