Showing papers by "University of Queensland published in 2014"
University of Washington1, Sapienza University of Rome2, Mekelle University3, University of Texas at San Antonio4, King Saud bin Abdulaziz University for Health Sciences5, Debre markos University6, Emory University7, University of Oxford8, University of Cartagena9, United Nations Population Fund10, University of Birmingham11, Stanford University12, Aga Khan University13, University of Melbourne14, National Taiwan University15, University of Cambridge16, University of California, San Diego17, Public Health Foundation of India18, Public Health England19, University of Peradeniya20, Harvard University21, National Institutes of Health22, Tehran University of Medical Sciences23, Auckland University of Technology24, University of Sheffield25, University of Western Australia26, Karolinska Institutet27, Birzeit University28, Brandeis University29, American Cancer Society30, Ochsner Medical Center31, Yonsei University32, University of Bristol33, Heidelberg University34, Vanderbilt University35, South African Medical Research Council36, Jordan University of Science and Technology37, New Generation University College38, Northeastern University39, Simmons College40, Norwegian Institute of Public Health41, Boston University42, Chinese Center for Disease Control and Prevention43, University of Bari44, University of São Paulo45, University of Otago46, University of Crete47, International Centre for Diarrhoeal Disease Research, Bangladesh48, Fred Hutchinson Cancer Research Center49, Teikyo University50, Bhabha Atomic Research Centre51, University of Tokyo52, Finnish Institute of Occupational Health53, Heriot-Watt University54, University of Alabama at Birmingham55, Griffith University56, National Center for Disease Control and Public Health57, University of California, Irvine58, Johns Hopkins University59, New York University60, University of Queensland61, Universidade Federal de Minas Gerais62, National Research University – Higher School of Economics63, University of Bergen64, Columbia University65, Shandong University66, University of North Carolina at Chapel Hill67, Fujita Health University68, Korea University69, Chongqing Medical University70, Zhejiang University71
TL;DR: The global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013 is estimated using a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs).
9,180 citations
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
6,809 citations
Eric A. Collisson1, Joshua D. Campbell2, Angela N. Brooks2, Angela N. Brooks3 +315 more•Institutions (41)
TL;DR: In this paper, the authors report molecular profiling of 230 resected lung adnocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses.
Abstract: Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
4,104 citations
TL;DR: UNLABELLED STAMP is a graphical software package that provides statistical hypothesis tests and exploratory plots for analysing taxonomic and functional profiles and a user-friendly graphical interface permits easy exploration of statistical results and generation of publication-quality plots.
Abstract: Summary: STAMP is a graphical software package that provides statistical hypothesis tests and exploratory plots for analysing taxonomic and functional profiles. It supports tests for comparing pairs of samples or samples organized into two or more treatment groups. Effect sizes and confidence intervals are provided to allow critical assessment of the biological relevancy of test results. A user-friendly graphical interface permits easy exploration of statistical results and generation of publication-quality plots.
Availability and implementation: STAMP is licensed under the GNU GPL. Python source code and binaries are available from our website at: http://kiwi.cs.dal.ca/Software/STAMP
Contact: moc.liamg@skrap.navonod
Supplementary information: Supplementary data are available at Bioinformatics online.
2,739 citations
Royal North Shore Hospital1, University of Queensland2, Charité3, University of Melbourne4, University of Sydney5, University of Western Sydney6, University of Lorraine7, University of Adelaide8, Menzies Research Institute9, Monash University10, Deakin University11, Institute for Health Metrics and Evaluation12, Royal Cornwall Hospital13
TL;DR: In this article, the global burden of hip and knee OA was estimated as part of the Global Burden of Disease 2010 study and the burden of OA compared with other conditions.
Abstract: Objective To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. Methods Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). Results Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). Conclusions Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world9s population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.
2,440 citations
TL;DR: LBP causes more global disability than any other condition and with the ageing population, there is an urgent need for further research to better understand LBP across different settings.
Abstract: Supported by the Bill and Melinda Gates Foundation (to Dr Hoy and Prof
Vos), the Australian Commonwealth Department of Health and Ageing (to Dr Smith
(University of Sydney, Institute of Bone and Joint Research) and Prof March), the
Australian National Health and Medical Research Council (Postgraduate Scholarship
569772 to Dr Hoy and Practitioner Fellowships 334010 (2005–2009) and 606429
(2010–2014) to Prof Buchbinder, and the Ageing and Alzheimers Research
Foundation (Asst Prof Blyth).
2,085 citations
Harvard University1, Broad Institute2, Monash University3, Kyoto University4, Genentech5, Vanderbilt University6, New York University7, NewYork–Presbyterian Hospital8, Second Military Medical University9, University of Queensland10, University of Toronto11, University of Groningen12, University of Tartu13, Beijing Jiaotong University14, Icahn School of Medicine at Mount Sinai15, Radboud University Nijmegen16, Medisch Spectrum Twente17, Leiden University18, University of Paris19, French Institute of Health and Medical Research20, University of Alabama at Birmingham21, University of Cambridge22, GlaxoSmithKline23, University of Amsterdam24, Hanyang University25, Spanish National Research Council26, Complutense University of Madrid27, Umeå University28, Boston University29, Council on Education for Public Health30, McGill University31, University of Manchester32, National Health Service33, University of Pittsburgh34, University of California, San Francisco35, Karolinska Institutet36, North Shore-LIJ Health System37, University of Chicago38, University of Tokyo39
TL;DR: A genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries provides empirical evidence that the genetics of RA can provide important information for drug discovery, and sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis.
Abstract: A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
1,910 citations
TL;DR: This article identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height, and all common variants together captured 60% of heritability.
Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
1,872 citations
TL;DR: This work couple graphitic-carbon nitride with nitrogen-doped graphene to produce a metal-free hybrid catalyst, which shows an unexpected hydrogen evolution reaction activity with comparable overpotential and Tafel slope to some of well-developed metallic catalysts.
Abstract: Electrocatalytic reduction of water to molecular hydrogen via the hydrogen evolution reaction may provide a sustainable energy supply for the future, but its commercial application is hampered by the use of precious platinum catalysts. All alternatives to platinum thus far are based on nonprecious metals, and, to our knowledge, there is no report about a catalyst for electrocatalytic hydrogen evolution beyond metals. Here we couple graphitic-carbon nitride with nitrogen-doped graphene to produce a metal-free hybrid catalyst, which shows an unexpected hydrogen evolution reaction activity with comparable overpotential and Tafel slope to some of well-developed metallic catalysts. Experimental observations in combination with density functional theory calculations reveal that its unusual electrocatalytic properties originate from an intrinsic chemical and electronic coupling that synergistically promotes the proton adsorption and reduction kinetics.
1,774 citations
Alistair R. R. Forrest, Hideya Kawaji, Michael Rehli1, J Kenneth Baillie2 +277 more•Institutions (63)
TL;DR: For example, the authors mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body.
Abstract: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research
1,715 citations
TL;DR: NeEstimator v2 includes three single‐sample estimators (updated versions of the linkage disequilibrium and heterozygote‐excess methods, and a new method based on molecular coancestry), as well as the two‐sample (moment‐based temporal) method.
Abstract: NeEstimator v2 is a completely revised and updated implementation of software that produces estimates of contemporary effective population size, using several different methods and a single input file. NeEstimator v2 includes three single-sample estimators (updated versions of the linkage disequilibrium and heterozygote-excess methods, and a new method based on molecular coancestry), as well as the two-sample (moment-based temporal) method. New features include the following: (i) an improved method for accounting for missing data; (ii) options for screening out rare alleles; (iii) confidence intervals for all methods; (iv) the ability to analyse data sets with large numbers of genetic markers (10000 or more); (v) options for batch processing large numbers of different data sets, which will facilitate cross-method comparisons using simulated data; and (vi) correction for temporal estimates when individuals sampled are not removed from the population (Plan I sampling). The user is given considerable control over input data and composition, and format of output files. The freely available software has a new JAVA interface and runs under MacOS, Linux and Windows.
TL;DR: The remediation of heavy metal(loid) contaminated soils through manipulating their bioavailability using a range of soil amendments will be presented.
TL;DR: A step change involving increased recognition, funding, planning and enforcement is urgently needed if protected areas are going to fulfil their potential.
Abstract: Originally conceived to conserve iconic landscapes and wildlife, protected areas are now expected to achieve an increasingly diverse set of conservation, social and economic objectives. The amount of land and sea designated as formally protected has markedly increased over the past century, but there is still a major shortfall in political commitments to enhance the coverage and effectiveness of protected areas. Financial support for protected areas is dwarfed by the benefits that they provide, but these returns depend on effective management. A step change involving increased recognition, funding, planning and enforcement is urgently needed if protected areas are going to fulfil their potential.
Nicholas J Kassebaum1, Amelia Bertozzi-Villa1, Megan Coggeshall1, Katya Anne Shackelford1 +349 more•Institutions (179)
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.
TL;DR: This review focuses on important recent developments that have enhanced the understanding of each phase of the cancer immunoediting process, summarizes the discovery of new predictive and prognostic biomarkers and discusses development of novel and objectively effective cancer immunotherapies.
TL;DR: This paper updates the earlier work by Keating et?al.
Abstract: Agricultural systems models worldwide are increasingly being used to explore options and solutions for the food security, climate change adaptation and mitigation and carbon trading problem domains. APSIM (Agricultural Production Systems sIMulator) is one such model that continues to be applied and adapted to this challenging research agenda. From its inception twenty years ago, APSIM has evolved into a framework containing many of the key models required to explore changes in agricultural landscapes with capability ranging from simulation of gene expression through to multi-field farms and beyond.Keating et?al. (2003) described many of the fundamental attributes of APSIM in detail. Much has changed in the last decade, and the APSIM community has been exploring novel scientific domains and utilising software developments in social media, web and mobile applications to provide simulation tools adapted to new demands.This paper updates the earlier work by Keating et?al. (2003) and chronicles the changing external challenges and opportunities being placed on APSIM during the last decade. It also explores and discusses how APSIM has been evolving to a "next generation" framework with improved features and capabilities that allow its use in many diverse topics. APSIM is an agricultural modelling framework used extensively worldwide.It can simulate a wide range of agricultural systems.It begins its third decade evolving into an agro-ecosystem framework.
Cornell University1, University of Missouri2, California State University, Fresno3, University of Leeds4, University of Massachusetts Amherst5, University of Melbourne6, North-West University7, University of Waikato8, Butler University9, Swedish University of Agricultural Sciences10, Helmholtz Centre for Environmental Research - UFZ11, Royal Institute of Technology12, Academy of Sciences of the Czech Republic13, Stellenbosch University14, Charles University in Prague15, University of Queensland16
TL;DR: It is found that the majority of urban bird and plant species are native in the world's cities, with the most common being Columba livia and Poa annua and few plants and birds are cosmopolitan.
Abstract: Urbanization contributes to the loss of the world's biodiversity and the homogenization of its biota. However, comparative studies of urban biodiversity leading to robust generalities of the status and drivers of biodiversity in cities at the global scale are lacking. Here, we compiled the largest global dataset to date of two diverse taxa in cities: birds (54 cities) and plants (110 cities). We found that the majority of urban bird and plant species are native in the world's cities. Few plants and birds are cosmopolitan, the most common being Columba livia and Poa annua. The density of bird and plant species (the number of species per km2) has declined substantially: only 8% of native bird and 25% of native plant species are currently present compared with estimates of non-urban density of species. The current density of species in cities and the loss in density of species was best explained by anthropogenic features (landcover, city age) rather than by non-anthropogenic factors (geography, climate, topography). As urbanization continues to expand, efforts directed towards the conservation of intact vegetation within urban landscapes could support higher concentrations of both bird and plant species. Despite declines in the density of species, cities still retain endemic native species, thus providing opportunities for regional and global biodiversity conservation, restoration and education.
United Nations Environment Programme1, Dalhousie University2, Bedford Institute of Oceanography3, Queen's University4, American Museum of Natural History5, BirdLife International6, University of Paris-Sud7, Netherlands Environmental Assessment Agency8, United Nations9, Utrecht University10, University of British Columbia11, Organisation for Economic Co-operation and Development12, The Lodge13, Marine Stewardship Council14, Global Biodiversity Information Facility15, University of Wisconsin-Madison16, University of Queensland17, Zoological Society of London18, Martin Luther University of Halle-Wittenberg19, International Union for Conservation of Nature and Natural Resources20, College of William & Mary21, Sapienza University of Rome22, University of Sussex23, Environment Agency24, University of Vienna25, Microsoft26
TL;DR: A comprehensive mid-term assessment of progress toward 20 biodiversity-related “Aichi Targets” to be achieved within a decade is provided using 55 indicator data sets and pinpoints the problems and areas that will need the most attention in the next few years.
Abstract: In 2010, the international community, under the auspices of the Convention on Biological Diversity, agreed on 20 biodiversity-related “Aichi Targets” to be achieved within a decade. We provide a comprehensive mid-term assessment of progress toward these global targets using 55 indicator data sets. We projected indicator trends to 2020 using an adaptive statistical framework that incorporated the specific properties of individual time series. On current trajectories, results suggest that despite accelerating policy and management responses to the biodiversity crisis, the impacts of these efforts are unlikely to be reflected in improved trends in the state of biodiversity by 2020. We highlight areas of societal endeavor requiring additional efforts to achieve the Aichi Targets, and provide a baseline against which to assess future progress.
TL;DR: Results showed that methodological factors contributed over half (51.6%) of the heterogeneity in prevalence estimates, and, after adjusting for these factors, NSSI prevalence did not increase over time.
Abstract: Published prevalence estimates of nonsuicidal self-injury (NSSI) among nonclinical samples are highly heterogeneous, raising concerns about their reliability and hindering attempts to explore the alleged increase in NSSI over time. Accordingly, the objectives of this study were to investigate the influence of methodological factors on heterogeneity in NSSI prevalence estimates, explore changes over time, and estimate overall international NSSI prevalence. Results showed that methodological factors contributed over half (51.6%) of the heterogeneity in prevalence estimates, and, after adjusting for these factors, NSSI prevalence did not increase over time. Overall, pooled NSSI prevalence was 17.2% among adolescents, 13.4% among young adults, and 5.5% among adults. Clearly, development of standardized methodology in NSSI research is crucial if accurate estimates are desired.
TL;DR: A unique sandwich structure with pure sulfur between two graphene membranes is designed as a very simple but effective approach for the fabrication of Li–S batteries with ultrafast charge/discharge rates and long-life.
Abstract: Lithium-sulfur (Li–S) batteries have high specific capacities and are considered as next-generation batteries for large-scale energy storage and electric vehicles. However, rapid capacity fade and low sulfur utilisation inhibit their use. We designed a unique sandwich structure with pure sulfur between two graphene membranes, which are continuously produced over a large area, as a very simple but effective approach for the fabrication of Li–S batteries with ultrafast charge/discharge rates and long-life. One membrane was used as a graphene current collector (GCC) to replace the conventional aluminium foil current collector, and sulfur was coated onto this membrane as the active material. The other membrane was coated onto a conventional polymer separator (G-separator). This electrode showed a high specific capacity of 1340 mA h g−1 at 300 mA g−1, a Coulombic efficiency approaching 100%, excellent high-rate performance and long cyclic stability. The GCC and G-separator not only effectively reduce the internal resistance of the sulfur cathode but also function as buffer layers to trap/immobilise and reuse the dissolved lithium polysulfides. Furthermore, for the first time, three-dimensional X-ray microtomography was used to investigate sulfur diffusion during electrochemical charge/discharge.
TL;DR: HIIT significantly increases CRF by almost double that of MICT in patients with lifestyle-induced chronic diseases, with a significantly higher increase in the VO2peak after HIIT.
Abstract: Background/Aim Cardiorespiratory fitness (CRF) is a strong determinant of morbidity and mortality. In athletes and the general population, it is established that high-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) in improving CRF. This is a systematic review and metaanalysis to quantify the efficacy and safety of HIIT compared to MICT in individuals with chronic cardiometabolic lifestyle diseases. Methods The included studies were required to have a population sample of chronic disease, where poor lifestyle is considered as a main contributor to the disease. The procedural quality of the studies was assessed by use of a modified Physiotherapy Evidence Base Database (PEDro) scale. A meta-analysis compared the mean difference (MD) of preintervention versus postintervention CRF (VO2peak) between HIIT and MICT. Results 10 studies with 273 patients were included in the meta-analysis. Participants had coronary artery disease, heart failure, hypertension, metabolic syndrome and obesity. There was a significantly higher increase in the VO2peak after HIIT compared to MICT (MD 3.03 mL/kg/ min, 95% CI 2.00 to 4.07), equivalent to 9.1%. Conclusions HIIT significantly increases CRF by almost double that of MICT in patients with lifestyle-induced chronic diseases.
TL;DR: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.
Abstract: A B S T R AC T BACKGROUND The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the nonnucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of ABT-450/r–ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of om bitasvir), and dasabuvir (250 mg twice daily) with ribavirin (in doses determined according to body weight) (group A) or matching placebos (group B). The patients received the study treatment during a 12-week double-blind period. The primary end point was sustained virologic response at 12 weeks after the end of treatment. The primary analysis compared the response rate in group A with the response rate (78%) in a historical control group of previously untreated patients without cirrhosis who received telaprevir with peginterferon and ribavirin. Adverse events occurring during the double-blind period were compared between group A and group B. RESULTS A total of 631 patients received at least one dose of the study drugs. The rate of sustained virologic response in group A was 96.2% (95% confidence interval, 94.5 to 97.9), which was superior to the historical control rate. Virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of the patients in group A. The response rates in group A were 95.3% among patients with HCV genotype 1a infection and 98.0% among those with HCV genotype 1b infection. The rate of discontinuation due to adverse events was 0.6% in each study group. Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more patients in group A than in group B (P<0.05 for all comparisons). Reductions in the hemoglobin level were all of grade 1 or 2; reductions of grade 1 and 2 occurred in 47.5% and 5.8%, respectively, of the patients in group A, whereas grade 1 reductions occurred in 2.5% of the patients in group B. CONCLUSIONS In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r–ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation. (Funded by AbbVie; SAPPHIRE-I ClinicalTrials.gov number, NCT01716585.)
TL;DR: This study may stimulate the development of metal-free electrocatalysts for other key energy conversion processes including hydrogen evolution and oxygen evolution reactions and largely expand the spectrum of catalysts for energy-related electrocatalysis reactions.
Abstract: The mutually corroborated electrochemical measurements and density functional theory (DFT) calculations were used to uncover the origin of electrocatalytic activity of graphene-based electrocatalysts for oxygen reduction reaction (ORR). A series of graphenes doped with nonmetal elements was designed and synthesized, and their ORR performance was evaluated in terms of four electrochemical descriptors: exchange current density, on-set potential, reaction pathway selectivity and kinetic current density. It is shown that these descriptors are in good agreement with DFT calculations, allowing derivation of a volcano plot between the ORR activity and the adsorption free energy of intermediates on metal-free materials, similarly as in the case of metallic catalysts. The molecular orbital concept was used to justify this volcano plot, and to theoretically predict the ORR performance of an ideal graphene-based catalyst, the ORR activity of which is comparable to the state-of-the-art Pt catalyst. Moreover, this study may stimulate the development of metal-free electrocatalysts for other key energy conversion processes including hydrogen evolution and oxygen evolution reactions and largely expand the spectrum of catalysts for energy-related electrocatalysis reactions.
Crops Research Institute1, Australian Centre for Plant Functional Genomics2, Agriculture and Agri-Food Canada3, Purdue University4, Plant Genome Mapping Laboratory5, Southwest University6, University of York7, Seoul National University8, Southern Cross University9, University of Missouri10, Centre national de la recherche scientifique11, Huazhong Agricultural University12, Hunan Agricultural University13, University of Queensland14, National Research Council15, Central University, India16, Sahmyook University17, King Abdulaziz University18
TL;DR: A draft genome sequence of Brassica oleracea is described, comparing it with that of its sister species B. rapa to reveal numerous chromosome rearrangements and asymmetrical gene loss in duplicated genomic blocks.
Abstract: Polyploidization has provided much genetic variation for plant adaptive evolution, but the mechanisms by which the molecular evolution of polyploid genomes establishes genetic architecture underlying species differentiation are unclear Brassica is an ideal model to increase knowledge of polyploid evolution Here we describe a draft genome sequence of Brassica oleracea, comparing it with that of its sister species B rapa to reveal numerous chromosome rearrangements and asymmetrical gene loss in duplicated genomic blocks, asymmetrical amplification of transposable elements, differential gene co-retention for specific pathways and variation in gene expression, including alternative splicing, among a large number of paralogous and orthologous genes Genes related to the production of anticancer phytochemicals and morphological variations illustrate consequences of genome duplication and gene divergence, imparting biochemical and morphological variation to B oleracea This study provides insights into Brassica genome evolution and will underpin research into the many important crops in this genus
TL;DR: Titanium dioxide (TiO2) has been the most intensively investigated binary transition metal oxide in the past four decades and the annual number of papers published on TiO2 has seen a continuous increase, particularly since the beginning of this century.
Abstract: Titanium dioxide (TiO2) has been the most intensively investigated binary transition metal oxide in the past four decades as indicated by Figure S1. Furthermore, the annual number of papers published on TiO2 has seen a continuous increase, particularly since the beginning of this century (Figure S2). This is understandable when one considers the wide range of applications of TiO2 from the conventional areas (i.e., pigment, cosmetic, toothpaste, and paint) to the later developed functional areas such as photoelectrochemical cell,(1-3) dye-sensitized solar cells (DSSCs),(4-11) photocatalysis,(12-24) catalysis,(25-31) photovoltaic cell,(32-34) lithium ion batteries,(35-41) sensors,(42-46) electron field emission,(47-51) microwave absorbing material, biomimetic growth, and biomedical treatments.(52-57) Nearly all these functional applications of TiO2 fall in the scope of energy, environment, and health, which are definitely the three most important and challenging themes facing the Human race that need to be addressed in this century. Besides the apparent merits including nontoxicity, elemental abundance, good chemical stability, and easy synthesis, TiO2 has attracted strong research interest worldwide due to its physicochemical properties for realizing various functions.(15, 58, 59) Especially, very encouraging progresses in photocatalysis and DSSCs with the involvement of TiO2 have greatly stimulated the rapid development of TiO2 crystals with controllable phase, size, shape, defect, and heteroatom.(58, 60-68)
Christopher J L Murray1, Katrina F Ortblad1, Caterina Guinovart1, Stephen S Lim1 +367 more•Institutions (179)
TL;DR: The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.
TL;DR: In this paper, a review focuses on recent progress in the experimental and computational studies of the roles of heteroatoms in heterogeneous nanocarbons for electrocatalytic oxygen reduction reaction (ORR).
Abstract: Heterogeneous nanocarbon materials are being increasingly investigated and deployed in numerous new technologies and devices for sustainable energy conversion and storage. Nanocarbons often consist of fullerene, graphene and carbon nanotubes. Their derivatives include quantum dots, nanofibres, nanoribbons, nanospheres/capsules and other nanostructured morphologies. The heterogeneous forms of these nanocarbons stem from the implantation of alien atoms into the aromatic carbon lattice or the covalent grafting of functional groups onto the carbon basal plane or edge sites. Heterogeneous nanocarbons have shown remarkable advantages in solar cells, water splitting, supercapacitors, lithium ion batteries and catalysis. This review focuses on recent progress in the experimental and computational studies of the roles of heteroatoms in heterogeneous nanocarbons for electrocatalytic oxygen reduction reaction (ORR). Critical perspectives are devoted to the ambiguous phenomena in this emerging research area. The long standing debate about the active sites is discussed with an emphasis on more rational development of advanced nanocarbon-based electrocatalysts for ORR.
TL;DR: In this paper, the authors estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions.
Abstract: Objectives To estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions. Methods The optimum case definition of RA for the study was the American College of Rheumatology 1987 criteria. A series of systematic reviews were conducted to gather age-sex-specific epidemiological data for RA prevalence, incidence and mortality. Cause-specific mortality data were also included. Data were entered into DisMod-MR, a tool to pool available data, making use of study-level covariates to adjust for country, region and super-region random effects to estimate prevalence for every country and over time. The epidemiological data, in addition to disability weights, were used to calculate years of life lived with disability (YLDs). YLDs were added to the years of life lost due to premature mortality to estimate the overall burden (disability-adjusted life years (DALYs)) for RA for the years 1990, 2005 and 2010. Results The global prevalence of RA was 0.24% (95% CI 0.23% to 0.25%), with no discernible change from 1990 to 2010. DALYs increased from 3.3 million (M) (95% CI 2.6 M to 4.1 M) in 1990 to 4.8 M (95% CI 3.7 M to 6.1 M) in 2010. This increase was due to a growth in population and increase in aging. Globally, of the 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency (measured in YLDs). Conclusions RA continues to cause modest global disability, with severe consequences in the individuals affected.
TL;DR: The advantages and pitfalls of MLMA methods as a function of study design are described and quantify and recommendations for the application of these methods in practical settings are provided.
Abstract: Mixed linear models are emerging as a method of choice for conducting genetic association studies in humans and other organisms. The advantages of the mixed-linear-model association (MLMA) method include the prevention of false positive associations due to population or relatedness structure and an increase in power obtained through the application of a correction that is specific to this structure. An underappreciated point is that MLMA can also increase power in studies without sample structure by implicitly conditioning on associated loci other than the candidate locus. Numerous variations on the standard MLMA approach have recently been published, with a focus on reducing computational cost. These advances provide researchers applying MLMA methods with many options to choose from, but we caution that MLMA methods are still subject to potential pitfalls. Here we describe and quantify the advantages and pitfalls of MLMA methods as a function of study design and provide recommendations for the application of these methods in practical settings.
TL;DR: Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.
Abstract: Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether ?-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 ?-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f TMIC) and 100% (100% f T MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f TMIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P =. 009). Positive clinical outcome was associated with increasing 50% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P