Showing papers by "University of Leeds published in 2010"
TL;DR: The state-of-the-art in evaluated methods for both classification and detection are reviewed, whether the methods are statistically different, what they are learning from the images, and what the methods find easy or confuse.
Abstract: The Pascal Visual Object Classes (VOC) challenge is a benchmark in visual object category recognition and detection, providing the vision and machine learning communities with a standard dataset of images and annotation, and standard evaluation procedures. Organised annually from 2005 to present, the challenge and its associated dataset has become accepted as the benchmark for object detection.
This paper describes the dataset and evaluation procedure. We review the state-of-the-art in evaluated methods for both classification and detection, analyse whether the methods are statistically different, what they are learning from the images (e.g. the object or its context), and what the methods find easy or confuse. The paper concludes with lessons learnt in the three year history of the challenge, and proposes directions for future improvement and extension.
15,935 citations
TL;DR: It is demonstrated in macrophages and B cells that collaborative interactions of the common factor PU.1 with small sets of macrophage- or B cell lineage-determining transcription factors establish cell-specific binding sites that are associated with the majority of promoter-distal H3K4me1-marked genomic regions.
9,620 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
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
TL;DR: The nature and extent of reported declines, and the potential drivers of pollinator loss are described, including habitat loss and fragmentation, agrochemicals, pathogens, alien species, climate change and the interactions between them are reviewed.
Abstract: Pollinators are a key component of global biodiversity, providing vital ecosystem services to crops and wild plants. There is clear evidence of recent declines in both wild and domesticated pollinators, and parallel declines in the plants that rely upon them. Here we describe the nature and extent of reported declines, and review the potential drivers of pollinator loss, including habitat loss and fragmentation, agrochemicals, pathogens, alien species, climate change and the interactions between them. Pollinator declines can result in loss of pollination services which have important negative ecological and economic impacts that could significantly affect the maintenance of wild plant diversity, wider ecosystem stability, crop production, food security and human welfare.
4,608 citations
Tanya M. Teslovich1, Kiran Musunuru, Albert V. Smith2, Andrew C. Edmondson3 +215 more•Institutions (46)
TL;DR: The results identify several novel loci associated with plasma lipids that are also associated with CAD and provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
Abstract: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
3,469 citations
TL;DR: This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management of Clostridium difficile.
Abstract: Since publication of the Society for Healthcare Epidemiology of America position paper on Clostridium difficile infection in 1995, significant changes have occurred in the epidemiology and treatment of this infection. C. difficile remains the most important cause of healthcareassociated diarrhea and is increasingly important as a community pathogen. A more virulent strain of C. difficile has been identified and has been responsible for more-severe cases of disease worldwide. Data reporting the decreased effectiveness of metronidazole in the treatment of severe disease have been published. Despite the increasing quantity of data available, areas of controversy still exist. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management.
2,872 citations
Elizabeth K. Speliotes1, Elizabeth K. Speliotes2, Cristen J. Willer3, Sonja I. Berndt +410 more•Institutions (86)
TL;DR: Genetic loci associated with body mass index map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor, which may provide new insights into human body weight regulation.
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
2,632 citations
TL;DR: It is shown that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, and indicates that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
1,768 citations
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).
1,676 citations
Medical University of Vienna1, Maastricht University2, Leiden University3, Paris Descartes University4, University of Leeds5, Pierre-and-Marie-Curie University6, Utrecht University7, Humboldt State University8, University of Montpellier9, University of Genoa10, University of Santiago, Chile11, Autonomous University of Madrid12, University of Glasgow13, Charles University in Prague14, Radboud University Nijmegen15, King's College London16, Sapienza University of Rome17, Karolinska Institutet18, Oregon Health & Science University19, Tufts University20, Charité21
TL;DR: In this article, the authors present a set of recommendations for the treatment of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects.
Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.
Brigham and Women's Hospital1, Harvard University2, Massachusetts Institute of Technology3, National Institutes of Health4, University of Toronto5, University of Manchester6, Celera Corporation7, Leiden University8, Karolinska Institutet9, University of Texas at Austin10, Radboud University Nijmegen Medical Centre11, University of California, San Francisco12, VU University Amsterdam13, University of Leeds14, University of Oxford15, University of Aberdeen16, The Feinstein Institute for Medical Research17, Karolinska University Hospital18, University of Groningen19, University of California, Davis20, King's College21, University of Amsterdam22, University of Sheffield23, Hoffmann-La Roche24, University Health Network25, North Shore-LIJ Health System26, Broad Institute27
TL;DR: Seven new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 × 10−8) in an analysis of all 41,282 samples, and an additional 11 SNPs replicated at P < 0.05, suggesting that most represent genuine rhearatoid arthritisrisk alleles.
Abstract: To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.
TL;DR: In this article, the authors suggest mechanisms for encouraging "wildlife-friendly" management of collections of gardens across scales from the neighbourhood to the city, where the individual garden is much smaller than the unit of management needed to retain viable populations.
Abstract: As urbanisation increases globally and the natural environment becomes increasingly fragmented, the importance of urban green spaces for biodiversity conservation grows. In many countries, private gardens are a major component of urban green space and can provide considerable biodiversity benefits. Gardens and adjacent habitats form interconnected networks and a landscape ecology framework is necessary to understand the relationship between the spatial configuration of garden patches and their constituent biodiversity. A scale-dependent tension is apparent in garden management, whereby the individual garden is much smaller than the unit of management needed to retain viable populations. To overcome this, here we suggest mechanisms for encouraging 'wildlife-friendly' management of collections of gardens across scales from the neighbourhood to the city.
TL;DR: Social learning is increasingly becoming a normative goal in natural resource management and policy, but there remains little consensus over its meaning or theoretical basis as discussed by the authors. This lack of conceptual clarity has limited our capacity to assess whether social learning has occurred, and if so, what kind of learning has taken place, to what extent, between whom, when, and how.
Abstract: Social learning is increasingly becoming a normative goal in natural resource management and policy. However, there remains little consensus over its meaning or theoretical basis. There are still considerable differences in understanding of the concept in the literature, including a number of articles published in Ecology & Society. Social learning is often conflated with other concepts such as participation and proenvironmental behavior, and there is often little distinction made between individual and wider social learning. Many unsubstantiated claims for social learning exist, and there is frequently confusion between the concept itself and its potential outcomes. This lack of conceptual clarity has limited our capacity to assess whether social learning has occurred, and if so, what kind of learning has taken place, to what extent, between whom, when, and how. This response attempts to provide greater clarity on the conceptual basis for social learning. We argue that to be considered social learning, a process must: (1) demonstrate that a change in understanding has taken place in the individuals involved; (2) demonstrate that this change goes beyond the individual and becomes situated within wider social units or communities of practice; and (3) occur through social interactions and processes between actors within a social network. A clearer picture of what we mean by social learning could enhance our ability to critically evaluate outcomes and better understand the processes through which social learning occurs. In this way, it may be possible to better facilitate the desired outcomes of social learning processes.
TL;DR: In this paper, recent advances in the stabilization of emulsions and foams by particles of nanoscale and microscopic dimensions are described, providing insight into the molecular factors controlling particle wettability and adsorption, structural and mechanical properties of particle-laden liquid interfaces, and stabilization mechanisms of particlecoated droplets and bubbles.
Abstract: Recent advances in the stabilization of emulsions and foams by particles of nanoscale and microscopic dimensions are described. Ongoing research in this highly active field is providing insight into (i) the molecular factors controlling particle wettability and adsorption, (ii) the structural and mechanical properties of particle-laden liquid interfaces, and (ii) the stabilization mechanisms of particle-coated droplets and bubbles. There is much potential for exploiting the emerging knowledge in new food product applications. The preparation of cheap and effective colloidal particles based on food-grade ingredients, especially proteins, is the key technological challenge.
TL;DR: It is proposed that an understanding of the connections between these different levels of organization can help to develop a more coherent theoretical framework based on metabolic scaling, foraging theory and ecological stoichiometry, to predict the ecological consequences of climate change.
Abstract: Fresh waters are particularly vulnerable to climate change because (i) many species within these fragmented habitats have limited abilities to disperse as the environment changes; (ii) water temperature and availability are climate-dependent; and (iii) many systems are already exposed to numerous anthropogenic stressors. Most climate change studies to date have focused on individuals or species populations, rather than the higher levels of organization (i.e. communities, food webs, ecosystems). We propose that an understanding of the connections between these different levels, which are all ultimately based on individuals, can help to develop a more coherent theoretical framework based on metabolic scaling, foraging theory and ecological stoichiometry, to predict the ecological consequences of climate change. For instance, individual basal metabolic rate scales with body size (which also constrains food web structure and dynamics) and temperature (which determines many ecosystem processes and key aspects of foraging behaviour). In addition, increasing atmospheric CO2 is predicted to alter molar CNP ratios of detrital inputs, which could lead to profound shifts in the stoichiometry of elemental fluxes between consumers and resources at the base of the food web. The different components of climate change (e.g. temperature, hydrology and atmospheric composition) not only affect multiple levels of biological organization, but they may also interact with the many other stressors to which fresh waters are exposed, and future research needs to address these potentially important synergies.
TL;DR: It is argued that there is no single optimum approach for integrating local and scientific knowledge and a shift in science is encouraged from the development of knowledge integration products to theDevelopment of problem-focussed, knowledge integration processes.
01 Jan 2010
TL;DR: A new annotated database of challenging consumer images is introduced, an order of magnitude larger than currently available datasets, and over 50% relative improvement in pose estimation accuracy over a state-of-the-art method is demonstrated.
Abstract: We investigate the task of 2D articulated human pose estimation in unconstrained still images This is extremely challenging because of variation in pose, anatomy, clothing, and imaging conditions Current methods use simple models of body part appearance and plausible configurations due to limitations of available training data and constraints on computational expense We show that such models severely limit accuracy Building on the successful pictorial structure model (PSM) we propose richer models of both appearance and pose, using state-of-the-art discriminative classifiers without introducing unacceptable computational expense We introduce a new annotated database of challenging consumer images, an order of magnitude larger than currently available datasets, and demonstrate over 50% relative improvement in pose estimation accuracy over a stateof-the-art method
TL;DR: The UK Medical Research Council CLASICC trial assessed the safety and efficacy of laparoscopically assisted surgery in comparison with open surgery for colorectal cancer and the 5‐year follow‐up analysis is presented.
Abstract: INTRODUCTION: The UK Medical Research Council CLASICC trial assessed the safety and efficacy of laparoscopically assisted surgery in comparison with open surgery for colorectal cancer. The results of the 5-year follow-up analysis are presented. METHODS: Five-year outcomes were analysed and included overall and disease-free survival, and local, distant and wound/port-site recurrences. Two exploratory analyses were performed to evaluate the effect of age (70 years or less, or more than 70 years) on overall survival between the two groups, and the effect of the learning curve. RESULTS: No differences were found between laparoscopically assisted and open surgery in terms of overall survival, disease-free survival, and local and distant recurrence. Wound/port-site recurrence rates in the laparoscopic arm remained stable at 2.4 per cent. Conversion to open operation was associated with significantly worse overall but not disease-free survival, which was most marked in the early follow-up period. The effect of surgery did not differ between the age groups, and surgical experience did not impact on the 5-year results. CONCLUSION: The 5-year analyses confirm the oncological safety of laparoscopic surgery for both colonic and rectal cancer. The use of laparoscopic surgery to maximize short-term outcomes does not compromise the long-term oncological results. REGISTRATION NUMBER: ISRCTN74883561 (http://www.controlled-trials.com).
University of Melbourne1, University of Reading2, Stockholm University3, University of Leeds4, Stockholm Environment Institute5, University of Cape Town6, Commonwealth Scientific and Industrial Research Organisation7, United Nations8, Potsdam Institute for Climate Impact Research9, University of Georgia10, University of East Anglia11
TL;DR: In this paper, the authors explore the emerging linkages and complementarities between the concepts of resilience and vulnerability to identify areas of synergy, with regard to theory, methodology, and application.
Abstract: Resilience and vulnerability represent two related yet different approaches to understanding the response of systems and actors to change; to shocks and surprises, as well as slow creeping changes. Their respective origins in ecological and social theory largely explain the continuing differences in approach to social-ecological dimensions of change. However, there are many areas of strong convergence. This paper explores the emerging linkages and complementarities between the concepts of resilience and vulnerability to identify areas of synergy. We do this with regard to theory, methodology, and application. The paper seeks to go beyond just recognizing the complementarities between the two approaches to demonstrate how researchers are actively engaging with each field to coproduce new knowledge, and to suggest promising areas of complementarity that are likely to further research and action in the field.
TL;DR: This review focuses on the variable selection methods in NIR spectroscopy with some classical approaches and sophisticated methods such as successive projections algorithm (SPA), uninformative variable elimination (UVE) and elaborate search-based strategies.
TL;DR: This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural), and allows the evaluation of the strength of health claims about the effects of foods on appetite.
Abstract: This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural). An overarching priority has been to enable potential evaluators of health claims about foods to identify justified claims and to exclude claims that are not supported by scientific evidence for the effect cited. This priority follows precisely from the principles set down in the PASSCLAIM report. The report allows the evaluation of the strength of health claims, about the effects of foods on appetite, which can be sustained on the basis of the commonly used scientific designs and experimental procedures. The report includes different designs for assessing effects on satiation as opposed to satiety, detailed coverage of the extent to which a change in hunger can stand alone as a measure of appetite control and an extensive discussion of the statistical procedures appropriate for handling data in this field of research. Because research in this area is continually evolving, new improved methodologies may emerge over time and will need to be incorporated into the framework. One main objective of the report has been to produce guidance on good practice in carrying out appetite research, and not to set down a series of commandments that must be followed.
TL;DR: In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months, and this effect was significantly reduced when assessed all 10 trials.
Abstract: Objective To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. Design A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. Data sources Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months’ follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P Conclusions In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.
TL;DR: Despite the need for a better evidence-base on mycotoxins and human health, supported by better biomarkers of exposure and effect in epidemiological studies, the existing data are sufficient to prioritize exposure reduction in vulnerable populations.
Abstract: Aflatoxins and fumonisins (FB) are mycotoxins contaminating a large fraction of the world's food, including maize, cereals, groundnuts and tree nuts. The toxins frequently co-occur in maize. Where these commodities are dietary staples, for example, in parts of Africa, Asia and Latin America, the contamination translates to high-level chronic exposure. This is particularly true in subsistence farming communities where regulations to control exposure are either non-existent or practically unenforceable. Aflatoxins are hepatocarcinogenic in humans, particularly in conjunction with chronic hepatitis B virus infection, and cause aflatoxicosis in episodic poisoning outbreaks. In animals, these toxins also impair growth and are immunosuppressive; the latter effects are of increasing interest in human populations. FB have been reported to induce liver and kidney tumours in rodents and are classified as Group 2B 'possibly carcinogenic to humans', with ecological studies implying a possible link to increased oesophageal cancer. Recent studies also suggest that the FB may cause neural tube defects in some maize-consuming populations. There is a plausible mechanism for this effect via a disruption of ceramide synthase and sphingolipid biosynthesis. Notwithstanding the need for a better evidence-base on mycotoxins and human health, supported by better biomarkers of exposure and effect in epidemiological studies, the existing data are sufficient to prioritize exposure reduction in vulnerable populations. For both toxins, there are a number of practical primary and secondary prevention strategies which could be beneficial if the political will and financial investment can be applied to what remains a largely and rather shamefully ignored global health issue.
TL;DR: The evidence for the changing epidemiology, clinical virulence and outcome of treatment of CDI is reviewed, and the similarities and differences between data from various countries and continents are reviewed.
Abstract: Summary: The epidemiology of Clostridium difficile infection (CDI) has changed dramatically during this millennium. Infection rates have increased markedly in most countries with detailed surveillance data. There have been clear changes in the clinical presentation, response to treatment, and outcome of CDI. These changes have been driven to a major degree by the emergence and epidemic spread of a novel strain, known as PCR ribotype 027 (sometimes referred to as BI/NAP1/027). We review the evidence for the changing epidemiology, clinical virulence and outcome of treatment of CDI, and the similarities and differences between data from various countries and continents. Community-acquired CDI has also emerged, although the evidence for this as a distinct new entity is less clear. There are new data on the etiology of and potential risk factors for CDI; controversial issues include specific antimicrobial agents, gastric acid suppressants, potential animal and food sources of C. difficile, and the effect of the use of alcohol-based hand hygiene agents.
Nicholas John Craddock1, Matthew E. Hurles2, Niall Cardin3, Richard D. Pearson3 +232 more•Institutions (34)
TL;DR: A large, direct genome-wide study of association between CNVs and eight common human diseases concludes that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis ofcommon human diseases.
Abstract: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
INAF1, University of Colorado Boulder2, University College London3, University of Toulouse4, University of Toronto5, Liverpool John Moores University6, California Institute of Technology7, University of Calgary8, European Southern Observatory9, University of Provence10, University of Paris-Sud11, Paris Diderot University12, Katholieke Universiteit Leuven13, University of Bordeaux14, University of Exeter15, University of New South Wales16, University of Leeds17, Spanish National Research Council18, Sapienza University of Rome19, University of Rome Tor Vergata20, Nagoya University21, University of Manchester22, University of Paris23, Jet Propulsion Laboratory24, Cardiff University25, Chinese Academy of Sciences26, Laval University27, University of Helsinki28, Harvard University29, Max Planck Society30, University of Hertfordshire31, University of Cologne32, University of Kent33, Open University34
TL;DR: In this paper, the first results from the science demonstration phase for the Hi-GAL survey, the Herschel key program that will map the inner Galactic plane of the Milky Way in 5 bands, were presented.
Abstract: We present the first results from the science demonstration phase for the Hi-GAL survey, the Herschel key program that will map the inner Galactic plane of the Milky Way in 5 bands. We outline our data reduction strategy and present some science highlights on the two observed 2° × 2° tiles approximately centered at l = 30° and l = 59°. The two regions are extremely rich in intense and highly structured extended emission which shows a widespread organization in filaments. Source SEDs can be built for hundreds of objects in the two fields, and physical parameters can be extracted, for a good fraction of them where the distance could be estimated. The compact sources (which we will call cores' in the following) are found for the most part to be associated with the filaments, and the relationship to the local beam-averaged column density of the filament itself shows that a core seems to appear when a threshold around AV ~ 1 is exceeded for the regions in the l = 59° field; a AV value between 5 and 10 is found for the l = 30° field, likely due to the relatively higher distances of the sources. This outlines an exciting scenario where diffuse clouds first collapse into filaments, which later fragment to cores where the column density has reached a critical level. In spite of core L/M ratios being well in excess of a few for many sources, we find core surface densities between 0.03 and 0.5 g cm-2. Our results are in good agreement with recent MHD numerical simulations of filaments forming from large-scale converging flows.
TL;DR: In this article, the authors developed and tested the effectiveness of a new and comprehensive set of emotional film excerpts and found that the film clips were effective with regard to several criteria such as emotional discreteness, arousal, positive and negative affect.
Abstract: Using emotional film clips is one of the most popular and effective methods of emotion elicitation. The main goal of the present study was to develop and test the effectiveness of a new and comprehensive set of emotional film excerpts. Fifty film experts were asked to remember specific film scenes that elicited fear, anger, sadness, disgust, amusement, tenderness, as well as emotionally neutral scenes. For each emotion, the 10 most frequently mentioned scenes were selected and cut into film clips. Next, 364 participants viewed the film clips in individual laboratory sessions and rated each film on multiple dimensions. Results showed that the film clips were effective with regard to several criteria such as emotional discreteness, arousal, positive and negative affect. Finally, ranking scores were computed for 24 classification criteria: Subjective arousal, positive and negative affect (derived from the PANAS; Watson & Tellegen, 1988), a positive and a negative affect scores derived from the Differential Emotions Scale (DES; Izard et al., 1974), six emotional discreteness scores (for anger, disgust, sadness, fear, amusement and tenderness), and 15 “mixed feelings” scores assessing the effectiveness of each film excerpt to produce blends of specific emotions. In addition, a number of emotionally neutral film clips were also validated. The database and editing instructions to construct the film clips have been made freely available in a website.
TL;DR: The Theory Coding Scheme is an important methodological innovation, providing a research tool to reliably describe the theoretical base of interventions, inform evidence syntheses within literature reviews and meta-analyses, and stimulate the use of empirical data for theory development.
Abstract: Objective: Interventions are increasingly described as theory-based; however, the basis for this is often not clear. Advancing behavioral science requires a good understanding of how interventions are informed by, and test, theory. This study aims to develop a reliable method for assessing the extent to which behavioral interventions are theory-based. Design: The reliability, usability, and comprehensiveness of an initial coding scheme were improved in 13 iterative stages on the basis of its application to 29 papers, from a systematic review of interventions to promote physical activity and healthy eating. Results: The final Theory Coding Scheme contained 19 items, each with satisfactory interrater reliabilities, coding whether a theory or model was mentioned, how theories were used in intervention design, how intervention evaluations tested theory, and the implications of the results for future theory development. Conclusion: The Theory Coding Scheme is an important methodological innovation, providing a research tool to reliably describe the theoretical base of interventions, inform evidence syntheses within literature reviews and meta-analyses, and stimulate the use of empirical data for theory development.
TL;DR: A blended learning approach was not superior to a QCs approach for improving knowledge about dementia management, however, a subgroup of GPs who were motivated to actually use the online modules had a gain in knowledge.
Abstract: The implementation of new medical knowledge into general practice is a complex process. Blended learning may offer an effective and efficient educational intervention to reduce the knowledge-to-practice gap. The aim of this study was to compare knowledge acquisition about dementia management between a blended learning approach using online modules in addition to quality circles (QCs) and QCs alone. In this cluster-randomised trial with QCs as clusters and general practitioners (GPs) as participants, 389 GPs from 26 QCs in the western part of Germany were invited to participate. Data on the GPs' knowledge were obtained at three points in time by means of a questionnaire survey. Primary outcome was the knowledge gain before and after the interventions. A subgroup analysis of the users of the online modules was performed. 166 GPs were available for analysis and filled out a knowledge test at least two times. A significant increase of knowledge was found in both groups that indicated positive learning effects of both approaches. However, there was no significant difference between the groups. A subgroup analysis of the GPs who self-reported that they had actually used the online modules showed that they had a significant increase in their knowledge scores. A blended learning approach was not superior to a QCs approach for improving knowledge about dementia management. However, a subgroup of GPs who were motivated to actually use the online modules had a gain in knowledge. Current Controlled Trials ISRCTN36550981.