Showing papers by "University of Oxford published in 2008"
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University of Sydney1, Icahn School of Medicine at Mount Sinai2, University of Paris3, The Heart Research Institute4, University of Oxford5, University of Queensland6, Utrecht University7, Université de Montréal8, University of Melbourne9, University of Sheffield10, Aarhus University11, St Mary's Hospital12, University of Auckland13, University of Leicester14, The George Institute for Global Health15, Radboud University Nijmegen16
TL;DR: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21%relative reduction in nephropathy.
Abstract: BACKGROUND: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. METHODS: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. RESULTS: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). CONCLUSIONS: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)
6,477 citations
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TL;DR: Graphene dispersions with concentrations up to approximately 0.01 mg ml(-1), produced by dispersion and exfoliation of graphite in organic solvents such as N-methyl-pyrrolidone are demonstrated.
Abstract: Fully exploiting the properties of graphene will require a method for the mass production of this remarkable material. Two main routes are possible: large-scale growth or large-scale exfoliation. Here, we demonstrate graphene dispersions with concentrations up to approximately 0.01 mg ml(-1), produced by dispersion and exfoliation of graphite in organic solvents such as N-methyl-pyrrolidone. This is possible because the energy required to exfoliate graphene is balanced by the solvent-graphene interaction for solvents whose surface energies match that of graphene. We confirm the presence of individual graphene sheets by Raman spectroscopy, transmission electron microscopy and electron diffraction. Our method results in a monolayer yield of approximately 1 wt%, which could potentially be improved to 7-12 wt% with further processing. The absence of defects or oxides is confirmed by X-ray photoelectron, infrared and Raman spectroscopies. We are able to produce semi-transparent conducting films and conducting composites. Solution processing of graphene opens up a range of potential large-area applications, from device and sensor fabrication to liquid-phase chemistry.
5,600 citations
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22 Sep 2008TL;DR: In this paper, the authors propose a new algorithm called 1.8.1.1-2.0-1.8-1/2.8/1/1.
Abstract: 8.
3,933 citations
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University of Oxford1, Wellcome Trust Centre for Human Genetics2, University of Michigan3, Fred Hutchinson Cancer Research Center4, Duke University5, University of Ottawa6, Tufts University7, Foundation for Research & Technology – Hellas8, Boston Children's Hospital9, Harvard University10, Broad Institute11
TL;DR: This Review highlights the knowledge gained, defines areas of emerging consensus, and describes the challenges that remain as researchers seek to obtain more complete descriptions of the susceptibility architecture of biomedical traits of interest and to translate the information gathered into improvements in clinical management.
Abstract: The past year has witnessed substantial advances in understanding the genetic basis of many common phenotypes of biomedical importance. These advances have been the result of systematic, well-powered, genome-wide surveys exploring the relationships between common sequence variation and disease predisposition. This approach has revealed over 50 disease-susceptibility loci and has provided insights into the allelic architecture of multifactorial traits. At the same time, much has been learned about the successful prosecution of association studies on such a scale. This Review highlights the knowledge gained, defines areas of emerging consensus, and describes the challenges that remain as researchers seek to obtain more complete descriptions of the susceptibility architecture of biomedical traits of interest and to translate the information gathered into improvements in clinical management.
2,908 citations
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TL;DR: HIF plays a central role in the transcriptional response to changes in oxygen availability and is modulated by FIH1-mediated asparagine hydroxylation, and HIF-modulatory drugs are now being developed for diverse diseases.
2,623 citations
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16 Dec 2008TL;DR: Results show that learning the optimum kernel combination of multiple features vastly improves the performance, from 55.1% for the best single feature to 72.8% forThe combination of all features.
Abstract: We investigate to what extent combinations of features can improve classification performance on a large dataset of similar classes. To this end we introduce a 103 class flower dataset. We compute four different features for the flowers, each describing different aspects, namely the local shape/texture, the shape of the boundary, the overall spatial distribution of petals, and the colour. We combine the features using a multiple kernel framework with a SVM classifier. The weights for each class are learnt using the method of Varma and Ray, which has achieved state of the art performance on other large dataset, such as Caltech 101/256. Our dataset has a similar challenge in the number of classes, but with the added difficulty of large between class similarity and small within class similarity. Results show that learning the optimum kernel combination of multiple features vastly improves the performance, from 55.1% for the best single feature to 72.8% for the combination of all features.
2,619 citations
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Wellcome Trust Centre for Human Genetics1, University of Liège2, University of Chicago3, Yale University4, University of Pittsburgh5, Montreal Heart Institute6, Massachusetts Institute of Technology7, Johns Hopkins University8, University of Toronto9, Cedars-Sinai Medical Center10, McGill University11, Harvard University12, Ghent University Hospital13, Katholieke Universiteit Leuven14, Free University of Brussels15, Paris Diderot University16, Western General Hospital17, King's College London18, University of Oxford19, Wellcome Trust Sanger Institute20, University of Cambridge21, Newcastle University22
TL;DR: The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1, which offer promise for informed therapeutic development.
Abstract: Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.
2,584 citations
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University of Rochester1, University of Washington2, Saint Louis University3, University of Toronto4, University of Texas MD Anderson Cancer Center5, University of Pennsylvania6, Johns Hopkins University7, Yale University8, National Institutes of Health9, Pfizer10, Food and Drug Administration11, NorthShore University HealthSystem12, Merck & Co.13, Allergan14, University of Copenhagen15, Purdue Pharma16, Celgene17, University of Oxford18, Élan19, GlaxoSmithKline20, Johnson & Johnson21, Duke University22, Oregon Health & Science University23, Endo International plc24, AstraZeneca25
TL;DR: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments as discussed by the authors.
2,581 citations
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Harvard University1, University of California, Santa Cruz2, University of British Columbia3, University of Oxford4, University of Washington5, University of California, San Diego6, Oak Ridge National Laboratory7, Arizona State University8, Brown University9, Case Western Reserve University10, Boston University11, University of North Carolina at Chapel Hill12, North Carolina State University13, National Institutes of Health14
TL;DR: A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility.
Abstract: A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of 'third generation' instruments that will sequence a diploid mammalian genome for ∼$1,000 in ∼24 h.
2,512 citations
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TL;DR: In this paper, the authors presented a European land-only daily high-resolution gridded data set for precipitation and minimum, maximum, and mean surface temperature for the period 1950-2006.
Abstract: We present a European land-only daily high-resolution gridded data set for precipitation and minimum, maximum, and mean surface temperature for the period 1950-2006. This data set improves on previous products in its spatial resolution and extent, time period, number of contributing stations, and attention to finding the most appropriate method for spatial interpolation of daily climate observations. The gridded data are delivered on four spatial resolutions to match the grids used in previous products as well as many of the rotated pole Regional Climate Models (RCMs) currently in use. Each data set has been designed to provide the best estimate of grid box averages rather than point values to enable direct comparison with RCMs. We employ a three-step process of interpolation, by first interpolating the monthly precipitation totals and monthly mean temperature using three-dimensional thin-plate splines, then interpolating the daily anomalies using indicator and universal kriging for precipitation and kriging with an external drift for temperature, then combining the monthly and daily estimates. Interpolation uncertainty is quantified by the provision of daily standard errors for every grid square. The daily uncertainty averaged across the entire region is shown to be largely dependent on the season and number of contributing observations. We examine the effect that interpolation has on the magnitude of the extremes in the observations by calculating areal reduction factors for daily maximum temperature and precipitation events with return periods up to 10 years. Copyright 2008 by the American Geophysical Union.
2,359 citations
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TL;DR: Regression and mediation analyses showed that several of the facets of the Five Facet Mindfulness Questionnaire contributed independently to the prediction of well-being and significantly mediated the relationship between meditation experience andWell-being.
Abstract: Previous research on assessment of mindfulness by self-report suggests that it may include five component skills: observing, describing, acting with awareness, nonjudging of inner experience, and nonreactivity to inner experience. These elements of mindfulness can be measured with the Five Facet Mindfulness Questionnaire (FFMQ). The authors investigated several aspects of the construct validity of the FFMQ in experienced meditators and nonmeditating comparison groups. Consistent with predictions, most mindfulness facets were significantly related to meditation experience and to psychological symptoms and well-being. As expected, relationships between the observing facet and psychological adjustment varied with meditation experience. Regression and mediation analyses showed that several of the facets contributed independently to the prediction of well-being and significantly mediated the relationship between meditation experience and well-being. Findings support the construct validity of the FFMQ in a combination of samples not previously investigated.
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TL;DR: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva).
Abstract: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The initial configuration and expected performance of the detector and associated systems, as established by test beam measurements and simulation studies, is described.
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TL;DR: The spatiotemporal specializations in cortical circuits reveal that cellular diversity and temporal dynamics coemerged during evolution, providing a basis for cognitive behavior.
Abstract: In the cerebral cortex, diverse types of neurons form intricate circuits and cooperate in time for the processing and storage of information. Recent advances reveal a spatiotemporal division of labor in cortical circuits, as exemplified in the CA1 hippocampal area. In particular, distinct GABAergic (γ-aminobutyric acid–releasing) cell types subdivide the surface of pyramidal cells and act in discrete time windows, either on the same or on different subcellular compartments. They also interact with glutamatergic pyramidal cell inputs in a domain-specific manner and support synaptic temporal dynamics, network oscillations, selection of cell assemblies, and the implementation of brain states. The spatiotemporal specializations in cortical circuits reveal that cellular diversity and temporal dynamics coemerged during evolution, providing a basis for cognitive behavior.
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Wellcome Trust Centre for Human Genetics1, University of Michigan2, University of Oxford3, Massachusetts Institute of Technology4, Harvard University5, Brigham and Women's Hospital6, Lund University7, Steno Diabetes Center8, University of Southern California9, National Institutes of Health10, Health Science University11, Novartis12, Ninewells Hospital13, University of Exeter14, University of Düsseldorf15, Queen Mary University of London16, Glostrup Hospital17, deCODE genetics18, University of Eastern Finland19, University of Cambridge20, Aarhus University21, University of North Carolina at Chapel Hill22, Norwegian University of Science and Technology23, Wellcome Trust Sanger Institute24, University of Bristol25, University of Helsinki26, Newcastle University27
TL;DR: The results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D, and detect at least six previously unknown loci with robust evidence for association.
Abstract: Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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TL;DR: Genotyping these variants may help to achieve the benefits of statin therapy more safely and effectively and identify common variants in SLCO1B1 that are strongly associated with an increased risk ofstatin-induced myopathy.
Abstract: Background Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger benefits. In rare cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications. Methods We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants. Replication was tested in a trial of 40 mg of simvastatin daily involving 20,000 participants. Results The genomewide scan yielded a single strong association of myopathy with the rs4363657 single-nucleotide polymorphism (SNP) located within SLCO1B1 on chromosome 12 (P=4x10(-9)). SLCO1B1 encodes the organic anion-transporting polypeptide OATP1B1, which has been shown to regulate the hepatic uptake of statins. The noncoding rs4363657 SNP was in nearly complete linkage disequilibrium with the nonsynonymous rs4149056 SNP (r(2)=0.97), which has been linked to statin metabolism. The prevalence of the rs4149056 C allele in the population was 15%. The odds ratio for myopathy was 4.5 (95% confidence interval [CI], 2.6 to 7.7) per copy of the C allele, and 16.9 (95% CI, 4.7 to 61.1) in CC as compared with TT homozygotes. More than 60% of these myopathy cases could be attributed to the C variant. The association of rs4149056 with myopathy was replicated in the trial of 40 mg of simvastatin daily, which also showed an association between rs4149056 and the cholesterol-lowering effects of simvastatin. No SNPs in any other region were clearly associated with myopathy. Conclusions We have identified common variants in SLCO1B1 that are strongly associated with an increased risk of statin-induced myopathy. Genotyping these variants may help to achieve the benefits of statin therapy more safely and effectively. (Current Controlled Trials number, ISRCTN74348595.)
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Aalborg University1, Utrecht University2, University of Oxford3, National and Kapodistrian University of Athens4, French Institute of Health and Medical Research5, German Cancer Research Center6, Harvard University7, University of Turin8, Imperial College London9, University of Naples Federico II10, Umeå University11, Lund University12, University of Tromsø13, University of Cambridge14, International Agency for Research on Cancer15
TL;DR: It is suggested that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing therisk of death.
Abstract: Background Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. Methods We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. Results During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumfer...
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TL;DR: Among people with diabetes the proportional effects of statin therapy were similar irrespective of whether there was a prior history of vascular disease and irrespective of other baseline characteristics and should be considered for all diabetic individuals who are at sufficiently high risk of vascular events.
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TL;DR: In this paper, the authors argue that policy measures are available to improve urban sustainability in transport terms but that the main challenges relate to the necessary conditions for change, and the need to gain public confidence and acceptability to support these measures through active involvement and action.
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University of Alberta1, Harvard University2, Johns Hopkins University3, Mayo Clinic4, University of São Paulo5, University of Maryland, Baltimore6, Vanderbilt University7, University of Manitoba8, University of Paris9, Wake Forest University10, Katholieke Universiteit Leuven11, National Institutes of Health12, University of Basel13, Westmead Hospital14, University of North Carolina at Chapel Hill15, University of Pittsburgh16, University of Vienna17, University of Oxford18, University of Padua19
TL;DR: Emerging research data led to the establishment of collaborative working groups addressing issues like isolated ‘v’ lesion and incorporation of omics‐technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process.
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TL;DR: This is the first description of circulating microRNAs and suggests that micro RNAs have potential as non‐invasive diagnostic markers for DLBCL and possibly other cancers.
Abstract: Circulating nucleic acids have been shown to have potential as non-invasive diagnostic markers in cancer. We therefore investigated whether microRNAs also have diagnostic utility by comparing levels of tumour-associated MIRN155 (miR-155), MIRN210 (miR-210) and MIRN21 (miR-21) in serum from diffuse large B-cell lymphoma (DLBCL) patients (n = 60) with healthy controls (n = 43). Levels were higher in patient than control sera (P = 0.009, 0.02 and 0.04 respectively). Moreover, high MIRN21 expression was associated with relapse-free survival (P = 0.05). This is the first description of circulating microRNAs and suggests that microRNAs have potential as non-invasive diagnostic markers for DLBCL and possibly other cancers.
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23 Jun 2008TL;DR: In this paper, a weighted set of visual words is obtained by selecting words based on proximity in descriptor space, and this representation may be incorporated into a standard tf-idf architecture and how spatial verification is modified in the case of this soft-assignment.
Abstract: The state of the art in visual object retrieval from large databases is achieved by systems that are inspired by text retrieval. A key component of these approaches is that local regions of images are characterized using high-dimensional descriptors which are then mapped to ldquovisual wordsrdquo selected from a discrete vocabulary.This paper explores techniques to map each visual region to a weighted set of words, allowing the inclusion of features which were lost in the quantization stage of previous systems. The set of visual words is obtained by selecting words based on proximity in descriptor space. We describe how this representation may be incorporated into a standard tf-idf architecture, and how spatial verification is modified in the case of this soft-assignment. We evaluate our method on the standard Oxford Buildings dataset, and introduce a new dataset for evaluation. Our results exceed the current state of the art retrieval performance on these datasets, particularly on queries with poor initial recall where techniques like query expansion suffer. Overall we show that soft-assignment is always beneficial for retrieval with large vocabularies, at a cost of increased storage requirements for the index.
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TL;DR: It is shown that multigrid ideas can be used to reduce the computational complexity of estimating an expected value arising from a stochastic differential equation using Monte Carlo path simulations.
Abstract: We show that multigrid ideas can be used to reduce the computational complexity of estimating an expected value arising from a stochastic differential equation using Monte Carlo path simulations. In the simplest case of a Lipschitz payoff and a Euler discretisation, the computational cost to achieve an accuracy of O(e) is reduced from O(e-3) to O(e-2 (log e)2). The analysis is supported by numerical results showing significant computational savings.
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University of Michigan1, National Institutes of Health2, University of Oxford3, University of Bristol4, National Research Council5, University of Maryland, Baltimore6, French Institute of Health and Medical Research7, University of Paris8, National Institute for Health and Welfare9, University of Southern California10, University of London11, University of Helsinki12, University of North Carolina at Chapel Hill13
TL;DR: In this paper, the authors used genotype imputation and meta-analysis to identify genetic variants influencing plasma lipid concentrations, using three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to their study.
Abstract: To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.
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21 Apr 2008TL;DR: Fairburn, Cooper, Shafran, Bohn, Hawker, Fairburn, Inpatient, Day Patient and Two Forms of Outpatient CBT-E: An Overview.
Abstract: Introduction. Fairburn, This Book and How to Use It. Fairburn, Eating Disorders: The Transdiagnostic View and the Cognitive Behavioral Theory. Fairburn, Cooper, Shafran, Enhanced Cognitive Behavior Therapy for Eating Disorders (CBT-E): An Overview. Fairburn, Cooper, Waller, The Patients: Their Assessment, Preparation for Treatment and Medical Management. Fairburn, Cooper, Shafran, Bohn, Hawker, Murphy, Straebler, Enhanced Cognitive Behavior Therapy for Eating Disorders: The Core Protocol. Starting Well. Achieving Early Change. Taking Stock and Designing the Rest of Treatment. Shape Concern. Shape Checking. Feeling Fat and Mindsets. Dietary Restraint, Dietary Rules and Controlling Eating. Events, Moods and Eating. Underweight and Under-eating. Ending Well. Adaptations of CBT-E. Fairburn, Cooper, Shafran, Bohn, Hawker, Clinical Perfectionism, Core Low Self-esteem and Interpersonal Problems. Cooper, Stewart, CBT-E and the Younger Patient. Grave, Bohn, Hawker, Fairburn, Inpatient, Day Patient and Two Forms of Outpatient CBT-E. Fairburn, Cooper, Waller, 'Complex Cases' and Comorbidity. Postscript. Fairburn, Looking Forward. Appendices. Fairburn, Cooper, O'Connor, Appendix A: Eating Disorder Examination (16.0D). Fairburn, Beglin, Appendix B: Eating Disorder Examination Questionnaire (EDE-Q6.0). Bohn, Fairburn, Appendix C: Clinical Impairment Assessment Questionnaire (CIA 3.0).
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TL;DR: A probabilistic approach to the problem of recognizing places based on their appearance that can determine that a new observation comes from a previously unseen place, and so augment its map, and is particularly suitable for online loop closure detection in mobile robotics.
Abstract: This paper describes a probabilistic approach to the problem of recognizing places based on their appearance. The system we present is not limited to localization, but can determine that a new observation comes from a previously unseen place, and so augment its map. Effectively this is a SLAM system in the space of appearance. Our probabilistic approach allows us to explicitly account for perceptual aliasing in the environment—identical but indistinctive observations receive a low probability of having come from the same place. We achieve this by learning a generative model of place appearance. By partitioning the learning problem into two parts, new place models can be learned online from only a single observation of a place. The algorithm complexity is linear in the number of places in the map, and is particularly suitable for online loop closure detection in mobile robotics.
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TL;DR: There is evidence that drugs that inhibit one of these pathways in such tumours could prove useful as single-agent therapies, with the potential advantage that this approach could be selective for tumour cells and have fewer side effects.
Abstract: DNA repair pathways can enable tumour cells to survive DNA damage that is induced by chemotherapeutic treatments; therefore, inhibitors of specific DNA repair pathways might prove efficacious when used in combination with DNA-damaging chemotherapeutic drugs. In addition, alterations in DNA repair pathways that arise during tumour development can make some cancer cells reliant on a reduced set of DNA repair pathways for survival. There is evidence that drugs that inhibit one of these pathways in such tumours could prove useful as single-agent therapies, with the potential advantage that this approach could be selective for tumour cells and have fewer side effects.
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Joint Genome Institute1, University of Oxford2, University of St Andrews3, University of California, Berkeley4, Washington University in St. Louis5, University of Lausanne6, Swiss Institute of Bioinformatics7, Kyoto University8, California Institute of Technology9, National Institute for Medical Research10, University of Barcelona11, Children's Hospital Oakland12, Genetic Information Research Institute13, National Institute of Genetics14, Stanford University15, National Institute of Informatics16, University of California, San Diego17
TL;DR: Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization.
Abstract: Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approximately 520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution.
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TL;DR: To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling, and more-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed.
Abstract: Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.
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Broad Institute1, Harvard University2, Massachusetts Institute of Technology3, Cardiff University4, University College London5, University of Edinburgh6, Trinity College, Dublin7, Uppsala University8, Karolinska Institutet9, University of Southern California10, University of Aberdeen11, University of North Carolina at Chapel Hill12, QIMR Berghofer Medical Research Institute13, Royal College of Surgeons in Ireland14, National Health Service15, University of Oxford16, Queen Mary University of London17, State University of New York System18, University of Coimbra19
TL;DR: A genome-wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls provides strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.
Abstract: Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73 - 90% ( ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants ( CNVs) have been identified in individual patients with schizophrenia(2-7) and also in neurodevelopmental disorders(8-11), but large- scale genome- wide surveys have not been performed. Here we report a genome- wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high- density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15- fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single- occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo- cardio- facial syndrome, which includes psychotic symptoms in 30% of patients(12). Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome- wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.
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TL;DR: Eight CONSORT checklist items for reporting of pragmatic trials are recommended, including the background, participants, interventions, outcomes, sample size, blinding, participant flow, and generalisability of the findings.
Abstract: Background The CONSORT statement is intended to improve reporting of randomised controlled trials and focuses on minimising the risk of bias (internal validity). The applicability of a trial’s results (generalisability or external validity) is also important, particularly for pragmatic trials. A pragmatic trial (a term first used in 1967 by Schwartz and Lellouch) can be broadly defined as a randomised controlled trial whose purpose is to inform decisions about practice. This extension of the CONSORT statement is intended to improve the reporting of such trials and focuses on applicability. Methods At two, two-day meetings held in Toronto in 2005 and 2008, we reviewed the CONSORT statement and its extensions, the literature on pragmatic trials and applicability, and our experiences in conducting pragmatic trials. Recommendations We recommend extending eight CONSORT checklist items for reporting of pragmatic trials: the background, participants, interventions, outcomes, sample size, blinding, participant flow, and generalisability of the findings. These extensions are presented, along with illustrative examples of reporting, and an explanation of each extension. Adherence to these reporting criteria will make it easier for decision makers to judge how applicable the results of randomised controlled trials are to their own conditions. Empirical studies are needed to ascertain the usefulness and comprehensiveness of these CONSORT checklist item extensions. In the meantime we recommend that those who support, conduct, and report pragmatic trials should use this extension of the CONSORT statement to facilitate the use of trial results in decisions about health care.