7,297 research outputs found

    A dynamic spatial model of conflict escalation

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    In both historical and modern conflicts, space plays a critical role in how interactions occur over time. Despite its importance, the spatial distribution of adversaries has often been neglected in mathematical models of conflict. In this paper, we propose an entropy-maximising spatial interaction method for disaggregating the impact of space, employing a general notion of ‘threat’ between two adversaries. This approach addresses a number of limitations that are associated with partial differential equation approaches to spatial disaggregation. We use this method to spatially disaggregate the Richardson model of conflict escalation, and then explore the resulting model with both analytical and numerical treatments. A bifurcation is identified that dramatically influences the resulting spatial distribution of conflict and is shown to persist under a range of model specifications. Implications of this finding for real-world conflicts are discussed

    Developing an open data portal for the ESA climate change initiative

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    We introduce the rationale for, and architecture of, the European Space Agency Climate Change Initiative (CCI) Open Data Portal (http://cci.esa.int/data/). The Open Data Portal hosts a set of richly diverse datasets – 13 “Essential Climate Variables” – from the CCI programme in a consistent and harmonised form and to provides a single point of access for the (>100 TB) data for broad dissemination to an international user community. These data have been produced by a range of different institutions and vary across both scientific and spatio-temporal characteristics. This heterogeneity of the data together with the range of services to be supported presented significant technical challenges. An iterative development methodology was key to tackling these challenges: the system developed exploits a workflow which takes data that conforms to the CCI data specification, ingests it into a managed archive and uses both manual and automatically generated metadata to support data discovery, browse, and delivery services. It utilises both Earth System Grid Federation (ESGF) data nodes and the Open Geospatial Consortium Catalogue Service for the Web (OGC-CSW) interface, serving data into both the ESGF and the Global Earth Observation System of Systems (GEOSS). A key part of the system is a new vocabulary server, populated with CCI specific terms and relationships which integrates OGC-CSW and ESGF search services together, developed as part of a dialogue between domain scientists and linked data specialists. These services have enabled the development of a unified user interface for graphical search and visualisation – the CCI Open Data Portal Web Presence

    High g-Force Rollercoaster Rides Induce Sinus Tachycardia but No Cardiac Arrhythmias in Healthy Children

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    This is the final version of the article. Available from Springer Verlag via the DOI in this record.Theme park operators and medical professionals advise children with heart conditions against using rollercoaster rides, but these recommendations are not evidence-based. The underlying assumption is that the combination of adrenergic stimulation through stress and acceleration might trigger arrhythmias in susceptible individuals. We conducted a cross-sectional observational study to assess heart rate and rhythm in healthy children during commercial rollercoaster rides. Twenty healthy children (9 male) aged 11-15 (mean 13.3 ± 1.4) years underwent continuous heart rate and rhythm monitoring (2-lead ECG) from 5 min before until 10 min after each of 4 high speed (>50 km h(-1)), high g-force (>4) commercial rollercoaster rides. Total recording time was 13 h 20 min. No arrhythmic events were detected. Resting heart rate was 81 ± 10 b min(-1) and increased to 158 ± 20 b·min(-1) during rides. The highest mean HR (165 ± 23 b min(-1)) was observed on the ride with the lowest g-force (4.5 g), but one of the highest speeds (100 km h(-1)). Anticipatory tachycardia (126 ± 15 b min(-1)) within 5 min was frequently observed. A 10 min recovery HR (124 ± 17 b min(-1)) was 56 % greater than resting HR. The speed and g-force experienced on roller coasters induce sinus tachycardia but do not elicit pathological arrhythmias in healthy children.This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. Dr Pieles is the holder of an NIHR Academic Clinical Lectureship in Paediatric Cardiology. We would like to thank Novacor Ltd (Swanley, Kent, UK) for providing portable ECG monitoring equipment and Thorpe Park (Merlin Entertainments PLC, Poole, Dorset, UK) for their support during data acquisition. We thank all of the children and their families for participating in this study

    Managing healthcare budgets in times of austerity: the role of program budgeting and marginal analysis

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    Given limited resources, priority setting or choice making will remain a reality at all levels of publicly funded healthcare across countries for many years to come. The pressures may well be even more acute as the impact of the economic crisis of 2008 continues to play out but, even as economies begin to turn around, resources within healthcare will be limited, thus some form of rationing will be required. Over the last few decades, research on healthcare priority setting has focused on methods of implementation as well as on the development of approaches related to fairness and legitimacy and on more technical aspects of decision making including the use of multi-criteria decision analysis. Recently, research has led to better understanding of evaluating priority setting activity including defining ‘success’ and articulating key elements for high performance. This body of research, however, often goes untapped by those charged with making challenging decisions and as such, in line with prevailing public sector incentives, decisions are often reliant on historical allocation patterns and/or political negotiation. These archaic and ineffective approaches not only lead to poor decisions in terms of value for money but further do not reflect basic ethical conditions that can lead to fairness in the decision-making process. The purpose of this paper is to outline a comprehensive approach to priority setting and resource allocation that has been used in different contexts across countries. This will provide decision makers with a single point of access for a basic understanding of relevant tools when faced with having to make difficult decisions about what healthcare services to fund and what not to fund. The paper also addresses several key issues related to priority setting including how health technology assessments can be used, how performance can be improved at a practical level, and what ongoing resource management practice should look like. In terms of future research, one of the most important areas of priority setting that needs further attention is how best to engage public members

    Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially important subgroup of diseases

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    At the population level, rheumatoid arthritis (RA) is generally viewed as autoimmune in nature with a small subgroup of cases having a palindromic form or systemic autoinflammatory disorder (SAID) phenotype. Herein, we describe resistant cases of classical autoantibody associated RA that had clinical, genetic and therapeutic responses indicative of coexistent autoinflammatory disease. Five patients with clinically overlapping features between RA and SAID including polysynovitis and autoantibody/shared epitope positivity, and who had abrupt severe self-limiting attacks including fevers and serositis, are described. Mutations or single nucleotide polymorphisms in recognised autoinflammatory pathways were evident. Generally, these cases responded poorly to conventional Disease-modifying anti-rheumatic drugs (DMARD) treatment with some excellent responses to colchicine or interleukin 1 pathway blockade. A subgroup of RA cases have a mixed autoimmune-autoinflammatory phenotype and genotype with therapeutic implications

    Detection of anti-drug antibodies using a bridging ELISA compared with radioimmunoassay in adalimumab-treated rheumatoid arthritis patients with random drug levels

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    Objective: To determine the concordance between RIA and bridging ELISA at detecting anti-drug antibodies (ADAbs) in the context of random adalimumab levels and investigate the additional clinical utility of detecting ADAbs in RA patients who test ADAb positive by RIA and negative by ELISA. Methods: ADAb levels were determined using RIA and bridging ELISA in 63 adalimumab treated RA patients (159 samples). Immunogenicity concordance was determined using receiver-operating characteristic (ROC) curves. To determine the additional clinical value provided by a positive RIA in the presence of negative ELISA, association between treatment response (ΔDAS28), adalimumab drug levels and ADAbs was evaluated longitudinally using generalised estimating equation. Results: Of the 60 RIA+ samples (n=31 patients), 19 (n=10 patients) were also ELISA+, corresponding to 31.7% of samples. Area under the curve (AUC) for detecting ADAbs using ELISA (compared with RIA) using ROC curves was 0.65 (95% CI: 0.59-0.71); this increased to 0.91 (95% CI: 0.81-0.99) if ADAbs were ≄100 AU/ml using RIA. In RIA+/ELISA- patients, adalimumab levels were associated with ΔDAS28 over 12 months [regression coefficient: 0.098 (0.043-0.15), p<0.0001] and whilst ADAbs were significantly associated with drug level, they were not directly associated with ΔDAS28 over 12 months [ÎČ coefficient: 0.00083 (-0.0038 to 0.0054), p=0.72]. Conclusion: ADAbs were detected using ELISA more frequently when present in high titres as measured by RIA. In RIA+/ELISA- patients, only drug levels were significantly associated with treatment response. Although ADAbs were not independently associated with treatment response, they may be helpful in determining the aetiology of low drug levels

    The discovery of a novel antibiotic for the treatment of Clostridium difficile infections: a story of an effective academic-industrial partnership

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    Academic drug discovery is playing an increasingly important role in the identification of new therapies for a wide range of diseases. There is no one model that guarantees success. We describe here a drug discovery story where chance, the ability to capitalise on chance, and the assembling of a range of expertise, have all played important roles in the discovery and subsequent development of an antibiotic chemotype based on the bis-benzimidazole scaffold, with potency against a number of current therapeutically challenging diseases. One compound in this class, SMT19969, has recently entered Phase 2 human clinical trials for the treatment of Clostridium difficile infections

    Young children's cognitive achievement: home learning environment, language and ethnic background

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    For decades, research has shown differences in cognitive assessment scores between White and minority ethnic group(s) learners as well as differences across different minority ethnic groups. More recent data have indicated that the home learning environment and languages spoken can impact cognitive assessment and other corollary outcomes. This study uses the Millennium Cohort Study to jointly assess how minority ethnic group, home learning environment and home languages predict child cognitive assessment scores. Regression analyses were conducted using two assessment measures. The following is hypothesised: (1) cognitive achievement scores vary by minority ethnic group, (2) more home learning environment in early childhood leads to higher cognitive development scores and (3) English only in the home yields the highest cognitive scores while no English in the home yields the lowest. Findings reveal that there are differences in cognitive scores along ethnic group categories although there are also some unexpected findings. Home learning environment does not play as large a role as was predicted in raising the assessment scores overall for learners while speaking English in the home does, irrespective of ethnic background
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