16 research outputs found

    Real-time adaptive track generation in racing games

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    Real-time Adaptive Track Generation in Racing Game

    Predictors of Depression in Very Young Children: A Prospective Study

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    There have been only a few previous population-based studies of symptoms of depression in young children. There are no previous population-based studies which examine the factors which might be casually associated with depression in very young children

    WireWall: a new approach to coastal wave hazard monitoring

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    WireWall will be the first agile in situ system to make field measurements of overtopping on a wave-by-wave basis. Such data will enable site-specific calibration of (i) numerical tools used in sea defence design, (ii) flood forecasting models and (iii) public safety tolerances used by shoreline managers. The new approach transfers existing laboratory and offshore wave monitoring capabilities to the problem of coastal hazard monitoring. The capacitance wire system will collect high frequency field data to quantify wave overtopping velocity and volume. Our approach will replace the use of water collection tanks, which provide very limited information, are cumbersome, and hence rarely deployed. The method will use a coupled modelling-observational-modelling approach. Industry standard overtopping tools will generate a numerical dataset of plausible overtopping conditions at our study site Crosby (NW England). This data will inform the configuration of the wire units to be used in dockside and flume tests prior to the design of the field rig. The newly collected field observations will allow site-specific calibration and validation of the numerical tools, which will then be applied for a range of storm and beach conditions to develop site-specific overtopping safety tolerances and identify overtopping trigger levels for the existing sea wall

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Scaling up community activism: the role of intermediaries in collective approaches to community energy

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    Intermediary organisations can play a significant role in the changing environment of UK energy, transcending the perceived divides between individual action, activism and top-down policy. This paper discusses a Bristol based action research project which, working with local community energy groups, explored the role of intermediary organisations not just in bringing together learning, providing support and aggregating impact but also in helping to shape stronger local energy action by connecting across and beyond existing activity in ways that put communities first. This approach enabled the development of the ‘Bristol Community Strategy for Energy’, which takes a different approach to the national ‘Community Energy Strategy’ which it preceded. We consider the roles of intermediary organisations in scaling up community activity: linking with policy and supporting shared action to accelerate community responses to energy concerns. We also draw on the underpinning theory before concluding with recommendations to reinforce the maturing and changing local energy landscape

    Variceal Recurrence, Rebleeding, and Survival After Endoscopic Injection Sclerotherapy in 287 Alcoholic Cirrhotic Patients With Bleeding Esophageal Varices

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    OBJECTIVE: This study tested the validity of the hypothesis that eradication of esophageal varices by repeated injection sclerotherapy would reduce recurrent variceal bleeding and death from bleeding varices in a high-risk cohort of alcoholic patients with cirrhosis. SUMMARY BACKGROUND DATA: Although banding of esophageal varices is now regarded as the most effective method of endoscopic intervention, injection sclerotherapy is still widely used to control acute esophageal variceal bleeding as well as to eradicate varices to prevent recurrent bleeding. This large single-center prospective study provides data on the natural history of alcoholic cirrhotic patients with bleeding varices who underwent injection sclerotherapy. METHODS: Between 1984 and 2001, 287 alcoholic cirrhotic patients (225 men, 62 women; mean age, 51.9 years; range, 24–87 years; Child-Pugh grades A, 39; B, 116; C, 132) underwent a total of 2565upper gastrointestinal endoscopic sessions, which included 353 emergency and 1015 elective variceal injection treatments. Variceal rebleeding, eradication, recurrence, and survival were recorded. RESULTS: Before eradication of varices was achieved, 104 (36.2%) of the 287 patients had a total of 170 further bleeding episodes after the first endoscopic intervention during the index hospital admission. Rebleeding was markedly reduced after eradication of varices. In 147 (80.7%) of 182 patients who survived more than 3 months, varices were eradicated after a mean of 5 injection sessions and remained eradicated in 69 patients (mean follow-up, 34.6 months; range, 1–174 months). Varices recurred in 78 patients and rebled in 45 of these patients. Median follow-up was 32.3 months (mean, 42.1 months; range, 3–198.9 months). Cumulative overall survival by life-table analysis was 67%, 42%, and 26% at 1, 3, and 5 years, respectively. A total of 201 (70%) patients died during follow-up. Liver failure was the most common cause of death. CONCLUSION: Repeated sclerotherapy eradicates esophageal varices in most alcoholic cirrhotic patients with a reduction in rebleeding. Despite control of variceal bleeding, survival at 5 years was only 26% because of death due to liver failure in most patients
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