Genetic variation at 16q24.2 is associated with small vessel stroke.

OBJECTIVE: Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger-onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger-onset SVS population, to identify novel associations with stroke. METHODS: We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on messenger RNA (mRNA) expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain. RESULTS: We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (odds ratio [OR; 95% confidence interval {CI}] = 1.16 [1.10-1.22]; p = 3.2 × 10-9 ). The lead single-nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05-1.16]; p = 5.3 × 10-5 ; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84-1.12]; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10-7 ) and DNA methylation at probe cg16596957 in whole blood (p = 5.3 × 10-6 ). INTERPRETATION: 16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. Ann Neurol 2017;81:383-394.Matthew Traylor is funded by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by NIHR Comprehensive Biomedical Research Unit funding awarded to Cambridge University Hospitals Trust. Cathryn Lewis receives salary support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Collection of the UK Young Lacunar Stroke DNA Study (DNA Lacunar) was primarily supported by the Wellcome Trust (WT072952) with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA Lacunar samples was supported by a Stroke Association Grant (TSA 2013/01). Robin Lemmens is a senior clinical investigator of FWO Flanders. Martin Dichgans received funding from the DFG (CRC 1123, B3) and a EU Horizon 2020 grant (agreement No 666881 SVDs@target). The TwinsUK study was funded in part by the European Research Council (ERC 250157), and from the TwinsUK resource, which receives support from the Wellcome Trust and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. SNP Genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. The SiGN study was funded by a cooperative agreement grant from the US National Institute of Neurological Disorders and Stroke, National Institutes of Health (U01 NS069208)

2010a) “ICT for Energy Efficiency: Towards Smart Buildings, Manufacturing, Lighting and Grids

ABSTRACT The European Union (EU) has set its specific target of a 20% energy reduction in EU energy consumption by 2020. Achieving this goal will require major breakthroughs in the research and development (R&D) of new technologies. Information and Communication Technologies (ICT) are today pervasive to all industrial and business sectors. They are expected to have a significant impact on energy efficiency in the future. In this paper, the four industrial disciplines of buildings, manufacturing, lighting and power grids are identified to have great potential to deploy ICT to improve their energy efficiency. These four sectors often come together in delivering infrastructures and environments for production, business and living, and together they produce and consume a significant proportion of Europe's energy. The state-of-the-art ICT for Energy Efficiency (ICT4EE) in these four sectors are discussed with focuses mainly on their available data on the potential impact, potential to improve through research, development and deployment, obstacles impeding the realisation of full potential, and actions which can be taken to accelerate achievement of potential. This leads to an ICT4EE impact assessment model which is needed to identify complementarities and synergies among these four sectors, harmonising common research and technological development (RTD) priorities, and establishing a cross-sectoral community with links to key stakeholders from them. A methodology for impact assessment model of ICT4EE has been designed on the basis of life cycle assessment and causal relationships which come from the currently existing research. The paper concludes that in order to achieve the full potential of ICT4EE, further support of multidisciplinary R&D and innovation demonstrating the potential of ICT based solutions are needed to boost, reinforce, foster and accelerate the deployment of energy efficient solutions in these four industrial domains

Snake bite in Chittagong Division, Bangladesh: a study of bitten patients who developed no signs of systemic envenoming.

The demographics, epidemiology, first aid, clinical management, treatment and outcome of snake bites causing no significant signs of systemic envenoming were documented in Chittagong Medical College Hospital, Bangladesh, between May 1999 and October 2002. Among 884 patients admitted, 350 were systemically envenomed and 534 were without signs of either systemic or significant local envenoming. The average age of patients with physical evidence of snake bite but no systemic envenoming was 26.4 years. Most had been bitten on their feet or hands. Ligatures had been applied proximal to the bite site in >95% of cases and the bite site had been incised in 13%. Patients were typically discharged at 24h. Those with clinical signs of systemic envenoming resembled the non-envenomed cases demographically and epidemiologically except that they arrived at hospital significantly later than non-envenomed patients, having spent longer with traditional healers. No non-envenomed patient was treated with antivenom and none went on to develop symptoms of systemic envenoming after discharge. The potential complications and confusing signs caused by ligatures and incision demand that all patients admitted with a history of snake bite be kept under observation for 24h after admission even if they have no signs of systemic envenoming

MULTI-DISCIPLINARY STRATEGIC RESEARCH AGENDA FOR ICT-ENABLED ENERGY EFFICIENCY

ABSTRACT Information and Communication Technologies (ICTs) are today pervasive to all industrial sectors which are faced with a sustainability paradox in maintaining economic growth while consuming fewer resources. ICTs have proven central to the performance driven development of modern industry in supporting production systems at all levels. Given this pervasiveness ICTs have a unique opportunity to address the sustainability paradox by enabling energy efficient viable operations. However, often the issue is not a lack of technological options, but rather a problem in understanding what choices will have the greatest impact. This paper introduces a multi-disciplinary strategic research agenda (SRA) for ICT-enabled energy efficiency developed by the REViSITE (Roadmap Enabling Vision and Strategy for ICT-enabled Energy Efficiency) EU funded project covering migration pathways from the state of the art to a common vision of ICT for energy efficiency (ICT4EE). These pathways are based on research and technology development (RTD) topics for short, medium and long term delivery in terms of industrial take-up. The developed SRA suggests ICT4EE research priorities for four targeted sectors: building, grids, manufacturing and lighting, since these four sectors often come together in delivering infrastructures and environments for production, service, business and living. It is anticipated that the identified RTD topics will be relevant to many other sectors in which ICTs can contribute to improving energy efficiency

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease