1,219 research outputs found

    A proposal for ethical research conduct in Madagascar

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    This journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge. The attached file is the published version of the article

    Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis

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    BACKGROUND\textbf{BACKGROUND}: 18F-Fluoride positron emission tomography (PET) and computed tomography (CT) can measure disease activity and progression in aortic stenosis. Our objectives were to optimize the methodology, analysis, and scan-rescan reproducibility of aortic valve 18F-fluoride PET-CT imaging. METHODS AND RESULTS\textbf{METHODS AND RESULTS}: Fifteen patients with aortic stenosis underwent repeated 18F-fluoride PET-CT. We compared nongated PET and noncontrast CT, with a modified approach that incorporated contrast CT and ECG-gated PET. We explored a range of image analysis techniques, including estimation of blood-pool activity at differing vascular sites and a most diseased segment approach. Contrast-enhanced ECG-gated PET-CT permitted localization of 18F-fluoride uptake to individual valve leaflets. Uptake was most commonly observed at sites of maximal mechanical stress: the leaflet tips and the commissures. Scan-rescan reproducibility was markedly improved using enhanced analysis techniques leading to a reduction in percentage error from ±63% to ±10% (tissue to background ratio MDS mean of 1.55, bias -0.05, limits of agreement -0·20 to +0·11). CONCLUSIONS\textbf{CONCLUSIONS}: Optimized 18F-fluoride PET-CT allows reproducible localization of calcification activity to different regions of the aortic valve leaflet and commonly to areas of increased mechanical stress. This technique holds major promise in improving our understanding of the pathophysiology of aortic stenosis and as a biomarker end point in clinical trials of novel therapies. CLINICAL TRIAL REGISTRATION\textbf{CLINICAL TRIAL REGISTRATION} - URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026.The study was funded by the British Heart Foundation (FS/14/78/31020). Drs Pawade, Cartlidge, Jenkins, Dweck, and Newby are supported by the British Heart Foundation (SS/CH/09/002/26360, FS/13/77/30488, SS/CH/09/002/2636, FS/14/78/31020, and CH/09/002). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr Dweck is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015. Dr Adamson is supported by New Zealand Overseas Training and Research Fellowship (1607) and Edinburgh and Lothians Health Foundation (50–534). The Wellcome Trust Clinical Research Facility and the Clinical Research Imaging Centre are supported by NHS Research Scotland (NRS) through NHS Lothian. Dr Rudd is partly supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust

    Contribution of the cyclic nucleotide gated channel subunit, CNG-3, to olfactory plasticity in Caenorhabditis elegans.

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    In Caenorhabditis elegans, the AWC neurons are thought to deploy a cGMP signaling cascade in the detection of and response to AWC sensed odors. Prolonged exposure to an AWC sensed odor in the absence of food leads to reversible decreases in the animal's attraction to that odor. This adaptation exhibits two stages referred to as short-term and long-term adaptation. Previously, the protein kinase G (PKG), EGL-4/PKG-1, was shown necessary for both stages of adaptation and phosphorylation of its target, the beta-type cyclic nucleotide gated (CNG) channel subunit, TAX-2, was implicated in the short term stage. Here we uncover a novel role for the CNG channel subunit, CNG-3, in short term adaptation. We demonstrate that CNG-3 is required in the AWC for adaptation to short (thirty minute) exposures of odor, and contains a candidate PKG phosphorylation site required to tune odor sensitivity. We also provide in vivo data suggesting that CNG-3 forms a complex with both TAX-2 and TAX-4 CNG channel subunits in AWC. Finally, we examine the physiology of different CNG channel subunit combinations

    Essential elements of an early intervention service for psychosis: the opinions of expert clinicians

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    BACKGROUND: Early intervention teams attempt to improve outcome in schizophrenia through earlier detection and the provision of phase-specific treatments. Whilst the number of early intervention teams is growing, there is a lack of clarity over their essential structural and functional elements. METHODS: A 'Delphi' exercise was carried out to identify how far there was consensus on the essential elements of early intervention teams in a group of 21 UK expert clinicians. Using published guidelines, an initial list was constructed containing 151 elements from ten categories of team structure and function. RESULTS: Overall there was expert consensus on the importance of 136 (90%) of these elements. Of the items on which there was consensus, 106 (70.2%) were rated essential, meaning that in their absence the functioning of the team would be severely impaired. CONCLUSION: This degree of consensus over essential elements suggests that it is reasonable to define a model for UK early intervention teams, from which a measure of fidelity could be derived

    Responses of marine benthic microalgae to elevated CO<inf>2</inf>

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    Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

    Intensified shigellosis epidemic associated with sexual transmission in men who have sex with men - Shigella fexneri and s. Sonnei in England, 2004 to end of February 2015

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    Surveillance data suggest an intensification of the shigellosis epidemic associated with sexual transmission in men who have sex with men (MSM) in England with separate introductions into the population. In 2014, sexual transmission between MSM might have accounted for 97%, 89%, and 43% of non-travel associated Shigella flexneri 3a and S. flexneri 2a, and S. sonnei diagnoses. Clinicians should sensitively ascertain sexual history for men with enteric infections to facilitate prompt diagnosis and appropriate management

    On the creation of future probabilistic design weather years from UKCP09

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    Copyright © 2011 by SAGE PublicationsWeather data are used extensively by building scientists and engineers to study the performance of their designs, help compare design alternatives and ensure compliance with building regulations. Given a changing climate, there is a need to provide data for future years so that practising engineers can investigate the impact of climate change on particular designs and examine any risk the commissioning client might be exposed to. In addition, such files are of use to building scientists in developing generic solutions to problems such as elevated internal temperatures and poor thermal comfort. With the publication of the UK Climate Projections (UKCP09) such data can be created for future years up to 2080 and for various probabilistic projections of climate change by the use of a weather generator. Here, we discuss a method for the creation of future probabilistic reference years for use within thermal models. In addition, a comparison is made with the current set of future weather years based on the UKCIP02 projections. When used within a dynamic thermal simulation of a building, the internal environments created by the current set of future weather files lie within the range of the internal environments created by the probabilistic reference years generated by the weather generator. Hence, the main advantages of the weather generator are seen to lie in its potentially greater spatial resolution, its ability to inform risk analysis and that such files, unlike ones based on observed data, carry no copyright. Practical applications: The methodology presented in this article will allow academics and buildings engineers to create realistic hourly future weather files using the future climate data of UKCP09 weather generator. This will allow the creation of consistent future weather years for use in areas such as building thermal simulation
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