464 research outputs found

    QT peak prolongation predicts cardiac death following stroke

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    Cardiac death has been linked in many populations to prolongation of the QT interval (QTe). However, basic science research suggested that the best estimate of the time point when repolarisation begins is near the T-wave peak. We found QT peak (QTp) was longer in hypertensive subjects with LVH. A prolonged “depolarisation” phase, rather than “repolarisation” (T peak to T end) might therefore account for the higher incidence of cardiac death linked to long QT. Hypothesis: We have tested the hypothesis that QT peak (QTp) prolongation predicts cardiac death in stroke survivors. Methods and Results: ECGs were recorded from 296 stroke survivors (152 male), mean age 67.2 (SD 11.6) approximately 1 year after the event. Their mean blood pressure was 152/88 mmHg (SD 29/15mmHg). These ECGs were digitised by one observer who was blinded to patient outcome. The patients were followed up for a median of 3.3 years. The primary endpoint was cardiac death. A prolonged heart rate corrected QT peak (QTpc) of lead I carried the highest relative risk of death from all cause as well as cardiac death, when compared with the other more conventional QT indices. In multivariate analyses, when adjusted for conventional risk factors of atherosclerosis, a prolonged QTpc of lead I was still associated with a 3-fold increased risk of cardiac death. (adjusted relative risk 3.0 [95% CI 1.1 - 8.5], p=0.037). Conclusion: QT peak prolongation in lead I predicts cardiac death after strok

    Wave- and tidally-driven flow and sediment flux across a fringing coral reef : southern Molokai, Hawaii

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    This paper is not subject to U.S. copyright. The definitive version was published in Continental Shelf Research 24 (2004): 1397-1419, doi:10.1016/j.csr.2004.02.010.The fringing coral reef off the south coast of Molokai, Hawaii is currently being studied as part of a US Geological Survey (USGS) multi-disciplinary project that focuses on geologic and oceanographic processes that affect coral reef systems. For this investigation, four instrument packages were deployed across the fringing coral reef during the summer of 2001 to understand the processes governing fine-grained terrestrial sediment suspension on the shallow reef flat (h=1 m) and its advection across the reef crest and onto the deeper fore reef. The time–series measurements suggest the following conceptual model of water and fine-grained sediment transport across the reef: Relatively cool, clear water flows up onto the reef flat during flooding tides. At high tide, more deep-water wave energy is able to propagate onto the reef flat and larger Trade wind-driven waves can develop on the reef flat, thereby increasing sediment suspension. Trade wind-driven surface currents and wave breaking at the reef crest cause setup of water on the reef flat, further increasing the water depth and enhancing the development of depth-limited waves and sediment suspension. As the tide ebbs, the water and associated suspended sediment on the reef flat drains off the reef flat and is advected offshore and to the west by Trade wind- and tidally- driven currents. Observations on the fore reef show relatively high turbidity throughout the water column during the ebb tide. It therefore appears that high suspended sediment concentrations on the deeper fore reef, where active coral growth is at a maximum, are dynamically linked to processes on the muddy, shallow reef flat

    Towards understanding the clinical significance of QT peak prolongation: a novel marker of myocardial ischemia independently demonstrated in two prospective studies

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    Background: QT peak prolongation identified patients at risk of death or non-fatal MI. We tested the hypothesis that QT peak prolongation might be associated with significant myocardial ischaemia in two separate cohorts to see how widely applicable the concept was. Methods and Results: In the first study, 134 stroke survivors were prospectively recruited and had 12-lead ECGs and Nuclear myocardial perfusion scanning. QT peak was measured in lead I of a 12-lead ECG and heart rate corrected by Bazett’s formula (QTpc). QTpc prolongation to 360ms or more was 92% specific at diagnosing severe myocardial ischaemia. This hypothesis-generating study led us to perform a second prospective study in a different cohort of patients who were referred for dobutamine stress echocardiography. 13 of 102 patients had significant myocardial ischaemia. Significant myocardial ischaemia was associated with QT peak prolongation at rest (mean 354ms, 95% CI 341-367ms, compared with mean 332ms, 95% CI 327-337ms in those without significant ischaemia; p=0.002). QT peak prolongation to 360ms or more was 88% specific at diagnosing significant myocardial ischaemia in the stress echocardiography study. QT peak prolongation to 360ms or more was associated with over 4-fold increase odds ratio of significant myocardial ischaemia. The Mantel- Haenszel Common Odds Ratio Estimate=4.4, 95% CI=1.2-16.0, p=0.023. Conclusion: QT peak (QTpc) prolongation to 360ms or more should make us suspect the presence of significant myocardial ischaemia. Such patients merit further investigations for potentially treatable ischaemic heart disease to reduce their risk of subsequent death or non-fatal MI

    Changes in wave climate over the northwest European shelf seas during the last 12,000 years

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    Because of the depth attenuation of wave orbital velocity, wave-induced bed shear stress is much more sensitive to changes in total water depth than tidal-induced bed shear stress. The ratio between wave- and tidal-induced bed shear stress in many shelf sea regions has varied considerably over the recent geological past because of combined eustatic changes in sea level and isostatic adjustment. In order to capture the high-frequency nature of wind events, a two-dimensional spectral wave model is here applied at high temporal resolution to time slices from 12 ka BP to present using paleobathymetries of the NW European shelf seas. By contrasting paleowave climates and bed shear stress distributions with present-day conditions, the model results demonstrate that, in regions of the shelf seas that remained wet continuously over the last 12,000 years, annual root-mean-square (rms) and peak wave heights increased from 12 ka BP to present. This increase in wave height was accompanied by a large reduction in the annual rms wave- induced bed shear stress, primarily caused by a reduction in the magnitude of wave orbital velocity penetrating to the bed for increasing relative sea level. In regions of the shelf seas which remained wet over the last 12,000 years, the annual mean ratio of wave- to (M-2) tidal-induced bed shear stress decreased from 1 (at 12 ka BP) to its present-day value of 0.5. Therefore compared to present- day conditions, waves had a more important contribution to large-scale sediment transport processes in the Celtic Sea and the northwestern North Sea at 12 ka BP

    Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

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    Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

    Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

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    © 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

    Determining the neurotransmitter concentration profile at active synapses

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    Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission
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