1,784 research outputs found

    The effects of matter density uncertainties on neutrino oscillations in the Earth

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    We compare three different methods to evaluate uncertainties in the Earth's matter density profile, which are relevant to long baseline experiments, such as neutrino factories.Comment: 3 pages, 1 figure. Talk given at the NuFact'02 Workshop, London, 1-6 July, 200

    Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

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    This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

    The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

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    Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

    Innovative gait robot for the repetitive practice of floor walking and stair climbing up and down in stroke patients

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    <p>Abstract</p> <p>Background</p> <p>Stair climbing up and down is an essential part of everyday's mobility. To enable wheelchair-dependent patients the repetitive practice of this task, a novel gait robot, G-EO-Systems (EO, Lat: I walk), based on the end-effector principle, has been designed. The trajectories of the foot plates are freely programmable enabling not only the practice of simulated floor walking but also stair climbing up and down. The article intended to compare lower limb muscle activation patterns of hemiparetic subjects during real floor walking and stairs climbing up, and during the corresponding simulated conditions on the machine, and secondly to demonstrate gait improvement on single case after training on the machine.</p> <p>Methods</p> <p>The muscle activation pattern of seven lower limb muscles of six hemiparetic patients during free and simulated walking on the floor and stair climbing was measured via dynamic electromyography. A non-ambulatory, sub-acute stroke patient additionally trained on the G-EO-Systems every workday for five weeks.</p> <p>Results</p> <p>The muscle activation patterns were comparable during the real and simulated conditions, both on the floor and during stair climbing up. Minor differences, concerning the real and simulated floor walking conditions, were a delayed (prolonged) onset (duration) of the thigh muscle activation on the machine across all subjects. Concerning stair climbing conditions, the shank muscle activation was more phasic and timely correct in selected patients on the device. The severely affected subject regained walking and stair climbing ability.</p> <p>Conclusions</p> <p>The G-EO-Systems is an interesting new option in gait rehabilitation after stroke. The lower limb muscle activation patterns were comparable, a training thus feasible, and the positive case report warrants further clinical studies.</p

    Do horizontal propulsive forces influence the nonlinear structure of locomotion?

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    <p>Abstract</p> <p>Background</p> <p>Several investigations have suggested that changes in the nonlinear gait dynamics are related to the neural control of locomotion. However, no investigations have provided insight on how neural control of the locomotive pattern may be directly reflected in changes in the nonlinear gait dynamics. Our simulations with a passive dynamic walking model predicted that toe-off impulses that assist the forward motion of the center of mass influence the nonlinear gait dynamics. Here we tested this prediction in humans as they walked on the treadmill while the forward progression of the center of mass was assisted by a custom built mechanical horizontal actuator.</p> <p>Methods</p> <p>Nineteen participants walked for two minutes on a motorized treadmill as a horizontal actuator assisted the forward translation of the center of mass during the stance phase. All subjects walked at a self-select speed that had a medium-high velocity. The actuator provided assistive forces equal to 0, 3, 6 and 9 percent of the participant's body weight. The largest Lyapunov exponent, which measures the nonlinear structure, was calculated for the hip, knee and ankle joint time series. A repeated measures one-way analysis of variance with a t-test post hoc was used to determine significant differences in the nonlinear gait dynamics.</p> <p>Results</p> <p>The magnitude of the largest Lyapunov exponent systematically increased as the percent assistance provided by the mechanical actuator was increased.</p> <p>Conclusion</p> <p>These results support our model's prediction that control of the forward progression of the center of mass influences the nonlinear gait dynamics. The inability to control the forward progression of the center of mass during the stance phase may be the reason the nonlinear gait dynamics are altered in pathological populations. However, these conclusions need to be further explored at a range of walking speeds.</p

    Massive stars as thermonuclear reactors and their explosions following core collapse

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    Nuclear reactions transform atomic nuclei inside stars. This is the process of stellar nucleosynthesis. The basic concepts of determining nuclear reaction rates inside stars are reviewed. How stars manage to burn their fuel so slowly most of the time are also considered. Stellar thermonuclear reactions involving protons in hydrostatic burning are discussed first. Then I discuss triple alpha reactions in the helium burning stage. Carbon and oxygen survive in red giant stars because of the nuclear structure of oxygen and neon. Further nuclear burning of carbon, neon, oxygen and silicon in quiescent conditions are discussed next. In the subsequent core-collapse phase, neutronization due to electron capture from the top of the Fermi sea in a degenerate core takes place. The expected signal of neutrinos from a nearby supernova is calculated. The supernova often explodes inside a dense circumstellar medium, which is established due to the progenitor star losing its outermost envelope in a stellar wind or mass transfer in a binary system. The nature of the circumstellar medium and the ejecta of the supernova and their dynamics are revealed by observations in the optical, IR, radio, and X-ray bands, and I discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure

    Increased production of viral proteins by a 3'-LTR-deleted infectious clone of human T-cell leukemia virus type 1

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    We previously reported that a full-length provirus of HTLV-1 was directly constructed from the HTLV-1-transformed cell line MT-2 using overlapping polymerase chain reaction (PCR) and cloned into a plasmid vector (pFL-MT2). 293T cells transfected with pFL-MT2 alone did not produce virus particles because there was no expression of the viral transactivator protein Tax, whereas cells transfected with pFL-MT2 plus a Tax expression vector produced virus-like particles. In the process of constructing the HTLV-1 provirus by overlapping PCR, we also constructed an incomplete molecular clone, in which the 3' long terminal repeat (LTR) was replaced with the endogenous human gene, which resulted in the expression of a tax gene shorter by 43 bp. This incomplete molecular clone alone expressed Tax and produced the viral protein in transfected cells. Various clones were then constructed with different lengths of the 3' LTR and lacking the reverse-direction TATA box. The clones contained over 113 bp of the 3' LTR, with no reverse-direction TATA box, which might express the full-length tax gene, and did not produce the viral antigen. These results suggest that Tax in which the C-terminal portion is deleted is more strongly expressed than the wild-type protein and has transcriptional activity

    Assessment of left ventricular volumes using simplified 3-D echocardiography and computed tomography – a phantom and clinical study

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    <p>Abstract</p> <p>Objectives</p> <p>To compare the accuracy of simplified 3-dimensional (3-D) echocardiography vs. multi-slice computed tomography (MSCT) software for the quantification of left ventricular (LV) volumes.</p> <p>Design</p> <p>Three-D echocardiography (3-planes approach) and MSCT-CardIQ software were calibrated by measuring known volumes of 10 phantoms designed to closely mimic blood-endocardium interface. Subsequently, LV volumes were measured with both the methods in 9 patients referred routinely for coronary angiography and the agreement between the measurements was evaluated.</p> <p>Results</p> <p>Simplified 3D-echocardiography provided higher degree of agreement between the measured and true phantom volumes (mean difference 0 ± 1 ml, variation range +4 to -4 ml) than MSCT software (mean difference 6 ± 5 ml; variation range +22 to -10 ml). The agreement between LV measurements in the patients was considerably poorer, with significantly larger volumes produced by MSCT (mean difference -23 ± 40 ml, variation between +93 and -138 ml).</p> <p>Conclusion</p> <p>Simplified 3-D echocardiography provides more accurate assessment of phantom volumes than MSCT-CardIQ software. The discrepancy between the results of LV measurements with the two methods is even greater and does not warrant their interchangeable diagnostic use.</p
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