41,956 research outputs found

    Focus on Quality: Communication in the Health Care Encounter

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    Outlines findings from focus groups on the role of effective communication between physicians and patients in improving the quality of health care and outcomes. Analyzes responses by race/ethnicity and gender. Includes recommendations

    Pyrone-based inhibitors of metalloproteinase types 2 and 3 may work as conformation-selective inhibitors.

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    Matrix metalloproteinases are zinc-containing enzymes capable of degrading all components of the extracellular matrix. Owing to their role in human disease, matrix metalloproteinase have been the subject of extensive study. A bioinorganic approach was recently used to identify novel inhibitors based on a maltol zinc-binding group, but accompanying molecular-docking studies failed to explain why one of these inhibitors, AM-6, had approximately 2500-fold selectivity for MMP-3 over MMP-2. A number of studies have suggested that the matrix-metalloproteinase active site is highly flexible, leading some to speculate that differences in active-site flexibility may explain inhibitor selectivity. To extend the bioinorganic approach in a way that accounts for MMP-2 and MMP-3 dynamics, we here investigate the predicted binding modes and energies of AM-6 docked into multiple structures extracted from matrix-metalloproteinase molecular dynamics simulations. Our findings suggest that accounting for protein dynamics is essential for the accurate prediction of binding affinity and selectivity. Additionally, AM-6 and other similar inhibitors likely select for and stabilize only a subpopulation of all matrix-metalloproteinase conformations sampled by the apo protein. Consequently, when attempting to predict ligand affinity and selectivity using an ensemble of protein structures, it may be wise to disregard protein conformations that cannot accommodate the ligand

    Effect of cochlear implant electrode insertion on middle-ear function as measured by intra-operative laser Doppler vibrometry

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    Hypothesis: The aim of this study was to investigate the impact of cochlear implant electrode insertion on middle-ear low frequency function in humans.Background: Preservation of residual low frequency hearing with addition of electrical speech processing can improve the speech perception abilities and hearing in noise of cochlear implant users. Preservation of low frequency hearing requires an intact middle-ear conductive mechanism in addition to intact inner-ear mechanisms. Little is known about the effect of a cochlear implant electrode on middle-ear function.Methods: Stapes displacement was measured in seven patients undergoing cochlear implantation. Measurements were carried out intra-operatively before and after electrode insertion. Each patient acted as his or her own control. Sound was delivered into the external auditory canal via a speaker and calibrated via a probe microphone. The speaker and probe microphone were integrated into an individually custom-made ear mould. Ossicular displacement in response to a multisine stimulus at 80 dB SPL was measured at the incudostapedial joint via the posterior tympanotomy, using an operating microscope mounted laser Doppler vibrometry system.Results: Insertion of a cochlear implant electrode into the scala tympani had a variable effect on stapes displacement. In three patients, there was little change in stapes displacement following electrode insertion. In two patients, there was a significant increase, while in a further two there was a significant reduction in stapes displacement. This variability may reflect alteration of cochlear impedance, possibly due to differing loss of perilymph associated with the electrode insertion.Conclusion: Insertion of a cochlear implant electrode produces a change in stapes displacement at low frequencies, which may have an effect on residual low frequency hearing thresholds

    Low noise charge injection in the CCD22

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    The inclusion of a charge injection structure on a charge coupled device (CCD) allows for the mitigation of charge transfer loss which can be caused by radiation induced charge trapping defects. Any traps present in the pixels of the CCD are filled by the injected charge as it is swept through the device and consequently, the charge transfer efficiency is improved in subsequently acquired images. To date, a number of different types of CCD have been manufactured featuring a variety of charge injection techniques. The e2v Technologies CCD22, used in the EPIC MOS focal plane instruments of XMM-Newton, is one such device and is the subject of this paper. A detailed understanding of charge injection operation and the use of charge injection to mitigate charge transfer losses resulting from radiation damage to CCDs will benefit a number of space projects planned for the future, including the ESA GAIA and X-ray Evolving Universe Spectrometry (XEUS) missions.The charge injection structure and mode of operation of the CCD22 are presented, followed by a detailed analysis of the uniformity and repeatability of the charge injection amplitude across the columns of the device. The effects of proton irradiation on the charge injection characteristics are also presented, in particular the effect of radiation induced bright pixels on the injected charge level

    Open Piping: Towards an Open Visual Workflow Environment

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    The most popular visual programming tools focus on procedural, object-oriented and event-based programming. This paper describes a boxes-and-wires functional programming tool, aimed to be accessible to novice programmers, while also supporting open access to the specified processes, executable programs and results for study and deployment

    The role of parietal cortex in overimitation: a study with fNIRS

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    Previous studies have shown right parietal activation in response to observing irrational actions. Behavioural studies show that people sometimes imitate irrational actions, a phenomenon called overimitation. However, limitations on movement in fMRI mean that the neural basis of overimitation has not been studied. To address this, our study employed a less restrictive neuroimaging technique, functional near infrared spectroscopy (fNIRS). Measurements were taken while participants observed either rational or irrational movements before performing movements on a computerised puzzle task. Observing irrational actions produced greater activation in right anterior inferior parietal lobule (aIPL), replicating results from the fMRI literature. This is a proof of principle that fNIRS can be used as an alternative to fMRI in social cognition experiments, and that parietal cortex has a core role in responding to irrational actions

    Mathematical Modelling of Optical Coherence Tomography

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    In this chapter a general mathematical model of Optical Coherence Tomography (OCT) is presented on the basis of the electromagnetic theory. OCT produces high resolution images of the inner structure of biological tissues. Images are obtained by measuring the time delay and the intensity of the backscattered light from the sample considering also the coherence properties of light. The scattering problem is considered for a weakly scattering medium located far enough from the detector. The inverse problem is to reconstruct the susceptibility of the medium given the measurements for different positions of the mirror. Different approaches are addressed depending on the different assumptions made about the optical properties of the sample. This procedure is applied to a full field OCT system and an extension to standard (time and frequency domain) OCT is briefly presented.Comment: 28 pages, 5 figures, book chapte
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