997 research outputs found

    Health informatics in UK Medical Education: an online survey of current practice

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    OBJECTIVE: Health informatics has growing importance in clinical practice with successive General Medical Council recommendations. However, prior data suggest that undergraduate medical education largely neglects this area. An up-to-date, UK-wide view of health informatics training in medical schools is required. DESIGN: An online survey was developed using current guidance and recommendations of UK professional bodies. PARTICIPANTS AND SETTING: Senior academic staff and health informatics educators at all 34 UK medical schools were invited to complete the survey. MAIN OUTCOME AND MEASURES: Quantitative and qualitative data regarding health informatics in the undergraduate medical curriculum. RESULTS: A total of 26/34 (76%) of UK medical schools responded and 23 provided full information. Aspects most frequently mentioned were literature searching and research governance. Seventeen per cent of respondents felt there was little or no HI training, although clinical record keeping was addressed by all medical schools. Pedagogies used to teach health informatics were self-directed learning (78%) to lecture based (70%), seminars (70%), informal teaching in clinical settings (57%) and problem-based learning (22%). Health informatics was usually integrated vertically and horizontally across the curriculum (76%). Assessment and updates of the health informatics curriculum are limited (57 and 41%, respectively). Thirty-two per cent of respondents reported a low level of confidence among students to use health informatics as doctors. In the most up-to-date survey of health informatics teaching in UK medical schools, there are three major findings. First, the proportion of health informatics in the medical undergraduate curriculum is low. Second, there was variation in content, pedagogy and timing across medical schools. Third, health informatics is rarely assessed and course content is not regularly updated. CONCLUSIONS: There is a role for national guidelines and further research in this area of the curriculum which is rapidly gaining in prominence

    Accessing network databases via SQL transactions in a multi-model database system

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    http://archive.org/details/accessingnetwork00walpN

    The ecomics of ecosystems and biodiversity: scoping the scale

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    The G8 decided in March 2007 to initiate a “Review on the economics of biodiversity loss”, in the so called Potsdam Initiative: 'In a global study we will initiate the process of analysing the global economic benefit of biological diversity, the costs of the loss of biodiversity and the failure to take protective measures versus the costs of effective conservation. The study is being supported by the European Commission (together with the European Environmental Agency and in cooperation with the German Government. “The objective of the current study is to provide a coherent overview of existing scientific knowledge upon which to base the economics of the Review, and to propose a coherent global programme of scientific work, both for Phase 2 (consolidation) and to enable more robust future iterations of the Review beyond 2010.

    Mapping a novel positive allosteric modulator binding site in the central vestibule region of human P2X7

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    P2X7 receptors are important in the regulation of inflammatory responses and immune responses to intracellular pathogens such as Mycobacterium tuberculosis and Toxoplasma gondii. Enhancement of P2X7 receptor responses may be useful in pathogen clearance particularly in individuals with defective microbial killing mechanisms. Ginsenosides from Panax ginseng have been discovered to act as positive allosteric modulators of P2X7. Here we describe a novel modulator binding site identified by computational docking located in the central vestibule of P2X7 involving S60, D318, and L320 in the lower body ÎČ-sheets lining the lateral portals. Potentiation of ATP-mediated responses by ginsenosides CK and Rd caused enhanced ionic currents, Ca2+ influx and YOPRO-1 uptake in stably transfected HEK-293 cells (HEK-hP2X7) plus enhanced cell death responses. Potentiation of ATP responses by CK and Rd was markedly reduced by mutations S59A, S60A, D318L and L320A supporting the proposed allosteric modulator binding site. Furthermore, mutation of the conserved residues S60 and D318 led to alterations in P2X7 response and a higher sensitivity to ATP in the absence of modulators suggesting residues in the connecting rods play an important role in regulating P2X7 gating. Identification of this novel binding site location in the central vestibule may also be relevant for structurally similar channels

    Unbound states of 32Cl and the 31S(p,\gamma)32Cl reaction rate

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    The 31S(p,\gamma)32Cl reaction is expected to provide the dominant break-out path from the SiP cycle in novae and is important for understanding enrichments of sulfur observed in some nova ejecta. We studied the 32S(3He,t)32Cl charge-exchange reaction to determine properties of proton-unbound levels in 32Cl that have previously contributed significant uncertainties to the 31S(p,\gamma)32Cl reaction rate. Measured triton magnetic rigidities were used to determine excitation energies in 32Cl. Proton-branching ratios were obtained by detecting decay protons from unbound 32Cl states in coincidence with tritons. An improved 31S(p,\gamma)32Cl reaction rate was calculated including robust statistical and systematic uncertainties

    Unravelling the Specificity of Laminaribiose Phosphorylase from Paenibacillus sp. YM‐1 towards Donor Substrates Glucose/Mannose 1‐Phosphate by Using X‐ray Crystallography and Saturation Transfer Difference NMR Spectroscopy

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    Glycoside phosphorylases (GPs) carry out a reversible phosphorolysis of carbohydrates into oligosaccharide acceptors and the corresponding sugar 1‐phosphates. The reversibility of the reaction enables the use of GPs as biocatalysts for carbohydrate synthesis. Glycosyl hydrolase family 94 (GH94), which only comprises GPs, is one of the most studied GP families that have been used as biocatalysts for carbohydrate synthesis, in academic research and in industrial production. Understanding the mechanism of GH94 enzymes is a crucial step towards enzyme engineering to improve and expand the applications of these enzymes in synthesis. In this work with a GH94 laminaribiose phosphorylase from Paenibacillus sp. YM‐1 (PsLBP), we have demonstrated an enzymatic synthesis of disaccharide 1 (ÎČ‐d‐mannopyranosyl‐(1→3)‐d‐glucopyranose) by using a natural acceptor glucose and noncognate donor substrate α‐mannose 1‐phosphate (Man1P). To investigate how the enzyme recognises different sugar 1‐phosphates, the X‐ray crystal structures of PsLBP in complex with Glc1P and Man1P have been solved, providing the first molecular detail of the recognition of a noncognate donor substrate by GPs, which revealed the importance of hydrogen bonding between the active site residues and hydroxy groups at C2, C4, and C6 of sugar 1‐phosphates. Furthermore, we used saturation transfer difference NMR spectroscopy to support crystallographic studies on the sugar 1‐phosphates, as well as to provide further insights into the PsLBP recognition of the acceptors and disaccharide products

    The intrinsically disordered Tarp protein from chlamydia binds actin with a partially preformed helix

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    Tarp (translocated actin recruiting phosphoprotein) is an effector protein common to all chlamydial species that functions to remodel the host-actin cytoskeleton during the initial stage of infection. In C. trachomatis, direct binding to actin monomers has been broadly mapped to a 100-residue region (726-825) which is predicted to be predominantly disordered, with the exception of a ~10-residue α helical patch homologous to other WH2 actin-binding motifs. Biophysical investigations demonstrate that a Tarp726-825 construct behaves as a typical intrinsically disordered protein; within it, NMR relaxation measurements and chemical shift analysis identify the ten residue WH2-homologous region to exhibit partial α-helix formation. Isothermal titration calorimetry experiments on the same construct in the presence of monomeric G-actin show a well defined binding event with a 1:1 stoichiometry and Kd of 102 nM, whilst synchrotron radiation circular dichroism spectroscopy suggests the binding is concomitant with an increase in helical secondary structure. Furthermore, NMR experiments in the presence of G-actin indicate this interaction affects the proposed WH2-like α-helical region, supporting results from in silico docking calculations which suggest that, when folded, this α helix binds within the actin hydrophobic cleft as seen for other actin-associated proteins

    Channelized melt flow in downwelling mantle: Implications for 226Ra-210Pb disequilibria in arc magmas

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    We present the results of an analytical model of porous flow of viscous melt into a steadily dilating ‘‘channel’’ (defined as a cluster of smaller veins) in downwelling subarc mantle. The model predicts the pressure drop in the mantle wedge matrix surrounding the channel needed to drive melt flow as a function of position and time. Melt is sucked toward the dilatant region at a near-constant velocity (105 s1) until veins comprising the channel stop opening (t = t). Fluid elements that complete their journey within the time span t < t arrive at a channel. Our results make it possible to calculate the region of influence sampled by melt that surrounds the channel. This region is large compared to the model size of the channelized region driving flow. For a baseline dilation time of 1 year and channel half width of 2 m, melt can be sampled over an 80-m radius and has the opportunity to sample matrix material with potentially contrasting chemistry on geologically short timescales. Our mechanical results are consistent with a downgoing arc mantle wedge source region where melting and melt extraction by porous flow to a channel network are sufficiently rapid to preserve source-derived 238U-230Th-226Ra, and potentially also 226 Ra-210Pb, disequilibria, prior to magma ascent to the surface. Since this is the rate-determining step in the overall process, it allows the possibility that such short-lived disequilibria measured in arc rocks at the surface are derived from deep in the mantle wedge. Stresses due to partial melting do not appear capable of producing the desired sucking effect, while the order of magnitude rate of shear required to drive dilation of 107 s1 is much larger than values resulting from steady state subduction. We conclude that local deformation rates in excess of background plate tectonic rates are needed to ‘‘switch on’’ the dilatant channel network and to initiate the sucking effect
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