492 research outputs found
Health informatics education for clinicians and managers - What's holding up progress?
This paper reports outcomes of a national survey of health informatics (HI) education and training carried out in the UK. A questionnaire to elicit details of HI and IT skills teaching was derived from a national consensus document (Learning to Manage Health Information, LtMHI). Forms were sent to all pre-qualification medical and nursing schools and to a stratified sample of postgraduate and post-registration programmes. Three case studies were carried out in acute hospital trusts to gain insight into opportunities for continuing professional development in health informatics and IT. Our evidence suggests that in the UK, health informatics is not yet integrated into the clinical curriculum. Nearly all the pre-qualification courses made some provision for teaching IT skills. Nonetheless, many respondents felt that students did not receive sufficient training. There was considerable variation in the amount of HI teaching provided in the different educational sectors. The case studies suggested very little HI training was provided for clinical staff and take-up of provision was not monitored. A number of factors are holding up progress, the most important being a lack of staff with the knowledge and skills to provide academic leadership. The paper outlines some steps that need to be taken to ensure health informatics is embedded in all clinical curricula. © 2003 Elsevier Ireland Ltd. All rights reserved
Back-translation for discovering distant protein homologies
Frameshift mutations in protein-coding DNA sequences produce a drastic change
in the resulting protein sequence, which prevents classic protein alignment
methods from revealing the proteins' common origin. Moreover, when a large
number of substitutions are additionally involved in the divergence, the
homology detection becomes difficult even at the DNA level. To cope with this
situation, we propose a novel method to infer distant homology relations of two
proteins, that accounts for frameshift and point mutations that may have
affected the coding sequences. We design a dynamic programming alignment
algorithm over memory-efficient graph representations of the complete set of
putative DNA sequences of each protein, with the goal of determining the two
putative DNA sequences which have the best scoring alignment under a powerful
scoring system designed to reflect the most probable evolutionary process. This
allows us to uncover evolutionary information that is not captured by
traditional alignment methods, which is confirmed by biologically significant
examples.Comment: The 9th International Workshop in Algorithms in Bioinformatics
(WABI), Philadelphia : \'Etats-Unis d'Am\'erique (2009
Applying a User-centred Approach to Interactive Visualization Design
Analysing users in their context of work and finding out how and why they use different information resources is essential to provide interactive visualisation systems that match their goals and needs. Designers should actively involve the intended users throughout the whole process. This chapter presents a user-centered approach for the design of interactive visualisation systems. We describe three phases of the iterative visualisation design process: the early envisioning phase, the global specification hase, and the detailed specification phase. The whole design cycle is repeated until some criterion of success is reached. We discuss different techniques for the analysis of users, their tasks and domain. Subsequently, the design of prototypes and evaluation methods in visualisation practice are presented. Finally, we discuss the practical challenges in design and evaluation of collaborative visualisation environments. Our own case studies and those of others are used throughout the whole chapter to illustrate various approaches
A phase II trial of bryostatin-1 administered by weekly 24-hour infusion in recurrent epithelial ovarian carcinoma
Bryostatin-1 is a macrocyclic lactone whose main mechanism of action is protein kinase C modulation. We investigated its activity as a weekly 24-h infusion in recurrent ovarian carcinoma. In all, 17 patients were recruited and 11 had chemotherapy-resistant disease as defined by disease progression within 4 months of last cytotoxic therapy. All were evaluable for toxicity and 14 for response. There were no disease responses and the main toxicity was myalgia
A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor
The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the
`Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic
neurotransmission, and whose other members include receptors for glycine,
gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a
three dimensional structure of the nAChR in its closed state. However, the
exact nature and location of the channel gate remains uncertain. Although the
transmembrane pore is constricted close to its center, it is not completely
occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A.
Model calculations suggest that such a constriction may form a hydrophobic
gate, preventing movement of ions through a channel. We present a detailed and
quantitative simulation study of the hydrophobic gating model of the nicotinic
receptor, in order to fully evaluate this hypothesis. We demonstrate that the
hydrophobic constriction of the nAChR pore indeed forms a closed gate.
Potential of mean force (PMF) calculations reveal that the constriction
presents a barrier of height ca. 10 kT to the permeation of sodium ions,
placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A
radius hydrophobic pore can form a functional barrier to the permeation of a 1
A radius Na+ ion. Using a united atom force field for the protein instead of an
all atom one retains the qualitative features but results in differing
conductances, showing that the PMF is sensitive to the detailed molecular
interactions.Comment: Accepted by Physical Biology; includes a supplement and a
supplementary mpeg movie can be found at
http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp
SISYPHUS—structural alignments for proteins with non-trivial relationships
With the increasing amount of structural data, the number of homologous protein structures bearing topological irregularities is steadily growing. These include proteins with circular permutations, segment-swapping, context-dependent folding or chameleon sequences that can adopt alternative secondary structures. Their non-trivial structural relationships are readily identified during expert analysis but their automatic identification using the existing computational tools still remains difficult or impossible. Such non-trivial cases of protein relationships are known to pose a problem to multiple alignment algorithms and to impede comparative modeling studies. They support a new emerging concept of evolutionary changeable protein fold, which creates practical difficulties for the hierarchical classifications of protein structures.To facilitate the understanding of, and to provide a comprehensive annotation of proteins with such non-trivial structural relationships we have created SISYPHUS ([Σισυϕος]—in Greek crafty), a compendium to the SCOP database. The SISYPHUS database contains a collection of manually curated structural alignments and their inter-relationships. The multiple alignments are constructed for protein structural regions that range from oligomeric biological units, or individual domains to fragments of different size. The SISYPHUS multiple alignments are displayed with SPICE, a browser that provides an integrated view of protein sequences, structures and their annotations. The database is available from
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