357 research outputs found

    The role of the user within the medical device design and development process: medical device manufacturers' perspectives

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    Copyright @ 2011 Money et al.Background: Academic literature and international standards bodies suggest that user involvement, via the incorporation of human factors engineering methods within the medical device design and development (MDDD) process, offer many benefits that enable the development of safer and more usable medical devices that are better suited to users' needs. However, little research has been carried out to explore medical device manufacturers' beliefs and attitudes towards user involvement within this process, or indeed what value they believe can be added by doing so.Methods: In-depth interviews with representatives from 11 medical device manufacturers are carried out. We ask them to specify who they believe the intended users of the device to be, who they consult to inform the MDDD process, what role they believe the user plays within this process, and what value (if any) they believe users add. Thematic analysis is used to analyse the fully transcribed interview data, to gain insight into medical device manufacturers' beliefs and attitudes towards user involvement within the MDDD process.Results: A number of high-level themes emerged, relating who the user is perceived to be, the methods used, the perceived value and barriers to user involvement, and the nature of user contributions. The findings reveal that despite standards agencies and academic literature offering strong support for the employment formal methods, manufacturers are still hesitant due to a range of factors including: perceived barriers to obtaining ethical approval; the speed at which such activity may be carried out; the belief that there is no need given the 'all-knowing' nature of senior health care staff and clinical champions; a belief that effective results are achievable by consulting a minimal number of champions. Furthermore, less senior health care practitioners and patients were rarely seen as being able to provide valuable input into the process.Conclusions: Medical device manufacturers often do not see the benefit of employing formal human factors engineering methods within the MDDD process. Research is required to better understand the day-to-day requirements of manufacturers within this sector. The development of new or adapted methods may be required if user involvement is to be fully realised.This study was in part funded by grant number Ref: GR/S29874/01 from the Engineering and Physical Sciences Research Council. This article is made available through the Brunel University Open Access Publishing Fund

    The Dental Neglect Scale in adolescents

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    <p>Abstract</p> <p>Background</p> <p>Dental neglect has been found to be related to poor oral health, a tendency not to have had routine check-ups, and a longer period of time since the last dental appointment in samples of children and adults. The Dental Neglect Scale (DNS) has been found to be a valid measure of dental neglect in samples of children and adults, and may be valid for adolescents as well. We administered the DNS to a sample of adolescents and report on the relationships between the DNS and oral health status, whether or not the adolescent has been to the dentist recently for routine check-ups, and whether or not the adolescent currently goes to a dentist. We also report the internal and test-retest reliabilities of the DNS in this sample, as well as the results of an exploratory factor analysis.</p> <p>Methods</p> <p>One hundred seventeen adolescents from seven youth groups in the Seattle-Tacoma metropolitan area (Washington State, U.S.) completed the DNS and indicated whether they currently go to a dentist, while parents indicated whether the adolescent had a check-up in the previous three years. Adolescents also received a dental screening. Sixty six adolescents completed the questionnaire twice. T-tests were used to compare DNS scores of adolescents who have visible caries or not, adolescents who have had a check-up in the past three years or not, and adolescents who currently go to a dentist or not. Internal reliability was measured by Cronbach's alpha, and test-rest reliability was measured by intra-class correlation. Factor analysis (Varimax rotation) was used to examine the factor structure.</p> <p>Results</p> <p>In each comparison, significantly higher DNS scores were observed in adolescents with visible caries, who have not had a check-up in the past three years, or who do not go to a dentist (all p values < 0.05). The test-retest reliability of the DNS was high (ICC = 0.81), and its internal reliability was acceptable (Cronbach's alpha = 0.60). Factor analysis yielded two factors, characterized by home care and visiting a dentist.</p> <p>Conclusion</p> <p>The DNS appears to operate similarly in this sample of adolescents as it has in other samples of children and adults.</p

    Inferring predominant pathways in cellular models of breast cancer using limited sample proteomic profiling

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    <p>Abstract</p> <p>Background</p> <p>Molecularly targeted drugs inhibit aberrant signaling within oncogenic pathways. Identifying the predominant pathways at work within a tumor is a key step towards tailoring therapies to the patient. Clinical samples pose significant challenges for proteomic profiling, an attractive approach for identifying predominant pathways. The objective of this study was to determine if information obtained from a limited sample (i.e., a single gel replicate) can provide insight into the predominant pathways in two well-characterized breast cancer models.</p> <p>Methods</p> <p>A comparative proteomic analysis of total cell lysates was obtained from two cellular models of breast cancer, BT474 (HER2+/ER+) and SKBR3 (HER2+/ER-), using two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Protein interaction networks and canonical pathways were extracted from the Ingenuity Pathway Knowledgebase (IPK) based on association with the observed pattern of differentially expressed proteins.</p> <p>Results</p> <p>Of the 304 spots that were picked, 167 protein spots were identified. A threshold of 1.5-fold was used to select 62 proteins used in the analysis. IPK analysis suggested that metabolic pathways were highly associated with protein expression in SKBR3 cells while cell motility pathways were highly associated with BT474 cells. Inferred protein networks were confirmed by observing an up-regulation of IGF-1R and profilin in BT474 and up-regulation of Ras and enolase in SKBR3 using western blot.</p> <p>Conclusion</p> <p>When interpreted in the context of prior information, our results suggest that the overall patterns of differential protein expression obtained from limited samples can still aid in clinical decision making by providing an estimate of the predominant pathways that underpin cellular phenotype.</p

    TRY plant trait database - enhanced coverage and open access

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    Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

    Detailed Regulatory Mechanism of the Interaction between ZO-1 PDZ2 and Connexin43 Revealed by MD Simulations

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    The gap junction protein connexin43 (Cx43) binds to the second PDZ domain of Zonula occludens-1 (ZO-1) through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9) and Ser (-10) of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD) simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9) significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation

    Visualization and Curve-Parameter Estimation Strategies for Efficient Exploration of Phenotype Microarray Kinetics

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    The Phenotype MicroArray (OmniLog® PM) system is able to simultaneously capture a large number of phenotypes by recording an organism's respiration over time on distinct substrates. This technique targets the object of natural selection itself, the phenotype, whereas previously addressed '-omics' techniques merely study components that finally contribute to it. The recording of respiration over time, however, adds a longitudinal dimension to the data. To optimally exploit this information, it must be extracted from the shapes of the recorded curves and displayed in analogy to conventional growth curves.The free software environment R was explored for both visualizing and fitting of PM respiration curves. Approaches using either a model fit (and commonly applied growth models) or a smoothing spline were evaluated. Their reliability in inferring curve parameters and confidence intervals was compared to the native OmniLog® PM analysis software. We consider the post-processing of the estimated parameters, the optimal classification of curve shapes and the detection of significant differences between them, as well as practically relevant questions such as detecting the impact of cultivation times and the minimum required number of experimental repeats.We provide a comprehensive framework for data visualization and parameter estimation according to user choices. A flexible graphical representation strategy for displaying the results is proposed, including 95% confidence intervals for the estimated parameters. The spline approach is less prone to irregular curve shapes than fitting any of the considered models or using the native PM software for calculating both point estimates and confidence intervals. These can serve as a starting point for the automated post-processing of PM data, providing much more information than the strict dichotomization into positive and negative reactions. Our results form the basis for a freely available R package for the analysis of PM data

    Comparative mitochondrial proteomics: perspective in human diseases

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    Mitochondria are the most complex and the most important organelles of eukaryotic cells, which are involved in many cellular processes, including energy metabolism, apoptosis, and aging. And mitochondria have been identified as the "hot spot" by researchers for exploring relevant associated dysfunctions in many fields. The emergence of comparative proteomics enables us to have a close look at the mitochondrial proteome in a comprehensive and effective manner under various conditions and cellular circumstances. Two-dimensional electrophoresis combined with mass spectrometry is still the most popular techniques to study comparative mitochondrial proteomics. Furthermore, many new techniques, such as ICAT, MudPIT, and SILAC, equip researchers with more flexibilities inselecting proper methods. This article also reviews the recent development of comparative mitochondrial proteomics on diverse human diseases. And the results of mitochondrial proteomics enhance a better understanding of the pathogenesis associated with mitochondria and provide promising therapeutic targets
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