21 resultados para Critical path analysis.


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Glycogen synthase kinase 3 (GSK3, of which there are two isoforms, GSK3alpha and GSK3beta) was originally characterized in the context of regulation of glycogen metabolism, though it is now known to regulate many other cellular processes. Phosphorylation of GSK3alpha(Ser21) and GSK3beta(Ser9) inhibits their activity. In the heart, emphasis has been placed particularly on GSK3beta, rather than GSK3alpha. Importantly, catalytically-active GSK3 generally restrains gene expression and, in the heart, catalytically-active GSK3 has been implicated in anti-hypertrophic signalling. Inhibition of GSK3 results in changes in the activities of transcription and translation factors in the heart and promotes hypertrophic responses, and it is generally assumed that signal transduction from hypertrophic stimuli to GSK3 passes primarily through protein kinase B/Akt (PKB/Akt). However, recent data suggest that the situation is far more complex. We review evidence pertaining to the role of GSK3 in the myocardium and discuss effects of genetic manipulation of GSK3 activity in vivo. We also discuss the signalling pathways potentially regulating GSK3 activity and propose that, depending on the stimulus, phosphorylation of GSK3 is independent of PKB/Akt. Potential GSK3 substrates studied in relation to myocardial hypertrophy include nuclear factors of activated T cells, beta-catenin, GATA4, myocardin, CREB, and eukaryotic initiation factor 2Bvarepsilon. These and other transcription factor substrates putatively important in the heart are considered. We discuss whether cardiac pathologies could be treated by therapeutic intervention at the GSK3 level but conclude that any intervention would be premature without greater understanding of the precise role of GSK3 in cardiac processes.

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Iatrogenic errors and patient safety in clinical processes are an increasing concern. The quality of process information in hardcopy or electronic form can heavily influence clinical behaviour and decision making errors. Little work has been undertaken to assess the safety impact of clinical process planning documents guiding the clinical actions and decisions. This paper investigates the clinical process documents used in elective surgery and their impact on latent and active clinical errors. Eight clinicians from a large health trust underwent extensive semi- structured interviews to understand their use of clinical documents, and their perceived impact on errors and patient safety. Samples of the key types of document used were analysed. Theories of latent organisational and active errors from the literature were combined with the EDA semiotics model of behaviour and decision making to propose the EDA Error Model. This model enabled us to identify perceptual, evaluation, knowledge and action error types and approaches to reducing their causes. The EDA error model was then used to analyse sample documents and identify error sources and controls. Types of knowledge artefact structures used in the documents were identified and assessed in terms of safety impact. This approach was combined with analysis of the questionnaire findings using existing error knowledge from the literature. The results identified a number of document and knowledge artefact issues that give rise to latent and active errors and also issues concerning medical culture and teamwork together with recommendations for further work.

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Existing capability models lack qualitative and quantitative means to compare business capabilities. This paper extends previous work and uses affordance theories to consistently model and analyse capabilities. We use the concept of objective and subjective affordances to model capability as a tuple of a set of resource affordance system mechanisms and action paths, dependent on one or more critical affordance factors. We identify an affordance chain of subjective affordances by which affordances work together to enable an action and an affordance path that links action affordances to create a capability system. We define the mechanism and path underlying capability. We show how affordance modelling notation, AMN, can represent affordances comprising a capability. We propose a method to quantitatively and qualitatively compare capabilities using efficiency, effectiveness and quality metrics. The method is demonstrated by a medical example comparing the capability of syringe and needless anaesthetic systems.

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Using a combination of idealized radiative transfer simulations and a case study from the first field campaign of the Saharan Mineral Dust Experiment (SAMUM) in southern Morocco, this paper provides a systematic assessment of the limitations of the widely used Spinning Enhanced Visible and Infrared Imager (SEVIRI) red-green-blue (RGB) thermal infrared dust product. Both analyses indicate that the ability of the product to identify dust, via its characteristic pink coloring, is strongly dependent on the column water vapor, the lower tropospheric lapse rate, and dust altitude. In particular, when column water vapor exceeds ∼20–25 mm, dust presence, even for visible optical depths of the order 0.8, is effectively masked. Variability in dust optical properties also has a marked impact on the imagery, primarily as a result of variability in dust composition. There is a moderate sensitivity to the satellite viewing geometry, particularly in moist conditions. The underlying surface can act to confound the signal seen through variations in spectral emissivity, which are predominantly manifested in the 8.7μm SEVIRI channel. In addition, if a temperature inversion is present, typical of early morning conditions over the Sahara and Sahel, an increased dust loading can actually reduce the pink coloring of the RGB image compared to pristine conditions. Attempts to match specific SEVIRI observations to simulations using SAMUM measurements are challenging because of high uncertainties in surface skin temperature and emissivity. Recommendations concerning the use and interpretation of the SEVIRI RGB imagery are provided on the basis of these findings.

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Dominant paradigms of causal explanation for why and how Western liberal-democracies go to war in the post-Cold War era remain versions of the 'liberal peace' or 'democratic peace' thesis. Yet such explanations have been shown to rest upon deeply problematic epistemological and methodological assumptions. Of equal importance, however, is the failure of these dominant paradigms to account for the 'neoliberal revolution' that has gripped Western liberal-democracies since the 1970s. The transition from liberalism to neoliberalism remains neglected in analyses of the contemporary Western security constellation. Arguing that neoliberalism can be understood simultaneously through the Marxian concept of ideology and the Foucauldian concept of governmentality – that is, as a complementary set of 'ways of seeing' and 'ways of being' – the thesis goes on to analyse British security in policy and practice, considering it as an instantiation of a wider neoliberal way of war. In so doing, the thesis draws upon, but also challenges and develops, established critical discourse analytic methods, incorporating within its purview not only the textual data that is usually considered by discourse analysts, but also material practices of security. This analysis finds that contemporary British security policy is predicated on a neoliberal social ontology, morphology and morality – an ideology or 'way of seeing' – focused on the notion of a globalised 'network-market', and is aimed at rendering circulations through this network-market amenable to neoliberal techniques of government. It is further argued that security practices shaped by this ideology imperfectly and unevenly achieve the realisation of neoliberal 'ways of being' – especially modes of governing self and other or the 'conduct of conduct' – and the re-articulation of subjectivities in line with neoliberal principles of individualism, risk, responsibility and flexibility. The policy and practice of contemporary British 'security' is thus recontextualised as a component of a broader 'neoliberal way of war'.

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Given capacity limits, only a subset of stimuli 1 give rise to a conscious percept. Neurocognitive models suggest that humans have evolved mechanisms that operate without awareness and prioritize threatening stimuli over neutral stimuli in subsequent perception. In this meta analysis, we review evidence for this ‘standard hypothesis’ emanating from three widely used, but rather different experimental paradigms that have been used to manipulate awareness. We found a small pooled threat-bias effect in the masked visual probe paradigm, a medium effect in the binocular rivalry paradigm and highly inconsistent effects in the breaking continuous flash suppression paradigm. Substantial heterogeneity was explained by the stimulus type: the only threat stimuli that were robustly prioritized across all three paradigms were fearful faces. Meta regression revealed that anxiety may modulate threat biases, but only under specific presentation conditions. We also found that insufficiently rigorous awareness measures, inadequate control of response biases and low level confounds may undermine claims of genuine unconscious threat processing. Considering the data together, we suggest that uncritical acceptance of the standard hypothesis is premature: current behavioral evidence for threat-sensitive visual processing that operates without awareness is weak.