65 resultados para SNC-AP


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Speeding is a major contributor to road injuries and fatalities and remains prevalent. Changing community perceptions about speeding is an important priority. Austroads commissioned research to identify a range of potential interventions for future trial and evaluation aimed at creating, increasing, and/or sustaining public demand for safer speeds. This project had three phases: a literature review; consultations with key stakeholders regarding intervention options (including feasibility, and likely benefits and costs of identified interventions); and providing research results, including recommendations for future phases of the program of work. The literature review led to the development of a draft Campaign Strategy targeting nine aims across three themes underpinning this research: 1) creating, 2) increasing, and 3) sustaining public demand for safer speeds on the road. Twenty-one stakeholders commented on the suitability and feasibility of, and likely barriers to, countermeasures within the draft Campaign Strategy and its applicability to the Australian and New Zealand context. There was overwhelming positive support for the proposed Campaign Strategy by the majority of respondents; many, noting that it addressed key misperceptions and complemented many existing approaches. A small number of respondents expressed some concerns with various aspects. Stakeholder feedback was incorporated into the final proposed Campaign Strategy to enhance its potential effectiveness. Wide diversity across jurisdictions makes the recommendation of individual interventions for specific areas problematic. Individual jurisdictions should consider a range of costs and benefits of the proposed Campaign Strategy to determine the likely feasibility from their unique perspective. Issues to be addressed when considering implementation of the proposed Campaign Strategy include speed limit setting policies, resourcing, messaging and advertising strategies, and political will associated with promoting safer speeds.

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The leucine zipper region of activator protein-1 (AP-1) comprises the c-Jun and c-Fos proteins and constitutes a well-known coiled coil protein−protein interaction motif. We have used molecular dynamics (MD) simulations in conjunction with the molecular mechanics/Poisson−Boltzmann generalized-Born surface area [MM/PB(GB)SA] methods to predict the free energy of interaction of these proteins. In particular, the influence of the choice of solvation model, protein force field, and water potential on the stability and dynamic properties of the c-Fos−c-Jun complex were investigated. Use of the AMBER polarizable force field ff02 in combination with the polarizable POL3 water potential was found to result in increased stability of the c-Fos−c-Jun complex. MM/PB(GB)SA calculations revealed that MD simulations using the POL3 water potential give the lowest predicted free energies of interaction compared to other nonpolarizable water potentials. In addition, the calculated absolute free energy of binding was predicted to be closest to the experimental value using the MM/GBSA method with independent MD simulation trajectories using the POL3 water potential and the polarizable ff02 force field, while all other binding affinities were overestimated.

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While the two decades since the study by Kavanagh et al. (1993) has given additional insights into effective dissemination of family interventions, the accompanying papers show that progress remains limited. The effectiveness trial that triggered this series of papers offers a cautionary tale. Despite management support, 30–35 hr of workshop training and training of local supervisors who could act as champions, use of the full intervention was limited. In part, this seemed due to the demanding nature of the intervention and its incompatibility with practitioners’ roles, in part, to limitations in the training, among other factors. While the accompanying papers note these and other barriers to dissemination, they miss a more disturbing finding in the original paper: Practitioners said they were using several aspects in routine care, despite being unable to accurately describe what they were. This finding highlights the risks in taking practitioners’ reports of their practice in files or supervision sessions at face value and potentially has implications for reports of other clinical work. The fidelity of disseminated treatments can only be assured by audits of practice, accompanied by affirming but also corrective feedback.

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