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Tom Evans

Publications and source records attributed to Tom Evans.

11 recordsLinked to original sources

Opportunities to replace the use of animals in sepsis research. The report and recommendations of a Focus on Alternatives workshop.

Sepsis and multiple organ failure are common causes of death in patients admitted to intensive care units. The incidence of sepsis and associated mortalities has been steadily increasing over the past 20 years. Sepsis is a complex inflammatory condition, the precise causes of which are still poorly understood. Animal models of sepsis have the potential to cause substantial suffering, and many of them have been poorly representative of the human syndrome. However, a number of non-animal approaches, including in vitro, in silico and clinical studies, show promise for addressing this situation. This report is based on discussions held at an expert workshop convened by Focus on Alternatives and held in 2004 at the Wellcome Trust, London. It provides an overview of some non-animal approaches to sepsis research, including their strengths and weaknesses, and argues that they should be prioritised for further development.

Animal Testing Alternatives↗

Observer performance in assessing anemia on thoracic CT.

OBJECTIVE: The purpose of this study was to evaluate the ability of expert reviewers to differentiate an anemic from a nonanemic state on the basis of visual assessment of the relative attenuation of blood in the left ventricle on noncontrast thoracic CT images and to compare reviewer performance with quantitative measurement of CT density in Hounsfield units. MATERIALS AND METHODS: One hundred two noncontrast thoracic CT examinations were qualitatively reviewed by three independent reviewers. Hounsfield unit measurements of the blood in the left ventricle were recorded by a fourth individual. Anemia was defined as a hemoglobin level of less than 10 g/dL. Receiver operating characteristic (ROC) analyses of expert reviewers were compared with measured Hounsfield units. RESULTS: Hounsfield unit measurements performed significantly better than subjective reviewer analyses for differentiation of an anemic from a nonanemic state (area under ROC curve = 0.85 vs 0.72, 0.70, and 0.69; 95% confidence interval, 0.78-0.92 vs 0.63-0.81, 0.61-0.79, and 0.60-0.78, respectively; p < 0.05). With use of a CT density threshold of 35 H, the sensitivity for anemia was 76% and specificity was 81%, whereas the sensitivity of three reviewers was 40-72% with a specificity of 60-83%. Interobserver agreement was found to be poor by kappa statistic (0.0906-0.2128). The correlation coefficient for the analysis of Hounsfield unit versus hemoglobin level was 0.72. Separating data by patient sex revealed a correlation coefficient of 0.81 for men versus 0.52 for women, although the actual regression lines were not statistically different (p > 0.05). CONCLUSION: Despite expert reviewer analyses, subjective evaluations of blood attenuation characteristics are prone to inaccuracy and show poor interobserver agreement. Quantitative measurements of CT density in Hounsfield units should be performed to accurately differentiate an anemic from a nonanemic state when serum hemoglobin levels are not readily available.

Adult↗

Large-scale molecular dynamics simulation of DNA: implementation and validation of the AMBER98 force field in LAMMPS.

Molecular modelling played a central role in the discovery of the structure of DNA by Watson and Crick. Today, such modelling is done on computers: the more powerful these computers are, the more detailed and extensive can be the study of the dynamics of such biological macromolecules. To fully harness the power of modern massively parallel computers, however, we need to develop and deploy algorithms which can exploit the structure of such hardware. The Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) is a scalable molecular dynamics code including long-range Coulomb interactions, which has been specifically designed to function efficiently on parallel platforms. Here we describe the implementation of the AMBER98 force field in LAMMPS and its validation for molecular dynamics investigations of DNA structure and flexibility against the benchmark of results obtained with the long-established code AMBER6 (Assisted Model Building with Energy Refinement, version 6). Extended molecular dynamics simulations on the hydrated DNA dodecamer d(CTTTTGCAAAAG)(2), which has previously been the subject of extensive dynamical analysis using AMBER6, show that it is possible to obtain excellent agreement in terms of static, dynamic and thermodynamic parameters between AMBER6 and LAMMPS. In comparison with AMBER6, LAMMPS shows greatly improved scalability in massively parallel environments, opening up the possibility of efficient simulations of order-of-magnitude larger systems and/or for order-of-magnitude greater simulation times.

Algorithms↗

Evidence of immune reconstitution in antiretroviral drug-experienced patients with advanced HIV disease.

Highly active antiretroviral therapy (HAART) of HIV disease is associated with effective virologic control, immune reconstitution, and clinical improvements. This study addresses the potential for improvements in lymphocyte phenotype and virologic responses of HIV-infected persons with extensive experience with dual nucleoside reverse transcriptase (NRTI) treatment and advanced HIV disease after a change to a potent antiretroviral therapy (NRTI + protease inhibitor). The majority of participants achieved virologic success. There was a median rise in CD4+ lymphocytes of 99 cells/mm(3) by 48 weeks, because of an increase in memory CD4+ cells at 4 and 16 weeks, followed by a later increase in naive CD4+ cells between weeks 16 and 48. The proportion of activated, DR+ CD38+ CD8+ lymphocytes decreased during the 48 weeks of follow-up. The immunologic findings (increased memory and naive T cells and reduced activation levels) were significantly improved in participants with persistent suppression of viral replication over the 48 weeks of the study. Baseline HIV RNA copy number was lower (median, 14,784 copies/ml) in persons who responded virologically than in those not suppressing viral replication (median, 49,454 copies/ml). CD4+ cell counts above the median (125/mm(3)) at time 0 for the participants, was the only baseline immunologic marker significantly associated with viral suppression at week 48. Participants older than 40 years of age demonstrated less immunologic recovery. The results of the study show that patients with extensive experience with NRTIs respond both virologically and immunologically during the first 48 weeks of therapy with a potent antiretroviral regimen.

Adult↗

Defibrillators in public places: the introduction of a national scheme for public access defibrillation in England.

OBJECTIVE: To implement a government-led project-the 'Defibrillators in Public Places' Initiative-to deploy Automated External Defibrillators (AEDs) in public places. BACKGROUND: A Defibrillator Advisory Committee (DAC) was formed to assist the government with the implementation of the project. Its particular tasks were to: recommend criteria for the selection, training and assessment of those individuals likely to use the devices; procure the equipment necessary for the implementation of the project; procure the training services required for the implementation of the project; ensure the AEDs are sited where they are most likely to be of benefit; establish a mechanism to audit the use of this equipment and the outcome of this initiative. To co-ordinate this project a National Project Manager was appointed. Consultation with Ambulance Services NHS Trusts established the places where cardiac arrest occurred under circumstance where the availability of a defibrillator might be most likely to be effective. Defibrillators were procured under the direction of the NHS Purchasing and Supply Agency in conjunction with medical advisors. Devices that were reliable, safe, simple in operation and with good data retrieval systemes were selected. Training contracts were awarded under the direction of the NHS Purchasing and Supply Agency in conjunction with medical and educational advisors. Organisations with accredited training experience and possessing the appropriate administrative and data handling abilities were selected. The ability to undertake training in an area concordant with current NHS regions was an essential requirement. In the first stage of implementation, pilot trials were successfully established at sites where persons were willing to be trained in the use of automated defibrillators. Arrangements for national progress of the project were made on the basis of the experience gained at pilot sites. A robust system for monitoring the outcome of the project has been established in partnership with the Resuscitation Council UK. The long-term success of this innovative project requires: Continuing central administrative support in the short to medium term. Central audit and data collection. The results of this project should contribute to national databases being established by the Resuscitation Council UK. Continuing adequate funding. The recognition that the provision of defibrillation to the victims of cardiac arrest is a key feature of the NHS.

Cardiopulmonary Resuscitation↗

The POWER campaign for promotion of female and male condoms: audience research and campaign development.

In this study, we conducted and content analyzed 12 focus groups with women aged 15-25 living in inner city Denver as a process of audience research to develop a male and female condom promotion campaign. We recruited 89 women from school and community sites in central Denver neighborhoods to discuss their knowledge, attitudes, and practices regarding both male and female condoms, then solicited opinions about how to increase knowledge about and familiarity with female condoms, increase positive attitudes toward both male and female condoms, and how to increase access to and use of both male and female condoms. Opinions on these topics drove the development of a targeted media campaign promoting condom use in this population. We report here on the general findings from focus groups and provide details about the campaign the participants helped to develop.

Adolescent↗

Our challenging times.

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Cooperative Behavior↗