Biomedical subjects

David B Evans

Publications and source records attributed to David B Evans.

23 records · Page 2Linked to original sources

PubMed2002

Direct interaction of soluble human recombinant tau protein with Abeta 1-42 results in tau aggregation and hyperphosphorylation by tau protein kinase II.

We report here that aggregated beta-amyloid (Abeta) 1-42 promotes tau aggregation in vitro in a dose-dependent manner. When Abeta-mediated aggregated tau was used as a substrate for tau protein kinase II (TPK II), an 8-fold increase in the rate of TPK II-mediated tau phosphorylation was observed. The extent of TPK II-dependent tau phosphorylation increased as a function of time and Abeta 1-42 concentration, and hyperphosphorylated tau was found to be decorated with an Alzheimer's disease-related phosphoepitope (P-Thr-231). In HEK 293 cells co-expressing CT-100 amyloid precursor protein and tau, the release of Abeta 1-42 from these cells was impaired. Taken together, these in vitro results suggest that Abeta 1-42 promotes both tau aggregation and hyperphosphorylation.

Alzheimer Disease↗

PubMed2002

A scintillation proximity assay for studying inhibitors of human tau protein kinase II/cdk5 using a 96-well format.

Dysregulation of the brain-specific tau protein kinase II (TPK II)/cdk5 is reported to play an important role in the pathogenesis of Alzheimer's disease. We report here a quantitative scintillation proximity assay (SPA), which is suitable for determining TPK II/cdk5 activity and its inhibition. It depends upon the phosphorylation of a synthetic histone-based peptide substrate (PKTPKKAKKL), which has been biotinylated at its C-terminus. When this biotinylated peptide is incubated with [gamma-33P] ATP and TPK II/cdk5 under defined assay conditions, product formation is linear with respect to time and enzyme concentration. The production of [33P] phosphorylated peptide is inhibited in the presence of a known TPK II/cdk5 inhibitor but is unaffected in the presence of 1% DMSO. A signal-to-noise ratio of 16:1 was obtained in a 60-min assay with an intra-assay variability of <10% in the 96-well microtiter format. The TPK II/cdk5 SPA is very robust, sensitive and simple to perform.

Alzheimer Disease↗

PubMed2002

Uncertainty in cost-effectiveness analysis. Probabilistic uncertainty analysis and stochastic league tables.

Interest is growing in the application of standard statistical inferential techniques to the calculation of cost-effectiveness ratios (CER), but individual level data will not be available in many cases because it is very difficult to undertake prospective controlled trials of many public health interventions. We propose the application of probabilistic uncertainty analysis using Monte Carlo simulations, in combination with nonparametric bootstrapping techniques where appropriate. This paper also discusses how decision makers should interpret the CER of interventions where uncertainty intervals overlap. We show how the incorporation of uncertainty around costs and effects of interventions into a stochastic league table provides additional information to decision makers for priority setting. Stochastic league tables inform decision makers about the probability that a specific intervention would be included in the optimal mix of interventions for different resource levels, given the uncertainty surrounding the interventions.

Cost-Benefit Analysis↗

PubMed2002

Generalised cost-effectiveness analysis: an aid to decision making in health.

Health economics literature provides ample evidence for existing inefficiencies in health. Economic appraisal seeks to improve efficiency by guiding policy makers in how scarce resources can be used to derive the greatest possible social benefit. In the past many cost-effectiveness (CE) studies have addressed sector-wide cost-effectiveness in health. However, as described in this paper, current studies suffer from a number of shortcomings including the inability to assess the current mix of interventions, low generalisability and inconsistent methodological approaches. Most importantly, it is argued that the current incremental approach to cost-effectiveness analysis (CEA) does not provide decision makers with sufficient guidance for sector-wide priority setting in health. Instead, a broader complementary sectorial approach is proposed via the application of a generalised CEA framework, which allows the examination of existing inefficiencies in health systems. The wide variations in cost-effectiveness ratios observed among interventions that are currently in use, suggest there is considerable room to improve efficiency by moving from inefficient interventions to efficient interventions that are underutilized. This information will contribute to a more informed debate on resource allocation in the long-term.

Cost-Benefit Analysis↗

PubMedDate not supplied

Achieving the WHO/UNAIDS antiretroviral treatment 3 by 5 goal: what will it cost?

The "3 by 5" goal to have 3 million people in low and middle income countries on antiretroviral therapy (ART) by the end of 2005 is ambitious. Estimates of the necessary resources are needed to facilitate resource mobilisation and rapid channelling of funds to where they are required. We estimated the financial costs needed to implement treatment protocols, by use of country-specific estimates for 34 countries that account for 90% of the need for ART in resource-poor settings. We first estimated the number of people needing ART and supporting programmes for each country. We then estimated the cost per patient for each programme by country to derive total costs. We estimate that between US5.1 billion dollars and US5.9 billion dollars will be needed by the end of 2005 to provide ART, support programmes, and cover country-level administrative and logistic costs for 3 by 5.

Anti-Retroviral Agents↗