Synthesis report with pro-poor trade research findings and policy recommandations

The purpose of the project was to investigate international trade in fisheries products and its relationship to poverty alleviation and livelihoods of poor aquatic resource users in developing countries in Asia, and to identify options to improve the effectiveness of poverty reduction through international seafood trade. The project directly addressed the EC-PREP priority area of trade and development, and indirectly provided valuable insight to two other priority areas: food security and sustainable rural development; and institutional capacity building. [PDF contains 60 pages.]

Evidence for classification of c.1852_1853AA > GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

Transfer of Medical Sensor Technologies to Environmental Monitoring, Solomons, Maryland, April 6-8, 2005: workshop proceedings

(pdf contains 23 pages)

Simulated pathogenic conformational switch regions matched well with the biochemical findings

Pathogenic conformational conversion is a general causation of many disease, such as transmissible spon- giform encephalopathy (TSE) caused by misfolding of prion, sickle cell anemia, and etc. In such structural changes, misfolding occurs in regions important for the stability of native structure firstly. This destabi- lizes the normal conformation and leads to subsequent errors in folding pathway. Sites involved in the first stage can be deemed switch regions of the protein, and are vital for conformational conversion. Namely it could be a switch of disease at residue level. Here we report an algorithm that can identify such sites computationally with an accuracy of 93%, by calculating the probability of the native structure of a short segment jumping to a mistake one. Knowledge of such switch sites could be used to target clinical therapy, study physiological and pathologic mechanism of protein, and etc.

Designing for validation of medical devices and equipment

Validation is important in the design, development and production of medical devices since effective and appropriate validation plays a vital role in defining the success of a product in both technical and economic terms. Regulations and quality standards lay out the requirements for product validation, but it is left to each individual manufacturer to establish and maintain their own validation procedures. More recently, there has also been a change of emphasis in the regulations and standards that encourage the integration of validation into the development process. However, this poses particular challenges to the manufacturer since there is a distinct lack of guidance to assist this integration. This workbook provides the first real guidance on good design practices for medical device development. It has been developed through extensive consultation with device manufacturers and analysis of regulatory requirements. The approach is intended to assist manufacturers in meeting the new regulations.