Lyn Niel

Recently, the ENFSI/EDNAP groups issued advice on the design of the next generation of STR multiplexes in order to encourage standardisation within Europe. As the result of collaborative experimentation within the EDNAP group, we demonstrated that the low molecular weight STRs had substantial benefits to detect degraded samples. We subsequently recommended adoption of three new mini-STR loci to improve the success rate of degraded DNA markers, concurrent with the reduction in size of the existing STR markers in current use. This also improves the discriminating power of the system which is important to improve the power of national DNA databases. Subsequent discussions have occurred with manufacturers and members of the ENFSI/EDNAP groups. Because significant time and investment is required to develop new multiplexes of 13+ STR loci, manufacturers indicated that it would be preferable to adopt a staged approach. Two differing, but parallel strategies have now emerged. The first strategy employs a 13 STR loci multiplex incorporating three mini-STRs into the current multiplex test. The second strategy employs a multiplex of six high molecular weight STRs (in current use), modified to provide smaller amplicons combined with an additional two loci of high discriminating power. Eventually, the two strategies will converge to provide a single multiplex of 15 STR loci. The process will be guided by the ENFSI/EDNAP groups.

Exosomes are small membranous vesicles secreted by a number of cell types and can be isolated from conditioned cell media or bodily fluids such as urine and plasma. Exosome biogenesis involves the inward budding of multivesicular bodies (MVB) to form intraluminal vesicles (ILV). When fused with the plasma membrane, the MVB releases the vesicles into the extracellular environment as exosomes. Proposed functions of these vesicles include roles in cell–cell signalling, removal of unwanted proteins, and the transfer of pathogens between cells, such as HIV-1. Another such pathogen which exploits this pathway is the prion, the infectious particle responsible for the transmissible neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) of humans or bovine spongiform encephalopathy (BSE) of cattle. Interestingly, this work is mirrored by studies on another protein involved in neurodegenerative disease, the amyloid precursor protein (APP) which is associated with Alzheimer’s disease (AD). Recent work has found APP proteolytic fragments in association with exosomes, suggesting a common pathway previously unknown for proteins associated with neurodegenerative diseases. This review will be discussing the current literature regarding the role of exosomes in secretion of the proteins, PrP and APP, and the subsequent implications for neurodegenerative disease.

Following a recent meeting by the ENFSI and EDNAP groups on the 4–5 April, 2005, in Glasgow, UK, it was unanimously agreed that the process of standardization within Europe should take account of recent work that unequivocally demonstrated that chance of obtaining a result from a degraded sample was increased when small amplicons (mini-STRs) were analysed. Consequently, it was recommended that existing multiplexes are re-engineered to enable small amplicon detection, and that three new mini-STR loci with alleles <130 bp (D10S1248, D14S1434 and D22S1045) are adopted as universal. This will increase the number of European standard Interpol loci from 7 to 10.

Background Our objective was to investigate whether a consensus exists between the general public and health care providers regarding the reasoning and values at stake on the subject of life-sustaining treatment. Methods A postal questionnaire was sent to a random sample of members of the adult population (n = 989) and to a random sample of intensive care doctors and neurosurgeons (n = 410) practicing in Sweden in 2004. The questionnaire was based on a case involving a severely ill patient and presented arguments for and against withholding and withdrawing treatment, and providing treatment that might hasten death. Results Approximately 70% of the physicians and 51% of the general public responded. A majority of doctors (82.3%) stated that they would withhold treatment, whereas a minority of the general public (40.2%) would do so; the arguments forwarded (for instance, belief that the first task of health care is to save life) and considerations regarding quality of life differed significantly between the two groups. Most physicians (94.1%) and members of the general public (77.7%) were prepared to withdraw treatment, and most (95.1% of physicians and 82% of members of the general public) agreed that sedation should be provided. Conclusion There are indeed considerable differences in how physicians and the general public assess and reason in critical care situations, but the more hopelessly ill the patient became the more the groups' assessments tended to converge, although they prioritized different arguments. In order to avoid unnecessary dispute and miscommunication, it is important that health care providers be aware of the public's views, expectations, and preferences.