Post-mortem stability and redistribution of carbohydrate-deficient transferrin (CDT)

Post-mortem diagnosis of chronic alcohol abuse is a challenge for forensic experts due to the lack of pathognomonic morphological findings and often also inadequate background information. Objective methods demonstrating chronic excessive alcohol consumption would therefore be a useful tool for forensic pathologists. In clinical practice, several markers of chronic alcohol abuse have recently been introduced, among which carbohydrate-deficient transferrin (CDT) is the most accepted, but the use of these markers in autopsy has not yet been established. We examined post-mortem stability and possible post-mortem redistribution of CDT and compared two analytical methods, capillary zone electrophoresis and high-performance liquid chromatography. According to our results, CDT remains stable for an appreciable time after death. The results further indicate that CDT is not subject to major post-mortem redistribution.     

Validation of an ELISA-based screening assay for the detection of amphetamine, MDMA and MDA in blood and oral fluid

The use of amphetamine and 'ecstasy' (MDMA) has increased exponentially in many European countries since the late nineties, leading to a rapid growth in the number of clinical and forensic analyses. Therefore, a rapid screening procedure for these substances in biological specimens has become an important part of routine toxicological analysis in forensic laboratories. The objective of this study was to evaluate the Cozart amphetamine enzyme-linked immunosorbent assay (ELISA) for the screening of plasma samples and oral fluid samples (collected with the Intercept device). Authentic plasma samples from drivers (n=360) were screened, using an 1:5-fold dilution. True positive, true negative, false positive and false negative results were determined relative to the in-house routine GC-MS analysis. Samples consisted of 144 amphetamine-only positives, 141MDMA/MDA-only positives, and 74 negatives when using the limit of quantitation as the cut-off level for confirmation (10 ng/mL). Using these results, receiver operating characteristic (ROC) curves were generated and optimal cut-off values for the screening assay were calculated. Analysis showed that the ELISA is able to predict the presence of either amphetamine or *MDMA/MDA (*MDMA as its metabolite MDA) in plasma samples with 98.3% sensitivity and 100% specificity at a cut-off value of 66.5 ng/mL d-amphetamine equivalents. A similar analysis was conducted on 216 oral fluid specimens collected from a controlled double blind study. Subjects received placebo or a high (100 mg) or low (75 mg) dose of MDMA. Oral fluid samples were collected at 1.5 and 5.5h after administration. Combined results of the analysis of the high and low dose oral fluid samples indicated a screening cut-off of 51 ng/mL d-amphetamine equivalents with both a sensitivity and specificity of 98.6% (using a LC-MS/MS confirmation cut-off of 10 ng/mL). In conclusion, these data indicate that the Cozart AMP EIA plates constitute a fast and accurate screening technique for the identification of amphetamine and MDMA/MDA positive plasma samples and oral fluid specimens (collected with Intercept. It should be emphasized that method validation should be performed for each type of biological matrix.     

Behold the shut-eyed sentry!

Whistleblowers, employees of conscience who report on wrongdoing, integrate into their socially useful role one of exposing institutional torpor and bureaucratic incompetence in those official structures responsible for the investigation and correction of wrongdoing. This paper reports on the finding from Australia's largest study into whistleblowers. It shows a crisis of competence in the official capacity of government structures to respond effectively to disclosures made in the public interest.     

Validating policy indicators

Although validity of an indicator, that is, whether it means what it purports to, is critical to its legitimate use in policy, there are few systematic approaches to validation. The reason lies largely in the traditions of positivist social science which require the separation of fact and theory and allow no place for meaning and valuation. The paper proposes approaches to test the validity of both indicators and the conceptual frameworks on which they are based. The most powerful forms of validation require the application of a priori concepts and models. Validation is partly judgmental and never simply mechanical. The validity of a measure is dependent on the context of its use. Social and political processes are an important part of validation, particularly in determining the appropriateness of the assumptions. If an indicator is to be valid, it should be chosen or designed iteratively with the policies it will help to shape.The author wishes to thank Sir Geoffrey Vickers, Professor Martin Krieger and Dr. Norman Shulman for their thoughtful comments on an earlier version of this paper.