Postmortem Blood Concentrations of R‐ and S‐Enantiomers of Methadone and EDDP in Drug Users: Influence of Co‐Medication and P‐glycoprotein Genotype

Abstract: We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R‐ and S‐methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R‐enantiomer concentrations significantly exceeded that of the S‐enantiomers (Wilcoxon’s test, p < 0.001). The samples were divided into four groups according to other drugs detected (methadone only, methadone and strong analgesics, methadone and benzodiazepines, or methadone and other drugs). There was no significant difference in any of the R‐methadone/total methadone ratios among the four groups. The median R/S ratio was 1.38, which tends to be higher than that reported for the plasma of living subjects. In addition, we investigated whether small nucleotide polymorphisms in the MDR1 gene that encode the drug transporter P‐glycoprotein were associated with the concentrations of R‐ and S‐methadone and its metabolite 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine. No significant association was detected.     

Are ‘pseudonymised’ data always personal data? Implications of the GDPR for administrative data research in the UK

There has naturally been a good deal of discussion of the forthcoming General Data Protection Regulation. One issue of interest to all data controllers, and of particular concern for researchers, is whether the GDPR expands the scope of personal data through the introduction of the term ‘pseudonymisation’ in Article 4(5). If all data which have been ‘pseudonymised’ in the conventional sense of the word (e.g. key-coded) are to be treated as personal data, this would have serious implications for research. Administrative data research, which is carried out on data routinely collected and held by public authorities, would be particularly affected as the sharing of de-identified data could constitute the unconsented disclosure of identifiable information.Instead, however, we argue that the definition of pseudonymisation in Article 4(5) GDPR will not expand the category of personal data, and that there is no intention that it should do so. The definition of pseudonymisation under the GDPR is not intended to determine whether data are personal data; indeed it is clear that all data falling within this definition are personal data. Rather, it is Recital 26 and its requirement of a ‘means reasonably likely to be used’ which remains the relevant test as to whether data are personal. This leaves open the possibility that data which have been ‘pseudonymised’ in the conventional sense of key-coding can still be rendered anonymous. There may also be circumstances in which data which have undergone pseudonymisation within one organisation could be anonymous for a third party. We explain how, with reference to the data environment factors as set out in the UK Anonymisation Network's Anonymisation Decision-Making Framework.     

Pinyin Roumaji to Wade-Giles conversion table

Abstract

Ben Kiernan and Chanthou Boua, in collaboration with numerous Khmer people, have produced a unique, scholarly volume about Kampuchea that endeavors to answer the critical question of “why?” What are the events that precipitated the rule of the Khmer Rouge and why did they turn against their own people? This book is a collection of well-documented essays, arranged in chronological order, that examines the long-term, endemic conditions that resulted in Kampuchea's dark age of 1975–79. Much of the work was translated from original Khmer sources, and two of the Kampuchean writers, Hou Yuon and Hu Nim, were prominent socialists who were executed by the Khmer Rouge after 1975. Well-known and sometimes obscure events are described through the eyes of witnesses interviewed in Kampuchea, Thailand, Australia and France. This book is not a diatribe against the unspeakable horrors that befell the Kampuchean people. The facts have their own grim eloquence.     

BADASSES: The Rise of Women in Criminal Justice

Little is known about the experiences and career trajectories of women working in the criminal justice field. Criminal justice, particularly law enforcement, has historically been largely a male-dominated career field. This study examines the experiences of 850 women working in the criminal justice field; in policing, courts, corrections, victim services, and academia. The present study collected data in 2017 and asked women working in the criminal justice field about their employment. Respondents said that they experienced a wide range of gender discrimination but did not see gender discrimination as a barrier to their success. The women identified personal and professional perseverance, strong mentorship, and family support as contributing factors to their success. Findings highlight the experience and challenges of women working at all levels and in all components of the criminal justice system and the journey of these women at a unique time in the history of criminal justice and evolution of women in the workplace. Implications for criminal justice, advice for current and aspiring women working in the field, and the nature of the experience for women in criminal justice are discussed.     

A fatal overdose of the ergot derivative cabergoline

A 79-year-old woman, with Parkinson's disease treated with cabergoline, was admitted to a hospital due to jaundice and weakness. She was found confused, absent minded, and died after 2 weeks. Autopsy showed an extrahepatic bile duct adenocarcinoma with spread to the gall bladder, the liver, and regional lymphnodes. While cleaning the hospital bed after her death, the nurses found several tablets hidden in the bed. Biological samples obtained at the autopsy were screened for common drugs and narcotics. Several drugs such as buprenorphine, codeine, paracetamol, and propranolol were detected in the blood at therapeutic levels. A method to determine cabergoline in whole blood and other forensic matrices was developed, and further investigations determined cabergoline concentrations in whole blood and liver tissue of 94 and 3100 microg/kg, respectively. The blood concentration was 100 times above the therapeutic level reported on cabergoline in plasma and in combination with her symptoms, suggest she took a fatal overdose of cabergoline.     

"The red zone": temporal risk for unwanted sex among college students

The "red zone" usually refers to the first few weeks of the first semester at college, when female students are believed to be at greatest risk for experiencing unwanted sex. We tested this notion using data from a survey study of 207 first-and second-year students (121 women, 84 men) at a small, liberal arts university. Results demonstrated only one significant elevation in incidence rates of first- and second-year women's unwanted sexual experiences (sexual touching, attempted and completed anal, oral, and vaginal sex), between the end of the first month and fall break (mid-October) during the second year at school. Previous research and local information about the relevant behaviors of sorority and fraternity members is discussed in light of these findings to provide heuristic material for further empirical testing. Because risk may involve both temporal and situational factors, systematic collection and dissemination of local data are recommended.     

Dominance of pre-analytical over analytical variation for measurement of methadone and its main metabolite in postmortem femoral blood

On the basis of simultaneously sampled postmortem blood specimens from the left and right femoral veins the pre-analytical variation of methadone measurements was evaluated and compared to the analytical variation. The material consisted of a series of 27 duplicate samples from routine autopsy cases comprising mainly drug addicts. A chiral LC-MS/MS method was used for measurement of the R- and S-enantiomers of methadone and its main metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP). The analytical CV% was determined to be in the range 3-4% for methadone enantiomers and 4-6% for EDDP enantiomers. The total measurement uncertainty (CV(T)) was estimated from the pre-analytical variation (CV(PA)), analytical variation proper (CV(A)), and variation related to calibration (traceability) (CV(Cal)) according to the relationship CV(T) = [CV(2)(PA) + CV(2)(A) + CV(2)(cal)](0.5). Uncertainty related to calibration concerned a component related to the purity of drug reference compound and a contribution from the production of calibrator solutions (CV(Cal)<1%). Pre-analytical sampling variation was estimated from the duplicate measurements of blood samples after subtraction of the analytical component. The pre-analytical variation amounted to a CV% of 19-21% for R- and S-methadone and 30-38% for R- and S-EDDP, i.e. considerably larger than the other components. Due to the squared addition principle, the resulting total uncertainty (CV(T)) became largely identical to the CV(PA), i.e. 19-21% for R- and S-methadone and 31-38% for R- and S-EDDP enantiomers. Accordingly, CV(T) exceeded CV(A) by a factor 5 or more. Dominance of the pre-analytical component of variation may also be likely for other compounds measured in postmortem blood samples. Thus, the width of the 95%-uncertainty interval (+/-2CV(T)) for a postmortem measurement is largely determined by the pre-analytical component of variation. This should be kept in mind when judging on the uncertainty of postmortem measurement results.     

THE MANAGEMENT OF PUBLIC PROVISION

Abstract: This work addresses the special character of public management by positing some important distinctions under-represented in current academic literature. In exploring the primary distinction between public administration and public management, the analysis proceeds from a treatment of public management as control of a production process uniquely configured as a combination of policy brokerage and resource management, to a demonstration of the economic agency (value addition) of public managers. The paper also presents a contextual analysis of the scope and scale of the public sector as this pertains to a model of "public provision", and introduces some new ideas regarding the temporal characteristics of public management as it responds to a discrete set of three cycles: the budget cycle, the product cycle and the policy cycle.
This work aims to provide tools for analysis which both distinguish public administration from public management and distinguish the economic agency of private managers from that of public managers. The general argument is that the "public provision process", while similar to a conventional production process, contains unique and important responsibilities which need to be understood and defended. By the same token, public managers ought to be empowered by a knowledge and identity which express their importance as economic agents who contribute both to the commonweal and to the wealth of the nation.