Time-resolved hair analysis of MDMA enantiomers by GC/MS-NCI

The aim of the study was to determine the enantioselective disposition of 3,4-methylenedioxymethamphetamine (MDMA) and other amphetamine-type stimulants (ATS) in segmented hair specimens of self-declared ecstasy abusers, who took part in a double-blind placebo-controlled six-way crossover study during approximately 7 weeks, during which they received a 75 and a 100 mg dose of racemic MDMA twice. Hair specimens were washed and cut into pieces of 2 cm length. After digestion and solid phase extraction, the enantiomers were derivatized with a chiral agent (2S,4R)-N-heptafluorobutyryl-4-heptafluorobutoyloxy-prolyl chloride, developed at the authors laboratory and quantified by gas chromatography coupled to mass spectrometry operating in the negative chemical ionization mode. Most of the hair specimens that were tested positive for MDMA showed a predominance of the (R)-enantiomer. The R/S ratios of MDMA varied between 1.02 and 2.75 and total concentrations ranged from 0.1 to 20.1 ng/mg. The enantiomers of its metabolite 3,4-methylenedioxyamphetamine (MDA) were also quantified in most hair segments. The R/S ratios of MDA varied between 0.60 and 1.60, while the concentrations of the enantiomers ranged from 10 to 160 pg/mg hair. When segmental analysis was performed on single hair specimens, no inversion of the R versus S ratios of MDMA and MDA was observed. The predominance of (R)-MDMA in hair was in accordance with those already published for other matrices. Furthermore, both enantiomers of amphetamine (AM) were also detected in hair segments of four volunteers and the R/S ratios ranged from 1.00 to 1.47.     

Morphine and 6-acetylmorphine concentrations in blood, brain, spinal cord, bone marrow and bone after lethal acute or chronic diacetylmorphine administration to mice

The aim of this study was to evaluate postmortem incorporation of opiates in bone and bone marrow after diacetylmorphine (heroin) administration to mice. Mice were given acute (lethal dose of 300 mg/kg) or chronic (10 and 20 mg/kg/24 h for 20 days) intraperitoneal administration of diacetylmorphine. The two metabolites of diacetylmorphine, 6-acetylmorphine (6-AM) and morphine, were extracted from whole blood, brain, spinal cord, bone marrow and bone (after hydrolysis) using a liquid/liquid method. Quantification was performed by gas chromatography-mass spectrometry (GC/MS). Results showed that after acute administration, opiates were present in all studied tissues. Morphine concentrations appeared to be higher than those of 6-AM in blood (52.4 microg/mL versus 27.7 microg/mL, n=12), bone marrow (87.8 ng/mg versus 8.9 ng/mg, n=6) and bone (0.85 ng/mg versus 0.43 ng/mg, n=6), but 6-AM concentrations were higher than those of morphine in brain (14.0 ng/mg versus 7.4 ng/mg, n=12) and spinal cord (27.8 ng/mg versus 20.8 ng/mg, n=12). No correlation was found for both compounds between blood concentrations and either brain, spinal cord, bone or bone marrow concentrations while a significant one was found between brain and spinal cord concentrations either for morphine (r=0.89, n=12, p<0.001) or 6-AM (r=0.93, n=12, p<0.001), the concentration being higher in spinal cord than in brain. When bones were stored for 2 months, only 6-AM remained in bone marrow but not in bone. After chronic administration, mice being sacrificed by cervical dislocation 24 h after the last injection, no opiate was detected in any studied tissues. Further studies are required, in particular in human bones, but these results seem to show that 6-AM could be detect in bone marrow several weeks after the death and could be an alternative tissue for forensic toxicologist to detect a fatal diacetylmorphine overdose, even if no correlation between blood and bone marrow was observed. On the other hand, neither bone tissue nor bone marrow will allow the confirmation of a chronic diacetylmorphine use.     

Environmental effectiveness and economic consequences of fragmented versus universal regimes: what can we learn from model studies?

A post-2012 regime aimed at reducing greenhouse gas (GHG) emissions could develop towards a universal or fragmented regime. The fundamental difference between a universal and a fragmented regime is that the first involves a single comprehensive climate regime in which all countries participate, whereas the second involves either multiple treaties or a single treaty in which not all countries participate. This study assesses the literature on a wide range of different model studies concerning the environmental effectiveness and economic consequences of various universal and fragmented climate regimes. The most important conclusions (e.g. relative position of regions in terms of costs) are generally consistent across different studies, despite the differences in methodology. We conclude that stabilising GHG concentrations at low levels is more costly with a fragmented regime than with a universal regime, because reduction targets must be achieved by a smaller number of countries or because fragmented treaties may prevent reducing GHGs where it is cheapest to do so. However, establishing a universal regime will be challenging due to cost differences between regions if emissions are allocated based on specific allocation rules and incentives to free-ride on a universal regime. Even though alternative behaviours such as responsibility, the implementation of transfer schemes or exclusive membership can increase the likelihood of achieving a universal regime, a fragmented regime seems more feasible. Therefore, a transitional fragmented ‘coalition of the willing’ could be established first, which could provide the basis for a larger, universal regime in the long term.

Potentially Lethal Behaviors Associated With Rapid Eye Movement Sleep Behavior Disorder: Review of the Literature and Forensic Implications

Abstract:  Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss of the muscle atonia of REM sleep, with release of complex and violent behaviors that are often attempted dream-enactments. This study reviewed the literature on RBD with regard to potentially lethal behavior. A total of 39–41 clinical cases of RBD associated with potentially lethal behaviors to self and/or others were found, involving a child and adults of all age groups, that manifested as choking/headlock ( n  = 22–24), defenestration/near-defenestration ( n  = 7), and diving from bed ( n  = 10). A total of 80.8% ( n  = 21) were males; 19.2% ( n  = 5) were females; mean age was 65.6 ± (SD) 13.8 years (range: 27–81 years, and a child). (Gender/age data were not listed in the remaining cases.) An etiologic association of RBD with a neurologic disorder (or with pharmacotherapy of psychiatric disorders, n  = 4) was present in 21–23 patients. Thus, RBD carries well-documented, potential forensic consequences during RBD episodes that could possibly have been misinterpreted as suicidal or homicidal behavior.     

Drug Testing in the Public Sector: An Interpretation Grounded in Rosenbloom's Competing-Perspectives Model

In the last few decades, drug testing has become a major policy issue in the workplace, with a host of actors competing to promote their own needs and interests. Employers, for example, seek ways to combat the use and abuse of illegal substances by employees. At the same time, unions and their employees legitimately seek to limit overly intrusive or unfair methods of testing. The courts have also been major players in the policy arena of drug testing, as witnessed by the surfeit of case law setting parameters around what is and is not legal and constitutional in terms of drug testing.
In an effort to move the drug-testing debate forward, this article examines the competing interests in drug testing, interests that ultimately frustrate the courts, policy makers, employees, and their unions from reaching a consensus on the use of drug tests in the public sector. To systematically examine this issue, Rosenbloom's competing-perspectives model of public administration is applied. The article concludes with policy recommendations for public managers.     

Fable pour économistes

Sommaire. Cette fable satirique veut décrire, en puisant fortement dans le vocabulaire ésotérique des économistes, la manie qu'ont ces demiers d'aborder un problième par le biais d'un modèle et la tentation qu'ils possèdent de pérorer a partir de ce modèle sur ce que devrait être la réalité. Donc, il était une fois, une tribu appelée les Economix. Etant les sages de la contrée, ils observaient la nature (économique) afin d'extrapoler des com-portements permanents et universels pour les autres membres de la tribu, les chasseurs. Toutefois, survint une querelle épique sur l'analyse du comportement de l'oiseau, l'objet de leurs observations. Après quelques moments de reflexion, l'on organisa un symposium et les deux écoles présentèrent leurs modèles. La première, après avoir observé, dans des conditions données, Ie comportement de l'oiseau, émit l'opinion que la meilleure représentation de l'oiseau en vol l'était par un avion à hélice tandis que la seconde avança, sur des prémisses totalement différentes, une fusée à un étage, comme étant la représentation de l'essence même de l'oiseau. Cependant, le symposium prit une toumure inattendue lorsque l'on s'engagea à parler de l'aéronef en tant qu'aéronef plutôt que de l'aéronef comme étant une simple approximation (par l'homme) de l'oiseau. Durant ce temps-là, les chasseurs (non-Economix), privés de leurs sages, cuntinuaient leur chasse quotidienne en utilisant beaucoup d'information a priori que les Economix ne pouvaient insérer dans leur moditle. En effet, les non-Economix n'avaient jamais oublié que la réalité est concriète! Abstract. The purpose of this satirical fable is to illustrate, by borrowing freely from the esoteric vocabulary of the economists, the craze they have for approaching problems by way of a model and their temptation to spout, basing themselves on that model, on what reality should be. So, once upon a time, there was a tribe called the Economix. Being the wise men of the country, they watched (economic) nature in order to extrapolate continuing and universal behaviour patterns for the other members of the tribe, the Hunters. However, a spectacular quarrel developed about the behavioural analysis of the bird, subject of their study. After some time to think it over, it was decided to organize a symposium for the two schools to present their models. The fist one, having observed - in controlled conditions - the behaviour of the bird, suggested that the best representation of the bird in flight was a propeller lane, while the second school, basing itself on a completely different set oP premises, contended that a one-stage rocket was the representation of the very nature of the bird. However, the symposium took an unexpected turn when it was decided to discuss the aircraft as an aircraft, rather than as an approximation of the bird (by man). In the meantime, the Hunters (non-Economix), deprived of their wise men, went on with their daily hunt, using a lot of a riori information that the Economk could not incorporate in their models. The non-Economix, you see, had never forgotten the concrete character of reality.