The Swiss German chapter of the Exit Association provides conditional assistance to individuals wishing to end their own lives. The Exit Association advocates death with dignity and fights for the ...right to freely choose the timing of one's own death. According to the Swiss criminal code (articles 114 and 115), altruistic assistance to suicide is not punishable. Active euthanasia is punished by imprisonment. An individual commits active euthanasia if he or she is driven by honorable motives (e.g., pity) and causes the death of another person wishing to die who seriously and insistently requests such action. Based on our information, the preparation for suicide and its completion relies on a well-defined protocol. First, the candidate's eligibility for Exit Association assistance is verified. The candidate then writes a farewell declaration that explicitly confirms the will to terminate his or her own life. A written report describes the events during the suicide procedure. Depending on the circumstances, the investigative judge requests a forensic autopsy and toxicologic analyses. The results of the forensic investigations conducted in the cases presented here are in agreement with the scenario described in the reports of the Exit Association, namely, suicide by massive ingestion of pentobarbital.
To cite this article: C. Aulagnier, P. Rayner, P. Ciais, R. Vautard, L. Rivier & M. Ramonet (2010) Is the recent build-up of atmospheric CO 2 over Europe reproduced by models. Part 2: an overview ...with the atmospheric mesoscale transport model CHIMERE, A B S T R A C T In this issue, Ramonet et al. revealed a positive trend in European, atmospheric CO 2 concentrations relative to a marine, North Atlantic reference baseline, for the years 2001-2006. The observed build up mainly occurred during the cold season where it reaches a 0.8 ppm yr −1 at low-altitude stations to a 0.3 ppm yr −1 at mid-altitude stations. We explore the cause of this build-up using the mesoscale model CHIMERE. We first model the observed trends, using interannually varying fluxes and transport, then suppress the interannual variability in fluxes or aspects of transport to elucidate the cause. The run with no interannual variability in fluxes still matches observed trends suggesting that transport is the major cause. Separate runs varying either boundary layer height or winds show that changes in boundary layer height explain the trends at low-altitude stations within the continents while changes in wind regimes drive changes elsewhere.
The present study tested the hypothesis that the cytokine tumor necrosis factor-alpha (TNF-alpha) is an important central nervous system mediator of the rat hypothalamo-pituitary-adrenal (HPA) axis ...response to the i.v. administration of lipopolysaccharide (LPS; 5 microg/kg). LPS produced a rapid (within 30 min) rise in plasma TNF-alpha levels, which preceded elevations in plasma ACTH (commencing at 45 min). Despite a lack of detectable TNF-alpha biological activity in the brain 30 min to 2 h after LPS administration, intracerebroventricular (i.c.v.) pretreatment (-20 h) with 5 microl anti-TNF-alpha antiserum significantly delayed the onset of the plasma ACTH response to LPS, suggesting that TNF-alpha acts within the brain. However, we also noted that the i.c.v. infusion of anti-TNF-alpha 20 h earlier produced experimentally significant concentrations of the same anti-TNF-alpha antibodies in systemic blood. This suggested the possibility that the effect of this antiserum was due to its leakage to the periphery. Indeed, 5 microl anti-TNF-alpha administered i.v. at -20 h produced an inhibition of the ACTH response to LPS that was temporally and quantitatively similar to that produced by i.c.v. anti-TNF-alpha. Intracerebroventricular administration of anti-TNF-alpha immediately before LPS produced only low systemic blood levels of corresponding anti-TNF-alpha antibodies and did not significantly alter the plasma ACTH response, whereas i.v. administration of anti-TNF-alpha immediately before LPS was clearly effective. Collectively, these results show that 1) biologically active levels of TNF-alpha in systemic plasma and the ensuing ACTH responses to LPS were always temporally and qualitatively related; and 2) even though i.c.v. administration of anti-TNF-alpha could inhibit the HPA axis response to LPS, this was apparent only when substantial amounts of anti-TNF-alpha antibodies had reached systemic blood. We, therefore, conclude that at the dose of LPS used in this study (5 microg/kg), TNF-alpha is an important mediator of the HPA axis response to LPS by an action within the periphery, but probably not within the brain.
A series of analogs of gonadotropin-releasing hormone (GnRH) containing the conformationally restrictive residue tetrahydroisoquinoline carboxylic acid (Tic) or its non-restricted parent ...phenylalanine were synthesized and evaluated for anti-ovulatory activity in the rat. The series, based on the potent linear parent compound Ac-DNal1-DCpa2-DPal3- Ser4-Tyr5-DPal6-Leu7-Arg8-Pro9-DAla10-NH2, included L-Tic in positions 1, 2, 3, 7 and 9, D-Tic in positions 1, 2, 3, 6 and 9, or D-Phe in positions 2 and 3 for comparison. The most potent analog in this series, with D-Tic in position 6, fully inhibited ovulation at 2.5 micrograms compared to near complete inhibition at 0.5 microgram for the parent compound. A theoretical analysis of the conformational restrictions imposed on mainchain and sidechain torsional angles by the incorporation of Tic was conducted in vacuo using molecular mechanics techniques. Using cyclo(4-10)-Ac-delta 3Pro1,DCpa2,DTrp3,Asp4,DNal6,Dpr10- GnRH as a template conformer for which NMR conformational data is available, it was found that the potency of the different analogs correlated with the strain energy required to deform the mainchain and backbone angles of residues to values which would be expected if Tic were present and if the analog assumed the same solution structure. In particular, the effect of DTic at position 6 is to maintain the type II' beta-turn involving residues 5-8 found in active GnRH analogs.
In a case where a 32-year-old man lost control of his vehicle, urine and blood samples were taken 6 h after the crash for toxicological investigations. In the hospital, the driver admitted ...consumption of some drugs, in particular digoxin and midazolam just before the crash which corresponded to the results of blood analyses. Toxicological findings indicated the presence of digoxin at 12.9 ng/ml and midazolam at 7 ng/ml in the blood. These results suggested that at the moment of the crash digoxin and midazolam blood levels were in the range of toxic and therapeutic concentrations, respectively. Therefore the respective roles of the drugs in the impairment of the ability to drive at the moment of the crash is discussed.
Simultaneous determination of opiates and their glucuronides in body fluids has a great practical interest in the forensic assessment of heroin intoxication. A selective and sensitive method for ...quantification of morphine and its 3- and 6-glucuronides, codeine, codeine glucuronide and 6-monoacetylmorphine (6-MAM) based on liquid chromatography–electrospray ionisation mass spectrometry is described. The drugs were analysed in human autopsy whole blood after solid-phase extraction on a C8 cartridge. The separation was performed on an ODS column in acetonitrile (analysis time 15 min). For the quantitative analysis, deuterated analogues of each compound were used as internal standards. Selected-ion monitoring was applied where the molecular ion was chosen for quantification. The limits of quantification were 0.5 ng/ml for morphine and 6-MAM and 1 ng/ml for the 6-glucuronide of morphine, codeine-6-glucuronide and codeine and 5 ng/ml for the 3-glucuronide of morphine.
This paper documents a global Bayesian variational inversion of CO
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surface fluxes during the period 1988–2008. Weekly fluxes are estimated on a 3.75° × 2.5° (longitude‐latitude) grid throughout the ...21 years. The assimilated observations include 128 station records from three large data sets of surface CO
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mixing ratio measurements. A Monte Carlo approach rigorously quantifies the theoretical uncertainty of the inverted fluxes at various space and time scales, which is particularly important for proper interpretation of the inverted fluxes. Fluxes are evaluated indirectly against two independent CO
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vertical profile data sets constructed from aircraft measurements in the boundary layer and in the free troposphere. The skill of the inversion is evaluated by the improvement brought over a simple benchmark flux estimation based on the observed atmospheric growth rate. Our error analysis indicates that the carbon budget from the inversion should be more accurate than the a priori carbon budget by 20% to 60% for terrestrial fluxes aggregated at the scale of subcontinental regions in the Northern Hemisphere and over a year, but the inversion cannot clearly distinguish between the regional carbon budgets within a continent. On the basis of the independent observations, the inversion is seen to improve the fluxes compared to the benchmark: the atmospheric simulation of CO
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with the Bayesian inversion method is better by about 1 ppm than the benchmark in the free troposphere, despite possible systematic transport errors. The inversion achieves this improvement by changing the regional fluxes over land at the seasonal and at the interannual time scales.
A chemical investigation of the bark of Mimosa tenuiflora (Willd.) Poiret, performed in our laboratory, allowed the isolation and identification of three new triterpenoid saponins (mimonosides A, B ...and C), three steroid saponins (3-O-beta-D-glucopyranosyl campesterol, 3-O-beta-D-glucopyranosyl stigmasterol and 3-O-beta-D-glucopyranosyl beta-sitosterol) together with lupeol, campesterol, stigmasterol and beta-sitosterol. The three new triterpenoid saponins were subjected to in vitro biological tests (immunomodulation and proliferation) using different animal and human cells in culture. The results of these tests contribute to explain the traditional use of this plant material.
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