DIGISAFE® XME: High Availability Vital Computer

International audienceDuring the 1980s, progress achieved in automation systems led us to computerize functions that had hitherto used hard wired or relay logic. This especially included system safety related functions which previously used hardware based systems. The safety of these functions was based on a "failsafe" principle: any failure placed the equipment in a non dangerous state

Exploring a Tetrahydroquinoline Antimalarial Hit from the Medicines for Malaria Pathogen Box and Identification of its Mode of Resistance as PfeEF2

New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that are resistant to first-line therapeutics. Here we report the exploration of MMV692140 ( 2 ) from the Pathogen Box, a collection of 400 compounds that was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 was profiled in in vitro models of malaria and was found to be active against multiple life-cycle stages of Plasmodium parasites. The mode of resistance, and putatively its mode of action, was identified as Plasmodium falciparum translation elongation factor 2 ( Pf eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA. The compound maintains activity against a series of drug-resistant parasite strains. The structural motif of the tetrahydroquinoline ( 2 ) was explored in a chemistry program with its structure-activity relationships examined, resulting in the identification of an analog with 30-fold improvement of antimalarial asexual blood stage potency

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

Resistant ultralaminae in soils

International audienceObservation of a chemically resistant organic residue from maize crop soils by transmission electron microscopy reveals the occurrence of thin laminae with 10-50 nm thickness, similar to resistant, highly aliphatic biopolymers found in kerogens and microbes. This discovery shows evidence for a novel and alternative mode of formation of soil organic matter by selective preservation of resistant biopolymers from soil microbes, in addition to the classical recondensation pathway proposed by the French chemist Maillard in 1917

Rôle des récepteurs 5-HT1B et de la dopamine dans l'activité de type antidépresseur des IRSSs dans le test de la nage forcée chez la souris

Les inhibiteurs de recapture sélectifs de la sérotonine (IRSSs) exercent leur activité antidépressive en augmentant la concentration extracellulaire de sérotonine dans la fente synaptique qui induit l'activation de 14 sous types de récepteurs. Parmi ces récepteurs, le sous type 1B possède un rôle fondamental car son activation (injection locale ou systémique d anpirtoline) induit un effet antidépresseur alors que son blocage empêche l apparition des effets des IRSSs. Le maintien de l activité antidépressive de l anpirtoline chez des animaux dont les autorécepteurs ont été détruits démontre que se sont les hétérorécepteurs 5-HT1B qui sont responsables des effets comportementaux. L activité de type antidépresseur des IRSSs disparaissant chez des animaux dont le système dopaminergique a été préalablement lésé, nous avons donc suggéré que l effet des IRSSs nécessite une augmentation de la neurotransmission dopaminergique consécutive à l activation des récepteurs 5-HT1B.SSRIs induce an increase in extracellular serotonin which is responsible of their antidepressant-like (AD-like) properties. Among all 5-HT receptors subtypes activated, 5-HT1B subtype appears to be strongly involved in the mediation of this anti-immobility effect. Indeed, 5-HT1B receptors activation (following local or systemic infusion of anpirtoline) induces an AD-like effect, whereas 5-HT1B receptor blockade antagonises the activity of SSRIs. Anpirtoline being still efficient in 5-HT1B autoreceptors of lesioned mice it suggests that AD-like effects of 5-HT1B receptors agonists are mediated by activation of 5-HT1B heteroreceptors. Since AD-like effect of SSRIs is absent on dopamine lesioned mice, we have suggested that SSRIs activity requires an enhancement of dopamine neurotransmission to occur, and that this enhancement appears further to the activation of 5-HT1B receptor.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

[What investigations should be done following the first episode of pulmonary embolism?].

International audienceThromboembolic venous disease is both common and potentially serious, thus the first episode of pulmonary embolus calls for careful assessment. This involves two stages: a search for a venous localization of the pulmonary embolus and a search for risk factors contributing to thromboembolic venous disease. The emergence of non-invasive echographic-Doppler techniques and echocardiography make possible the localization of any residual venous thrombus. The risk of post thrombotic disease is raised in symptomatic thrombotic venous disease which requires wearing elastic stockings for a least two years. On the other hand this risk has not been assessed in asymptomatic cases of venous thrombosis. A search for risk factors requires a detailed history, a rigorous clinical examination and a routine list of laboratory investigations. Some complex investigations for detecting the early stages of a neoplasm would not appear justified unless there is objective evidence to support his. At the same time thrombophilia studies are not currently performed routinely for a first episode but may be suggested in the following cases: family history of thromboembolic venous disease, age less than 45, including those in whom the episode occurs at the same time as pregnancy, or whilst taking hormone therapy, idiopathic thromboembolism, the association of arterial and venous thrombi and finally venous thromboses occurring in an unusual anatomical site. Prospective studies have shown the value of long term anticoagulation in patients suffering from constitutional hemostatic anomalies. Finally, if there is an after thought of occult cancer or constitutional thrombocytopenia a careful follow up should be performed particularly during the first year

[What investigations should be done following the first episode of pulmonary embolism?].

International audienceThromboembolic venous disease is both common and potentially serious, thus the first episode of pulmonary embolus calls for careful assessment. This involves two stages: a search for a venous localization of the pulmonary embolus and a search for risk factors contributing to thromboembolic venous disease. The emergence of non-invasive echographic-Doppler techniques and echocardiography make possible the localization of any residual venous thrombus. The risk of post thrombotic disease is raised in symptomatic thrombotic venous disease which requires wearing elastic stockings for a least two years. On the other hand this risk has not been assessed in asymptomatic cases of venous thrombosis. A search for risk factors requires a detailed history, a rigorous clinical examination and a routine list of laboratory investigations. Some complex investigations for detecting the early stages of a neoplasm would not appear justified unless there is objective evidence to support his. At the same time thrombophilia studies are not currently performed routinely for a first episode but may be suggested in the following cases: family history of thromboembolic venous disease, age less than 45, including those in whom the episode occurs at the same time as pregnancy, or whilst taking hormone therapy, idiopathic thromboembolism, the association of arterial and venous thrombi and finally venous thromboses occurring in an unusual anatomical site. Prospective studies have shown the value of long term anticoagulation in patients suffering from constitutional hemostatic anomalies. Finally, if there is an after thought of occult cancer or constitutional thrombocytopenia a careful follow up should be performed particularly during the first year

Impact des pratiques culturales de l’agriculture conventionnelle, l’agriculture biologique et l’agriculture de conservation sur les microorganismes et les nématodes du sol

Impact des pratiques culturales de l’agriculture conventionnelle, l’agriculture biologique et l’agriculture de conservation sur les microorganismes et les nématodes du sol. 11. Journées d'Etude des Sols (JES