Alkoxy- and hydroxycyclization of enynes catalyzed by Pd(II) and Pt(II) catalysts

The development of a novel reaction ideal in terms of atom economy was achieved. The scope of the reaction was evaluated in the presence of Pd and Pt catalysts. The first enantioselective Pt-promoted enyne carboalkoxycyclization was developed in up to 85 % stereoselectivity. This ideal atom-economical reaction afforded the corresponding functionalized five-membered carbo- and heterocycles in good to excellent yields. The use of silver salts combined with (R)-Ph-BINEPINE, a monophosphane atropisomeric ligand, was found to be the best-suited combination for moderate to high enantioselectivities on carbonated and nitrogenated substrates

Influence of support on intra-abdominal pressure, hepatic kinetics of indocyanine green and extravascular lung water during prone positioning in patients with ARDS: a randomized crossover study

INTRODUCTION: Prone positioning (PP) on an air-cushioned mattress is associated with a limited increase in intra-abdominal pressure (IAP) and an absence of organ dysfunction. The respective influence of posture by itself and the type of mattress on these limited modifications during the PP procedure remains unclear. The aim of this study was to evaluate whether the type of support modifies IAP, extravascular lung water (EVLW) and the plasma disappearance rate of indocyanine green (PDR(ICG)) during PP. METHODS: A prospective, randomized, crossover study of 20 patients with acute respiratory distress syndrome (ARDS) was conducted in a medical intensive care unit in a teaching hospital. Measurements were made at baseline and repeated after 1 and 6 hours of two randomized periods of 6 hours of PP with one of two support types: conventional foam mattress or air-cushioned mattress. RESULTS: After logarithmic transformation of the data, an analysis of variance (ANOVA) showed that IAP and PDR(ICG )were significantly influenced by the type of support during PP with an increase in IAP (P < 0.05 by ANOVA) and a decrease in PDR(ICG )on the foam mattress (P < 0.05 by ANOVA). Conversely, the measurements of EVLW did not show significant modification between the two supports whatever the posture. The ratio of the arterial oxygen tension to the fraction of inspired oxygen significantly increased in PP (P < 0.0001 by ANOVA) without any influence of the support. CONCLUSION: In comparison with a conventional foam mattress, the use of an air-cushioned mattress limited the increase in IAP and prevented the decrease in PDR(ICG )related to PP in patients with ARDS. Conversely, the type of support did not influence EVLW or oxygenation

To set up pedagogical experiments in a virtual lab: methodology and first results

This paper concerns a methodology for setting up web based experiments by distinguishing two perspectives: the learning perspective (which tasks will be scheduled for pupils and tutors, how they are planned and what learning objectives they may attempt), and separately, the experiment perspective (how teachers or researchers may use trails of this experiment, the first to improve their teaching, the last to various research objectives). The both are described by computable “scenarios” expressed with an educational modeling language, Learning Design Language (LDL). Scenarios are then implemented on a platform (LearningLab platform) to be played by pupils and tutors and further analyzed by exploiting trails of each run

Une infrastructure logicielle pour instrumenter l'expérimentation des EIAH

International audienceCet article a pour objet de présenter une plate-forme logicielle développée dans le but de faciliter le travail des chercheurs dans la mise en place et la réalisation d'expérimentations dans le domaine des EIAH. Ce travail a été réalisé dans le cadre de l'action « Shared Virtual Lab » (SVL) du réseau d'excellence Kaleidoscope, et les outils ont été exploités pour la réalisation d'une expérimentation complexe mettant en oeuvre simultanément plusieurs EIAH développés au sein de l'équipe MeTAH du LIG. Le scénario décrivant l'activité des élèves et des enseignants impliqués dans l'expérimentation est décrit en langage LDL et interprété par la plate-forme. Les traces d'activité produites par les logiciels expérimentés et par la plate-forme sont centralisées dans une base de données XML. Elles ont été exploitées en temps réel par un outil de suivi destiné aux enseignants

Single Medial Prefrontal Neurons Cope with Error

Learning from mistakes is a key feature of human behavior. However, the mechanisms underlying short-term adaptation to erroneous action are still poorly understood. One possibility relies on the modulation of attentional systems after an error. To explore this possibility, we have designed a Stroop-like visuo-motor task in monkeys that favors incorrect action. Using this task, we previously found that single neurons recorded from the anterior cingulate cortex (ACC) were closely tuned to behavioral performance and, more particularly, that the activity of most neurons was biased towards the evaluation of erroneous action. Here we describe single neurons engaged in both error detection and response alertness processing, whose activation is closely associated with the improvement of subsequent behavioral performance. Specifically, we show that the effect of a warning stimulus on neuronal firing is enhanced after an erroneous response rather than a successful one and that this outcome is correlated with an error rate decrease. Our results suggest that the anterior cingulate cortex, which exhibits this activity, serves as a powerful computational locus for rapid behavioral adaptation

Ruptures d'approvisionnement en médicaments anti-infectieux: causes et conséquences

International audienceAnti-infective drugs stock-outs are increasingly frequent, and this is unlikely to change. There are numerous causes for this, mostly related to parameters difficult to control: i) 60 to 80% of raw material or components are produced outside of Europe (compared to 20% 30 years ago), with subsequent loss of independence for their procurement; ii) the economic crisis drives the pharmaceutical companies to stop producing drugs of limited profitability (even among important drugs); iii) the enforcement of regulatory requirements and quality control procedures result in an increasing number of drugs being blocked during production. The therapeutic class most affected by drug stock-outs is that of anti-infective drugs, especially injectable ones, and many therapeutic dead ends have recently occurred. We provide an update on this issue, and suggest 2 major actions for improvement: i) to implement a group dedicated to anticipating drug stock-outs within the anti-infective committee in each health care center, with the objectives of organizing and coordinating the response whenever a drug stock-out is deemed at risk (i.e., contingency plans, substitution, communication to prescribers); ii) a national reflection lead by scientific societies, in collaboration with government agencies, upstream of the most problematic drug stock-outs, to elaborate and disseminate consensus guidelines for the management of these stock-outs

Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness

Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder. Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013–June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia. We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ± 1.50 μg/L; DCS: 0.0061 ± 0.0040; controls: 0.0090 ± 0.01; IPE versus DCS or controls: P < 0.01). The combined “BNP-cTnI” levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers. We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE

039: Platelet reactivity predicts both ischemic and bleeding events at one year follow-up in acute coronary syndome patients receiving prasugrel

There are evidences of a link between platelet reactivity inhibition and thrombotic and bleeding events. We have previously demonstrated that PR after prasugrel loading dose (LD) predicts short-term thrombotic events. We aimed to further investigate the relationship between PR under prasugrel and one-year thrombotic and bleeding events.MethodPatients were prospectively included in this multicentre study if they had a successful PCI for an acute coronary syndrome (ACS) and received prasugrel. Vasodilator-Stimulated Phosphoprotein (VASP index) was measured after prasugrel LD. Endpoint included the rate of thrombotic events (cardiovascular death, myocardial infarction and stent thrombosis) and bleeding events (TIMI) at one year.ResultsThree hundreds and one patients were enrolled. Nine patients (3%) were lost to follow-up at one year. The rates of thrombotic and bleeding events at one year were 7.5 and 6.8% respectively. The mean VASP index after a 60mg LD of prasugrel was 34}23% and 76 patients (25%) were considered as having high on-treatment platelet reactivity (HTPR). Patients with HTPR had a higher rate of thrombotic events compared to good responders (19.7 vs 3.1%;p<0.001). Patients with a minor or major non-CABG related TIMI bleeding had lower PR compared to patients with no bleeding events (21}18 vs 35}23%;p=0.008). In multivariate analysis, the VASP index predicted both thrombotic and bleeding events (OR: 1.44 (95% CI: 1.2–1.72; p<0.001 and 0.75 (95% CI: 0.59–0.96;p=0.024 (respectively, per 10% increase)).ConclusionPlatelet reactivity measurement after prasugrel LD predicts both ischemic and bleedings events at one year follow-up for ACS patients undergoing PCI