Base-Catalyzed Intramolecular Hydroamination of Cyclohexa-2,5-dienes: Insights into the Mechanism through DFT Calculations and Application to the Total Synthesis of epi-Elwesine

The base-catalyzed intramolecular hydroamination of 1-ethylaminocyclohexa-2,5-dienes is described. The transformation proceeds through isomerization of the cyclohexa-1,4-dienyl fragment into the corresponding conjugated 1,3-diene prior to the hydroamination step. Attaching a chiral glycinol ether auxiliary on the amino group allows the protonation to occur with complete diastereocontrol. The resulting lithium amide then adds onto the 1,3-dienyl moiety, affording the desired fused pyrrolidine ring along with the corresponding lithium allylic anion. Protonation of the latter then proceeds with high regiocontrol to favor the resulting allylic amines. In contrast, when the reaction was performed on primary amines, fused pyrrolidines bearing a homoallylic amino group were obtained. The stereochemical course of the process and determination of the reaction pathways were established based on calculations performed at the DFT level. Finally, application of the methodology to the enantioselective synthesis of (+)-epi-elwesine, a crinane alkaloid, is described

High-speed III-V nanowire photodetector monolithically integrated on Si

Direct epitaxial growth of III-Vs on silicon for optical emitters and detectors is an elusive goal. Nanowires enable the local integration of high-quality III-V material, but advanced devices are hampered by their high-aspect ratio vertical geometry. Here, we demonstrate the in-plane monolithic integration of an InGaAs nanostructure p-i-n photodetector on Si. Using free space coupling, photodetectors demonstrate a spectral response from 1200-1700 nm. The 60 nm thin devices, with footprints as low as ~0.06 μm2, provide an ultra-low capacitance which is key for high-speed operation. We demonstrate high-speed optical data reception with a nanostructure photodetector at 32 Gb s−1, enabled by a 3 dB bandwidth exceeding ~25 GHz. When operated as light emitting diode, the p-i-n devices emit around 1600 nm, paving the way for future fully integrated optical links.ISSN:2041-172

Journée d’actualité de la recherche archéologique organisée par le service archéologique d’Autun /11 février 2011

International audienceLa troisième édition des « Journée d’ actualité de la recherche archéologique » s’est déroulée pourla seconde année consécutive à Autun, le 11 février 2011, sous la houlette du service municipald’archéologie. Elle a permis aux archéologues d’horizons divers de présenter le résultat desprincipales fouilles d’archéologie préventives et programmées menées en 2010 en Bourgogne,ainsi qu’en Champagne. Cette journée a été ouverte au grand public autunois pour qu’ilpuisse s’approprier ce riche patrimoine et profiter d’exposés parfois diffusés de manière tropconfidentielle. Ce petit document synthétique permet de garder une trace de ces enrichissantescommunications

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

ObjectivesAmong patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p p p p p p p p = 0.007).ConclusionsAmong STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions