Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Development of a screening device for prion diseases

L'objectif de ce travail de thèse vise à élaborer un dispositif de dépistage de maladies à prions à partir de la synthèse et greffage sur support de molécules actives vis-à-vis de la structure de la protéine prion pathogène (PrPSc). Dans les résultats antérieurs, l'équipe du Dr. Mike Robitzer a mis en évidence des molécules qui présentent une forte affinité vis-à-vis de la protéine prion pathologique. Les tests réalisés (du type Western-Blot) avec les homogénats de cerveaux contaminés avec le prion traités avec ces composés, montrent la formation d'oligomères (dimères et trimères) de la PrPSc uniquement avec les échantillons contaminés. L'identification de ces formes oligomériques caractérise l'échantillon comme étant contaminé. Les molécules synthétisées ouvrent les portes à une nouvelle famille de molécules avec une activité sélective confirmée avec la PrPSc.Parmi les molécules synthétisées par l'équipe du Dr. Mike Robitzer, une en particulier présente une affinité accentuée dans le processus d'oligomerisation de la protéine prion pathologique. Cette molécule, nommée MR100, porte deux fonctions du type 1,3,5-triazine-2,4-diamine couplées à un espaceur quaterthiophène et présente une forte activité d'oligomerization de la PrPSc.Les tests réalisés et le mécanisme d'action de cette molécule sont encore en début d'étude (en partenariat avec l'unité 710 d'INSERM et l'EFS) et pour cela, l'amélioration de la synthèse du MR100 et la synthèse de nouvelles molécules porteuses de fonctions chimiques différentes augmentant l'affinité avec la PrPSc ont été réalisée dans cette thèse doctorale.La synthèse du dispositif de dépistage de maladies à prion a été réalisée en deux étapes principales. La première était basée sur la synthèse de molécules actives et les tests in vitro pour l'induction de l'oligomérisation du prion pathogène.La deuxième étape a consisté à sélectionner et à greffer les meilleurs candidats sur des supports solides pour tester leur stabilité, réactivité et réponse vis-à-vis des échantillons contaminés.Ces dispositifs sensibles au prion pathogène ont été utilisés pour la détection de la maladie avec les échantillons contaminés.The objective of this thesis was to develop a diagnostic device to prion diseases departing from the synthesis and functionalization of molecules having a high selectivity with the pathogenic form of the prion protein (PrPSc).In previous results, the Dr. Mike Robtizer's team has highlighted molecules that exhibit a strong affinity with the pathological form of the prion protein. The Western-Blot tests with contaminated brains homogenates treated with these compounds showed the formation of oligomeric forms (dimers and trimers) of the PrPSc only with contaminated samples. The identification of these oligomeric forms characterizes the sample as contaminated. The synthesized molecules represent a new family of compounds with a confirmed selectivity with the PrPSc.Among the synthesized molecules, one in particular has a pronounced affinity in the process of oligomerization of the pathological prion protein. This molecule, named MR100, has two 1,3,5-triazine-2,4-diamines functions coupled to a quaterthiophene spacer presents a high activity with the PrPSc.The tests with this molecule are still in the beginning (in partnership with INSERM - Unité 710 and EFS) and for this reason the improved synthesis of MR100 and the synthesis of new compounds carrying different chemical functions were developed in this doctoral thesis.The elaboration of the diagnostic device was made in two main steps. The first one was based on the synthesis of active molecules and its in vitro tests to verify their oligomeric-induced activity with PrPSc contaminated samples, inspired by the molecular approach developed in previous work.The active molecules have a high selectivity and specificity to the pathogenic forms of prion proteins and induce the formation of dimers and trimers of the PrPSc. The identification by Western Blot of these oligomeric forms characterizes the sample as contaminated.The second step was to select and graft the best candidates on solid supports to test their stability, reactivity and response in the same conditions

Improved synthesis of a quaterthiophene-triazine-diamine derivative, a promising molecule to study pathogenic prion proteins

International audienceThe 6,6'-([2,2':5',2'':5'',2'''-quaterthiophene]-5,5000-diyl)bis(1,3,5-triazine-2,4-diamine) (MR100), has been previously investigated in our research group through its biological activities toward pathogenic prion proteins (PrPSc). This compound presents a high affinity to protein strains and interacts selectively with at least one b-sheet rich isoform of prion protein. Herein we present the improved total synthesis of MR100, through a palladium-catalyzed direct double arylation using the concerted metalationdeprotonation mechanism (CMD)

Chapter 5. Alginate and Carrageenan Based Aerogels: Processing and Morphology

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Dialkyl imidazolium acetate ionosilica as efficient and recyclable organocatalyst for cyanosilylation reactions of ketones

International audienceWe report new heterogeneous organocatalyst based on silica hybrid supported N-heterocyclic carbene (NHC-) species. The organocatalyst is formed from an imidazolium iodide based ionosilica material, followed by iodide/acetate anion exchange. The imidazolium acetate generates the organocatalytic carbene via partial deprotonation of the imidazolium ring in situ. As monitored via EDX, solid state NMR and ion chromatography measurements, the iodide/acetate exchange involving the imidazolium ionosilica material took place only in small extent. Despite the fact that the exchanged material contains only a very small amount of acetate, we observed good catalytic activity and recyclability in cyanosilylation reactions of ketones with trimethylsilyl cyanide. The versatility of the catalyst was highlighted via reaction with several substrates, yielding the corresponding cyanohydrins in good yields. In recycling experiments, the material showed decreasing catalytic activity starting from the third reaction cycle, but high catalytic activity can be regenerated via another acetate treatment. Our work is important as it highlights the possibility to combine carbene chemistry and silica, which are antagonistic at a first glance. We show that imidazolium acetate based ionosilicas are therefore heterogeneous 'proto-carbenes', and that there is no need to form strongly basic silica supported NHCs to obtain heterogeneous NHC-organocatalysts. This work therefore opens the route towards heterogeneous and re-usable NHC-organocatalysts from supported ionic liquid imidazolium acetates

Carbon Adsorbents from Spent Coffee for Removal of Methylene Blue and Methyl Orange from Water

Activated carbons (ACs) were prepared from dried spent coffee (SCD), a biological waste product, to produce adsorbents for methylene blue (MB) and methyl orange (MO) from aqueous solution. Pre-pyrolysis activation of SCD was achieved via treatment of the SCD with aqueous sodium hydroxide solutions at 90 °C. Pyrolysis of the pretreated SCD at 500 °C for 1 h produced powders with typical characteristics of AC suitable and effective for dye adsorption. As an alternative to the rather harsh base treatment, calcium carbonate powder, a very common and abundant resource, was also studied as an activator. Mixtures of SCD and CaCO3 (1:1 w/w) yielded effective ACs for MO and MB removal upon pyrolysis needing only small amounts of AC to clear the solutions. A selectivity of the adsorption process toward anionic (MO) or cationic (MB) dyes was not observed

Original synthesis and spectroscopic study of thiophene triazine derivatives with enhanced luminescence properties

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Quaternary Ammonium-Based Ionosilica Hydrogels as Draw Solutes in Forward Osmosis

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Activated Carbon from Sugarcane Bagasse: A Low-Cost Approach towards Cr(VI) Removal from Wastewater

The potential of pretreated sugarcane bagasse (SCB) as a low-cost and renewable source to yield activated carbon (AC) for chromate CrO42− removal from an aqueous solution has been investigated. Raw sugarcane bagasse was pretreated with H2SO4, H3PO4, HCl, HNO3, KOH, NaOH, or ZnCl2 before carbonization at 700 °C. Only pretreatments with H2SO4 and KOH yield clean AC powders, while the other powders still contain non-carbonaceous components. The point of zero charge for ACs obtained from SCB pretreated with H2SO4 and KOH is 7.71 and 2.62, respectively. Batch equilibrium studies show that the most effective conditions for chromate removal are a low pH (i.e., below 3) where >96% of the chromate is removed from the aqueous solution