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.

Revisiting the Security of the ALRED Design and Two of Its Variants: Marvin and LetterSoup

The ALRED construction is a lightweight strategy for constructing message authentication algorithms from an underlying iterated block cipher. Even though this construction's original analyses show that it is secure against some attacks, the absence of formal security proofs in a strong security model still brings uncertainty on its robustness. In this paper, aiming to give a better understanding of the security level provided by different authentication algorithms based on this design strategy, we formally analyze two ALRED variants-the MARVIN message authentication code and the LETTERSOUP authenticated-encryption scheme,-bounding their security as a function of the attacker's resources and of the underlying cipher's characteristics.

Mathematical modeling and analysis of the particle interactions in the direct filtration using the colloidal theory

This work used the colloidal theory to describe forces and energy interactions of colloidal complexes in the water and those formed during filtration run in direct filtration. Many interactions of particle energy profiles between colloidal surfaces for three geometries are presented here in: spherical, plate and cylindrical; and four surface interactions arrangements: two cylinders, two spheres, two plates and a sphere and a plate. Two different situations were analyzed, before and after electrostatic destabilization by action of the alum sulfate as coagulant in water studies samples prepared with kaolin. In the case were used mathematical modeling by extended DLVO theory (from the names: Derjarguin-Landau-Verwey-Overbeek) or XDLVO, which include traditional approach of the electric double layer (EDL), surfaces attraction forces or London-van der Waals (LvdW), esteric forces and hydrophobic forces, additionally considering another forces in colloidal system, like molecular repulsion or Born Repulsion and Acid-Base (AB) chemical function forces from Lewis.

Representation and analysis of control surface freeplay nonlinearity

Different representations for a control surface freeplay nonlinearity in a three degree of freedom aeroelastic system are assessed. These are the discontinuous, polynomial and hyperbolic tangent representations. The Duhamel formulation is used to model the aerodynamic loads. Assessment of the validity of these representations is performed through comparison with previous experimental observations. The results show that the instability and nonlinear response characteristics are accurately predicted when using the discontinuous and hyperbolic tangent representations. On the other hand, the polynomial representation fails to predict chaotic motions observed in the experiments. (c) 2012 Elsevier Ltd. All rights reserved.

Design and synthesis of a new coumarin-based 'turn-on' fluorescent probe selective for Cu+2

The novel coumarin-based 'turn-on' fluorescent probe (E)-3-(2,5-dimethoxybenzylideneamino)-7-hydroxy-2H-chromen-2-one (MGM) was designed, synthesized, and characterized. This compound shows high selectivity for Cu+2, combined with a large fluorescence enhancement upon binding to Cu2+. Benesi-Hildebrand and Job plots demonstrate that the stoichiometry of the Cu+2 complex formed is 2:1. Preliminary studies employing epifluorescence microscopy demonstrated that Cu+2 could be imaged in human neuroblastoma SH-SY5Y cells treated with MGM. (c) 2012 Elsevier Ltd. All rights reserved.

Design and synthesis of new (E)-cinnamic N-acylhydrazones as potent antitrypanosomal agents

We report herein the synthesis and trypanocidal profile of new (E)-cinnamic N-acylhydrazones (NAHs) designed by exploiting molecular hybridization between the potent cruzain inhibitors (E)-1-(benzo[d] 11,3)dioxol-5-yl)-3-(4-bromophenyl)prop-2-en-1-one and (E)-3-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)-7-methoxy-2-naphthohydrazide. These derivatives were evaluated against both amastigote and trypomastigote forms of Trypanosoma cruzi and lead us to identify two compounds that were approximately two times more active than the reference drug, benznidazole, and with good cytotoxic index. Although designed as cruzain inhibitors, the weak potency displayed by the best cinnamyl NAH derivatives indicated that another mechanism of action was likely responsible for their trypanocide action. (C) 2012 Elsevier Masson SAS. All rights reserved.