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

Visual Servoing and Appearance for Navigation

We address the problem of visual-based navigation of a mobile robot in indoors environments. The robot control system is based on a single camera to provide the required visual feedback information. The control strategy merges two distinct paradigms that appeared recently in the technical literature, in order to provide the robustness and computation speed needed for closed loop control. On one hand, we servo on the vanishing point defined by the intersection of the corridor guidelines. This mode is used for the heading control and ensures that the vehicle moves along corridors. On the other hand, we use appearance based processes to monitor the robot position along the path and to launch different navigation tasks (e.g. turn left, enter door, etc). The combination of visual servoing techniques that provide stable control loops for specific local tasks, and appearance based methods that embed a representation of the environment at a larger scale, results in extended autonomy even with ..

Expression Of Cyclooxygenase-2 (cox-2) And P53 In Neighboring Invasive And In Situ Components Of Breast Tumors.

The aim of the study was to assess the relationship between the expression of COX-2 and p53, hormone receptors and HER-2 in the in situ (DCIS) and invasive components of ductal carcinomas (IDC) of the same breast. The expression of COX-2, p53, and hormone receptors was assessed in 87 cases of IDC with contiguous areas of DCIS. Results showed that there was no difference in COX-2 expression comparing the in situ and invasive components of the tumors. In the in situ component, there was a statistically borderline increase in p53 expression in tumors that also expressed COX-2. ER-positive specimens were more common in the group of tumors that expressed COX-2 in the invasive component. From this study we conclude that the expression of COX-2 was similar in the in situ and invasive components of the breast carcinomas. COX-2 positivity was marginally related with the expression of p53 in the in situ components, and with the ER expression in the invasive components.114226-3

Comparative Evaluation Of The Erbb2 And Hormone Receptor Status Of Neighboring Invasive And In Situ Components Of Ductal Carcinomas Of The Breast.

It remains unknown whether erbB2 expression and hormone receptor status predict the invasive potential of ductal carcinoma in situ (DCIS) of the breast. To examine erbB2 and estrogen/progesterone receptor (ER/PR) status in the precise areas where DCIS turns into invasive ductal carcinoma (IDC). Eighty-seven cases of breast malignancies harboring contiguous regions of DCIS and IDC were selected. Separate histological samples from the DCIS and the neighboring IDC were obtained using tissue microarrays. The erbB2 and ER/PR statuses were assessed using immunohistochemistry (erbB2 and ER/PR) and fluorescence in situ hybridization (FISH - only erbB2). The expression of erbB2 did not differ in the DCIS and IDC components of the breast tumors (p=0.35). There was good agreement in sample-by-sample comparisons of erbB2 (intraclass correlation coefficient [ICC]=0.78), PR (ICC=0.61) and ER (ICC=0.70) expression in the DCIS and IDC components. Our findings suggest that the expressions of erbB2 and ER/PR do not differ in the contiguous regions from DCIS to IDC.24238-4

B-Cell Epitopes-Based Chimeric Protein from SARS-CoV-2 N and S Proteins Is Recognized by Specific Antibodies in Serum and Urine Samples from Patients

The impact of the COVID-19 pandemic caused by the SARS-CoV-2 virus underscored the crucial role of laboratorial tests as a strategy to control the disease, mainly to indicate the presence of specific antibodies in human samples from infected patients. Therefore, suitable recombinant antigens are relevant for the development of reliable tests, and so far, single recombinant proteins have been used. In this context, B-cell epitopes-based chimeric proteins can be an alternative to obtain tests with high accuracy through easier and cheaper production. The present study used bioinformatics tools to select specific B-cell epitopes from the spike (S) and the nucleocapsid (N) proteins from the SARS-CoV-2 virus, aiming to produce a novel recombinant chimeric antigen (N4S11-SC2). Eleven S and four N-derived B-cell epitopes were predicted and used to construct the N4S11-SC2 protein, which was analyzed in a recombinant format against serum and urine samples, by means of an in house-ELISA. Specific antibodies were detected in the serum and urine samples of COVID-19 patients, which were previously confirmed by qRT-PCR. Results showed that N4S11-SC2 presented 83.7% sensitivity and 100% specificity when using sera samples, and 91.1% sensitivity and 100% specificity using urine samples. Comparable findings were achieved with paired urine samples when compared to N and S recombinant proteins expressed in prokaryotic systems. However, better results were reached for N4S11-SC2 in comparison to the S recombinant protein when using paired serum samples. Anti-N4S11-SC2 antibodies were not clearly identified in Janssen Ad26.COV2.S COVID-19-vaccinated subjects, using serum or paired urine samples. In conclusion, this study presents a new chimeric recombinant antigen expressed in a prokaryotic system that could be considered as an alternative diagnostic marker for the SARS-CoV-2 infection, with the potential benefits to be used on serum or urine from infected patients