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 cmH2O 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 6430 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 metho

Trigger and Aperture of the Surface Detector Array of the Pierre Auger Observatory

The surface detector array of the Pierre Auger Observatory consists of 1600 water-Cherenkov detectors, for the study of extensive air showers (EAS) generated by ultra-high-energy cosmic rays. We describe the trigger hierarchy, from the identification of candidate showers at the level of a single detector, amongst a large background (mainly random single cosmic ray muons), up to the selection of real events and the rejection of random coincidences. Such trigger makes the surface detector array fully efficient for the detection of EAS with energy above $3\times 10^{18}$ eV, for all zenith angles between 0$^\circ$ and 60$^\circ$, independently of the position of the impact point and of the mass of the primary particle. In these range of energies and angles, the exposure of the surface array can be determined purely on the basis of the geometrical acceptance.Comment: 29 pages, 12 figure

Ultrahigh energy neutrinos at the Pierre Auger observatory

The observation of ultrahigh energy neutrinos (UHEνs) has become a priority in experimental astroparticle physics. UHEνs can be detected with a variety of techniques. In particular, neutrinos can interact in the atmosphere (downward-going ν) or in the Earth crust (Earth-skimming ν), producing air showers that can be observed with arrays of detectors at the ground. With the surface detector array of the Pierre Auger Observatory we can detect these types of cascades. The distinguishing signature for neutrino events is the presence of very inclined showers produced close to the ground (i.e., after having traversed a large amount of atmosphere). In this work we review the procedure and criteria established to search for UHEνs in the data collected with the ground array of the Pierre Auger Observatory. This includes Earth-skimming as well as downward-going neutrinos. No neutrino candidates have been found, which allows us to place competitive limits to the diffuse flux of UHEνs in the EeV range and above.P. Abreu ... K. B. Barber ... J. A. Bellido ... R. W. Clay ... M. J. Cooper ... B. R. Dawson ... T. A. Harrison ... A. E. Herve ... V. C. Holmes ... J. Sorokin ... P. Wahrlich ... B. J. Whelan ... et al

Morphometric changes of Rhodnius neglectus (Hemiptera: Reduviidae): in the transition from sylvatic to laboratory conditions

In the present work, we investigated whether it is possible to detect morphometric changes in Rhodnius neglectus Lent, 1954 (a candidate vector of Chagas disease in Central Brazil) populations in the transition from sylvatic to laboratory conditions. We analyzed size and shape variation in wings of sylvatic parents and their laboratory descendents (first, third and fifth generations) using geometric morphometric techniques. Sexual size dimorphism and shape of wings were maintained, but wing size decreased from sylvatic specimens to their laboratory generations. Size variation in R. neglectus should reflect the expected morphometric changes between sylvatic and domestic populations and can be applied to analyze the level of adaptation of R. neglectus to domestic habitats. This information might be useful to detect persistent infestations in dwellings after insecticide application, or new infestations from the sylvatic environment, and is therefore important to guide vector surveillance strategies for Chagas disease

Evaluation of biochemical and serological methods to identify and clustering yeast cells of oral Candida species by CHROMagar test, SDS-PAGE and ELISA

The purpose of this work was to evaluate biochemical and serological methods to characterize and identify Candida species from the oral cavity. The strains used were five Candida species previously identified: C. albicans, C. guilliermondii, C. parapsilosis, C. krusei, C. tropicalis, and Kluyveromyces marxianus, as a negative control. The analyses were conducted through the SDS-PAGE associated with statistical analysis using software, chromogenic medium, and CHROMagar Candida (CA), as a differential medium for the isolation and presumptive identification of clinically important yeasts and an enzyme-linked immunoabsorbent assay (ELISA), using antisera produced against antigens from two C. albicans strains. This method enabled the screening of the three Candida species: C. albicans, C. tropicalis, and C. Krusei, with 100% of specificity. The ELISA using purified immunoglobulin G showed a high level of cross-reaction against protein extracts of Candida species. The SDS-PAGE method allowed the clustering of species-specific isolates using the Simple Matching coefficient, S SM = 1.0. The protein profile analysis by SDS-PAGE increases what is known about the taxonomic relationships among oral yeasts. This methodology showed good reproducibility and allows collection of useful information for numerical analysis on information relevant to clinical application, and epidemiological and systematical studies

Protein-Related Dietary Parameters and Frailty Status in Older Community-Dwellers across Different Frailty Instruments

The present study investigated the associations between frailty status and (a) daily protein intake, (b) daily body weight-adjusted protein intake, (c) branched-chain amino acid (BCAA) consumption, (d) evenness of protein distribution across main meals, (e) number of daily meals providing at least 30 g of protein, and (f) number of daily meals providing at least 0.4 g protein/kg of body weight in community-dwelling older adults. The relationship between frailty status and protein-related dietary parameters was explored across different frailty assessment tools. Two hundred older adults were enrolled in the study. Participant frailty status was determined according to a modified Fried's frailty phenotype (mFP), the FRAIL scale, and the Study of Osteoporotic Fracture (SOF) index. Diet was assessed by 24-h dietary recall, while diet composition was estimated using a nutritional software. A frailty instrument-dependent relationship was observed between frailty status and protein-related dietary parameters. Protein consumption was associated with frailty status only in participants identified as frail according to the mFP. In addition, protein and BCAA intake was found to be greater in robust and pre-frail participants relative to their frail counterparts. Our findings suggest that the association between frailty and protein-related dietary parameters is tool dependent. Specifically, protein and BCAA consumption appears to be lower only in older adults identified as frail by the mFP

ESC Core Curriculum for the General Cardiologist (2013)

Preface The previous Core Curriculum for the General Cardiologist defined a model for cardiology training in Europe and it has been adopted as the standard for regulating training, for access to the specialty (certification), and for revalidation in several countries.1 During the last 5 years we have witnessed profound changes in cardiological practice. The work of both hospital and independent cardiologists has been better integrated with that of general practitioners. It has taken into account the requirements of national authorities, re-imbursement organizations, and hospital administrations. Cardiologists face changing patient expectations. General cardiologists, interventional cardiologists, anaesthetists, and cardiac surgeons work together in Heart Teams.2,3 The age of cardiac patients has increased and they are presenting with more co-morbidities. Knowledge, technology, and treatment are constantly advancing: new imaging modalities have become widely available. Stent technology has evolved and competes with cardiac surgery for all but complex cases.2 Percutaneous valve implantations are increasingly successful.4 Interventional electrophysiology and device therapy have become cornerstones in the practice of cardiology.5,6 Care of the patient with heart failure is now a multi-disciplinary undertaking.7 New powerful anti-thrombotic and anticoagulant therapies have been introduced and are often used in combination, with clear benefits but increased bleeding risks.6,8,9 Use of diagnostic and therapeutic tools and the approaches to management of common conditions have been systematically clarified in regularly updated ESC consensus guideline documents. Against the background of these developments, the Board of the ESC decided in 2011 to revise and update the Core Curriculum. The chairman of the Committee for Education 2010–2012, Otto A. Smiseth, delegated this project to a task force, whose members were drawn from general cardiologists. The 2013 version of the Core Curriculum outlines the knowledge and skills of the general clinically oriented cardiologist, rather than those required for the sub-specialties. The document provides a framework for training and certification, continuous medical education (CME), and recertification. The Core Curriculum will inevitably continue to evolve as authors and reviewers are aware that there are still important differences in training and means throughout Europe and ESC member states. In the Core Curriculum, the ESC is setting a standard that national societies can use in their dealings with political institutions and national authorities. A deliberate decision was taken to outline an optimal rather than a minimum standard, allowing for the fact that not every training system will be able, or may not wish, to adopt the full curriculum. In countries (or centres) that are currently unable to deliver training in all its aspects, the Core Curriculum can and should be used as a benchmark to promote improvement. The 2013 Core Curriculum defines the clinical, patient-oriented, training of the general cardiologist. The overall structure of the previous version has been retained, but the table format has been abandoned to limit the number of printed pages and to make the document more easily searchable on-line. In most subject areas, there was a wide if not unanimous consensus among the task force members on the training required for the cardiologist of the future. The document recommends that acquisition of competence in general cardiology requires at least 6 years of full-time postgraduate training, of which 4 years are devoted to cardiology. The general aspects of training and all individual chapters have been updated. The document focuses on knowledge of mechanisms of disease, clinical and communication skills, empathy for the patient and their relatives, and teamwork. A clear boundary has been set between the competencies required of the general cardiologist and those of the sub-specialist.10–13 The first part of the curriculum covers general aspects of training, and is followed by a comprehensive description of the specific components in 28 chapters. Each of the chapters includes statements of the objectives, and is further sub-divided into the required knowledge, skills and behaviours, and attitudes. Some chapters have been renamed and/or sub-divided into sub-sections. The most salient changes are summarized here. Non-invasive imaging (Chapter 2.3) has been divided into five sections: Non-invasive imaging (general aspects), Echocardiography, Cardiac magnetic resonance (CMR), Cardiac X-ray computed tomography, and Nuclear techniques. Cardiovascular prevention (Chapter 2.7) has been divided into sections on Cardiovascular risk factors and Arterial hypertension. Cardiac tumours (Chapter 2.12) has been replaced by a new and broader chapter on Oncology and the heart. The chapter Cardiac Rehabilitation and Exercise Physiology (Chapter 2.19) has become Physical activity and Sport in primary and secondary prevention and includes sections on Sports cardiology and Cardiac rehabilitation. A new chapter entitled Acute cardiovascular care (Chapter 2.27) has been added. The Cardiac consult (Chapter 2.28) has been expanded and divided into sections dealing with the patient undergoing non-cardiac surgery, the patient with neurological symptoms or diseases, and the patient with conditions not presenting primarily as cardiovascular disease [elderly patients, patients with diabetes, chronic kidney disease (CKD), erectile dysfunction, and others]. The 2013 Core Curriculum underwent a thorough review process based on the template of the review of the ESC guidelines. The document does not include minimum or optimal numbers of procedures to be undertaken, and does not address periodic evaluation, certification, or revalidation. This does not obviate the importance of regular, structured, and formally documented assessment, which is crucial to implementation of the curriculum. This should include knowledge-based assessments (formative and summative), formally observed procedures and practices, a log-book, and a recognition of the potential of simulation techniques in both training and assessment

Electroweak measurements in electron–positron collisions at w-boson-pair energies at lep

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