Ataxin-1 and ataxin-2 intermediate-length PolyQ expansions in amyotrophic lateral sclerosis.

OBJECTIVE: Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 (ATXN-2) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 (ATXN-1) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy. METHODS: We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders. RESULTS: We found significantly higher intermediate PolyQ expansions ≥ 32 for ATXN-1 alleles and ≥ 28 for ATXN-2 alleles in the sALS cohort (ATXN-1: ALS, 7.07% vs controls, 2.38%; p = 0.0001; ATXN-2: ALS, 2.72% vs controls, 0.5%; p = 0.001). ATXN-1 CAT and ATXN-2 CAA interruptions were detected in patients with ALS only. Age at onset, site of onset, and sex were not significantly related to the ATXN-1 or ATXN-2 PolyQ repeat length expansions. CONCLUSIONS: Both ATXN-1 and ATXN-2 PolyQ intermediate expansions are independently associated with an increased risk for ALS

Equatorial Atlantic Ocean dynamics in a coupled ocean–atmosphere model simulation

The ocean temperatures and zonal currents at the equatorial Atlantic simulated by an improved version of the Brazilian earth system model (BESM), with changes in the cloud cover scheme and optical properties of the atmospheric component, are analyzed and compared to those obtained from a previous version of BESM and also from other seven selected CMIP5 models. It is shown that this updated version of BESM, despite some persistent biases, more accurately represents the surface temperature variation at the Equator and the equatorial thermocline east–west slope. These improvements are associated to a more realistic seasonal cycle achieved for the Atlantic equatorial undercurrent, as well as sea surface temperatures and zonal wind stress. The better simulation of the equatorial undercurrent is, in its turn, credited to a more realistic representation of the surface wind position and strength at the tropical Atlantic by the coupled model. With many of the systematic errors noticed in the previous version of the model alleviated, this version of BESM can be considered as a useful tool for modelers involved in Atlantic variability studies

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

A Finite Element Model Approach to Determine the Influence of Electrode Design and Muscle Architecture on Myoelectric Signal Properties.

INTRODUCTION: Surface electromyography (sEMG) is the measurement of the electrical activity of the skeletal muscle tissue detected at the skin's surface. Typically, a bipolar electrode configuration is used. Most muscles have pennate and/or curved fibres, meaning it is not always feasible to align the bipolar electrodes along the fibres direction. Hence, there is a need to explore how different electrode designs can affect sEMG measurements. METHOD: A three layer finite element (skin, fat, muscle) muscle model was used to explore different electrode designs. The implemented model used as source signal an experimentally recorded intramuscular EMG taken from the biceps brachii muscle of one healthy male. A wavelet based intensity analysis of the simulated sEMG signal was performed to analyze the power of the signal in the time and frequency domain. RESULTS: The model showed muscle tissue causing a bandwidth reduction (to 20-92- Hz). The inter-electrode distance (IED) and the electrode orientation relative to the fibres affected the total power but not the frequency filtering response. The effect of significant misalignment between the electrodes and the fibres (60°- 90°) could be reduced by increasing the IED (25-30 mm), which attenuates signal cancellation. When modelling pennated fibres, the muscle tissue started to act as a low pass filter. The effect of different IED seems to be enhanced in the pennated model, while the filtering response is changed considerably only when the electrodes are close to the signal termination within the model. For pennation angle greater than 20°, more than 50% of the source signal was attenuated, which can be compensated by increasing the IED to 25 mm. CONCLUSION: Differences in tissue filtering properties, shown in our model, indicates that different electrode designs should be considered for muscle with different geometric properties (i.e. pennated muscles)

Monitoring and data quality assessment of the ATLAS liquid argon calorimeter

The liquid argon calorimeter is a key component of the ATLAS detector installed at the CERN Large Hadron Collider. The primary purpose of this calorimeter is the measurement of electron and photon kinematic properties. It also provides a crucial input for measuring jets and missing transverse momentum. An advanced data monitoring procedure was designed to quickly identify issues that would affect detector performance and ensure that only the best quality data are used for physics analysis. This article presents the validation procedure developed during the 2011 and 2012 LHC data-taking periods, in which more than 98% of the proton-proton luminosity recorded by ATLAS at a centre-of-mass energy of 7-8 TeV had calorimeter data quality suitable for physics analysis