Clinical review: Ventilator-induced diaphragmatic dysfunction - human studies confirm animal model findings!

Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation. However, the use of controlled mechanical ventilation in animal models results in a major reduction of diaphragmatic force-generating capacity together with structural injury and atrophy of diaphragm muscle fibers, a condition termed ventilator-induced diaphragmatic dysfunction (VIDD). Increased oxidative stress and exaggerated proteolysis in the diaphragm have been linked to the development of VIDD in animal models, but much less is known about the extent to which these phenomena occur in humans undergoing mechanical ventilation in the ICU. In the present review, we first briefly summarize the large body of evidence demonstrating the existence of VIDD in animal models, and outline the major cellular mechanisms that have been implicated in this process. We then relate these findings to very recently published data in critically ill patients, which have thus far been found to exhibit a remarkable degree of similarity with the animal model data. Hence, the human studies to date have indicated that mechanical ventilation is associated with increased oxidative stress, atrophy, and injury of diaphragmatic muscle fibers along with a rapid loss of diaphragmatic force production. These changes are, to a large extent, directly proportional to the duration of mechanical ventilation. In the context of these human data, we also review the methods that can be used in the clinical setting to diagnose and/or monitor the development of VIDD in critically ill patients. Finally, we discuss the potential for using different mechanical ventilation strategies and pharmacological approaches to prevent and/or to treat VIDD and suggest promising avenues for future research in this area

Sodium bicarbonate for severe metabolic acidaemia – Authors' reply

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Covalency and magnetic anisotropy in lanthanide single molecule magnets: the DyDOTA archetype

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Stable localized pulses and zigzag stripes in a two-dimensional diffractive-diffusive Ginzburg-Landau equation

We introduce a model of a two-dimensional (2D) optical waveguide with Kerr nonlinearity, linear and quintic losses, cubic gain, and temporal-domain filtering. In the general case, temporal dispersion is also included, although it is not necessary. The model provides for description of a nonlinear planar waveguide incorporated into a closed optical cavity. It takes the form of a 2D cubic-quintic Ginzburg-Landau equation with an anisotropy of a novel type: the equation is diffractive in one direction, and diffusive in the other. By means of systematic simulations, we demonstrate that the model gives rise to \emph{stable} fully localized 2D pulses, which are spatiotemporal ``light bullets'', existing due to the simultaneous balances between diffraction, dispersion, and Kerr nonlinearity, and between linear and quintic losses and cubic gain. A stability region of the 2D pulses is identified in the system's parameter space. Besides that, we also find that the model generates 1D patterns in the form of simple localized stripes, which may be stable, or may exhibit an instability transforming them into oblique stripes with zigzags. The straight and oblique stripes may stably coexist with the 2D pulse, but not with each other.Comment: 16pages, 9figure

Procalcitonin biomarker kinetics fails to predict treatment response in perioperative abdominal infection with septic shock

International audienceIntroduction: Procalcitonin (PCT) biomarker is suggested to tailor antibiotic therapy in the medical intensive care unit (ICU) but studies in perioperative medicine are scarce. The aim of this study was to determine whether PCT reported thresholds are associated with the initial treatment response in perioperative septic shock secondary to intra-abdominal infection. Methods: This single ICU, observational study included patients with perioperative septic shocks secondary to intra-abdominal infection. Demographics, PCT at days 0, 1, 3, 5, treatment response and outcome were collected. Treatment failure included death related to the initial infection, second source control treatment or a new onset intra-abdominal infection. The primary endpoint was to assess whether PCT thresholds (0.5 ng/ml or a drop from the peak of at least 80%) predict the initial treatment response. Results: We included 101 consecutive cases. Initial treatment failed in 36 patients with a subsequent mortality of 75%. Upon admission, PCT was doubled when treatment ultimately failed (21.7 ng/ml +/- 38.7 vs. 41.7 ng/ml +/- 75.7; P = 0.04). Although 95% of the patients in whom PCT dropped down below 0.5 ng/ml responded to treatment, 50% of the patients in whom PCT remained above 0.5 ng/ml also responded successfully to treatment. Moreover, despite a PCT drop of at least 80%, 40% of patients had treatment failure. Conclusions: In perioperative intra-abdominal infections with shock, PCT decrease to 0.5 ng/ml lacked sensitivity to predict treatment response and its decrease of at least 80% from its peak failed to accurately predict treatment response. Studies in perioperative severe infections are needed before using PCT to tailor antibiotic use in this population

Positive end-expiratory pressure affects the value of intra-abdominal pressure in acute lung injury/acute respiratory distress syndrome patients: a pilot study

International audienceIntroduction: To examine the effects of positive end-expiratory pressure (PEEP) on intra-abdominal pressure (IAP) in patients with acute lung injury (ALI).Methods: Thirty sedated and mechanically ventilated patients with ALI or acute respiratory distress syndrome (ARDS) admitted to a sixteen-bed surgical medical ICU were included. All patients were studied with sequentially increasing PEEP (0, 6 and 12 cmH2O) during a PEEP-trial.Results: Age was 55 ± 17 years, weight was 70 ± 17 kg, SAPS II was 44 ± 14 and PaO2/FIO2 was 192 ± 53 mmHg. The IAP was 12 ± 5 mmHg at PEEP 0 (zero end-expiratory pressure, ZEEP), 13 ± 5 mmHg at PEEP 6 and 15 ± 6 mmHg at PEEP 12 (P < 0.05 vs ZEEP). In the patients with intra-abdominal hypertension defined as IAP ≥ 12 mmHg (n = 15), IAP significantly increased from 15 ± 3 mmHg at ZEEP to 20 ± 3 mmHg at PEEP 12 (P < 0.01). Whereas in the patients with IAP < 12 mmHg (n = 15), IAP did not significantly change from ZEEP to PEEP 12(8 ± 2 vs 10 ± 3 mmHg). In the 13 patients in whom cardiac output was measured, increase in PEEP from 0 to 12 cmH2O did not significantly change cardiac output, nor in the 8 out of 15 patients of the high-IAP group. The observed effects were similar in both ALI (n = 17) and ARDS (n = 13) patients.Conclusions: PEEP is a contributing factor that impacts IAP values. It seems necessary to take into account the level of PEEP whilst interpreting IAP values in patients under mechanical ventilation

Efficient GPU Implementation of Automatic Differentiation for Computational Fluid Dynamics

Many scientific and engineering applications require repeated calculation of derivatives of output functions with respect to input parameters. Automatic Differentiation (AD) is a methodology that automates derivative calculation and can significantly speed up the code development. In Computational Fluid Dynamics (CFD), derivatives of flux functions with respect to state variables (Jacobian) are needed for efficient solution of nonlinear governing equations. AD of the flux function on graphics processing units (GPUs) is challenging as flux computation involves many intermediate variables that create a high register pressure and requires significant memory traffic because of the need to store the derivatives. This paper presents a forward-mode AD method based om multivariate dual numbers that addresses these challenges and simultaneously reduces the operation count. The dimension of multivariate dual numbers is optimized for performance. The flux computations are restructured to minimize the number of temporary variables and reduce the register pressure. For effective utilization of the memory bandwidth, we use shared memory to store the local Jacobian. The threads assigned to process an edge (dual-face) collectively populate the local Jacobian in the shared memory. Shared memory is used to store local flux Jacobian. The threads assigned to process a flux differentiation at an edge collectively populate the local Jacobian in the shared memory. The use of shared memory allows further reducing temporary variables. The local Jacobian is written from the shared memory to the device memory taking advantage of coalesced stores. This is another major benefit of the shared memory approach. During this work, we assessed existing GPU-based forward-mode AD approaches for flux Jacobian computation and found them performing suboptimally. We demonstrated that our GPU implementation based on multivariate dual numbers of dimension 5 outperforms other tested implementations including the hand differentiated version optimized for NVIDIA V100. Our implementation achieves 75% of the peak floating point throughput and 61% of the peak device bandwidth on V100

Neutrino Physics, Superbeams, and the Neutrino Factory

We summarize what has been learned about the neutrino mass spectrum and neutrino mixing, identify interesting open questions that can be answered by accelerator neutrino facilities of the future, and discuss the importance and physics of answering them.Comment: To appear in the Proceedings of the 4th International Workshop on Neutrino Factories (Nu Fact 02). LaTeX, 10 pages, 1 eps figur