Definition of a Type System for Generic and Reflective Graph Transformations

This thesis presents the extension of the graph transformation language SDM (Story Driven Modeling) with generic and reflective features as well as the definition of type checking rules for this language. The generic and reflective features aim at improving the reusability and expressiveness of SDM, whereas the type checking rules will ensure the type-safety of graph transformations. This thesis starts with an explanation of the relevant concepts as well as a description of the context in order to provide the reader with a better understanding of our approach. The model driven development of software, today considered as the standard paradigm, is generally based on the use of domain-specific languages such as MATLAB Simulink and Stateflow. To increase the quality, the reliability,and the efficiency of models and the generated code, checking and elimination of detected guideline violations defined in huge catalogues has become an essential, but error-prone and time-consuming task in the development process. The MATE/MAJA projects, which are based on the use of the SDM language, aim at an automation of this task for MATLAB Simulink/Stateflow models. Modeling guidelines can be specified on a very high level of abstraction by means of graph transformations. Moreover, these specifications allow for the generation of guideline checking tools. Unfortunately, most graph transformation languages do not offer appropriate concepts for reuse of specification fragments - a MUST, when we deal with hundreds of guidelines. As a consequence we present an extension of the SDM language which supports the definition of generic rewrite rules and combines them with the reflective programming mechanisms of Java and the model repository interface standard JMI. Reusability and expressiveness are not the only aspects we want to improve. Another fundamental aspect of graph transformations must be ensured: their correctness in order to prevent type errors while executing the transformations. Checking and testing the graph transformations manually would ruin the benefit obtained by the automation of the guideline checking and by the generic and reflective features. Therefore, we propose in this work a type-checking method for graph transformations. We introduce a new notation for rules of inference and define a type system for SDM. We also proposed an algorithm to apply this type system. We illustrate and evaluate both contributions of our work by applying them on running examples. Proposals for other additional SDM features as well as for possible improvements of our type checking open new perspectives and future research to pursue our work

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Fièvre de la vallée du Rift : diagnostic d'une arbovirose peu classique en France métropolitaine, à ne pas méconnaître !

International audienc

Pharmacological Dissection of the Crosstalk between NaV and CaV Channels in GH3b6 Cells

Thanks to the crosstalk between Na+ and Ca2+ channels, Na+ and Ca2+ homeostasis interplay in so-called excitable cells enables the generation of action potential in response to electrical stimulation. Here, we investigated the impact of persistent activation of voltage-gated Na+ (NaV) channels by neurotoxins, such as veratridine (VTD), on intracellular Ca2+ concentration ([Ca2+]i) in a model of excitable cells, the rat pituitary GH3b6 cells, in order to identify the molecular actors involved in Na+-Ca2+ homeostasis crosstalk. By combining RT-qPCR, immunoblotting, immunocytochemistry, and patch-clamp techniques, we showed that GH3b6 cells predominantly express the NaV1.3 channel subtype, which likely endorses their voltage-activated Na+ currents. Notably, these Na+ currents were blocked by ICA-121431 and activated by the β-scorpion toxin Tf2, two selective NaV1.3 channel ligands. Using Fura-2, we showed that VTD induced a [Ca2+]i increase. This effect was suppressed by the selective NaV channel blocker tetrodotoxin, as well by the selective L-type CaV channel (LTCC) blocker nifedipine. We also evidenced that crobenetine, a NaV channel blocker, abolished VTD-induced [Ca2+]i elevation, while it had no effects on LTCC. Altogether, our findings highlight a crosstalk between NaV and LTCC in GH3b6 cells, providing a new insight into the mode of action of neurotoxins