A bias correction method for fast fuel-to-air ratio estimation in diesel engines

l probes in turbocharged diesel engines are usually located downstream of the turbine, exhibiting a good dynamic response but a significant delay because of the exhaust line transport and the hardware itself. With the introduction of after-treatment systems, new sensors that can measure the exhaust concentrations are required for optimal control and diagnosis. Zirconia-based potentiometric sensors permit the measurement of nitrogen oxides and oxygen with the same hardware. However, their dynamic response is slower and more filtered than that of traditional l probes and, in addition, the sensor location downstream of the after-treatment systems increases this problem. The paper uses a Kalman filter for online dynamic estimation of the relative fuel-to-air ratio l21 in a turbocharged diesel engine. The combination of a fast drifted fuel-to-air ratio model with a slow but accurate zirconia sensor permits the model bias to be corrected. This bias is modelled with a look-up table depending on the engine operating point and is integrated online on the basis of the Kalman filter output. The calculation burden is alleviated by using the converged gain of the steady-state Kalman filter, precalculated offline. Finally, robustness conditions for stopping the bias updating are included in order to account for the sensor and model uncertainties. The proposed algorithm and sensor layout are successfully proved in a turbocharged diesel engine. Experimental and simulation results are included to support validation of the algorithm.This work was partially supported through project HIREFIRE (grant number: IPT-370000-2010-022).Guardiola, C.; Plá Moreno, B.; Blanco-Rodriguez, D.; Mazer, A.; Hayat, O. (2013). A bias correction method for fast fuel-to-air ratio estimation in diesel engines. 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Sublethal necroptosis signaling promotes inflammation and liver cancer

It is currently not well known how necroptosis and necroptosis responses manifest in vivo. Here, we uncovered a molecular switch facilitating reprogramming between two alternative modes of necroptosis signaling in hepatocytes, fundamentally affecting immune responses and hepatocarcinogenesis. Concomitant necrosome and NF-κB activation in hepatocytes, which physiologically express low concentrations of receptor-interacting kinase 3 (RIPK3), did not lead to immediate cell death but forced them into a prolonged "sublethal" state with leaky membranes, functioning as secretory cells that released specific chemokines including CCL20 and MCP-1. This triggered hepatic cell proliferation as well as activation of procarcinogenic monocyte-derived macrophage cell clusters, contributing to hepatocarcinogenesis. In contrast, necrosome activation in hepatocytes with inactive NF-κB-signaling caused an accelerated execution of necroptosis, limiting alarmin release, and thereby preventing inflammation and hepatocarcinogenesis. Consistently, intratumoral NF-κB-necroptosis signatures were associated with poor prognosis in human hepatocarcinogenesis. Therefore, pharmacological reprogramming between these distinct forms of necroptosis may represent a promising strategy against hepatocellular carcinoma

Structural Basis for the Inhibitory Effects of Ubistatins in the Ubiquitin-Proteasome Pathway

The discovery of ubistatins, small molecules that impair proteasomal degradation of proteins by directly binding to polyubiquitin, makes ubiquitin itself a potential therapeutic target. Although ubistatins have the potential for drug development and clinical applications, the lack of structural details of ubiquitin-ubistatin interactions has impeded their development. Here, we characterized a panel of new ubistatin derivatives using functional and binding assays. The structures of ubiquitin complexes with ubistatin B and hemi-ubistatin revealed direct interactions with ubiquitin's hydrophobic surface patch and the basic/polar residues surrounding it. Ubistatin B binds ubiquitin and diubiquitin tighter than a high-affinity ubiquitin receptor and shows strong preference for K48 linkages over K11 and K63. Furthermore, ubistatin B shields ubiquitin conjugates from disassembly by a range of deubiquitinases and by the 26S proteasome. Finally, ubistatin B penetrates cancer cells and alters the cellular ubiquitin landscape. These findings highlight versatile properties of ubistatins and have implications for their future development and use in targeting ubiquitin-signaling pathways

O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

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Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Contribution à l'évaluation de la prestation agrément de conduite liée au comportement du groupe motopropulseur d'un véhicule automobile

Powertrain driveability is considered as one of the most important customer requirement of a vehicle. In fact, in a more and more competitive market, any car manufacturer tries to distinguish himself by improving the driving pleasure felt by its customer. However, the consideration of the powertrain driveability during the vehicle design cycle is not coarse because this customer requirement is a consequence of the optimisation of the global vehicle and not only of each subsystems (motor, gearbox, ...). The aim of this research concerns the use of dynamical modelling, analysis and simplification tools in order to herlp vehicle conception engineering departments to optimise the powertrain driveability. This work proposes more complex vehicle models. Based on a bibliographical study concerning representations of the various subsystems influencing the powetrain driveability, a complete vehicle model is built. For every studied sub-performance (tip-in or tip-out, takeoff, and gearshift), various proper models are proposed. The use of modelling and analysis tools like activity index of each energetic elements of the system (inertia, stiffness, dissipation) permits to select the good model complexity level to simulate the studied phenomena. Generated models enable not only to reproduce vehicle behaviours in agreement with our experimental results but also to analyse and to put in focus phenomena like interaction between the driveline dynamic, powertrain movements and wheel horizontal suspension. Moreover, influence of conception parmeters of various sub-systems can be study with the use of those proper models. An analysis of global dynamic behaviours of the vehicle is then performed. Finally, this study improves the comptetitiveness and of engineering departments by bringing better understantig of the global vehicle behaviour in upstream phase of vehicle design cycleLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Trois regards sur le mouvement des « Gilets jaunes

International audienceLe mouvement dit des « gilets jaunes », à bien des égards énigmatique, a nourri de nombreux débats d’interprétation, tant du côté du champ politique et médiatique, que scientifique. Sociologues du travail et des mouvements sociaux ont été particulièrement interpelés par cette mobilisation : les premiers, en particulier quant à l’absence apparente des enjeux du travail et de l’interlocuteur patronal ; les seconds, notamment à propos de son orientation consensualiste et de son refus de se désigner des représentants. Et pour tous les chercheurs il a posé à nouveau frais les questions classiques de leurs modes d’engagement dans l’appréhension d’un conflit social, et du moment pertinent de la publicisation de leurs interprétations. Trois chercheurs, spécialistes du travail et des conflits sociaux et qui ont étudié ce mouvement, en débattent