VHC: Quickly Building an Optimizer for Complex Embedded Architectures

International audienceTo meet the high demand for powerful embedded processors, VLIW architectures are increasingly complex (e.g., multiple clusters), and moreover, they now run increasingly sophisticated control-intensive applications. As a result, developing architecture-specific compiler optimizations is becoming both increasingly critical and complex, while time-to-market constraints remain very tight. We present a novel program optimization approach, called the virtual hardware compiler (VHC), that can perform as well as static compiler optimizations, but which requires far less compiler development effort, even for complex VLIW architectures and complex target applications. The principle is to augment the target processor simulator with superscalar-like features, observe how the target program is dynamically optimized during execution, and deduce an optimized binary for the static VLIW architecture. Developing an architecture-specific optimizer then amounts to modifying the processor simulator which is very fast compared to adapting static compiler optimizations to an architecture. We also show that a VHC-optimized binary trained on a number of data sets performs as well as a statically-optimized binary on other test data sets. The only drawback of the approach is a largely increased compilation time, which is often acceptable for embedded applications and devices. Using the Texas Instruments C62 VLIW processor and the associated compiler, we experimentally show that this approach performs as well as static compiler optimizations for a much lower research and development effort. Using a single-core C60 and a dual-core clustered C62 processors, we also show that the same approach can be used for efficiently retargeting binary programs within a family of processors

Door-in-the-Face and But-You-Are-Free

International audienceAccording to Howard's proposal of chaining compliance techniques and based on the proximity of interpretation of their effects, this study aimed to test a combination of two paradigms: a door-in-the-face request that makes a high-cost request before the target request and the but-you-are-free request that adds an evocation of freedom to the request. Two experiments were conducted (N = 120 and 1,292) to promote donations to non-profit organizations. There were four conditions. Participants were approached according to the door-in-the-face procedure, to the but-you-are-free procedure, to a combination of both of them, or directly in a control condition. There was an increase of compliance rates in experimental conditions compared to the control condition and an increase in the average amount donated in the combination condition compared to the control condition in the second study. Results are discussed in terms of responsibility and guilt mechanisms, and future developments are proposed

Orienter les consommations vers de nouvelles pratiques : Les particularités de l’apprentissage des pratiques alimentaires

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Eomes-Dependent Loss of the Co-activating Receptor CD226 Restrains CD8+ T Cell Anti-tumor Functions and Limits the Efficacy of Cancer Immunotherapy

International audienceCD8+ T cells within the tumor microenvironment (TME) are exposed to various signals that ultimately determine functional outcomes. Here, we examined the role of the co-activating receptor CD226 (DNAM-1) in CD8+ T cell function. The absence of CD226 expression identified a subset of dysfunctional CD8+ T cells present in peripheral blood of healthy individuals. These cells exhibited reduced LFA-1 activation, altered TCR signaling, and a distinct transcriptomic program upon stimulation. CD226neg CD8+ T cells accumulated in human and mouse tumors of diverse origin through an antigen-specific mechanism involving the transcriptional regulator Eomesodermin (Eomes). Despite similar expression of co-inhibitory receptors, CD8+ tumor-infiltrating lymphocyte failed to respond to anti-PD-1 in the absence of CD226. Immune checkpoint blockade efficacy was hampered in Cd226-/- mice. Anti-CD137 (4-1BB) agonists also stimulated Eomes-dependent CD226 loss that limited the anti-tumor efficacy of this treatment. Thus, CD226 loss restrains CD8+ T cell function and limits the efficacy of cancer immunotherap

Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

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Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

International audienceImportance Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).Objective To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.Design, Setting, and Particpants This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.Interventions Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.Main Outcomes and Measures Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.Results Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).Conclusions and Relevance In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT0433180

Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

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