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MOVIE phase II trial of tremelimumab plus durvalumab combined with metronomic oral vinorelbine in patients with head and neck cancer
No full textInternational audienceBackground: Treatment options for advanced solid tumors are limited. In recent years, anti-programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy as monotherapy has shown significant efficacy, albeit in a limited subset of patients. In the MOVIE trial, metronomic chemotherapy was combined with two immune checkpoint inhibitors (ICIs) to improve clinical outcomes in patients with advanced solid tumors. Patients and methods: MOVIE was a phase I/II French, multicenter, open-label, nonrandomized study with a Bayesian design that evaluated the antitumor activity and safety of metronomic vinorelbine associated with durvalumab plus tremelimumab. Here, we report on the cohort of patients with head and neck squamous cell carcinoma (HNSCC) from the MOVIE phase II study. Patients were aged >= 18 years with histologically confirmed recurrent or metastatic HNSCC, resistant to conventional therapies, and presented a measurable disease according to RECIST version 1.1. They received oral vinorelbine 40 mg three times a week, and durvalumab 1500 mg plus tremelimumab 75 mg via intravenous infusion on day 1 of 28-day cycles, for a maximum of four cycles of tremelimumab. The primary endpoint was the clinical benefit rate (CBR), defined as the rate of complete response (CR), partial response (PR), or stable disease (SD) lasting at least 24 weeks. Results: Fifteen HNSCC patients were included between May 2019 and October 2020. The mean estimated CBR according to a noninformative prior distribution was 23.5% (95% credible interval 7.3-45.6). One patient achieved CR, 1 PR, and 1 SD > 24 weeks, leading to an objective response rate of 14.3%. The median progression-free survival was 1.8 months (95% confidence interval 1.0-1.9 months), and the median overall survival was 8 months (95% confidence interval 2.5-12.7 months). The most common vinorelbine-related grade >= 3 adverse events were anemia (n = 2, 13%) and neutropenia (n = 3, 20%). The most common ICI-related grade >= 3 adverse events were anemia (n = 1) and hypokalemia (n = 1). There were no treatment interruptions for toxicity and no treatment-related deaths. Conclusions: Metronomic vinorelbine in combination with dual durvalumab plus tremelimumab immunotherapy had only moderate activity in pretreated advanced HNSCC
Reference and simplified parameterized LCA Models as decision-making tools in Early-Phase Energy Project Development: Application to Microalgae-Based Biogas Production Case Study
No full textInternational audienceRenewable energy project development is crucial to tackle environmental burdens in the energy sector. To achieve this, project developers must consider environmental aspects at early phases of development, including feasibility studies, conceptual design, design development and permitting. To analyze environmental impacts of such project, we propose parametrized Life Cycle Assessment (LCA) models. On the one hand, reference models, built in collaboration with experts, help identify processes most contributing to environmental impacts, enabling targeted project improvements during conceptual design, and design development and permitting. Simplified models, on the other hand, allow project developers to quickly assess environmental compliance during feasibility studies, considering only key parameters. The less influential parameters of the reference model are identified using Global Sensitivity Analysis to generate simplified models. The effectiveness of using reference and simplified models has been demonstrated considering climate change impacts for a case study on a microalgae-based biogas production system. The reference model built with 39 parameters allows identifying enzymes production and CO2 production as major contributors to climate change. From this reference model, a simplified one requiring only 6 parameters was generated to compute impacts on climate change.The application of reference and simplified models helps project developers make informed decisions to improve environmental sustainability in renewable energy projects. Key contributing processes can be identified, including background ones that may be improved through collaboration with their operators or using alternative solutions. Using a simplified model enables faster, easier impact estimation keeping good accuracy, requiring data for fewer parameters than the reference model
Impact of local taxation reforms on firms’ dynamics and local performances
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The first modeling, measurement, and confirmation of natural attenuation over a 30-year period in a uranium in-situ recovery context: Approaches and perspectives
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Identifying Patients With Low Relapse Rate Despite High-Risk Estrogen Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Early Breast Cancer: Development and Validation of a Clinicopathologic Assay
No full textInternational audiencePURPOSE Escalation of adjuvant systemic therapies (eg, with cyclin-dependent kinase 4 and 6 inhibitors) is now indicated for patients with clinically defined high-risk estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2–) early breast cancer, although it is unclear which will benefit from additional therapies. We developed and validated a prognostic clinicopathologic assay identifying a subpopulation of high-risk patients with good prognosis after standard adjuvant therapies, who may safely forgo treatment escalation. METHODS We trained a Cox proportional-hazards model that integrates clinicopathologic variables with features derived from digitized hematoxylin-and-eosin–stained resection slides from a retrospective data set. The model assigns each patient to a low-risk or not low-risk group, reflecting their predicted risk of recurrence. Blind validation was successively performed on high-risk patients from the prospective trials CANTO (ClinicalTrials.gov identifier: NCT01993498 ) and UNIRAD (ClinicalTrials.gov identifier: NCT01805271 ). RESULTS Built on data from 6,164 patients with ER+/HER2– early-stage breast cancer, this assay integrates four clinicopathologic variables, and 10 slide-derived features capturing tumor architecture, microenvironment, and proliferation. In the combined CANTO and UNIRAD trials (n = 633), 95.4% of the low-risk patients remained free of distant recurrence and death from breast cancer at 9 years, compared with 76.8% for the not low-risk group. Distant recurrence-free interval (subdistribution hazard ratio [HR], 0.21 [95% CI, 0.09 to 0.52]; P = .001), invasive disease-free survival (HR, 0.31 [95% CI, 0.16 to 0.60]; P = .001), and overall survival (HR, 0.35 [95% CI, 0.13 to 0.97]; P = .044) were all statistically significant. Multivariate analyses showed that the assay provided predictive information beyond clinicopathologic variables. Analytical validation showed robustness to data variability. CONCLUSION The assay demonstrated robust performance in identifying a core group of patients with high-risk ER+/HER2– breast cancer for whom additional adjuvant treatment may be futile
A hundred and two just-so stories: exploring the lay evolutionary hypotheses of the manosphere
No full textInternational audienceThe manosphere is a collection of online antifeminist men’s groups whose ideologies often invoke Darwinian principles and evolutionary psychological research. In the present study, we reveal that the manosphere generates its own untested and speculative evolutionary hypotheses, or ‘just-so stories’, about men, women, and society. This is a unique phenomenon, where lay (i.e. non-expert) individuals creatively employ evolutionary reasoning to explain phenomena in accordance with their particular worldview. We thus assembled the first dataset of lay evolutionary just-so stories extracted from manosphere content ( n = 102). Through qualitative analysis, we highlight the particularity of the manosphere’s lay evolutionism. It is a collective bottom-up endeavour, which often leads to practical advice and exhibits a male gender bias. We further show that 83.3% of manosphere just-so stories pertain to sex differences and that only 36.3% explicitly signal that they are speculative. Given this evidence that lay communities collectively engage in evolutionary hypothesizing, we reflect on implications for evolutionary scholars and for the field as a whole in terms of ethics and public image. Lastly, we issue a call for renewed discussion and reflection on evolutionary hypothesizing, a central yet somewhat neglected feature of evolutionary behavioural science
Collaborations de recherche entre génétique végétale et agronomie : une approche diachronique pour appréhender leurs enjeux actuels et leur renouvellement
No full textIn-Context Meta-Learning with Large Language Models for Automated Model and Hyperparameter Selection
No full textInternational audienceModel and hyperparameter selection is a critical yet costly step in machine learning, often requiring expert intuition or extensive search. We investigate whether large language models (LLMs) can reduce this cost by acting as in-context meta-learners that generalize across tasks to propose effective model-hyperparameter choices without iterative optimization. Each task is represented as structured metadata, and we prompt an LLM under two strategies: Zero-Shot, using only the target task metadata, and Meta-Informed, which augments the prompt withmetadata–recommendation pairs from prior tasks. Evaluated on 22 tabular Kaggle challenges, Meta-Informed prompting outperforms Zero-Shot and hyperparameter optimization baselines, approaching expert AutoML blends while yielding interpretable reasoning traces and efficiency gains under tight training budgets. These results suggest that LLMs can transfer knowledge across tasks to guide automatedmodel selection, establishing model and hyperparameter selection as a concrete testbed for studying emergent adaptation beyond language domain
Spatio-temporal Dynamics of the Surface Waves in a Liquid-Liquid Jet
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DISPOSITIF DE PASSAGE D'UN GAZ D'UN ÉTAT LIQUIDE À UN ÉTAT SUPERCRITIQUE
No full textL'invention vise un dispositif de changement d'état 1 comprenant une première branche 16 et une deuxième branche 18, au moins un collecteur 6 pourvu au moins d'une première entrée 7 raccordée à la première branche 16, d'une deuxième entrée 9 raccordée à la deuxième branche 18, d'une première sortie 42 par laquelle le fluide à l'état supercritique est extrait et d'une deuxième sortie 40, la première branche 16 comprenant un échangeur de chaleur 24 et un organe de compression 32, la première branche 16 et la deuxième branche 18 s'étendant à partir d'un point de divergence 20 et se rejoignant au sein du collecteur 6, le circuit (10) comprenant au moins une ligne de retour (46) raccordée à la deuxième sortie (40) du collecteur (6), ladite ligne de retour (46) étant configurée pour injecter entre l'échangeur de chaleur (24) et l'organe de compression (32) au moins une partie du fluide présent dans le collecteur (6)