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Real-life use of bone-targeting agents for bone metastases in France between 2009 and 2018: Results of the OPTIMOS study
No full textInternational audienceAim: To determine the use of bone-targeting agents (BTAs) in clinical practice in France and the occurrence of skeletal-related events (SREs) in cancer patients with bone metastases.Methods: This study analysed data, recorded prospectively in a French National Health Insurance database, for patients who had a first diagnosis of bone metastases between 2009 and 2018.Results: A total of 6,663 patients were analysed (mean age 69.7 ± 13.2 years, 53.2 % male) corresponding to 2,363 bone metastases only patients and 4,300 patients with SREs at inclusion. The most frequent primary cancers were breast (15.8 %), prostate (13.4 %), lung (12.6 %) and digestive cancer (10.6 %). Six-hundred and twenty-one patients (9.3 %) were treated with BTAs (52.7 % with denosumab). Median [IQR] time between inclusion and BTA initiation was similar with denosumab (3.3 months [1.2-7.9]) and bisphosphonates (3.3 months [1.2-8.7]). Patients with a SRE at inclusion and early BTA initiation (≤3 months) had a significative lower incidence of a second SRE at 12 months than those with late initiation (13.6 % [95 %CI: 8.1-20.4] vs. 21.6 % [14.8-29.2] respectively; p < 0.001).Conclusion: BTAs are underused in bone metastases patients in France. There is an urgent need to optimise bone metastases management in accordance with ESMO 2020 guidelines
Prediction of uncertain visual trajectories is biased toward motion continuity: La prédiction des trajectoires visuelles incertaines est biaisée en faveur de la continuité du mouvement
No full textInternational audienc
Vacuum electromagnetic field correlations between two moving points
No full textInternational audienceA renewed experimental interest in quantum vacuum fluctuations brings back the need to extend the study of electromagnetic vacuum correlations. Quantum or semi-classical models developed to understand various configurations should combine the effects of the zero-point fluctuations with those of blackbody radiation. In this paper, after a brief historical introduction and a rapid study of the electric field correlations in time domain, we propose exact and approximate expressions for the vacuum field correlations in Fourier space seen by moving points. We first present an exact computation of the electric field correlations, expressed in frequency space, between two points moving with opposite constant velocities on parallel trajectories. We also consider the electric field self-correlations, i.e. on the same moving point but at different frequencies, and comment the results related to special relativity. Then, we compute the exact main symmetrized quadratic electromagnetic field correlations between two points diametrically opposed on the same circular trajectory, with diameter r, covered at constant angular velocity Ω. We derive the expressions for the electromagnetic field correlations with itself and with its spatial derivatives, still at the locations of the moving points. Since the points we consider are accelerating, both the zero-point fluctuations and the blackbody spectrum give non-trivial results, for two-point correlations as well as for self-correlations. In both cases, results are shown at any vacuum temperature. For practical uses, we provide the first-order approximations in the small parameter Ωr/c with c being the speed of light
Active-passive microwave scattering in the Antarctica wind-glazed region: an analog for icy moons of Saturn
No full textInternational audienceMicrowave radiometry and scatterometry, two complementary modes of sensing the composition and structure of the upper meters to hundreds of meters of the subsurface, are often difficult to reconcile, both on the Earth cryosphere and on icy moons of Saturn. To help interpret and model microwave scattering in porous, high-purity ices, we examine jointly 6.9–89 GHz AMSR2 radiometry in vertical (V) and horizontal (H) polarizations as well as 5.2 GHz ASCAT, 13.4 GHz QuikSCAT, and 13.5 GHz OSCAT scatterometry in the wind-glazed region of the East Antarctic ice sheet. The data are simulated using the Snow Microwave Radiative Transfer (SMRT) model, assuming a simplified snowpack characterized by constant temperature and a continuous increase in grain size (represented by optical radius) and density with depth. For the first time, we show that scatterometry and 6.9–37 GHz radiometry at V polarization can be successfully simulated with a unique simple snowpack model, indicating that incoherent volume scattering on subsurface heterogeneities dominates both the active and passive signals. To also simulate H-polarized radiometry, a thin surface ice layer as observed in the wind-glazed regions is one solution. Additional complexity, such as seasonal temperature variations, surface roughness, or non-continuous density variations, is necessary to explain the 89 GHz data and HH-polarized backscatter. Meanwhile, applying the same approach to simulate simultaneously passive and active Ku-band observations of icy moons improves on previous attempts but remains unable to reproduce the very high backscatter observed, highlighting the importance of coherent scattering and possibly unknown large icy structures (at least millimetric) in the subsurface. More work is still to be done to fully reproduce the microwave signatures of icy surfaces in the solar system
Thermoacoustic instabilities linear study of a canonical thermally choked-flow nozzle
No full textQuasi-one-dimensional linear acoustic models provide an efficient framework for analyzing thermoacoustic interactions in combustion systems, such as dual-mode ramjet engines choked by a thermal throat. In this study, a coupled formulation is introduced that combines state-of-theart models of acoustic-wave scattering, steady heat-release-rate distribution, and a simplified flame–acoustic model assuming a one-dimensional linear acoustic dynamics, a non-uniformly heated flow and temperature-dependent gas properties. An extended boundary condition at the thermal throat is also incorporated to represent the influence of unsteady heat release on local flow fluctuations. The analysis focuses on the behavior of aeroacoustic coefficients and on the Rayleigh index. At high frequencies, the impact of flame–acoustic coupling is negligible, whereas at low frequencies, varying the flame speed and the flame-holder ratio leads to pronounced oscillations and amplification of the acoustic response. Using the Rayleigh index, it is shown that the most unstable configurations correspond to high flame speeds, regardless of the flame-holder geometry, for which unsteady heat-release fluctuations remain strongly in phase with the acoustic pressure
Revealing the diversity of collective experimentation in agriculture: Constructing idealtypes from French case studies
No full textInternational audienceContext: The agroecological transition underscores the need to rethink knowledge production in agriculture, especially in relation to experimentation. This includes involving a wider range of stakeholders and exploring diverse and complementary forms of experimentation. Objective: This article aims to shed light on the diversity of existing collective experimentations, in order to document the ongoing renewal of experimental approaches and to propose benchmarks for understanding and supporting them. Methods: We conducted 34 semi-structured interviews and 10 observant participations, leading to the identification of 28 case studies that we define as collective experimentations. We define collective experimentation as the process of implementing and monitoring an intervention with uncertain outcomes, which leads to the production of knowledge. We did a comprehensive analysis of these collective experimentations, to understand how and why they are conducted. To do so, our analysis considered both the physical design of the experimental setups and the questions addressed, as well as the collective organization of the actors involved. Results and Conclusions: We propose six idealtypes of collective experimentations: Idealtype A: Replicating experimental situations to generate standardized data, Idealtype B: Integrating data from diverse experimental practices in a joint analysis, Idealtype C: Distributing questions to generate knowledge on a common topic, Idealtype D: Pooling a diversity of experiences to explore a common subject, Idealtype E: Distributing activities within a single experimental situation and Idealtype F: Gathering human and material resources on a single site to experiment jointly on several experimental situations. Significance: These idealtypes shed light on the diversity of collective experimentation approaches in agriculture, which are often under described in the literature. By offering a set of structured reference points, it can support researchers, facilitators, and practitioners in recognizing, designing and valuing collective experimentations adapted to their contexts. It opens new perspectives for rethinking how experimental knowledge is produced, shared, and valued to support agroecological transitions
High brightness in bis(tri-isopropylsilyl)ethynyl-functionalized polycyclic aromatic hydrocarbons: localized representation versus Clar's model
No full textInternational audiencePeri-fused PAHs converge to a single localized representation: cata-condensation increases aromatic sextets and amplifies brightness while linear extension adds cis -diene units and diminishes it
An improved approach to estimate the natural land carbon sink
No full textInternational audienceThe natural land carbon sink (SLAND) absorbs roughly 25–30% of anthropogenic CO2 emissions, thus playing a critical role in offsetting climate warming. In the Global Carbon Budget (GCB), SLAND is estimated using model simulations that isolate the carbon response of land to environmental changes (i.e. rising atmospheric CO2, nitrogen deposition, and changes in climate). However, these simulations assume fixed pre-industrial land cover, failing to represent today's human-altered landscapes. This leads to a systematic overestimation of forest area, and thus CO2 sink strength, in regions heavily altered by human activity. We present a new process-based approach to estimate SLAND using Dynamic Global Vegetation Models. Our corrected estimate reduces SLAND by ~20% (0.6 PgC yr-1) over 2015–2024, from 3.00 ± 0.94 to 2.42 ± 0.77 PgC yr-1. We incorporate this new SLAND estimate with emissions from land-use change from bookkeeping models, to estimate a net land sink of 1.19 ± 1.04 PgC yr-1, which aligns closely with atmospheric inversion constraints. This downward revision of SLAND reduces the magnitude of the budget imbalance for 2015–2024, indicating a more consistent partitioning of the global carbon budget
Cytoplasmic FKBP7 reflux controls NFE2L1 levels as an adaptive response to chemotherapy in prostate cancer cells
No full textInternational audienceUnderstanding how cancer cells adapt to chemotherapy is essential for overcoming resistance. One mechanism involved in taxane resistance in prostate cancer is mediated by FKBP7, a still-understudied endoplasmic reticulum-resident cis-trans isomerase. Using cell fractionation, we demonstrate that the ERAD-independent retrotranslocation of FKBP7 into the cytosol correlates with the oxidative stress triggered by chemotherapy, as an escape response. Once in the cytosol, FKBP7 interacts with the translation machinery and with eIF4G1, specifically with its C-terminal HEAT3 domain. Following FKBP7 silencing, polysome profiling and RNA sequencing identified the transcription factor NFE2L1 - a key regulator of oxidative stress adaptation - as an effector of FKBP7. Here, we also produced the first NMR spectra of the FKBP7 catalytic domain, revealing a well-folded protein that binds to rapamycin and everolimus but not to FK506. Overall, our results demonstrate that chemotherapy-induced oxidative stress triggers an adaptive mechanism in which FKBP7 is translocated into the cytosol where it modulates NFE2L1, thereby enabling the survival of resistant cells. These findings lead us to propose the targeting of FKBP7/NFE2L1 signaling as a strategy to overcome adaptive resistance
kmindex and ORA: indexing and real-time user-friendly queries in terabyte-sized complex genomic datasets
No full textInternational audiencePublic sequencing databases contain vast amounts of biological information, yet they are largely underutilized as one cannot efficiently search them for any sequence(s) of interest. We present kmindex , an innovative approach that can index thousands of highly complex metagenomes and perform sequence searches in a fraction of a second. The index construction is an order of magnitude faster than previous methods, while search times are two orders of magnitude faster. With negligible false positive rates below 0.01%, kmindex outperforms the precision of existing approaches by four orders of magnitude. We demonstrate the scalability of kmindex by successfully indexing 1,393 complex marine seawater metagenome samples from the Tara Oceans project. Additionally, we introduce the publicly accessible web server “Ocean Read Atlas” ( ORA ) at https://ocean-read-atlas.mio.osupytheas.fr/ , which enables real-time queries on the Tara Oceans dataset. The open-source kmindex software is available at https://github.com/tlemane/kmindex