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Global dynamics of antibiotic resistance: a modeling study of the spread of endemic and emerging resistance in E. coli
No full textBackground Antibiotic resistance (ABR) poses a growing threat at the global level. Emergence and worldwide dissemination of multi-resistant clones are frequently reported. However, associated drivers are still largely unknown and are a crucial knowledge to mitigate ABR risk in humans. Methods We used mechanistic modeling to analyze annual trends of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) in 39 countries over 2006-2019. The model formalizes ESBL-EC transmission, colonization and infection at the country and global levels, accounting for heterogeneous antibiotic prescriptions and human mobility. The fitted model is used to explore hypothetical scenarios of emerging antibiotic-resistant clones like carbapenem-resistant E. coli (CR-EC) and evaluate their global dissemination risk. Findings International travels alone do not explain heterogeneous ESBL-EC dynamics. Reproducing observed trends requires accounting for antibiotics impact on ESBL-EC acquisition and heterogeneous within-country transmission rates. Strong differences in transmission rates are inferred between Europe and South-East Asia, ranging on average from 7.05×10 - 3 day -1 in Spain to 16.21×10 -3 day -1 in Thailand. For CR-EC, spatiotemporal dynamics depends on the explored emergence scenario. We show that mobility patterns drive 5-years resistance dynamics, while 20-years dynamics are mostly predicted by within-country transmission and antibiotic use. Interpretation This spatiotemporal analysis highlights the weight of international travel in the early global dissemination of antibiotic-resistant clones but suggests that reducing transmission and selection pressure is fundamental to avoid fixation. There is a need to strengthen surveillance and data collection of community colonization and infection to refine modeling and support decision and ABR control at the global scale. Funding Pfizer independent medical grant (number 57504809
Figures of reconciliation: making peace with the Soviet terror in contemporary Russian literature
No full textInternational audienceReconciliation is commonly regarded as the final goal in reckoning with past violence. While the concept is deeply rooted in the human rights discourse, its political applications have long fuelled intense debate. The Russian post-Soviet transition vividly illustrates the potential risks of this notion, which can be manipulated to serve a systematic instrumentalization of history and support institutionalized forms of oblivion. This article explores the inherent tensions within the notion of reconciliation through a comparative analysis of two recent Russian novels about Soviet camps: Lyudmila Ulitskaya’s "Jacob’s Ladder" (2015) and Evgeny Vodolazkin’s "The Aviator" (2016). Both novels underscore the necessity of confronting and making peace with the past by introducing contemporary characters who reflect on the legacy of Soviet terror and grapple with these historical injustices from a present-day standpoint. As I will argue, these characters serve as mediators for posthumous reconciliation, which is ultimately achieved through an eschatological and religious perspective. While emphasizing this shared drive, the article also sheds light on the distinct ways the two novels articulate reconciliation, especially in relation to the political dimension of the memory of Soviet state terror
Stratigraphy of Carbonate‐Bearing Rocks at the Margin of Jezero Crater, Mars: Evidence for Shoreline Processes?
No full textInternational audienceMartian carbonate‐bearing rocks are compelling targets for exploration because they preserve detailed records of past aqueous processes, climate, and habitability. The Margin unit in Jezero crater is a distinct olivine‐ and carbonate‐bearing unit stratigraphically underlying the western fan, lining the inner margin of the western crater rim and has a contested origin. Perseverance spent ∼350 sols investigating the unit as part of its fourth mission campaign, aiming to constrain its origin, alteration history and biosignature preservation potential. This study reports on the lithofacies and stratigraphy of the unit by analyzing Mastcam‐Z mosaics and derived 3D outcrop models, supplemented by long‐distance SuperCam observations and detailed textural analyses from SHERLOC WATSON and ACI images. We find that the Margin unit comprises two distinct subunits. The Eastern Margin Unit (EMU) comprises well‐stratified, low‐angle basinward‐, rimward‐ and subhorizontally inclined medium‐grained sandstones which preserve angular to rounded grains, occasional crossstratification, convex‐up bedding, and erosion surfaces. The Western Margin Unit (WMU) comprises distinctly structureless to decimeter‐scale parallel‐layered rocks which drape the crater rim and are inclined into the crater. The origin of the WMU is uncertain but may be most consistent with a variably carbonated olivine cumulate. The favored depositional model for the EMU is a lacustrine shore zone environment where sediments derived from the adjacent WMU have been locally reworked by wave action along a paleoshoreline at around –2,400 m elevation. These observations suggest that the Margin unit preserves diverse subsurface and surface aqueous environments and further extends the habitability window at Jezero crater
Unlocking 2D/3D+T myocardial mechanics from cine MRI: a mechanically regularized space-time finite element correlation framework
No full textInternational audienceAccurate and biomechanically consistent quantification of cardiac motion remains a major challenge in cine MRI analysis. While classical feature tracking and recent deep learning methods have improved frame wise strain estimation, they often lack biomechanical interpretability and tem poral coherence. In this study, we propose a spacetime regularized finite element digital image/volume correlation (FE DIC/DVC) framework that enables 2D 3D+T myocardial motion tracking and strain analysis using only routine cine MRI. The method unifies Mu ltiview alignment and 2D/3D+T motion estimation into a coherent pipeline, combining region specific biomechanical regularization with data driven based temporal decomposition to promote spatial fidelity and temporal consistency . A correlation based Multiv i ew alignment module further enhances anatomical consistency across short and long axis views. We evaluate the approach on one synthetic dataset (with ground truth motion and strain fields), three public datasets (with ground truth landmarks or myocardial masks), and a clinical dataset (with ground truth myocardial masks). 2D+T motion and strain are evaluated across all datasets, whereas Multiview alignment and 3D+T motion estimation is assessed only on the clinical dataset. Compared with two classical feat ure tracking methods and four state of the art deep learning baselines, the proposed method improves 2D+T motion and strain estimation accuracy as well as temporal consistency on the synthetic data, achieving a displacement RMSE of 0.35 pixel (vs. 0.73 pixel), an equivalent strain RMSE of 0.05 (vs. 0.097), and a temporal consistency of 0.97 (vs. 0.91). On public and clinical data, it achieves superior performance in terms of a landmark error of 1.96 mm (vs. 3.15 mm), a boundary tracking Dice of 0.80 0.87 (a 2 4% improvement over the best performing baseline), and overall registration quality that consistently ranks among the top two methods By leveraging only standard cine MRI, this work enables 2D/3D+T myocardial mechanics and provides a practical route toward 4D cardiac function assessment
On the Possibility of Melting Water Ice During the Recent Past of Mars: Implications for the Formation of Gullies
No full textInternational audienceAbstract The formation of gullies on Mars has often been attributed to the melting of (sub)surface water ice. However, melting‐based hypotheses generally overlook key processes: (a) sublimation cooling by latent heat absorption, (b) the non‐stability of ice where melting conditions can be reached, and (c) the particular microclimates of gullied slopes. Using state‐of‐the‐art climate simulations, we reassess ice melting scenarios over the past 4 million years (obliquity 35°), beyond the estimated period of gully formation. We find that the melting of opaque water snow or ice at the surface of Mars is unlikely anywhere due to sublimation cooling, while (quasi‐) stable subsurface ice is typically too deep to reach melting temperatures. We propose an alternative mechanism in which seasonal frost sublimation destabilizes the regolith and brings the underlying water ice close to the surface, allowing rapid heating. Even under these optimal conditions, melting requires unrealistic assumptions. Ice containing a small amount of dust could melt via a solid‐state greenhouse effect, but both its possibility and frequency in Mars' recent past remain uncertain
Not enough H<sub>2</sub>O<sub>2</sub> to warm early Mars
No full textInternational audienceThere exists strong geomorphological, sedimentary and mineralogical evidence that Mars had an active surface hydrological cycle during the Noachian period, about 3.8 Gyr ago (Ga). However, how surface temperatures compatible with perennial liquid water could be sustained in spite of a Sun that only had 75% of its present-day brightness has remained elusive, leading to the faint young Sun paradox for Mars. Recently, the greenhouse effect of hydrogen peroxide (H2O2) has been proposed as a solution by Ito et al. (2020). Radiative transfer models have shown that a few ppmv of H2O2 in a 1 or 2 bar CO2 atmosphere could solve the faint young Sun paradox on early Mars. In a warm and wet CO2 atmosphere, H2O2 is produced by photochemistry and contributes to the stability of the CO2 atmosphere along with the HOx (H, OH and HO2) catalytic cycles. Nevertheless, a thorough assessment of the viability of such a high H2O2 abundance is still lacking. Using 1D and 3D climate models coupled with a C–H–O photochemistry solver, we show that in the most favorable case for H2O2 to build up, its steady-state abundance is several orders of magnitude short from its required abundance of ∼ 1 ppmv to have a significant radiative effect. Furthermore, we also show that a transient warming episode associated with massive H2O2 release cannot exceed 10 Martian years. We therefore rule out H2O2 as a warming agent for early Mars
Monitoring morphometric drift in lifelong learning segmentation of the spinal cord
No full textInternational audienceMorphometric measures derived from spinal cord segmentations can serve as diagnostic and prognostic biomarkers in neurological diseases and injuries affecting the spinal cord. For instance, the spinal cord cross-sectional area can be used to monitor cord atrophy in multiple sclerosis and to characterize compression in degenerative cervical myelopathy. While robust, automatic segmentation methods to a wide variety of contrasts and pathologies have been developed over the past few years, whether their predictions are stable as the model is updated using new datasets has not been assessed. This is particularly important for deriving normative values from healthy participants. In this study, we present a spinal cord segmentation model trained on a multisite (n = 75 sites, 1,631 participants) dataset, including 9 different MRI contrasts and several spinal cord pathologies. We also introduce a lifelong learning framework to automatically monitor the morphometric drift as the model is updated using additional datasets. The framework is triggered by an automatic GitHub Actions workflow every time a new model is created, recording the morphometric values derived from the model's predictions over time. As a real-world application of the proposed framework, we employed the spinal cord segmentation model to update a recently introduced normative database of healthy participants containing commonly used measures of spinal cord morphometry. Results showed that (i) our model performs well compared with its previous versions and existing pathology-specific models on the lumbar spinal cord, images with severe compression, and in the presence of intramedullary lesions and/or atrophy achieving an average Dice score of 0.95 ± 0.03; (ii) the automatic workflow for monitoring morphometric drift provides a quick feedback loop for developing future segmentation models; and (iii) the scaling factor required to update the database of morphometric measures is nearly constant among slices across the given vertebral levels, showing minimum drift between the current and previous versions of the model monitored by the framework. The code and model are open source and accessible via Spinal Cord Toolbox v7.0.</div
Optimal cut-off point of left ventricular ejection fraction for prediction of death in end-stage hypertrophic cardiomyopathy with systolic dysfunction
No full textInternational audienceBackground: In hypertrophic cardiomyopathy (HCM), end-stage disease is traditionally defined by a left ventricular ejection fraction (LVEF) below 50%. This cut-off point is widely used and supported by observational data linking it to increased mortality. However, this binary definition may oversimplify the continuum of systolic dysfunction and fail to accurately capture its prognostic significance. We aim to determine the optimal cut-off point of LVEF for predicting long-term all-cause mortality in a large cohort of consecutive end-stage HCM patients.Methods: All patients referred for cardiovascular magnetic resonance (CMR) assessment of HCM at three French university hospitals between 2008 and 2024 were retrospectively screened. All patients with HCM and LVEF < 50% were included. The primary endpoint was all-cause mortality using the National Registry of Death. A conditional inference tree (C-Tree) and Youden index method were applied to identify the optimal cut-off point of LVEF for predicting all-cause mortality. A propensity score matching approach was applied to optimize covariate balance between groups, ensuring standardized mean differences < 0.1. Cox proportional hazards models were used both before and after propensity score matching, as well as after adjustment for traditional prognostic factors. A restricted cubic spline model assessed the continuous relationship between LVEF and all-cause mortality, adjusted for covariates used in the Cox model.Results: Among 2,875 eligible patients with HCM, we included 691 patients (mean age 53 ± 7 years, 54% male) with a LVEF < 50% for the study. The optimal cut-off point of LVEF for predicting all-cause mortality was 40% with both methods. Among those, 492 patients had a LVEF of 40–50%, and 199 a LVEF < 40%. The patients with LVEF < 40% had more advanced structural and functional abnormalities: larger LV end-diastolic volumes (LVEDV indexed 99 ±11 vs 83 ±7 mL/m², p< 0.001), higher prevalence of right ventricular dysfunction (28% vs 5%, p< 0.001), and greater presence (66% vs 26%) and extent (2.4 ± 1.9 vs 0.6 ± 1.2 segments; p< 0.001) of late gadolinium enhancement (LGE). After propensity score matching, two groups of 191 patients were obtained, with comparable baseline characteristics. After a median follow-up of 9 years (IQR 6–11), 226 patients died (32%). After adjustment for traditional prognostic factors, a LVEF value < 40% was strongly associated with increased mortality before and after propensity score matching (HR: 23.6 [95% CI: 14.6–38.1]; p< 0.001 and HR: 20.5 [95% CI: 12.4-33.9], p< 0.001 respectively) (Figure 1). Annualized mortality rate was strongly higher with LVEF< 40% (15.1 versus 0.7, p< 0.001).Conclusion: In this large multicenter cohort of end-stage HCM patients, a LVEF cut-off point of 40% delineated a subgroup with substantially increased mortality, which remained significant after adjustment for traditional prognostic factors and was confirmed following propensity score matching