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We report an unplanned pregnancy in an HIV-positive woman in her 20s who was undergoing treatment for 6 months with alectinib (Alecensa) for stage IV non-small-cell lung carcinoma. Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor alectinib, a molecule that inhibits proteins involved in tumour cell growth, is the recommended first-line treatment option in case of ALK mutation. Although the patient was informed of the need for definitive contraception, she became pregnant during the treatment with alectinib. A complete tumour response was observed at the time the pregnancy was discovered. Treatment discontinuation was proposed as the patient wanted to keep the pregnancy. Alectinib was temporarily stopped throughout the remaining pregnancy period inline with the patient’s wishes. The pregnancy was uncomplicated. She delivered a healthy female baby vaginally, with treatment being resumed after delivery. After 34 follow-up months, the patient remained in oncological remission and the child’s physical development is normal.

The sentinel plantation concept consists of assessing the impact of exotic factors, such as pests and pathogens, on plants of interest by planting them out of their native range. This tool is a way to enhance knowledge for pest risk analysis (PRA) by guiding decisions on how quarantine organisms should be regulated and where to focus prevention and surveillance efforts for an early detection. In this study, the sentinel method was used in the case of research on Xylella fastidiosa, a plant pathogenic bacterium that has recently been found established in southern Europe, but whose potential impact and possible host range are still poorly documented in northern areas where the bacterium is not known to occur. To improve knowledge on the susceptibility of potential hosts of X. fastidiosa in northern Europe, a sentinel plantation of Prunus domestica cv. Opal, Quercus petraea and Salix alba was established in the X. fastidiosa-infected area of Majorca. In order to assess the circulation of the bacterium in the sentinel plot and around it, surveys of the local flora and insect vectors were carried out, as well as the planting of a network of rosemary “spy plants”. Symptomatic monitoring and molecular analyses were performed on the sentinel plants for four years. During these years, X. fastidiosa was never detected in our sentinel plants most likely because of the low infectivity pressure recorded in the surroundings. This study underlines the complexity of conducting sentinel plantation assays combined with X. fastidiosa research, highlighting the need for long-term investigation and questioning the efficiency of the sentinel tool. However, this study is placed in perspective with other valuable sentinel plantations. It also highlights the complementarity of the tool and proposes elements to improve or re-orientate the implementation of future sentinel projects.

Ice aprons are defined as very small ice bodies covering steep rock slopes. They have only been the subject of increased scientific interest for a few years, despite the fact that they are a condition for mountaineering and obvious elements in the high-alpine landscapes. However, very little is known about their distribution, evolution and physical characteristics. In this paper, we review the existing knowledge on ice aprons, which have almost exclusively been investigated in the Mont-Blanc massif, Western Alps. We supplement this review with novel results from recent surveys of ice aprons. We used a wide array of methodologies, from remote sensing (multi-source imagery) to in situ (stakes and thermal monitoring) and laboratory (radiocarbon dating and texture analysis) glaciological investigations. In the Mont-Blanc massif, ice aprons occupy 4.2 km2 within the alpine permafrost zone. Temperature measured at the ice–rock interface is indeed largely negative. Thinness of ice aprons coupled with the cold context implies a quasi-stationary shear regime without basal Sliding. Only ice at the surface can possibly melt in warm periods. After a shrinking period from the end of the Little Ice Age to the mid-to-late-1960s, ice aprons experienced a short period of expansion, followed by an accelerated shrinkage since the beginning of the 21st century. This shrinkage now favours rockfall triggering and poses a serious threat to a glaciological heritage since ice aprons host several-thousand-year-old ice. Finally, we synthesize this information to assess the existing definition of ice aprons, and propose some future research directions.

A growing incidence of differentiated thyroid cancer (DTC) has been reported in most developed countries, corresponding mainly to incidentally discovered small papillary thyroid carcinomas. Given the excellent prognosis of most patients with DTC, optimal therapeutic management, minimizing complications, and preserving patient quality of life are essential. Thyroid surgery has a central role in both the diagnosis, staging, and treatment of patients with DTC. Thyroid surgery should be integrated into the global and multidisciplinary management of patients with DTC. However, the optimal surgical management of DTC patients is still controversial. In this review article, we discuss the recent advances and current debates in DTC surgery, including preoperative molecular testing, risk stratification, the extent of thyroid surgery, innovative surgical tools, and new surgical approaches.

Understanding the immediate impacts of oil spills is essential to recognizing their long-term consequences on the marine environment. In this study, we traced the early (within one week) signals of crude oil in seawater and plankton after a major oil spill in October 2019 in the Red Sea. At the time of sampling, the plume had moved eastward, but we detected significant signs of incorporation of oil carbon into the dissolved organic carbon pool, resulting in a 10–20% increase in the ultraviolet (UV) absorption coefficient (a254) of chromophoric dissolved organic matter (CDOM), elevated oil fluorescence emissions, and depletion of the carbon isotope composition (δ13C) of the seawater. The abundance of the picophytoplankton Synechococcus was not affected, but the proportion of low nucleic acid (LNA) bacteria was significantly higher. Moreover, specific bacterial genera (Alcanivorax, Salinisphaera, and Oleibacter) were enriched in the seawater microbiome. Metagenome-assembled genomes (MAGs) suggested that such bacteria presented pathways for growing on oil hydrocarbons. Traces of polycyclic aromatic hydrocarbons (PAHs) were also detected in zooplankton tissues, revealing the rapid entry of oil pollutants into the pelagic food web. Our study emphasizes the early signs of short-lived spills as an important aspect of the prediction of long-term impacts of marine oil spills.

The foundation of morality, and mainly, the possibility of moral sentiments that are universal and inalienable, is a central problem in Maine de Biran’s philosophy. Many studies focus on the part played by the self in Maine de Biran’s late philosophy, but relatively few consider with precision the importance of the concept of sympathy in this context. In this paper, I would like to show that this concept, which Biran mobilizes from his first to his last writings, is an important conceptual resource in his enterprise of founding morality. I will draw on three main texts that cover almost the entire period in which he wrote, namely, his Mémoire sur l’influence de l’habitude sur la faculté de penser, his Mémoire sur les perceptions obscures ou sur les impressions générales affectives et les sympathies en particulier, and his Fragments relatifs aux fondements de la morale et de la religion. The main finding is that sympathy occupies a central place in this enterprise of moral foundation but undergoes profound and almost contradictory conceptual re-elaborations throughout Biran’s intellectual journey. Although in his first philosophical texts Biran concentrates on the fundamental dimension of organic sympathy, he rejects it almost entirely in his last texts in favor of an analysis of the sympathy between the selves.

The magmatic rocks from Jabuka, Brusnik, Vis Islands and the submerged Brusnik plateau have been investigated to define their age and genetic affinity, identifying their role in the geodynamics of the Adria Plate. The plutonic and lava flow samples have been characterized for their petrography, mineral chemistry, whole rock major and trace elements, and Sr and Nd isotopic compositions. The two samples with the freshest plagioclase crystals have been selected for 40Ar/39Ar analysis, which gave ages of 221.5 ± 2.5 Ma (Brusnik) and 227 ± 5 Ma (Jabuka), similar to those of the Triassic magmatism from the northern part of the Adria Plate and neighbouring territories. Geochemical and isotopic data suggest that the magmatism dominantly sourced from spinel peridotites variously metasomatized during pre-Mesozoic subduction events. Furthermore, the investigated rocks evidence interactions of the magmas with Mid-Late Triassic evaporites. The comparison with other coeval magmatic occurrences from the Adria Plate and its edges shows that the subduction signature of the Triassic within-plate magmatism is mainly related to the evolution of the upper mantle of the Adria Plate.

The generation of photon pairs from nanoscale structures with high rates is still a challenge for the integration of quantum devices, as it suffers from parasitic signals from the substrate. In this work, we report type-0 spontaneous parametric down-conversion at 1550 nm from individual bottom-up grown zinc-blende GaAs nanowires with lengths of up to 5 mu m and diameters of up to 450 nm. The nanowires were deposited on a transparent ITO substrate, and we measured a background-free coincidence rate of 0.05 Hz in a Hanbury-Brown-Twiss setup. Taking into account transmission losses, the pump fluence, and the nanowire volume, we achieved a biphoton generation of 60 GHz/ Wm, which is at least 3 times higher than that of previously reported single nonlinear micro-and nanostructures. We also studied the correlations between the second-harmonic generation and the spontaneous parametric down-conversion intensities with respect to the pump polarization and in different individual nanowires., Nano Letters, 23 (8), ISSN:1530-6984, ISSN:1530-6992

In the next few years, numerous satellites with high-resolution instruments dedicated to the imaging of atmospheric gaseous compounds will be launched, to finely monitor emissions of greenhouse gases and pollutants. Processing the resulting images of plumes from cities and industrial plants to infer the emissions of these sources can be challenging. In particular traditional atmospheric inversion techniques, relying on objective comparisons to simulations with atmospheric chemistry transport models, may poorly fit the observed plume due to modelling errors rather than due to uncertainties in the emissions. The present article discusses how these images can be adequately compared to simulated concentrations to limit the weight of modelling errors due to the meteorology used to analyse the images. For such comparisons, the usual pixel-wise ℒ2 norm may not be suitable, since it does not linearly penalise a displacement between two identical plumes. By definition, such a metric considers a displacement as an accumulation of significant local amplitude discrepancies. This is the so-called double penalty issue. To avoid this issue, we propose three solutions: (i) compensate for position error, due to a displacement, before the local comparison; (ii) use non-local metrics of density distribution comparison; and (iii) use a combination of the first two solutions. All the metrics are evaluated using first a catalogue of analytical plumes and then more realistic plumes simulated with a mesoscale Eulerian atmospheric transport model, with an emphasis on the sensitivity of the metrics to position error and the concentration values within the plumes. As expected, the metrics with the upstream correction are found to be less sensitive to position error in both analytical and realistic conditions. Furthermore, in realistic cases, we evaluate the weight of changes in the norm and the direction of the four-dimensional wind fields in our metric values. This comparison highlights the link between differences in the synoptic-scale winds direction and position error. Hence the contribution of the latter to our new metrics is reduced, thus limiting misinterpretation. Furthermore, the new metrics also avoid the double penalty issue.

The panoramic cameras (PCs) on board Hexagon KH-9 (KH-9PC) satellite missions from 1971–1984 captured very high-resolution stereo imagery with up to 60 cm spatial resolution. This study explores the potential of this imagery for glacier mapping and change estimation. We assess KH-9PC imagery using data from the KH-9 mapping camera (KH-9MC), KH-4PC, and SPOT and Pléiades satellite imagery. The high resolution of KH-9PC leads to higher-quality DEMs, which better resolve the accumulation region of the glaciers in comparison to the KH-9MC. On stable terrain, KH-9PC DEMs achieve an elevation accuracy of

Cette introduction repart du constat que le signifiant, notamment dans le domaine de l’énaction et de la cognition incarnée ne prend en charge que certains aspects de l’émergence de la cognition liée au langage comme résultant des interactions vécues. Elle ne prend en effet pas assez en compte le fait que le signifiant linguistique, outre d’être le produit d’un acte corporel, possède une dimension éminemment systémique et culturelle. La question posée ici est de réconcilier la dimension réticulaire du signifiant et sa dimension corporelle.

This introduction starts from the observation that the signifier, especially in the field of enaction and embodied cognition, only takes into account certain aspects of the emergence of cognition linked to language as a result of lived interactions. Indeed, it does not take sufficiently into account the fact that the linguistic signifier, besides being the product of a bodily act, has an eminently systemic and cultural dimension. The question raised here is to reconcile the reticular dimension of the signifier and its bodily dimension.

CONTEXT: Endocrine therapy combined with CDK4/6 inhibitor is the standard frontline treatment for the vast majority of HR+/HER2- metastatic breast cancer (MBC) patients. Despite an overall survival benefit, patients eventually progress and mechanisms of resistance to this combination are not well identified. Non-invasive monitoring of the efficacy of treatment could help into tailoring therapeutic regimen. Extracellular vesicles (EVs) are a group of heterogeneous nanosized bioparticles (30-1000nm), released by almost all cell types - including tumor, platelets, and immune cells – carrying informative biological material emanating from the mother cell and circulating in the blood stream. In this project, we ambition to assess whether the vesiclemia, i.e. plasmatic extracellular vesicle concentration can be used as a clinic-biological parameter to assist in the monitoring of patients. METHODS: EPICURE is an ongoing pilot prospective cohort study of heterogeneous and massive data integration, i.e. multi-omics approaches in MBC patients. The present study focused on patients with HR+/HER2- MBC receiving frontline endocrine therapy+iCDK4/6. Plasma samples were drawn every 3 months during the treatment until progression. The workflow for the enrichment of circulating EVs was developed from frozen plasma. A semi-automatized isolation procedure using size exclusion chromatography combined with the newly developed interference light microscopy apparatus Videodrop allowed to routinely separate plasmatic EVs and quantify vesiclemia in a fast and reliable manner for a large number of samples (longitudinal follow-up of MBC patients). RESULTS: 26 patients were included and monitored for vesiclemia. Median age was 58.5y (±13.7). Metastatic disease sites were distributed as follows: bone metastases (21; 84%), liver (21; 84%), thoracic (10; 40%), node (2; 8%), brain (1; 4%), others (2; 8%). Endocrine therapy included aromatase inhibitors (20; 77%), fulvestrant (6; 29%), GnRH agonists (5; 19%) and CDK4/6 inhibitors palbocilib (15; 57%), abemaciclib (8; 31%) and ribociclib (3; 11%). With a median follow-up time of 22.1 months (95%CI 21.2 - not reached), median progression free survival was 21.8 months (95%CI 18.1 - not reached). Median time on treatment was 19.4 months (IQR 11.6 - 22.1). Objective response rate was confirmed in 12 patients (6 with complete response). Out of the 26 patients, 12 stopped the frontline treatment due to disease progression. 135 longitudinal follow-up samples were analyzed for EVs. All patients who progressed rapidly after treatment initiation (i.e median PFS< 6 months) had an increased vesiclemia at the months 2 and 6 after inclusion. Conversely, patients who had a median PFS >18m had a stable vesiclemia during this period. CONCLUSION This study aims to use circulating EVs as a therapeutic companion to anticipate treatment resistance and tumor progression in MBC patients. Our preliminary data suggest that the vesiclemia could be used as a predictive tool to anticipate treatment failure, and thus might be used to tailor treatments in time. Citation Format: Mathilde Richard, Jean Sebastien FRENEL, Laurent Mathiot, Mario Campone, Mathilde Colombie, Marie Robert, Anne Patsouris, Frederic Bigot, Julie Gavard, Gwennan André-Grégoire, Laetitia Guevel. Extracellular vesicle-based biomarker assay for the monitoring of the efficacy of frontline endocrine therapy + CDK4-6 inhibitors in metastatic breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-11-09.