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High-dose chemotherapy with autologous haematopoietic stem cell transplantation in patients with isolated vitreoretinal lymphoma: a LOC network study
No full textInternational audienceDespite its indolent evolution, vitreoretinal lymphoma (VRL) has a poor prognosis due to a major risk of relapse in the central nervous system (CNS) and may necessitate aggressive therapy. However, the use of high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is poorly documented. We retrospectively analysed from the French LOC network database the adult immunocompetent patients treated with HCT-ASCT for isolated VRL. Thirty-eight patients underwent consolidation with HCT-ASCT for isolated VRL between 2008 and 2019 after induction chemotherapy. Twenty patients had primary VRL, and 18 had an isolated VRL relapse of a primary CNS lymphoma. Three patients underwent HCT-ASCT in first-line treatment, 24 in second-line treatment, and 11 in subsequent lines. At HCT-ASCT, the median age was 61 years, and the median KPS was 90. Thirty-two patients (84%) received high-dose thiotepa-based HCT. One patient (3%) died from HCT-ASCT toxicity. Nineteen (50%) patients relapsed after HCT-ASCT, including 17 cases occurring in the brain. The median progression-free survival, brain-free survival and overall survival from HCT-ASCT were 96, 113 and 92 months, respectively. HCT-ASCT represents an effective therapeutic strategy for select VRL patients, with a tolerable safety profile. However, the risk of subsequent brain relapse remains significant
Elucidation of Switching Mechanisms in Memristive Junctions Integrating a Iron(II)‐Ter Pyridine Diazoted Complex
No full textInternational audienceAn original way of elaborating vertical metal/molecules/metal memristive junctions through diazonium electrografting of the organic layer and inkjet‐printed top electrodes is reported here. The molecule of interest is a Fe II coordination complex with ter‐pyridine ligands, having a diazonium anchoring group. The resulting junction exhibits a memristive behavior characterized by a high ON/OFF ratio and plasticity property. Through the application of advanced techniques such as UV–vis and Raman time‐resolved spectroelectrochemistry, the study demonstrates the significant role of switchable azo bonds derived from diazo electrografting in memristive behavior
List of critical drugs in dermatology: Results of a delphi consensus in France
No full textInternational audienceDrug shortages are increasing nowadays, affecting every country worldwide. The French Ministry of Health asked various scientific societies to establish a list of “critical” drugs for each specialty. The aim of this list was to enable the public authorities to control the production chain and guarantee the availability of drugs. We present the list of critical dermatological drugs, which is the result of a strong consensus between all representative entities of the French Society of Dermatology
Nature and significance of Late Pleistocene to Holocene thick evaporite deposits of the Danakil Depression, Afar, Ethiopia
No full textInternational audienceLarge evaporite deposits, reaching several hundreds of metres of thickness, occur in many basins of our planet but remain poorly understood due to the absence of modern analogues. The origin of ancient evaporites and their highly variable sedimentation rates are often debated and ambiguous. The Danakil rift basin in northern Afar (Ethiopia) features several hundreds of metres of evaporites with deposition still continuing today and, as such, represents a unique modern analogue for older thick evaporite deposits. This study focuses on the multi-proxy analysis of a 625 m long core from the central part of the basin. The core record, dominated by halite (ca 60%) with subordinate clastic sediments (ca 35%) and potash minerals (ca 5%) reveals, for the first time, the Late Pleistocene to Recent geological and environmental history of the basin. Sediments experienced restricted marine conditions after the last Late Pleistocene marine incursion in the basin, followed by a hypersaline stage leading to the near-desiccation of the basin with the deposition of thick halite and potash deposits. Subsequent recycling of marginal halite deposits by meteoric waters in lacustrine and salt pan environments significantly increased the evaporite thickness in the subsiding central part of the basin. These findings have implications for the understanding of older thick evaporite deposits that formed in similar depositional settings. They show that several hundred of metres of evaporite can form in less than 128 kyr by evaporation of meteoric and seawater following a single marine flooding of the basin
Organisational changes and depression: The mediating role of psychosocial work exposures in the SUMER study
No full textInternational audienceBackground: Studies are lacking on the associations between organisational changes and mental disorders and the underlying mechanisms. The objectives were to explore the associations between organisational changes and depression, measured using a validated instrument, and the mediating role of psychosocial work exposures.Methods: The study relied on the national representative sample of 25,977 employees of the French SUMER survey. The PHQ-9 instrument was used to measure depression. Weighted robust Poisson regression analyses were performed to explore the associations between organisational changes, psychosocial work exposures, and depression. The method by Karlson, Holm and Breen (KHB) was used to estimate the mediating role (contributions) of psychosocial work exposures in the associations between organisational changes and depression.Results: The exposure to any organisational change increased the risk of depression (Prevalence Ratio = 1.85, 95 % CI: 1.61-2.13). All types of organisational changes were found to be risk factors for depression. The risk of depression increased with the number of organisational changes. Psychosocial work exposures contributed to mediating the associations between organisational changes and depression. The exposures with the highest contributions were found to be high psychological demands, low esteem, low job promotion, low job security, workplace bullying, and ethical conflict. Taking all the exposures into account mediated the associations by 47-100 %.Limitations: The study limitations included the cross-sectional design and a potential healthy worker effect.Conclusions: More prevention oriented towards work organisation and the psychosocial work environment may help to reduce depression among working populations
Aqueous Alteration as an Origin of Martian Magnetization
No full textInternational audienceStrong magnetic fields have been measured from orbit around Mars over parts of the ancient southern highlands crust and on the surface at the InSight landing site. The geological processes that are responsible for generating strong magnetization within the crust remain poorly understood. One possibility is that intense aqueous alteration of crustal materials, through the process of serpentinization, could have produced magnetite that was magnetized in the presence of a global core‐generated magnetic field. Here, we test this idea with geophysical and geochemical models. We first determine the magnetizations required to account for the observed magnetic field strengths and then estimate the amount of magnetite necessary to account for these magnetizations. For the strongest orbital magnetic field strengths, about 7 wt% magnetite is required if the magnetic layer is 10 km thick. For the surface field strength observed at the InSight landing site, 0.4–1.1 wt% magnetite is required if the magnetic layer corresponds to one or more of the three crustal layers observed in the InSight seismic data (with thicknesses from 8 to 39 km). We then investigate the minerals that are produced by aqueous alteration for various possible crustal compositions and water‐to‐rock ratios using a thermodynamic model. Magnetite abundances up to 6 wt% can be generated for dunitic compositions that could account for the strongest magnetic anomalies. For more representative basaltic starting compositions, however, more than 0.4 wt% can only be generated when using high water‐to‐rock ratios, which could account for the weaker magnetizations beneath the InSight landing site
Arles : l’émergence d’une métascène artistique portée par trois initiatives privées
No full textInternational audienceThe aim of this chapter is to show how, starting from a singular territorial configuration, three initiatives by Arles-based players have, since the 1970s, profoundly transformed the city's economic trajectory and image, making it an internationally recognized arts scene. But while the first two (RIP and Actes Sud) are gradually expanding their activities to irrigate and enhance the area, the third (Fondation LUMA) is transforming the city to suit its project, replacing local authorities in the urban fabric at the risk of calling into question the mechanisms of choice inherent in a democracy.Ce chapitre a pour objectif de montrer comment, à partir d’une configuration territoriale singulière, trois initiatives d’acteurs arlésiens ont depuis les années 1970 profondément transformé la trajectoire économique et l’image de la ville en en faisant une scène artistique internationalement reconnue. Mais si les deux premières (RIP et Actes Sud) étendent progressivement leur activité pour irriguer le territoire et le mettre en valeur, la troisième (fondation LUMA) transforme la ville pour qu’elle corresponde à son projet, se substituant aux collectivités dans la fabrique urbaine au risque de mettre en cause les mécanismes de choix propres à une démocratie
Enumeration of walks in multidimensional orthants and reflection groups
No full text30 pagesWe consider (random) walks in a multidimensional orthant. Using the idea of universality in probability theory, one can associate a unique polyhedral domain to any given walk model. We use this connection to prove two sets of new results. First, we are interested in a group of transformations naturally associated with any small step model; as it turns out, this group is central to the classification of walk models. We show a strong connection between this group and the reflection group through the walls of the polyhedral domain. As a consequence, we can derive various conditions for the combinatorial group to be infinite. Secondly, we consider the asymptotics of the number of excursions, whose critical exponent is known to be computable in terms of the eigenvalue of the above polyhedral domain. We prove new results from spectral theory on the eigenvalues of polyhedral nodal domains. We believe that these results are interesting in their own right; they can also be used to find new exact asymptotic results for walk models corresponding to these nodal polyhedral domains
Single-cell data reveal heterogeneity of investment in ribosomes across a bacterial population
No full textInternational audienceRibosomes are responsible for the synthesis of proteins, the major component of cellular biomass. Classical experiments have established a linear relationship between the fraction of resources invested in ribosomal proteins and the rate of balanced growth of a microbial population. Very little is known, however, about how the investment in ribosomes varies over individual cells in a population. We therefore extended the study of ribosomal resource allocation from populations to single cells, using a combination of time-lapse fluorescence microscopy and statistical inference. We found a large variability of ribosome concentrations and growth rates in conditions of balanced growth of the model bacterium Escherichia coli in a given medium, which cannot be accounted for by the population-level growth law. A large variability in the allocation of resources to ribosomes was also found during the transition of the bacteria from a poor to a rich growth medium. While some cells immediately adapt their ribosome synthesis rate to the new environment, others do so only gradually. Our results thus reveal a range of strategies for investing resources in the molecular machines at the heart of cellular self-replication. This raises the fundamental question whether the observed variability is an intrinsic consequence of the stochastic nature of the underlying biochemical processes or whether it improves the fitness of Escherichia coli in its natural environment
G-quadruplex ligand RHPS4 compromises cellular radio-resistance by blocking the increase in mitochondrial mass and activity induced by ionising irradiation
No full textA major challenge in radiotherapy is to enhance tumor cell sensitivity to radiation while minimizing damage to healthy tissues. Ionising radiation (IR) induces mitochondrial DNA (mtDNA) alterations that can impair mitochondrial function and cell survival. Since mitochondria play a key role in tumor cell proliferation, they represent a promising therapeutic target for cancer treatment. In this study, we characterized the impact of different IR sources on mitochondrial function in radioresistant cancer cells. Our findings revealed several adaptive responses that may contribute to radioresistance, including increased mtDNA content, mitochondrial mass, enhanced activity, and hyperfusion of the mitochondrial network. Notably, the use of mitochondrial-targeted G-quadruplex (G4) ligands, which block mtDNA replication and transcription, disrupted these responses, reducing cancer cell survival in an mtDNA-dependent manner. These results demonstrate that mitochondrial adaptations contribute to radioresistance and highlight mitochondria as a novel target for the radiosensitizing effects of G4-ligands, extending their potential beyond telomere destabilization