Scientific Publications of the University of Toulouse II Le Mirail
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Exploring the link between personality dimensions and non-motor fluctuations in Parkinson's disease
No full textInternational audienceBackground: Parkinson's disease (PD) patients on dopaminergic drugs may experience non-motor fluctuations (NMFs) which are often heterogeneous and respond variably to treatments.Objective: We evaluated if personality was associated to NMFs and could modulate the NMFs responsiveness to dopaminergic medication and deep brain stimulation of the sub-thalamic nucleus (STN-DBS).Methods: From the PREDISTIM cohort, personality dimensions of 235 PD patients were assessed by the Temperament and Character Inventory (TCI) before STN-DBS (V0). NMFs were evaluated using the NMFs Severity Scale at V0 and one year after STN-DBS (V1). Linear regression models were performed between TCI dimensions and NMFs at V0; and logistic regression models were done between TCI dimensions and 1) groups of dopa-sensitive patients (responders to ON medication at V0) versus non-dopa-sensitive ones, and 2) responders versus non-responders to STN-DBS at V1. Odds ratios (OR) were also calculated.Results: Significant associations were found between two TCI personality dimensions (“Harm Avoidance” and “Self-Directedness”) and severity of NMFs in OFF medication at V0: PD patients with higher Harm Avoidance and lower Self-Directedness scores having more NMFs. TCI personality dimensions were not associated with the dopa-sensitivity while Novelty Seeking was significantly associated with the STN-DBS-responder group for the psychiatric (OR = 1.09 [1.02–1.17]) and for the dysautonomic NMFs (OR = 1.11 [1.04–1.18]).Conclusions: Certain personality dimensions (Harm Avoidance and Self-Directedness) are associated with NMFs severity at baseline, and PD patients with high Novelty Seeking seem to be better candidates for NMFs improvement after STN-DBS.Plain Language SummaryNon-motor fluctuations are highly invalidating for patients with Parkinson's disease and their response to treatments is variable. This new research examined personality dimensions impact on non-motor fluctuations and their responsiveness to dopaminergic medication and to deep brain stimulation. Two hundred and thirty-five patients with Parkinson's disease participated in the study and filled out several questionnaires to score their personality dimensions and their non-motor fluctuations severity before and after one year of deep brain stimulation. Comparisons were done between different groups of patients according to their response to dopaminergic treatments and to deep brain stimulation. As results, patients with personality traits of high “Harm Avoidance” (more anxious individuals) and low “Self-Directedness” (less goal-oriented individuals) had globally more non-motor fluctuations, and the personality dimension of “Novelty Seeking” (impulsive individuals) was related to a better non-motor fluctuations responsiveness to deep brain stimulation. Hence, non-motor fluctuations are associated with some specific personality dimensions on top of early onset of Parkinson's disease, long disease-duration, high doses of levodopa and female gender. Moreover, Parkinson's disease patients with impulsive-like personality seem to be better candidates for non-motor fluctuations improvement after deep brain stimulation
Dynamic Hypersequents for Public Announcement Logic
No full textDynamic Epistemic Logic extends classical epistemic logic by modeling not only static knowledge but also its evolution through information updates. Among its various systems, Public Announcement Logic (PAL) provides one of the simplest and most studied frameworks for representing epistemic change. While the semantics of PAL is well understood as transformation of Kripke models, the proof theory so far developed fails to represent this dynamism in purely syntactical terms. The aim of this paper is to repair this lack. In particular, building on a hypersequent calculus for S5, we extend it with a mechanism that models the transition between epistemic models induced by public announcements. We call these structures dynamic hypersequents. Using dynamic hypersequents, we construct a calculus for PAL and we show that it enjoys several desirable properties: admissibility of all structural rules (including contraction), invertibility of logical rules, as well as syntactic cut-elimination
L'abri Murat : des interactions humains - non humains au Tardiglaciaire
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On the Logic of Theory Base Change: Reformulation of Belief Bases
No full textInternational audienceIn the logic of theory change, the AGM model has acquired the status of a standard model. However, the AGM model does not seem adequate for some contexts and application domains. This inspired many researchers to propose extensions and generalizations to AGM. Among these extensions, one of the most important are belief bases. Belief bases have more expressivity than belief sets, as explicit and implicit beliefs have different statuses. In this paper, we present reformulation, a belief change operation that allows us to reformulate a belief base making some particular sentences explicit without modifying the consequences of the belief base. We provide a constructive method and its axiomatic characterization
A propos de la culture matérielle des phases anciennes de l'âge du Bronze dans le nord de Hauts-de-France : contribution de la technologie céramique à une nouvelle lecture
No full textInternational audienceThis article focuses on the technology of ceramic assemblages in The Somme and Nord-Pas-de-Calais from the Early Bronze Age, and more particularly from the better documented Middle Bronze phase II-Final Bronze I (1500-1250 BC). Describing the diagnostic traits the study differentiates three technical groups which do not have quite the same chronological and spatial distribution, but which can be found at the same sites or even within the same assemblages suggesting in this case, the coexistence of two groups of producers. Beyond what characterises a style called «Deverel Rimbury» that is found on both sides of the English Channel, the forms and decorations are the same and comparable, though the technical traditions, expressions of the cultural and social groups are different. The technological approach invites us to reconsider the idea of strong cultural homogeneity in the Middle Bronze period II-Final Bronze I, but also the phenomena marking the transition with the middle phases of the Bronze AgeCet article porte sur la technologie des assemblages céramiques des périodes anciennes de l’Âge du bronze dans la Somme et le Nord-Pas-de-Calais, et plus particulièrement de la phase Bronze moyen II-Bronze final I (1500-1250 BC), mieux documentée. Description des traits diagnostiques à l’appui, l’étude différencie trois groupes techniques qui n’ont pas tout à fait la même répartition chronologique et spatiale, mais qui peuvent se retrouver sur les mêmes sites, voire au sein des mêmes assemblages, suggérant, dans ce cas, la coexistence de deux groupes de producteurs. Les formes et décors sont les mêmes et comparables, au-delà, à ce qui caractérise un style dit « Deverel Rimbury » qui s’étend des deux côtés de la Manche, mais les traditions techniques, expression des groupes culturels et sociaux sont différentes. L’approche technologique invite à reconsidérer l’image de forte homogénéité culturelle de la période Bronze moyen II-Bronze final I, mais aussi les phénomènes marquant la transition avec les phases moyennes de l’âge du Bronze, en mettant en lumière une discontinuité techno- culturelle, à situer, dans tout ou partie de la région étudiée, au Ha A1 (1250-1150 BC)
Inhibition of p38α MAPK increases short-term astrocyte reactivity: the exploratory VIP trial in early Alzheimer’s disease
No full textInternational audienceBackgroundNeuro-inflammation is an early mechanistic target in Alzheimer’s disease (AD). However, the effect of anti-inflammatory drugs on biomarkers of neuro-inflammation has yet to be described. Biomarkers of neuro-inflammation showed distinct evolution over the course of AD, suggesting that anti-inflammatory interventions could be beneficial or interfere with mechanisms of immune defense.MethodsWe conducted a pilot and exploratory phase II trial to evaluate the short-term effects of neflamapimod, a drug known to inhibit the neuro-toxic pro-inflammatory properties of the p38α MAPK. Participants with early AD were randomized to receive neflamapimod 40 mg (n = 17) or placebo (n = 16) twice-daily for 12 weeks. The primary endpoint was the treatment-related change in PET imaging of the translocator protein (TSPO) using [18F]-DPA-714. The main secondary endpoints were cerebrospinal fluid (CSF) markers of microglial and astrocyte reactivity. We hypothesized that neuro-inflammation would be reduced at three months in PET and in CSF markers.ResultsNeuro-inflammation was not reduced between the neflamapimod and placebo groups, and no change was observed in [18F]-DPA-714 PET. However, neflamapimod induced a significant increase in CSF GFAP levels compared to placebo. Multivariate analyses based on CSF biomarkers highlighted the contribution of sTREM2 in the pattern of variation that discriminated the two groups (accuracy = 71%). Patients who received neflamapimod and had baseline sTREM2 level above the median had the highest increase in GFAP compared to placebo, suggesting that neflamapimod may exacerbate reactive astrogliosis as a function of the TREM2-related microglial state. Safety analysis showed that three cases of CSF pleocytosis occurred during follow-up in participants receiving neflamapimod.ConclusionsNeflamapimod at a dose of 40 mg twice-daily interfered with mechanisms of immune defense in early AD. Although this study is exploratory, our results may provide an explanation for the failure of previous anti-inflammatory interventions in early AD. Biomarkers of neuro-inflammation should be required in the next-generation trials targeting neuro-immune mechanisms in AD
Conformal Object Detection by Sequential Risk Control
No full textRecent advances in object detectors have led to their adoption for industrial uses. However, their deployment in safety-critical applications is hindered by the inherent lack of reliability of neural networks and the complex structure of object detection models. To address these challenges, we turn to Conformal Prediction, a post-hoc predictive uncertainty quantification procedure with statistical guarantees that are valid for any dataset size, without requiring prior knowledge on the model or data distribution. Our contribution is manifold. First, we formally define the problem of Conformal Object Detection (COD). We introduce a novel method, Sequential Conformal Risk Control (SeqCRC), that extends the statistical guarantees of Conformal Risk Control to two sequential tasks with two parameters, as required in the COD setting. Then, we present old and new loss functions and prediction sets suited to applying SeqCRC to different cases and certification requirements. Finally, we present a conformal toolkit for replication and further exploration of our method. Using this toolkit, we perform extensive experiments that validate our approach and emphasize trade-offs and other practical consequences
Porohyperelastic modeling of collagen-gel responses to periodic pressure actuation shows that embedded senescent fibroblasts induce tissue softening associated with fibrous-network reorganization
No full textInternational audienceThe poroelastic properties of tissues regulate molecular transport and mechanical signaling, yet their evolution during aging remains poorly understood. In particular, senescent fibroblasts accumulate in aged tissues, contributing to extracellular matrix (ECM) remodeling, but their impact on tissue mechanics and permeability is unclear. In this study, we developed a microfluidic-based in vitro model to assess the poroelastic properties of collagen gels embedded with senescent fibroblasts over time. Our approach integrates periodic pressure actuation with real-time pressure monitoring in a sealed air cavity, enabling the detection of fluid permeation and solid matrix deformations. We analyze our data using analytical and numerical models based on a porohyperelastic framework. This framework combines compressible Neo-Hookean elasticity with the Kozeny-Carman permeability relationship. We demonstrate that senescent fibroblasts induce a progressive softening of the ECM without altering its permeability. Immunostaining reveals that this softening correlates with structural reorganization of the collagen network, characterized by increased branching and network remodeling. Our findings provide insights into the biomechanical effects of senescent fibroblasts on ECM homeostasis. We further argue that our platform offers a unique solution to investigate ECM remodeling not only in aging but also fibrosis, cancer progression, or regenerative medicine strategies
Decreased cytoplasmic crowding via inhibition of ribosome biogenesis can trigger Candida albicans filamentous growth
No full textInternational audienceThe human fungal pathogen Candida albicans undergoes a morphological transition from a budding yeast to a filamentous form, which is associated with pathogenesis. Various cues mediate this transition including intracellular reorganisation. The cytoplasm is densely packed with proteins including large macromolecular complexes, such as ribosomes, and hence molecular crowding can impact a range of cellular processes. However, the relationship between cytoplasmic molecular crowding and morphological growth states is unclear. Using a fluorescent microrheological probe and single particle tracking, we observed a striking decrease in molecular crowding during filamentous growth in C. albicans. Based on simulations, proteomics and structural data from in situ cryo-EM, we show that the reduction in crowding is due to a decrease in ribosome concentration that results in part from an inhibition of ribosome biogenesis, combined with an increase in cytoplasmic volume; leading to a dilution of ribosomes. Filamentation was enhanced in a mutant defective in ribosome biogenesis, whilst translation was not affected, suggesting that inhibition of ribosome biogenesis is a trigger for C. albicans morphogenesis. Overall we show that filamentous growth is associated with reduced cytoplasmic crowding via changes in ribosome concentration, suggesting that combination therapies in which ribosome biogenesis is also targeted may be advantageous