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International audience; The aim of this paper is to provide a Bayesian formulation of the so-called magnitude-based inference approach to quantifying and interpreting effects, and in a case study example provide accurate probabilistic statements that correspond to the intended magnitude-based inferences. The model is described in the context of a published small-scale athlete study which employed a magnitude-based inference approach to compare the effect of two altitude training regimens (live high-train low (LHTL), and intermittent hypoxic exposure (IHE)) on running performance and blood measurements of elite triathletes. The posterior distributions, and corresponding point and interval estimates, for the parameters and associated effects and comparisons of interest, were estimated using Markov chain Monte Carlo simulations. The Bayesian analysis was shown to provide more direct probabilistic comparisons of treatments and able to identify small effects of interest. The approach avoided asymptotic assumptions and overcame issues such as multiple testing. Bayesian analysis of unscaled effects showed a probability of 0.96 that LHTL yields a substantially greater increase in hemoglobin mass than IHE, a 0.93 probability of a substantially greater improvement in running economy and a greater than 0.96 probability that both IHE and LHTL yield a substantially greater improvement in maximum blood lactate concentration compared to a Placebo. The conclusions are consistent with those obtained using a ‘magnitude-based inference’ approach that has been promoted in the field. The paper demonstrates that a fully Bayesian analysis is a simple and effective way of analysing small effects, providing a rich set of results that are straightforward to interpret in terms of probabilistic statements.

International audience; The Psychometric Hepatic Encephalopathy Score (PHES) has previously been standardized in thirteen countries on three continents, confirming its status of gold standard test to detect minimal hepatic encephalopathy (MHE). In the meantime, performance has also been shown to vary with variables such as age, education, and barely sex. The present study aimed at standardizing the PHES in a French population. One hundred and ninety-six French healthy participants completed a French version of the paper-and-pencil PHES, involving five tests and six measures. Importantly, the balance was perfect between all levels of the three controlled factors, which were sex, age (seven decade-levels from 20-29 to 80-89 years), and education (two levels below or above 12 years of education). Raw measures were transformed to fit the normal distribution. ANOVAs on transformed variables showed no effect of sex, but an effect of age on all measures, and of education on five measures. Multiple or simple regressions were completed to build up normograms. Thorough analysis of variability within each test failed to find outliers that may bias the results. Comparison between French and seminal German data showed that they highly fitted though cultural and cognitive style specificities could be observed. This is the first study to standardize the PHES in a French population and to extensively explore the effects of sex, age and education using perfectly balanced samples. Subtle differences between countries of the same continent emphasize the need to build up normative data in each country to get accurate PHES in patients.

Based on a meta-analysis, this paper highlights the strength and relevance of several social incentive factors concerning pro-environmental behaviors, including social influence, network factors (like network size, network connection and leadership), trust in others, and trust in institutions. Firstly, our results suggest that social influence is necessary for the emergence of pro-environmental behaviors. More specifically, an internal social influence (i.e., motivating people to change their perceptions and attitudes) is essential to promote pro-environmental behaviors. Secondly, network connection encourages pro-environmental behaviors, meaning that the effectiveness of a conservation policy can be improved if connections among individuals are increased. Finally, trust in institutions can dictate individual behaviors to shape policy design and generate desired policy outcomes.

Background: Medical-related professions are at high suicide risk. However, data are contradictory and comparisons were not made between gender, occupation and specialties, epochs of times. Methods: To conduct a systematic review and meta-analysis on suicide risk among health-care workers, were searched in PubMed, Cochrane Library, Science Direct and Embase databases without language restriction on April 2019. We stratified results by gender, countries, time, and specialties. Estimates were pooled using random-effect meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. Information on suicides, suicidal attempts, and suicidal ideation, and related-characteristics were retrieved from national or local specific registers or case records. In addition, suicide attempts and suicidal ideation were also retrieved from questionnaires (paper or internet). Findings: The overall SMR for suicide in physicians was 1.44 (95CI 1.16, 1.72) with an important heterogeneity (I2=93.9%, p

Cancer driver genes, i.e., oncogenes and tumor suppressor genes, are involved in the acquisition of important functions in tumors, providing a selective growth advantage, allowing uncontrolled proliferation and avoiding apoptosis. It is therefore important to identify these driver genes, both for the fundamental understanding of cancer and to help finding new therapeutic targets or biomarkers. Although the most frequently mutated driver genes have been identified, it is believed that many more remain to be discovered, particularly for driver genes specific to some cancer types. In this paper, we propose a new computational method called LOTUS to predict new driver genes. LOTUS is a machine-learning based approach which allows to integrate various types of data in a versatile manner, including information about gene mutations and protein-protein interactions. In addition, LOTUS can predict cancer driver genes in a pan-cancer setting as well as for specific cancer types, using a multitask learning strategy to share information across cancer types. We empirically show that LOTUS outperforms five other state-of-the-art driver gene prediction methods, both in terms of intrinsic consistency and prediction accuracy, and provide predictions of new cancer genes across many cancer types., Author summary Cancer development is driven by mutations and dysfunction of important, so-called cancer driver genes, that could be targeted by specific therapies. While a number of such cancer genes have already been identified, it is believed that many more remain to be discovered. To help prioritize experimental investigations of candidate genes, several computational methods have been proposed to rank promising candidates based on their mutations in large cohorts of cancer cases, or on their interactions with known driver genes in biological networks. We propose LOTUS, a new computational approach to identify genes with high oncogenic potential. LOTUS implements a machine learning approach to learn an oncogenic potential score from known driver genes, and brings two novelties compared to existing methods. First, it allows to easily combine heterogeneous sources of information into the scoring function, which we illustrate by learning a scoring function from both known mutations in large cancer cohorts and interactions in biological networks. Second, using a multitask learning strategy, it can predict different driver genes for different cancer types, while sharing information between them to improve the prediction for every type. We provide experimental results showing that LOTUS significantly outperforms several state-of-the-art cancer gene prediction software.

International audience; Object handovers between humans are common in our daily life but the mechanisms underlying handovers are still largely unclear. A good understanding of these mechanisms is important not only for a better understanding of human social behaviors, but also for the prospect of an automatized society in which machines will need to perform similar objects exchanges with humans. In this paper, we analyzed how humans determine the location of object transfer during handovers-to determine whether they can predict the preferred handover location of a partner, the variation of this prediction in 3D space, and to examine how much of a role vision plays in the whole process. For this we developed a paradigm that allows us to compare handovers by humans with and without on-line visual feedback. Our results show that humans have the surprising ability to modulate their handover location according to partners they have just met such that the resulting handover errors are in the order of few centimeters, even in the absence of vision. The handover errors are least along the axis joining the two partners, suggesting a limited role for visual feedback in this direction. Finally, we show that the handover locations are explained very well by a linear model considering the heights, genders and social dominances of the two partners, and the distance between them. We developed separate models for the behavior of 'givers' and 'receivers' and discuss how the behavior of the same individual changes depending on his role in the handover.

An important goal in researching the biology of olfaction is to link the perception of smells to the chemistry of odorants. In other words, why do some odorants smell like fruits and others like flowers? While the so-called stimulus-percept issue was resolved in the field of color vision some time ago, the relationship between the chemistry and psycho-biology of odors remains unclear up to the present day. Although a series of investigations have demonstrated that this relationship exists, the descriptive and explicative aspects of the proposed models that are currently in use require greater sophistication. One reason for this is that the algorithms of current models do not consistently consider the possibility that multiple chemical rules can describe a single quality despite the fact that this is the case in reality, whereby two very different molecules can evoke a similar odor. Moreover, the available datasets are often large and heterogeneous, thus rendering the generation of multiple rules without any use of a computational approach overly complex. We considered these two issues in the present paper. First, we built a new database containing 1689 odorants characterized by physicochemical properties and olfactory qualities. Second, we developed a computational method based on a subgroup discovery algorithm that discriminated perceptual qualities of smells on the basis of physicochemical properties. Third, we ran a series of experiments on 74 distinct olfactory qualities and showed that the generation and validation of rules linking chemistry to odor perception was possible. Taken together, our findings provide significant new insights into the relationship between stimulus and percept in olfaction. In addition, by automatically extracting new knowledge linking chemistry of odorants and psychology of smells, our results provide a new computational framework of analysis enabling scientists in the field to test original hypotheses using descriptive or predictive modeling., Author summary An important issue in olfaction sciences deals with the question of how a chemical information can be translated into percepts. This is known as the stimulus-percept problem. Here, we set out to better understand this issue by combining knowledge about the chemistry and cognition of smells with computational olfaction. We also assumed that not only one, but several physicochemical models may describe a given olfactory quality. To achieve this aim, a first challenge was to set up a database with ~1700 molecules characterized by chemical features and described by olfactory qualities (e.g. fruity, woody). A second challenge consisted in developing a computational model enabling the discrimination of olfactory qualities based on these chemical features. By meeting these 2 challenges, we provided for several olfactory qualities new chemical models describing why an odorant molecule smells fruity or woody (among others). For most qualities, multiple (rather than a single) chemical models were generated. These findings provide new elements of knowledge about the relationship between odorant chemistry and perception. They also make it possible to envisage concrete applications in the aroma and fragrance field where chemical characterization of smells is an important step in the design of new products.

International audience; Intravoxel incoherent motion (IVIM) imaging is a magnetic resonance imaging (MRI) technique widely used in clinical applications for various organs. However, IVIM imaging at low b-values is a persistent problem. This paper aims to investigate in a systematic and detailed manner how the number of low b-values influences the estimation of IVIM parameters. To this end, diffusion-weighted (DW) data with different low b-values were simulated to get insight into the distributions of subsequent IVIM parameters. Then, in vivo DW data with different numbers of low b-values and different number of excitations (NEX) were acquired. Finally, least-squares (LSQ) and Bayesian shrinkage prior (BSP) fitting methods were implemented to estimate IVIM parameters. The influence of the number of low b-values on IVIM parameters was analyzed in terms of relative error (RE) and structural similarity (SSIM). The results showed that the influence of the number of low b-values on IVIM parameters is variable. LSQ is more dependent on the number of low b-values than BSP, but the latter is more sensitive to noise.

International audience; We propose a new sparsification method for the singular value decomposition—called the constrained singular value decomposition (CSVD)—that can incorporate multiple constraints such as sparsification and orthogonality for the left and right singular vectors. The CSVD can combine different constraints because it implements each constraint as a projection onto a convex set, and because it integrates these constraints as projections onto the intersection of multiple convex sets. We show that, with appropriate sparsification constants, the algorithm is guaranteed to converge to a stable point. We also propose and analyze the convergence of an efficient algorithm for the specific case of the projection onto the balls defined by the norms L1 and L2. We illustrate the CSVD and compare it to the standard singular value decomposition and to a non-orthogonal related sparsification method with: 1) a simulated example, 2) a small set of face images (corresponding to a configuration with a number of variables much larger than the number of observations), and 3) a psychometric application with a large number of observations and a small number of variables. The companion R-package, csvd, that implements the algorithms described in this paper, along with reproducible examples, are available for download from https://github.com/vguillemot/csvd.

International audience; The purpose of this paper was to adapt and examine the psychometric properties of a French-language Drive for Muscularity Scale (DMS). First, a preliminary version of the scale, based on both the English-language version of the DMS and the literature on the drive for muscularity, was developed following a committee validation process. Second, the factor structure of the DMS-FR was investigated with principal component analysis (PCA) in a sample of 114 male athletes (Mage = 23.35; SDage = 4.93), leading to a nine-item scale (Study 1). Third, in Study 2, the internal factor structure, temporal stability, and concurrent validity were examined through a series of structural hypothetical modelisation in a sample of 129 male athletes (Mage = 27.03; SDage = 7.81). The results indicated that the scale has good psychometric properties. Specifically, the PCA, and the series of structural hypothetical modelisation, suggested two theoretical factors (i.e., Muscularity Body Dissatisfaction and Muscularity Behaviors), and more, with a bi-factor model in a SEM. The results also indicated sufficient concurrent validity with the Male Body Dissatisfaction Scale (MBDS) and adequate internal consistency (Cronbach's alphas were .87 for the Muscularity Body Dissatisfaction subscale, and .88 for the Muscularity Behaviors subscale). The findings overall suggest good reliability and construct validity for this French version of the DMS (DMS-FR), which will be useful for future research and clinical practice in French-speaking countries.

Spatial indicators are used to quantify the state of species and ecosystem status, that is the impacts of climate and anthropogenic changes, as well as to comprehend species ecology. These metrics are thus, determinant to the stakeholder's decisions on the conservation measures to be implemented. A detailed review of the literature (55 papers) showed that 18 spatial indicators were commonly used in marine ecology. Those indicators were than characterized and studied in detail, based on its application to empirical data (a time series of 35 marine species spatial distributions, sampled either with a random stratified survey or a regular transects surveys). The results suggest that the indicators can be grouped into three classes, that summarize the way the individuals occupy space: occupancy (the area occupied by a species), aggregation (spreading or concentration of species biomass) and quantity dependent (indicators correlated with biomass), whether these are spatially explicit (include the geographic coordinates, e.g. center of gravity) or not. Indicator's temporal variability was lower than between species variability and no clear effect was observed in relation to sampling design. Species were then classified accordingly to their indicators. One indicator was selected from each of the three categories of indicators, to represent the main axes of species spatial behavior and to interpret them in terms of occupancy-aggregation-quantity relationships. All species considered were then classified according to their relationships among those three axes, into species that under increasing abundancy, primarily increase occupancy or aggregation or both. We suggest to use these relationships along the three-axes as surveillance diagrams to follow the yearly evolution of species distributional patterns in the future. MSFD from France info:eu-repo/semantics/publishedVersion

International audience; Grade II gliomas are slowly growing primary brain tumors that affect mostly young patients. Cytotoxic therapies (radiotherapy and/or chemotherapy) are used initially only for patients having a bad prognosis. These therapies are planned following the " maximum dose in minimum time " principle, i. e. the same schedule used for high-grade brain tumors in spite of their very different behavior. These tumors transform after a variable time into high-grade gliomas, which significantly decreases the patient's life expectancy. In this paper we study mathematical models describing the growth of grade II gliomas in response to radiotherapy. We find that protracted metronomic fractionations, i.e. therapeutical schedules enlarging the time interval between low-dose radiotherapy fractions, may lead to a better tumor control without an increase in toxicity. Other non-standard fractionations such as protracted or hypoprotracted schemes may also be beneficial. The potential survival improvement depends on the tumor's proliferation rate and can be even of the order of years. A conservative metronomic scheme, still being a suboptimal treatment, delays the time to malignant progression by at least one year when compared to the standard scheme.

International audience; In the context of multivariate multilevel data analysis, this paper focuses on the multivariate linear mixed-effects model, including all the correlations between the random effects when the dimensional residual terms are assumed uncorrelated. Using the EM algorithm, we suggest more general expressions of the model's parameters estimators. These estimators can be used in the framework of the multivariate longitudinal data analysis as well as in the more general context of the analysis of multivariate multilevel data. By using a likelihood ratio test, we test the significance of the correlations between the random effects of two dependent variables of the model, in order to investigate whether or not it is useful to model these dependent variables jointly. Simulation studies are done to assess both the parameter recovery performance of the EM estimators and the power of the test. Using two empirical data sets which are of longitudinal multivariate type and multivariate multilevel type, respectively, the usefulness of the test is illustrated.

The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions., Author Summary Choosing an appropriate action as quickly and accurately as possible in a given situation is critical for the survival of animals and humans. One of the brain regions involved in action selection is a set of subcortical nuclei known as the basal ganglia. The importance of understanding information processing in the basal ganglia is further emphasised by the fact that their disturbed interactions in Parkinson’s disease results in profound difficulties in movement. Computational models have suggested how the basal ganglia could select actions in the fastest possible way for the required accuracy level. These models further predict that a part of basal ganglia, called the external globus pallidus (GPe), needs to calculate a particular function of its inputs. This paper proposes how this function could be computed in a mathematical model of a network within GPe. Furthermore, it shows that the experimentally observed connectivity and response properties of GPe neurons fulfil the requirements necessary to support optimal action selection. This suggests the GPe neurons have properties that allow them to contribute to optimal action selection in the whole basal ganglia.

Mathematics is often used to model biological systems. In mammary gland development, mathematical modeling has been limited to acinar and branching morphogenesis and breast cancer, without reference to normal duct formation. We present a model of ductal elongation that exploits the geometrically-constrained shape of the terminal end bud (TEB), the growing tip of the duct, and incorporates morphometrics, region-specific proliferation and apoptosis rates. Iterative model refinement and behavior analysis, compared with biological data, indicated that the traditional metric of nipple to the ductal front distance, or percent fat pad filled to evaluate ductal elongation rate can be misleading, as it disregards branching events that can reduce its magnitude. Further, model driven investigations of the fates of specific TEB cell types confirmed migration of cap cells into the body cell layer, but showed their subsequent preferential elimination by apoptosis, thus minimizing their contribution to the luminal lineage and the mature duct., Author Summary Our paper describes a mathematical model of mammary ductal elongation during pubertal development. We make several conclusions that will be of interest to scientists studying mammary gland biology, epithelial tube formation, and branching morphogenesis. First, our model indicates that a common measurement of developmental outgrowth (‘percent fat pad filled’) underestimates the total growth and leads to mischaracterization of mutant phenotypes. Second, we show that cap cells, a population enriched with putative mammary stem cells, do not contribute to the luminal lineage as previously hypothesized. Further, we find that a high percentage of proliferation in these cells is not used productively to actually form the mammary duct. We believe our model has future application to other branching organs and also for the modeling of disease states in the breast.

International audience; Sample sizes for randomized controlled trials are typically based on power calculations. They require us to specify values for parameters such as the treatment effect, which is often difficult because we lack sufficient prior information. The objective of this paper is to provide an alternative design which circumvents the need for sample size calculation. In a simulation study, we compared a meta-experiment approach to the classical approach to assess treatment efficacy. The meta-experiment approach involves use of meta-analyzed results from 3 randomized trials of fixed sample size, 100 subjects. The classical approach involves a single randomized trial with the sample size calculated on the basis of an a priori-formulated hypothesis. For the sample size calculation in the classical approach, we used observed articles to characterize errors made on the formulated hypothesis. A prospective meta-analysis of data from trials of fixed sample size provided the same precision, power and type I error rate, on average, as the classical approach. The meta-experiment approach may provide an alternative design which does not require a sample size calculation and addresses the essential need for study replication; results may have greater external validity.

International audience; System restoration from cascading failures is an integral part of the overall defense against catastrophic breakdown in networked critical infrastructures. From the outbreak of cascading failures to the system complete breakdown, actions can be taken to prevent failure propagation through the entire network. While most analysis efforts have been carried out before or after cascading failures, restoration during cascading failures has been rarely studied. In this paper, we present a modeling framework to investigate the effects of in-process restoration, which depends strongly on the timing and strength of the restoration actions. Furthermore, in the model we also consider additional disturbances to the system due to restoration actions themselves. We demonstrate that the effect of restoration is also influenced by the combination of system loading level and restoration disturbance. Our modeling framework will help to provide insights on practical restoration from cascading failures and guide improvements of reliability and resilience of actual network systems.

International audience; Background: In 3D gait analysis, the knee joint is usually described by the Eulerian way. It consists in breaking down the motion between the articulating bones of the knee into three rotations around three axes: flexion/extension, abduction/adduction and internal/external rotation. However, the definition of these axes is prone to error, such as the "cross-talk'' effect, due to difficult positioning of anatomical landmarks. This paper proposes a correction method, principal component analysis (PCA), based on an objective kinematic criterion for standardization, in order to improve knee joint kinematic analysis. Methods: The method was applied to the 3D gait data of two different groups (twenty healthy subjects and four with knee osteoarthritis). Then, this method was evaluated with respect to three main criteria: (1) the deletion of knee joint angle cross-talk (2) the reduction of variance in the varus/valgus kinematic profile (3) the posture trial varus/valgus deformation matching the X-ray value for patients with knee osteoarthritis. The effect of the correction method was tested statistically on variabilities and cross-talk during gait. Results: Cross-talk was lower (p