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Background Global estimates for cholera annually approximate 4 million cases worldwide with 95,000 deaths. Recent outbreaks, including Haiti and Yemen, are reminders that cholera is still a global health concern. Cholera outbreaks can rapidly induce high death tolls by overwhelming the capacity of health facilities, especially in remote areas or areas of civil unrest. Recent studies demonstrated that stool specimens preserved on filter paper facilitate molecular analysis of Vibrio cholerae in resource limited settings. Specimens preserved in a rapid, low-cost, safe and sustainable manner for sequencing provides previously unavailable data about circulating cholera strains. This may ultimately contribute new information to shape public policy response on cholera control and elimination. Methodology/Principal findings Whole genome sequencing (WGS) recovered close to a complete sequence of the V. cholerae O1 genome with satisfactory genome coverage from stool specimens enriched in alkaline peptone water (APW) and V. cholerae culture isolates, both spotted on filter paper. The minimum concentration of V. cholerae DNA sufficient to produce quality genomic information was 0.02 ng/μL. The genomic data confirmed the presence or absence of genes of epidemiological interest, including cholera toxin and pilus loci. WGS identified a variety of diarrheal pathogens from APW-enriched specimen spotted filter paper, highlighting the potential for this technique to explore the gut microbiome, potentially identifying co-infections, which may impact the severity of disease. WGS demonstrated that these specimens fit within the current global cholera phylogenetic tree, identifying the strains as the 7th pandemic El Tor. Conclusions WGS results allowed for mapping of short reads from APW-enriched specimen and culture isolate spotted filter papers. This provided valuable molecular epidemiological sequence information on V. cholerae strains from remote, low-resource settings. These results identified the presence of co-infecting pathogens while providing rare insight into the specific V. cholerae strains causing outbreaks in cholera-endemic areas., Author summary Cholera affects more than 4 million people globally every year; people predominantly living in poverty or in resource-constrained conditions including political crises or natural disasters. Cholera’s typical presentation is characterized by rapid onset of acute watery diarrhea and vomiting which can progress from watery stool to shock in as little as four hours. Laboratory conditions needed for culture confirmation and strain preservation are rarely to never present in these affected areas. In fact, many cholera endemic areas in Sub-Saharan African are so remote that even treatment response alone is often challenging. Here we present the genomic analysis of DNA extracted from dried filter paper, which is a low-cost, low-tech and sustainable method. Previously this method has facilitated cholera confirmation by PCR, but we demonstrate that this method is also suitable for whole genome sequencing and subsequent strain characterization by presenting the analysis of samples from an outbreak in a remote area of Cameroon. This method will facilitate the understanding of the molecular epidemiology in cholera-prone areas, which were previously too challenging to attempt. It also introduces a method that can be used on a broader scale for diarrheal disease surveillance, including providing a window into co-infection and microbiome analyses.

International audience; The differential diagnosis of differences or disorders of sex development (DSD) belongs to the most complex fields in medicine. It requires a multidisciplinary team conducting a synoptic and complementary approach consisting of thorough clinical, hormonal and genetic workups. This position paper of EU COST (European Cooperation in Science and Technology) Action BM1303 'DSDnet' was written by leading experts in the field and focuses on current best practice in genetic diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the three major diagnostic DSD subclasses and is therefore the mandatory initial step. Subsequently, further analyses comprise molecular studies of monogenic DSD causes or analysis of copy number variations (CNV) or both. Panels of candidate genes provide rapid and reliable results. Whole exome and genome sequencing (WES and WGS) represent valuable methodological developments that are currently in the transition from basic science to clinical routine service in the field of DSD. However, in addition to covering known DSD candidate genes, WES and WGS help to identify novel genetic causes for DSD. Diagnostic interpretation must be performed with utmost caution and needs careful scientific validation in each DSD case.

International audience; Background: Identification of the source of mosquito blood meals is an important component for disease control and surveillance. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling has emerged as an effective tool for mosquito blood meal identification, using the abdomens of freshly engorged mosquitoes. In the field, mosquito abdomens are crushed on Whatman filter papers to determine the host feeding patterns by identifying the origin of their blood meals. The aim of this study was to test whether crushing engorged mosquito abdomens on Whatman filter papers was compatible with MALDI-TOF MS for mosquito blood meal identification. Both laboratory reared and field collected mosquitoes were tested.Material and methods: Sixty Anopheles gambiae Giles were experimentally engorged on the blood of six distinct vertebrate hosts (human, sheep, rabbit, dog, chicken and rat). The engorged mosquito abdomens were crushed on Whatman filter papers for MALDI-TOF MS analysis. 150 Whatman filter papers, with mosquitoes engorged on cow and goat blood, were preserved. A total of 77 engorged mosquito abdomens collected in the Comoros Islands and crushed on Whatman filter papers were tested with MALDI-TOF MS. Results The MS profiles generated from mosquito engorged abdomens crushed on Whatman filter papers exhibited high reproducibility according to the original host blood. The blood meal host was correctly identified from mosquito abdomens crushed on Whatman filter papers by MALDI-TOF MS. The MS spectra obtained after storage were stable regardless of the room temperature and whether or not they were frozen. The MS profiles were reproducible for up to three months. For the Comoros samples, 70/77 quality MS spectra were obtained and matched with human blood spectra. This was confirmed by molecular tools.Conclusion: The results demonstrated that MALDI-TOF MS could identify mosquito blood meals from Whatman filter papers collected in the field during entomological surveys. The application of MALDI-TOF MS has proved to be rapid and successful, making it a new and efficient tool for mosquito-borne disease surveillance.

International audience; Mosquito control is implemented when arboviruses are detected in patients or in field-collected mosquitoes. However, mass screening of mosquitoes is usually laborious and expensive, requiring specialized expertise and equipment. Detection of virus in mosquito saliva using honey-impregnated filter papers seems to be a promising method as it is non-destructive and allows monitoring the viral excretion dynamics over time from the same mosquito. Here we test the use of filter papers to detect chikungunya virus in mosquito saliva in laboratory conditions, before proposing this method in large-scale mosquito surveillance programs. We found that 0.9 cm 2 cards impregnated with a 50% honey solution could replace the forced salivation technique as they offered a viral RNA detection until 7 days after oral infection of Aedes aegypti and Aedes albopictus mosquitoes with CHIKV.

International audience; The fermentation of dietary fibre (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastrointestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placebo) versus chitin-glucan (CG), an insoluble DF previously shown to be fermented into short-chain fatty acids (SCFA) by the human microbiota in vitro. Maltodextrin (4.5 g at day 0) or CG (4.5 g at day 2) were added to a standardized breakfast in fasting healthy volunteers (n = 15). BVM were measured using selected ion flow tube mass spectrometry (SIFT-MS) throughout the day. A single ingestion of 4.5 g CG did not induce significant gastrointestinal discomfort. Untargeted metabolomics analysis of breath highlighted that 13 MS-fragments (among 408 obtained from ionizations of breath) discriminated CG versus maltodextrin acute intake in the posprandial state. The targeted analysis revealed that CG increased exhaled butyrate and 5 other BVM - including the microbial metabolites 2,3-butanedione and 3-hydroxybutanone - with a peak observed 6 h after CG intake. Correlation analyses with fecal microbiota (Illumina 16S rRNA sequencing) spotlighted Mitsuokella as a potential genus responsible for the presence of butyric acid, triethylamine and 3-hydroxybutanone in the breath. In conclusion, measuring BMV in the breath reveals the microbial signature of the fermentation of DF after a single ingestion. This protocol allows to analyze the time-course of released bioactive metabolites that could be proposed as new biomarkers of DF fermentation, potentially linked to their biological properties. Trial registration: Clinical Trials NCT03494491. Registered 11 April 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03494491.

ObjectiveTo explore the associations of absolute and relative measures of exposure to food retailers with dietary patterns, using simpler and more complex measures.DesignCross-sectional survey.SettingUrban regions in Belgium, France, Hungary, the Netherlands and the UK.ParticipantsEuropean adults (n 4942). Supermarkets and local food shops were classified as ‘food retailers providing healthier options’; fast-food/takeaway restaurants, cafés/bars and convenience/liquor stores as ‘food retailers providing less healthy options’. Simpler exposure measures used were density of healthy and density of less healthy food retailers. More complex exposure measures used were: spatial access (combination of density and proximity) to healthy and less healthy food retailers; density of healthier food retailers relative to all food retailers; and a ratio of spatial access scores to healthier and less healthy food retailers. Outcome measures were a healthy or less healthy dietary pattern derived from a principal component analysis (based on consumption of fruits, vegetables, fish, fast foods, sweets and sweetened beverages).ResultsOnly the highest density of less healthy food retailers was significantly associated with the less healthy dietary pattern (β = −129·6; 95 % CI −224·3, −34·8). None of the other absolute density measures nor any of the relative measures of exposures were associated with dietary patterns.ConclusionsMore complex measures of exposure to food retailers did not produce stronger associations with dietary patterns. We had some indication that absolute and relative measures of exposure assess different aspects of the food environment. However, given the lack of significant findings, this needs to be further explored.

International audience; Food safety crises involving persistent organic pollutants (POPs) lead to systematic slaughter of livestock to prevent contaminants from entering the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs to reduce economic and social damage. This study aimed to test undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) 126 and 153 as a strategy to enhance the depuration of POPs through faecal excretion. To better understand the underlying mechanisms of the depuration process, lipophilic POPs and lipid fluxes were co-monitored in various body and excretion compartments. Body compartments (adipose tissues, muscle, liver and blood) and the total empty body were analyzed for lipids and POPs concentrations and burdens at slaughter, as well as excretion compartments (faeces and wool) collected during the depuration period. Decreases in empty body total and lipid weights were 6-fold higher in underfed and supplemented ewes compared to control ewes. In addition, over the depuration period undernutrition and supplementation treatment increased faecal TCDD, PCBs 126 and 153 excretions by 1.4- to 2.1-fold but tended to decrease wool PCB 153 excretion by 1.4-fold. This induced 2- to 3-fold higher decreases in the empty body POPs burdens for underfed and supplemented ewes. Nonetheless, when expressed relative to the calculated initial empty body burdens, burdens at slaughter decreased only slightly from 97%, 103% and 98% for control ewes to 92%, 97% and 94% for underfed and supplemented ones, for TCDD, PCBs 126 and 153, respectively. Fine descriptions at once of POPs kinetic (companion paper 1) and mass balance (companion paper 2), and of body lipid dynamics were very useful in improving our understanding of the fate of POPs in the ruminants.

This paper focuses on determining the structural similarity of two molecules, i.e., the similarity of the interconnection of all the elementary cycles in the corresponding molecular graphs. In this paper, we propose and analyze an algorithmic approach based on the resolution of the Maximum Common Edge Subgraph (MCES) problem with graphs representing the interaction of cycles molecules. Using the ChEBI database, we compare the effectiveness of this approach in terms of structural similarity and computation time with two calculations of similarity of molecular graphs, one based on the MCES, the other on the use of different fingerprints (Daylight, ECFP4, ECFP6, FCFP4, FCFP6) to measure Tanimoto coefficient. We also analyze the obtained structural similarity results for a selected subset of molecules.

International audience; Background: A review of literature published a decade ago noted a significant increase in empirical papers across nine bioethics journals. This study provides an update on the presence of empirical papers in the same nine journals. It first evaluates whether the empirical trend is continuing as noted in the previous study, and second, how it is changing, that is, what are the characteristics of the empirical works published in these nine bioethics journals.Method: A review of the same nine journals (Bioethics; Journal of Medical Ethics; Journal of Clinical Ethics; Nursing Ethics; Cambridge Quarterly of Healthcare Ethics; Hastings Center Report; Theoretical Medicine and Bioethics; Christian Bioethics; and Kennedy Institute of Ethics Journal) was conducted for a 12-year period from 2004 to 2015. Data obtained was analysed descriptively and using a non-parametric Chi-square test.Results: Of the total number of original papers (N = 5567) published in the nine bioethics journals, 18.1% (n = 1007) collected and analysed empirical data. Journal of Medical Ethics and Nursing Ethics led the empirical publications, accounting for 89.4% of all empirical papers. The former published significantly more quantitative papers than qualitative, whereas the latter published more qualitative papers. Our analysis reveals no significant difference (χ2 = 2.857; p = 0.091) between the proportion of empirical papers published in 2004–2009 and 2010–2015. However, the increasing empirical trend has continued in these journals with the proportion of empirical papers increasing from 14.9% in 2004 to 17.8% in 2015.Conclusions: This study presents the current state of affairs regarding empirical research published nine bioethics journals. In the quarter century of data that is available about the nine bioethics journals studied in two reviews, the proportion of empirical publications continues to increase, signifying a trend towards empirical research in bioethics. The growing volume is mainly attributable to two journals: Journal of Medical Ethics and Nursing Ethics. This descriptive study further maps the still developing field of empirical research in bioethics. Additional studies are needed to completely map the nature and extent of empirical research in bioethics to inform the ongoing debate about the value of empirical research for bioethics.

International audience; The perception and production of biological movements is characterized by the 1/3 power law, a relation linking the curvature and the velocity of an intended action. In particular, motions are perceived and reproduced distorted when their kinematics deviate from this biological law. Whereas most studies dealing with this perceptual-motor relation focused on visual or kinaesthetic modalities in a unimodal context, in this paper we show that auditory dynamics strikingly biases visuomotor processes. Biologically consistent or inconsistent circular visual motions were used in combination with circular or elliptical auditory motions. Auditory motions were synthesized friction sounds mimicking those produced by the friction of the pen on a paper when someone is drawing. Sounds were presented diotically and the auditory motion velocity was evoked through the friction sound timbre variations without any spatial cues. Remarkably, when subjects were asked to reproduce circular visual motion while listening to sounds that evoked elliptical kinematics without seeing their hand, they drew elliptical shapes. Moreover, distortion induced by inconsistent elliptical kinematics in both visual and auditory modalities added up linearly. These results bring to light the substantial role of auditory dynamics in the visuo-motor coupling in a multisensory context.

International audience; Virtual Reality (VR) has emerged as a promising tool in many domains of therapy and rehabilitation , and has recently attracted the attention of researchers and clinicians working with elderly people with MCI, Alzheimer's disease and related disorders. Here we present a study testing the feasibility of using highly realistic image-based rendered VR with patients with MCI and dementia. We designed an attentional task to train selective and sustained attention, and we tested a VR and a paper version of this task in a single-session within-subjects design. Results showed that participants with MCI and dementia reported to be highly satisfied and interested in the task, and they reported high feelings of security, low discomfort , anxiety and fatigue. In addition, participants reported a preference for the VR condition compared to the paper condition, even if the task was more difficult. Interestingly, apathetic participants showed a preference for the VR condition stronger than that of non-apathetic participants. These findings suggest that VR-based training can be considered as an interesting tool to improve adherence to cognitive training in elderly people with cognitive impairment.

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; AbstractSedentary behaviour (SB) has emerged as a potential risk factor for metabolic health in youth. Knowledge on the determinants of SB in youth is necessary to inform future intervention development to reduce SB. A systematic review was conducted to identify predictors and determinants of SB in youth. Pubmed, Embase, CINAHL, PsycINFO and Web of Science were searched, limiting to articles in English, published between January 2000 and May 2014. The search strategy was based on four key elements and their synonyms: (a) sedentary behaviour, (b) determinants, (c) types of sedentary behaviours, (d) types of determinants. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42014009823). Cross-sectional studies were excluded. The analysis was guided by the socio-ecological model. 37 studies were selected out of 2654 identified papers from the systematic literature search. Most studies were conducted in Europe (n = 13), USA (n = 11), and Australia (n = 10). The study quality, using the Qualsyst tool, was high with a median of 82 % (IQR: 74–91 %). Multiple potential determinants were studied in only one or two studies. Determinants were found at the individual, interpersonal, environmental and policy level but few studies examined a comprehensive set of factors at different levels of influences. Evidence was found for age being positively associated with total SB, and weight status and baseline assessment of screen time being positively associated with screen time (at follow-up). A higher playground density and a higher availability of play and sports equipment at school were consistently related to an increased total SB, although these consistent findings come from single studies. Evidence was also reported for the presence of safe places to cross roads and lengthening morning and lunch breaks being associated with less total SB. Future interventions to decrease SB levels should especially target children with overweight or obesity and should start at a young age. However, since the relationship of many determinants with SB remains inconsistent, there is still a need for more longitudinal research on determinants of SB in youth.

The formation of a diploid zygote is a highly complex cellular process that is entirely controlled by maternal gene products stored in the egg cytoplasm. This highly specialized transcriptional program is tightly controlled at the chromatin level in the female germline. As an extreme case in point, the massive and specific ovarian expression of the essential thioredoxin Deadhead (DHD) is critically regulated in Drosophila by the histone demethylase Lid and its partner, the histone deacetylase complex Sin3A/Rpd3, via yet unknown mechanisms. Here, we identified Snr1 and Mod(mdg4) as essential for dhd expression and investigated how these epigenomic effectors act with Lid and Sin3A to hyperactivate dhd. Using Cut&Run chromatin profiling with a dedicated data analysis procedure, we found that dhd is intriguingly embedded in an H3K27me3/H3K9me3-enriched mini-domain flanked by DNA regulatory elements, including a dhd promoter-proximal element essential for its expression. Surprisingly, Lid, Sin3a, Snr1 and Mod(mdg4) impact H3K27me3 and this regulatory element in distinct manners. However, we show that these effectors activate dhd independently of H3K27me3/H3K9me3, and that dhd remains silent in the absence of these marks. Together, our study demonstrates an atypical and critical role for chromatin regulators Lid, Sin3A, Snr1 and Mod(mdg4) to trigger tissue-specific hyperactivation within a unique heterochromatin mini-domain., Author summary Multicellular development depends on a tight control of gene expression in each cell type. This relies on the coordinated activities of nuclear proteins that interact with DNA or its histone scaffold to promote or restrict gene transcription. For example, we previously showed that the histone modifying enzymes Lid and Sin3A/Rpd3 are required in Drosophila ovaries for the massive expression of deadhead (dhd), a gene encoding for a thioredoxin that is essential for fertility. In this paper, we have further identified two additional dhd regulators, Snr1 and Mod(mdg4) and dissected the mechanism behind hyperactivation of this gene. Using the epigenomic profiling method Cut&Run with a dedicated data analysis approach, we unexpectedly found that dhd is embedded in an unusual chromatin mini-domain featuring repressive histone modifications H3K27me3 and H3K9me3 and flanked by two regulatory elements. However, we further showed that Lid, Sin3A, Snr1 and Mod(mdg4) behave like obligatory activators of dhd independently of this mini-domain. Our study unveils how multiple broad-acting epigenomic effectors operate in non-canonical manners to ensure a critical and specialized gene activation event. These findings challenge our knowledge on these regulatory mechanisms and their roles in development and pathology.

International audience; The Cyclic Alternating Pattern (CAP) is composed of cycles of two different electroencephalographic features: an activation A-phase followed by a B-phase representing the background activity. CAP is considered a physiological marker of sleep instability. Despite its informative nature, the clinical applications remain limited as CAP analysis is a time-consuming activity. In order to overcome this limit, several automatic detection methods were recently developed. In this paper, two new dimensions were investigated in the attempt to optimize novel, efficient and automatic detection algorithms: 1) many electroencephalographic leads were compared to identify the best local performance, and 2) the global contribution of the concurrent detection across several derivations to CAP identification. The developed algorithms were tested on 41 polysomnographic recordings from normal (n = 8) and pathological (n = 33) subjects. In comparison with the visual CAP analysis as the gold standard, the performance of each algorithm was evaluated. Locally, the detection on the F4-C4 derivation showed the best performance in comparison with all other leads, providing practical suggestions of electrode montage when a lean and minimally invasive approach is preferable. A further improvement in the detection was achieved by a multi-trace method, the Global Analysis-Common Events, to be applied when several recording derivations are available. Moreover, CAP time and CAP rate obtained with these algorithms positively correlated with the ones identified by the scorer. These preliminary findings support efficient automated ways for the evaluation of the sleep instability, generalizable to both normal and pathological subjects affected by different sleep disorders.

Miocene deposits of South America have yielded several species-rich assemblages of caviomorph rodents. They are mostly situated at high and mid- latitudes of the continent, except for the exceptional Honda Group of La Venta, Colombia, the faunal composition of which allowed to describe the late middle Miocene Laventan South American Land Mammal Age (SALMA). In this paper, we describe a new caviomorph assemblage from TAR-31 locality, recently discovered near Tarapoto in Peruvian Amazonia (San Martín Department). Based on mammalian biostratigraphy, this single-phased locality is unambiguously considered to fall within the Laventan SALMA. TAR-31 yielded rodent species found in La Venta, such as the octodontoid Ricardomys longidens Walton, 1990 (nom. nud.), the chinchilloids Microscleromys paradoxalis Walton, 1990 (nom. nud.) and M. cribriphilus Walton, 1990 (nom. nud.), or closely-related taxa. Given these strong taxonomic affinities, we further seize the opportunity to review the rodent dental material from La Venta described in the Ph.D. volume of Walton in 1990 but referred to as nomina nuda. Here we validate the recognition of these former taxa and provide their formal description. TAR-31 documents nine distinct rodent species documenting the four extant superfamilies of Caviomorpha, including a new erethizontoid: Nuyuyomys chinqaska gen. et sp. nov. These fossils document the most diverse caviomorph fauna for the middle Miocene interval of Peruvian Amazonia to date. This rodent discovery from Peru extends the geographical ranges of Ricardomys longidens, Microscleromys paradoxalis, and M. cribriphilus, 1,100 km to the south. Only one postcranial element of rodent was unearthed in TAR-31 (astragalus). This tiny tarsal bone most likely documents one of the two species of Microscleromys and its morphology indicates terrestrial generalist adaptations for this minute chinchilloid.

International audience; This study developed, validated, and evaluated a framework of factors influencing dietary behaviours in urban African food environments, to inform research prioritisation and intervention development in Africa. A multi-component methodology, drawing on concept mapping, was employed to construct a framework of factors influencing dietary behaviours in urban Africa. The framework adapted a widely used socio-ecological model (developed in a high-income country context) and was developed using a mixed-methods research approach that comprised: i. Evidence synthesis consisting of a systematic review of 39 papers covering 14 African countries; ii. Qualitative interview data collected for adolescents and adults (n = 144) using photovoice in urban Ghana and Kenya; and iii. Consultation with interdisciplinary African experts (n = 71) from 27 countries, who contributed to at least one step of the framework (creation, validation/evaluation, finalisation). The final framework included 103 factors influencing dietary behaviours. Experts identified the factors influencing dietary behaviours across all the four levels of the food environment i.e. the individual, social, physical and macro levels. Nearly half (n = 48) were individual-level factors and just under a quarter (n = 26) were at the macro environmental level. Fewer factors associated with social (n = 15) and physical (14) environments were identified. At the macro level, the factors ranked as most important were food prices, cultural beliefs and seasonality. Factors ranked as important at the social level were household composition, family food habits and dietary practices. The type of food available in the neighbourhood and convenience were seen as important at the physical level, while individual food habits, food preferences and socioeconomic status were ranked highly at the individual level. About half of the factors (n = 54) overlap with those reported in an existing socio-ecological food environment framework developed in a high-income country context. A further 49 factors were identified that were not reported in the selected high-income country framework, underlining the importance of contextualisation. Our conceptual framework offers a useful tool for research to understand dietary transitions in urban African adolescents and adults, as well as identification of factors to intervene when promoting healthy nutritious diets to prevent multiple forms of malnutrition.

Smallholder farmer and tribal communities are often characterised as marginalised and highly vulnerable to emerging zoonotic diseases due to their relatively poor access to healthcare, worse-off health outcomes, proximity to sources of disease risks, and their social and livelihood organisation. Yet, access to relevant and timely disease information that could strengthen their adaptive capacity remain challenging and poorly characterised in the empirical literature. This paper addresses this gap by exploring the role of disease information in shaping the adaptive capacity of smallholder farmer and tribal groups to Kyasanur Forest Disease (KFD), a tick-borne viral haemorrhagic fever. We carried out household surveys (n = 229) and in-depth interviews (n = 25) in two affected districts–Shimoga and Wayanad–in the Western Ghats region. Our findings suggest that, despite the generally limited awareness about KFD, access to disease information improved households’ propensity to implement adaptation strategies relative to households that had no access to it. Of the variety of adaptation strategies implemented, vaccination, avoiding forest visits, wearing of protective clothing and footwear, application of dimethyl phthalate (DMP) oil and income diversification were identified by respondents as important adaptive measures during the outbreak seasons. Even so, we identified significant differences between individuals in exposure to disease information and its contribution to substantive adaptive action. Households reported several barriers to implement adaptation strategies including, lack of disease information, low efficacy of existing vaccine, distrust, religio-cultural sentiments, and livelihood concerns. We also found that informal information sharing presented a promising avenue from a health extension perspective albeit with trade-offs with potential distortion of the messages through misinformation and/or reporting bias. Altogether, our findings stress the importance of contextualising disease information and implementing interventions in a participatory way that sufficiently addresses the social determinants of health in order to bolster households’ adaptive capacity to KFD and other neglected endemic zoonoses., Author summary There is widespread consensus that smallholder farmer and tribal communities are highly vulnerable to zoonotic diseases (illness passed between animals and people). This is largely due to their relatively poor access to healthcare and closeness to sources of disease risks. Although access to relevant and timely disease information could enhance their adaptive capacity, remain difficult and poorly understood. Drawing on survey data (n = 229) and in-depth interviews (n = 25) in two affected districts (Shimoga and Wayanad); we explored the role of disease information in shaping adaptation to Kyasanur Forest Disease (KFD), a tick-borne viral haemorrhagic fever. We found that despite the limited awareness about KFD, access to disease information improved households’ likelihood to implement adaptation strategies as compared to households that had no access to it. Households identified several barriers to implementation of adaptation strategies including, lack of disease information, low efficacy of existing vaccine, distrust, religio-cultural sentiments, and livelihood concerns. Our findings highlight the relevance of contextualising disease information and implementing interventions in a participatory manner in order to strengthen households’ adaptive capacity to KFD and other neglected endemic zoonoses.

Disease mapping aims to determine the underlying disease risk from scattered epidemiological data and to represent it on a smoothed colored map. This methodology is based on Bayesian inference and is classically dedicated to non-infectious diseases whose incidence is low and whose cases distribution is spatially (and eventually temporally) structured. Over the last decades, disease mapping has received many major improvements to extend its scope of application: integrating the temporal dimension, dealing with missing data, taking into account various a prioris (environmental and population covariates, assumptions concerning the repartition and the evolution of the risk), dealing with overdispersion, etc. We aim to adapt this approach to rare infectious diseases. In the context of a contagious disease, the outcome of a primary case can in addition generate secondary occurrences of the pathology in a close spatial and temporal neighborhood; this can result in local overdispersion and in higher spatial and temporal dependencies due to direct and/or indirect transmission. We have proposed and tested 60 Bayesian hierarchical models on 400 simulated datasets and bovine tuberculosis real data. This analysis shows the relevance of the CAR (Conditional AutoRegressive) processes to deal with the structure of the risk. We can also conclude that the negative binomial models outperform the Poisson models with a Gaussian noise to handle overdispersion. In addition our study provided relevant maps which are congruent with the real risk (simulated data) and with the knowledge concerning bovine tuberculosis (real data).Author summaryDisease mapping is dedicated to non-infectious diseases whose incidence is low and whose distribution is spatially (and eventually temporally) structured. In this paper, we aim to adapt this approach to rare infectious pathologies. In the context of a contagious disease, the outcome of a primary case can in addition generate secondary occurrences of the pathology in a close spatial and temporal neighborhood, resulting in local overdispersion and in high spatial and temporal dependencies. We thus explored different adapted spatial, temporal and spatiotemporal links and highlight the most adapted to likely risk structures for infectious diseases. We also conclude that the negative binomial models outperform the Poisson models with a Gaussian noise to handle overdispersion. Our study also provided relevant maps which are congruent with the real risk (in case of simulated data) and with the knowledge concerning bovine tuberculosis (when applying to real data). Thus disease mapping appears as a promising way to investigate rare infectious diseases.

Déposé dans medRxiv le 4 août 2020 : https://doi.org/10.1101/2020.08.01.20166538; International audience; To respond to the urgent need for COVID-19 testing, countries perform nucleic acid amplification tests (NAAT) for the detection of SARS-CoV-2 in centralized laboratories. Real-time RT-PCR (Reverse transcription-Polymerase Chain Reaction), used to amplify and detect the viral RNA., is considered, as the current gold standard for diagnostics. It is an efficient process, but the complex engineering required for automated RNA extraction and temperature cycling makes it incompatible for use in point of care settings [1]. In the present work, by harnessing progress made in the past two decades in isothermal amplification and paper microfluidics, we created a portable test, in which SARS-CoV-2 RNA is extracted, amplified isothermally by RT-LAMP (Loop-mediated Isothermal Amplification), and detected using intercalating dyes or fluorescent probes. Depending on the viral load in the tested samples, the detection takes between twenty minutes and one hour. Using a set of 16 pools of naso-pharyngal swab eluates, we estimated a limit of detection comparable to real-time RT-PCR (i.e. 1 genome copies per microliter of clinical sample) and no cross-reaction with eight major respiratory viruses currently circulating in Europe. We designed and fabricated an easy-to-use portable device called "COVIDISC" to carry out the test at the point of care. The low cost of the materials along with the absence of complex equipment will expedite the widespread dissemination of this device. What is proposed here is a new efficient tool to help managing the pandemics.

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.

International audience; Sulfur isotope composition of organic tissues is a commonly used tool for gathering information about provenance and diet in archaeology and paleoecology. However, the lack of maps predicting sulfur isotope variations on the landscape limits the possibility to use this isotopic system in quantitative geographic assignments. We compiled a database of 2,680 sulfur isotope analyses in the collagen of archaeological human and animal teeth from 221 individual locations across Western Europe. We used this isotopic compilation and remote sensing data to apply a multivariate machine-learning regression, and to predict sulfur isotope variations across Western Europe. The resulting model shows that sulfur isotope patterns are highly predictable, with 65% of sulfur isotope variations explained using only 4 variables representing marine sulfate deposition and local geological conditions. We used this novel sulfur isoscape and existing strontium and oxygen isoscapes of Western Europe to apply triple isotopes continuous-surface probabilistic geographic assignments to assess the origin of a series of teeth from local animals and humans from Brittany. We accurately and precisely constrained the origin of these individuals to limited regions of Brittany. This approach is broadly transferable to studies in archaeology and paleoecology as illustrated in a companion paper (Colleter et al. 2021).

International audience; Emerging infectious diseases represent a global and major health problem. The understanding of biological processes involved in the transmission and evolution of infectious agents in host reservoirs is critical. Disease ecology has, therefore, become an important area of research, aiming at investigating the interactions between infectious agents, their hosts, and environments. Interactions between infectious agents exploiting the same vertebrate host at the same time (coinfections) can affect disease outcomes and transmissibility. In this paper, we review this point, as this could have significant consequences on zoonoses emergence.

International audience; This paper analyses the evolution of COVID-19 in Cameroon over the period March 6-April 2020 using SIR models. Specifically, we 1) evaluate the basic reproduction number of the virus, 2) determine the peak of the infection and the spread-out period of the disease, and 3) simulate the interventions of public health authorities. Data used in this study is obtained from the Cameroonian Public Health Ministry. The results suggest that over the identified period, the reproduction number of COVID-19 in Cameroon is about 1.5, and the peak of the infection should have occurred at the end of May 2020 with about 7.7% of the population infected. Furthermore, the implementation of efficient public health policies could help flatten the epidemic curve.

Following fertilization of a mature oocyte, the formation of a diploid zygote involves a series of coordinated cellular events that ends with the first embryonic mitosis. In animals, this complex developmental transition is almost entirely controlled by maternal gene products. How such a crucial transcriptional program is established during oogenesis remains poorly understood. Here, we have performed an shRNA-based genetic screen in Drosophila to identify genes required to form a diploid zygote. We found that the Lid/KDM5 histone demethylase and its partner, the Sin3A-HDAC1 deacetylase complex, are necessary for sperm nuclear decompaction and karyogamy. Surprisingly, transcriptomic analyses revealed that these histone modifiers are required for the massive transcriptional activation of deadhead (dhd), which encodes a maternal thioredoxin involved in sperm chromatin remodeling. Unexpectedly, while lid knock-down tends to slightly favor the accumulation of its target, H3K4me3, on the genome, this mark was lost at the dhd locus. We propose that Lid/KDM5 and Sin3A cooperate to establish a local chromatin environment facilitating the unusually high expression of dhd, a key effector of the oocyte-to-zygote transition., Author summary Nuclear enzymes that add or remove epigenetic marks on histone tails potentially control gene expression by affecting chromatin structure and DNA accessibility. For instance, members of the KDM5 family of histone demethylases specifically remove methyl groups on the lysine 4 of histone H3, a mark generally correlated with gene expression. Lid (Little imaginal discs), the Drosophila KDM5, is essential for viability but is also required for female fertility. In this paper, we have found that the specific removal of Lid in developing oocytes perturbs the decompaction of the sperm nucleus at fertilization and the integration of paternal chromosomes in the zygote. Sperm nuclear decompaction normally requires the presence of a small redox protein called Deadhead (Dhd), which is massively expressed at the end of oogenesis. Strikingly, our analyses of ovarian transcriptomes revealed that the absence of Lid completely abolishes the expression of dhd. This direct functional link between a general histone modifier and the expression of an essential terminal effector gene represents a rare finding. We hope that our work will help understanding how histone demethylases function in controlling complex developmental transitions as well as cancer progression.

This paper proposes a model-based estimation of left ventricular (LV) pressure for the evaluation of constructive and wasted myocardial work of patients with aortic stenosis (AS). A model of the cardiovascular system is proposed, including descriptions of i) cardiac electrical activity, ii) elastance-based cardiac cavities, iii) systemic and pulmonary circulations and iv) heart valves. After a sensitivity analysis of model parameters, an identification strategy was implemented using a Monte-Carlo cross-validation approach. Parameter identification procedure consists in two steps for the estimation of LV pressures: step 1) from invasive, intraventricular measurements and step 2) from non-invasive data. The proposed approach was validated on data obtained from 12 patients with AS. The total relative errors between estimated and measured pressures were on average 11.9% and 12.27% and mean R2 were equal to 0.96 and 0.91, respectively for steps 1 and 2 of parameter identification strategy. Using LV pressures obtained from non-invasive measurements (step 2) and patient-specific simulations, Global Constructive (GCW), Wasted (GWW) myocardial Work and Global Work Efficiency (GWE) parameters were calculated. Correlations between measures and model-based estimations were 0.88, 0.80, 0.91 respectively for GCW, GWW and GWE. The main contributions concern the proposal of the parameter identification procedure, applied on an integrated cardiovascular model, able to reproduce LV pressure specifically to each AS patient, by non-invasive procedures, as well as a new method for the non-invasive estimation of constructive, wasted myocardial work and work efficiency in AS.

Introduction\ud Antiretroviral therapy (ART) has revolutionised the care of HIV-positive individuals resulting in marked decreases in morbidity and mortality, and markedly reduced transmission to sexual partners. However, these benefits can only be realised if individuals are aware of their HIV-positive status, initiated and retained on suppressive lifelong ART. Framed using the socio-ecological model, the present study explores factors contributing to poor ART uptake among community members despite high acceptance of HIV-testing within a Treatment as Prevention (TasP) trial. In this paper we identify barriers and facilitators to treatment across different levels of the socio-ecological framework covering individual, community and health system components.\ud \ud Methods\ud This research was embedded within a cluster-randomised trial (ClinicalTrials.gov, number NCT01509508) of HIV treatment as Prevention in rural KwaZulu-Natal, South Africa. Data were collected between January 2013 and July 2014 from resident community members. Ten participants contributed to repeat in-depth interviews whilst 42 participants took part in repeat focus group discussions. Data from individual interviews and focus group discussions were triangulated using community walks to give insights into community members’ perception of the barriers and facilitators of ART uptake. We used thematic analysis guided by a socio-ecological framework to analyse participants’ narratives from both individual interviews and focus group discussions.\ud \ud Results\ud Barriers and facilitators operating at the individual, community and health system levels influence ART uptake. Stigma was an over-arching barrier, across all three levels and expressed variably as fear of HIV disclosure, concerns about segregated HIV clinical services and negative community religious perceptions. Other barriers were individual (substance misuse, fear of ART side effects), community (alternative health beliefs). Facilitators cited by participants included individual (expectations of improved health and longer life expectancy following ART, single tablet regimens), community (availability of ART in the community through mobile trial facilities) and health system factors (fast and efficient service provided by friendly staff).\ud \ud Discussion\ud We identified multiple barriers to achieving universal ART uptake. To enhance uptake in HIV care services, and achieve the full benefits of ART requires interventions that tackle persistent HIV stigma, and offer people with HIV respectful, convenient and efficient services. These interventions require evaluation in appropriately designed studies.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing Joint Estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Evidence from mechanistic data suggests that exposure to long working hours may cause ischaemic heart disease (IHD). In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from IHD that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (three outcomes: prevalence, incidence and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including MEDLINE, Scopus, Web of Science, CISDOC, PsycINFO, and WHO ICTRP. We also searched grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged

International audience; Objectives: Large studies are needed to update risk factors of bronchiolitis hospitalization. We performed a nationwide analysis of hospitalization rates for bronchiolitis over four consecutive bronchiolitis seasons to identify underlying medical disorders at risk of bronchiolitis hospitalization and assess their frequency.Methods: Data were retrieved from the French National Hospital Discharge database. Of all infants discharged alive from maternity wards from January 2008 to December 2013 in France (N = 3,884,791), we identified four consecutive cohorts at risk of bronchiolitis during the seasons of 2009–2010 to 2012–2013. The main outcome was bronchiolitis hospitalization during a season. Individual risk factors were collected.Results: Among infants, 6.0% were preterm and 2.0% had ≥1 chronic condition including 0.2% bronchopulmonary dysplasia (BPD) and 0.2% hemodynamically significant congenital heart disease (HS-CHD). Bronchiolitis hospitalization rates varied between seasons (min: 1.26% in 2010–2011; max: 1.48% in 2012–2013; p

The movement of microswimmers is often described by active Brownian particle models. Here we introduce a variant of these models with several internal states of the swimmer to describe stochastic strategies for directional swimming such as run and tumble or run and reverse that are used by microorganisms for chemotaxis. The model includes a mechanism to generate a directional bias for chemotaxis and interactions with external fields (e.g., gravity, magnetic field, fluid flow) that impose forces or torques on the swimmer. We show how this modified model can be applied to various scenarios: First, the run and tumble motion of E. coli is used to establish a paradigm for chemotaxis and investigate how it is affected by external forces. Then, we study magneto-aerotaxis in magnetotactic bacteria, which is biased not only by an oxygen gradient towards a preferred concentration, but also by magnetic fields, which exert a torque on an intracellular chain of magnets. We study the competition of magnetic alignment with active reorientation and show that the magnetic orientation can improve chemotaxis and thereby provide an advantage to the bacteria, even at rather large inclination angles of the magnetic field relative to the oxygen gradient, a case reminiscent of what is expected for the bacteria at or close to the equator. The highest gain in chemotactic velocity is obtained for run and tumble with a magnetic field parallel to the gradient, but in general a mechanism for reverse motion is necessary to swim against the magnetic field and a run and reverse strategy is more advantageous in the presence of a magnetic torque. This finding is consistent with observations that the dominant mode of directional changes in magnetotactic bacteria is reversal rather than tumbles. Moreover, it provides guidance for the design of future magnetic biohybrid swimmers., Author summary In this paper, we propose a modified Active Brownian particle model to describe bacterial swimming behavior under the influence of external forces and torques, in particular of a magnetic torque. This type of interaction is particularly important for magnetic biohybrids (i.e. motile bacteria coupled to a synthetic magnetic component) and for magnetotactic bacteria (i.e. bacteria with a natural intracellular magnetic chain), which perform chemotaxis to swim along chemical gradients, but are also directed by an external magnetic field. The model allows us to investigate the benefits and disadvantages of such coupling between two different directionality mechanisms. In particular we show that the magnetic torque can speed chemotaxis up in some conditions, while it can hinder it in other cases. In addition to an understanding of the swimming strategies of naturally magnetotactic organisms, the results may guide the design of future biomedical devices.

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

The cell cycle is the fundamental process of cell populations, it is regulated by environmental cues and by intracellular checkpoints. Cell cycle variability in clonal cell population is caused by stochastic processes such as random partitioning of cellular components to progeny cells at division and random interactions among biomolecules in cells. One of the important biological questions is how the dynamics at the cell cycle scale, which is related to family dependencies between the cell and its descendants, affects cell population behavior in the long-run. We address this question using a “mechanistic” model, built based on observations of single cells over several cell generations, and then extrapolated in time. We used cell pedigree observations of NIH 3T3 cells including FUCCI markers, to determine patterns of inheritance of cell-cycle phase durations and single-cell protein dynamics. Based on that information we developed a hybrid mathematical model, involving bifurcating autoregression to describe stochasticity of partitioning and inheritance of cell-cycle-phase times, and an ordinary differential equation system to capture single-cell protein dynamics. Long-term simulations, concordant with in vitro experiments, demonstrated the model reproduced the main features of our data and had homeostatic properties. Moreover, heterogeneity of cell cycle may have important consequences during population development. We discovered an effect similar to genetic drift, amplified by family relationships among cells. In consequence, the progeny of a single cell with a short cell cycle time had a high probability of eventually dominating the population, due to the heritability of cell-cycle phases. Patterns of epigenetic heritability in proliferating cells are important for understanding long-term trends of cell populations which are either required to provide the influx of maturing cells (such as hematopoietic stem cells) or which started proliferating uncontrollably (such as cancer cells)., Author summary All cells in multicellular organisms obey orchestrated sequences of signals to ensure developmental and homeostatic fitness under a variety of external stimuli. However, there also exist self-perpetuating stem-cell populations, the function of which is to provide a steady supply of differentiated progenitors that in turn ensure persistence of organism functions. This “cell production engine” is an important element of biological homeostasis. A similar process, albeit distorted in many respects, plays a major role in cancer development; here the robustness of homeostasis contributes to difficulty in eradication of malignancy. An important role in homeostasis seems to be played by generation of heterogeneity among cell phenotypes, which then can be shaped by selection and other genetic forces. In the present paper, we present a model of a cultured cell population, which factors in relationships among related cells and the dynamics of cell growth and important proteins regulating cell division. We find that the model not only maintains homeostasis, but that it also responds to perturbations in a manner that is similar to that exhibited by the Wright-Fisher model of population genetics. The model-cell population can become dominated by the progeny of the fittest individuals, without invoking advantageous mutations. If confirmed, this may provide an alternative mode of evolution of cell populations.

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.

Macroscopic oscillations of different brain regions show multiple phase relationships that are persistent across time and have been implicated in routing information. While multiple cellular mechanisms influence the network oscillatory dynamics and structure the macroscopic firing motifs, one of the key questions is to identify the biophysical neuronal and synaptic properties that permit such motifs to arise. A second important issue is how the different neural activity coherence states determine the communication between the neural circuits. Here we analyse the emergence of phase-locking within bidirectionally delayed-coupled spiking circuits in which global gamma band oscillations arise from synaptic coupling among largely excitable neurons. We consider both the interneuronal (ING) and the pyramidal-interneuronal (PING) population gamma rhythms and the inter coupling targeting the pyramidal or the inhibitory neurons. Using a mean-field approach together with an exact reduction method, we reduce each spiking network to a low dimensional nonlinear system and derive the macroscopic phase resetting-curves (mPRCs) that determine how the phase of the global oscillation responds to incoming perturbations. This is made possible by the use of the quadratic integrate-and-fire model together with a Lorentzian distribution of the bias current. Depending on the type of gamma (PING vs. ING), we show that incoming excitatory inputs can either speed up the macroscopic oscillation (phase advance; type I PRC) or induce both a phase advance and a delay (type II PRC). From there we determine the structure of macroscopic coherence states (phase-locking) of two weakly synaptically-coupled networks. To do so we derive a phase equation for the coupled system which links the synaptic mechanisms to the coherence states of the system. We show that a synaptic transmission delay is a necessary condition for symmetry breaking, i.e. a non-symmetric phase lag between the macroscopic oscillations. This potentially provides an explanation to the experimentally observed variety of gamma phase-locking modes. Our analysis further shows that symmetry-broken coherence states can lead to a preferred direction of signal transfer between the oscillatory networks where this directionality also depends on the timing of the signal. Hence we suggest a causal theory for oscillatory modulation of functional connectivity between cortical circuits., Author summary Large scale brain oscillations emerge from synaptic interactions within neuronal circuits. Over the past years, such macroscopic rhythms have been suggested to play a crucial role in routing the flow of information across cortical regions, resulting in a functional connectome. The underlying mechanism is cortical oscillations that bind together following a well-known motif called phase-locking. While there is significant experimental support for multiple phase-locking modes in the brain, it is still unclear what is the underlying mechanism that permits macroscopic rhythms to phase lock. In the present paper we take up with this issue, and to show that, one can study the emergent macroscopic phase-locking within the mathematical framework of weakly coupled oscillators. We find that under synaptic delays, fully symmetrically coupled networks can display symmetry-broken states of activity, where one network starts to lead in phase the second (also sometimes known as stuttering states). When we analyse how incoming transient signals affect the coupled system, we find that in the symmetry-broken state, the effect depends strongly on which network is targeted (the leader or the follower) as well as the timing of the input. Hence we show how the dynamics of the emergent phase-locked activity imposes a functional directionality on how signals are processed. We thus offer clarification on the synaptic and circuit properties responsible for the emergence of multiple phase-locking patterns and provide support for its functional implication in information transfer.

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.

Background Epilepsy and progressively worsening severe chronic headaches (WSCH) are the two most common clinical manifestations of neurocysticercosis, a form of cysticercosis. Most community-based studies in sub-Saharan Africa (SSA) use a two-step approach (questionnaire and confirmation) to estimate the prevalence of these neurological disorders and neurocysticercosis. Few validate the questionnaire in the field or account for the imperfect nature of the screening questionnaire and the fact that only those who screen positive have the opportunity to be confirmed. This study aims to obtain community-based validity estimates of a screening questionnaire, and to assess the impact of verification bias and misclassification error on prevalence estimates of epilepsy and WSCH. Methodology/Principal findings Baseline screening questionnaire followed by neurological examination data from a cluster randomized controlled trial collected between February 2011 and January 2012 were used. Bayesian latent-class models were applied to obtain verification bias adjusted validity estimates for the screening questionnaire. These models were also used to compare the adjusted prevalence estimates of epilepsy and WSCH to those directly obtained from the data (i.e. unadjusted prevalence estimates). Different priors were used and their corresponding posterior inference was compared for both WSCH and epilepsy. Screening data were available for 4768 individuals. For epilepsy, posterior estimates for the sensitivity varied with the priors used but remained robust for the specificity, with the highest estimates at 66.1% (95%BCI: 56.4%;75.3%) for sensitivity and 88.9% (88.0%;89.8%) for specificity. For WSCH, the sensitivity and specificity estimates remained robust, with the highest at 59.6% (49.7%;69.1%) and 88.6% (87.6%;89.6%), respectively. The unadjusted prevalence estimates were consistently lower than the adjusted prevalence estimates for both epilepsy and WSCH. Conclusions/Significance This study demonstrates that in some settings, the prevalence of epilepsy and WSCH can be considerably underestimated when using the two-step approach. We provide an analytic solution to obtain more valid prevalence estimates of these neurological disorders, although more community-based validity studies are needed to reduce the uncertainty of the estimates. Valid estimates of these two neurological disorders are essential to obtain accurate burden values for neglected tropical diseases such as neurocysticercosis that manifest as epilepsy or WSCH. Trial registration ClinicalTrials.gov NCT03095339., Author summary Epilepsy and progressively worsening severe chronic headaches are the two most common clinical manifestations of neurocysticercosis, a form of cysticercosis. To understand where the prevalence of these neurological disorders is highest for targeted infection control, valid prevalence estimates are needed. Most neuroepidemiological studies conducted in low-resource settings use a two-step approach to identify cases (screening questionnaire followed by physician examination among screened positives) to obtain prevalence and burden estimates. We found that this most commonly-used two-step approach in community-based studies leads to an underestimation of the prevalence in our study. Our paper provides an analytic solution to reduce errors in estimating the prevalence of neurological disorders in community-based studies when using the two-step approach. Our proposed approach provides more valid estimates of the prevalence of these neurological disorders and could be used to better reflect the consequences that neglected tropical diseases manifesting as epilepsy or headaches have on people’s health and disabilities.

ObjectiveThis systematic review was to assess the presence of Trichomonas tenax in patients with periodontitis and to elucidate its potential role in the onset and development of this disease.MethodSystematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and by consulting the five databases: Medline, Science Direct, Web of Science, Dentistry and Oral Science Sources and Cochrane Central Register of Controlled Trials. Following Koch's postulates revisited by Socransky as PICO framework, this collection data was only including full text of clinical trials concerning patients with periodontitis, case-reports and in vitro research published between 1960 and March 2019.ResultsOn the 376 studies identified, only 25 fulfilled our eligible criteria. Most of these studies were in vitro research articles designed to evaluate potential virulence factors, and others were clinical trials (case-control studies, randomized controlled trial) and case-reports. The analysis of these papers has shown that i) Trichomonas tenax is more frequently detected in dental biofilm from sites with periodontitis than in healthy sites; ii) this live flagellate seems capable of producing diverse enzymes that could participate in periodontal breakdown and has the capacity to adhere to epithelial cells, its lysed form could induce the synthesis of IL-8 from macrophage cell lines; iii) the impact of non-surgical treatment of periodontitis have not been thoroughly evaluated on the presence of T. tenax.ConclusionsThis systematic review has reported the presence of T. tenax more frequently in diseased than healthy sites and the capacity of this flagellate to synthesis enzymes which could participate to the degradation of periodontal tissues. Nevertheless, these data do not meet all the postulates and are not enough to provide firm conclusions about the role of T. tenax in the etiopathogenesis of periodontitis.

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.

Introduction Sexually Transmitted Infections (STIs) have always represented a public health concern in the military, yet most studies rely on self-reports among non-random samples of military populations. In addition, most of the studies exploring STI rates among the military focus on US service members. This paper assesses the prevalence and correlates of STIs in the French military using biomarkers and compares self-reported versus diagnosed STIs. Methods Data are drawn from the COSEMIL study, a national sexual health survey conducted in the French military in 2014 and 2015. A random sample of 784 men and 141 women aged 18–57 years completed a self-administered questionnaire and provided biological samples for STI testing. We used logistic regression modeling to identify the correlates of STI diagnosis and self-reports. Results The prevalence of diagnosed STIs was 4.7% [3.8–5.9], mostly due to Chlamydia trachomatis. This rate was four times higher than the 12 months self-reported rate of 1.1% [0.6–2.3]. Reported STI rates were similar among men and women (1.1% versus 1.8%), but diagnosed STI rates were twice as high among females versus males (10.4% versus 4.1%, p = 0.007). There were significant differences in the determinants of reported versus diagnosed STIs. In particular, age and sexual orientation were associated with reported STIs, but not with diagnosed STIs. Conversely, STI counseling and depression were associated with STI diagnosis but not with STI reports. Conclusion This study underlines the need to use biomarkers in population-based surveys, given the differential and substantial underreporting of STIs. Results also highlight the need for programmatic adaptation to address gender inequalities in STI rates, by developing women’s health services in the French military. Addressing such needs not only benefits women but could also serve as a strategy to reduce overall STI rates as most military women have military partners, increasing the risk of internal transmission.

Robust, real-time event detection from physiological signals acquired during long-term ambulatory monitoring still represents a major challenge. In this paper, we propose an original and generic multi-feature probabilistic detector (MFPD) and apply it to real-time QRS complex detection.Methods: The proposed method first derives relevant features from one or more physiological signals and estimates their probability distributions. Bayesian probabilities are then calculated for each feature before being merged through a data fusion node, with regard to the Kullback-Leibler divergence measure. To this end, we derived a KLD estimation method between two Generalized Normal Distributions (GND), in the general case. The efficiency of our method is validated on two noisy ECG databases : 1) a benchmark database by adding noise recordings to the entire MIT-BIH arrhythmia database with noise levels ranging from -6dB to 24dB, 2) an exercise stress test database composed of 54 real ECG recordings (17.8 hours).Results: In both cases significant improvements in detection performance are obtained compared with reference methods. For the benchmark noise stress database, performance gains are consistent for all noise type and SNR levels, and are increasing in low SNR levels. For the exercise stress database, detection error criterion is lowered to 20.91%, as compared with Pan-Tompkins-based (33.08%) and wavelet-based QRS detector (29.02%). Conclusion: Thanks to its multi-feature aspect and its KLD-based decision method (able to adaptively adjust the relative contribution of each feature to the final decision in real-time), the proposed method yields some interesting results, especially on highly-artifacted signals.Significance: Robust, easy to implement and with a reasonable computational cost, MFPD offers some promising perspectives for various challenging monitoring situations., La détection robuste et en temps réel d'événements à partir des signaux physiologiques acquis lors de la surveillance ambulatoire à long terme représente toujours un défi majeur. Dans cet article, nous proposons un détecteur probabiliste multicaractéristique (MFPD) original et générique et l'appliquons à la détection du complexe QRS en temps réel.Méthodes : La méthode proposée dérive d'abord les caractéristiques pertinentes d'un ou de plusieurs signaux physiologiques et estime leur distribution de probabilité. Les probabilités bayésiennes sont ensuite calculées pour chaque caractéristique avant d'être fusionnées à travers un nœud de fusion de données basé sur la pondération de la divergence de Kullback-Leibler. Pour ce faire, nous avons dérivé une méthode d'estimation du KLD entre deux distributions normales généralisées (GND), dans le cas général. L'efficacité de notre méthode est validée sur deux bases de données d'ECG bruités : 1) une base de données simulées, en ajoutant des segments bruités à l'ensemble de la base de données d'arythmie du MIT-BIH avec des niveaux de bruit allant de -6dB à 24dB, 2) une base de données d'exercices sous contraintes composée de 54 enregistrements d'ECG (17,8 heures).Résultats : Dans les deux cas, des améliorations significatives des performances de détection sont obtenues par rapport aux méthodes de référence. En ce qui concerne la base de données simulée, les gains de performance sont importants pour tous les types de bruit et tous les niveaux de SNR, et ils augmentent dans les faibles niveaux de SNR. Pour la base de données d’exercices, le critère d'erreur de détection est abaissé à 20,91 %, comparativement au détecteur QRS basé sur la méthode Pan Tompkins (33,08 %) et au détecteur QRS basé sur les ondelettes (29,02 %). Conclusion : Grâce à son aspect multicaractéristique et sa méthode de décision basée sur le KLD (capable d'ajuster de manière adaptative la contribution relative de chaque fonction à la décision finale en temps réel), la méthode proposée permet d'obtenir des résultats intéressants, en particulier sur les signaux hautement bruités.

Shifts in perceptual boundaries resulting from speech motor learning induced by perturbations of the auditory feedback were taken as evidence for the involvement of motor functions in auditory speech perception. Beyond this general statement, the precise mechanisms underlying this involvement are not yet fully understood. In this paper we propose a quantitative evaluation of some hypotheses concerning the motor and auditory updates that could result from motor learning, in the context of various assumptions about the roles of the auditory and somatosensory pathways in speech perception. This analysis was made possible thanks to the use of a Bayesian model that implements these hypotheses by expressing the relationships between speech production and speech perception in a joint probability distribution. The evaluation focuses on how the hypotheses can (1) predict the location of perceptual boundary shifts once the perturbation has been removed, (2) account for the magnitude of the compensation in presence of the perturbation, and (3) describe the correlation between these two behavioral characteristics. Experimental findings about changes in speech perception following adaptation to auditory feedback perturbations serve as reference. Simulations suggest that they are compatible with a framework in which motor adaptation updates both the auditory-motor internal model and the auditory characterization of the perturbed phoneme, and where perception involves both auditory and somatosensory pathways., Author summary Experimental evidence suggest that motor learning influences categories in speech perception. These observations are consistent with studies of arm motor control showing that motor learning alters the perception of the arm location in the space, and that these perceptual changes are associated with increased connectivity between regions of the motor cortex. Still, the interpretation of experimental findings is severely handicapped by a lack of precise hypotheses about underlying mechanisms. We reanalyze the results of the most advanced experimental studies of this kind in speech, in light of a systematic and computational evaluation of hypotheses concerning motor and auditory updates that could result from motor learning. To do so, we mathematically translate these hypotheses into a unified Bayesian model that integrates for the first time speech production and speech perception in a coherent architecture. We show that experimental findings are best accounted for when motor learning is assumed to generate updates of the auditory-motor internal model and the auditory characterization of phonemes, and when perception is assumed to involve both auditory and somatosensory pathways. This strongly reinforces the view that auditory and motor knowledge intervene in speech perception, and suggests likely mechanisms for motor learning in speech production.

Objectives Our objective was to evaluate the effectiveness of peer-led self-management education in improving glycaemic control in patients with type 2 diabetes in a low-income country (Mali). Methods We conducted an open-label randomised controlled trial. A total of 151 adults (76% women, mean age 52.5) with type 2 diabetes (HbA1c≥8%), treated in the diabetes consultation units of two secondary health centres in Bamako, were allocated to peer-led structured patient education (n = 76) or conventional care alone (n = 75). The intervention group received 1 year of culturally tailored structured patient education (3 courses of 4 sessions) delivered in the community by five trained peer educators. Both groups underwent conventional diabetes monitoring and follow-up. Primary outcome was the mean absolute change in HbA1c from baseline to 12 months. Results 177 education sessions were delivered to the intervention group. Patient attrition was 8%. From baseline to 12 months, the decrease in HbA1c levels was 1.05% (SD = 2.0; CI95%: 1.54;-0.56) in the intervention group compared with 0.15% (SD = 1.7; CI95%: -0.56; 0.26) in the control group, p = 0.006. Mean BMI change was -1.65 kg/m2 (SD = 2.5; CI95%: -2.25; -1.06) in the intervention group and +0.05 kg/m2 (SD = 3.2; CI95%: -0.71; 0.81) in the control group, p = 0.0005. Mean waist circumference decreased by 3.34 cm (SD = 9.3; CI95%: -5.56;-1.13) in the intervention group and increased by 2.65 cm (SD = 10.3; CI95%: 0.20; 5.09) in the control group, p = 0.0003. Conclusions Peer-led structured patient education delivered over 1 year to patients with poorly controlled type 2 diabetes in Mali yielded substantial improvements in glycaemic control and anthropometric parameters. This is of importance for the scaling up of efficient interventions in low-resource settings in the future. Trial registration ClinicalTrials.gov NCT01485913

Over the last three decades, evidence has emerged that low-intensity magnetic fields can influence biological systems. It is now well established that migratory birds have the capacity to detect the Earth's magnetic field; it has been reported that power lines are associated with childhood leukemia and that pulsed magnetic fields increase the production of reactive oxidative species (ROS) in cellular systems. Justifiably, studies in this field have been viewed with skepticism, as the underlying molecular mechanisms are unknown. In the accompanying paper, Sherrard and colleagues report that low-flux pulsed electromagnetic fields (PEMFs) result in aversive behavior in Drosophila larvae and ROS production in cell culture. They further report that these responses require the presence of cryptochrome, a putative magnetoreceptor. If correct, it is conceivable that carcinogenesis associated with power lines, PEMF-induced ROS generation, and animal magnetoreception share a common mechanistic basis., This Primer explores recent evidence as to how low-intensity magnetic fields might influence biological systems.

This paper investigates age variations in foreign-born vs. native-born mortality ratios in an international comparative perspective, with the purpose of gaining insight into the mechanisms underlying the so-called migrant mortality advantage. We examine the four main explanations that have been proposed in the literature for the migrant mortality advantage (i.e., in-migration selection effects, out-migration selection effects, cultural effects, and data artifacts), and formulate expectations as to whether they should generate an increase, a decrease, or no change in relative mortality over the life course. Using data from France, the US and the UK for periods around 2010, we then examine typical age patterns of foreign-born vs. native-born mortality ratios in light of this theoretical framework. We find that these mortality ratios vary greatly by age, with important similarities across migrant groups and host countries. The most systematic age pattern we find is a U-shape pattern: at the aggregate level, migrants often experience excess mortality at young ages, then exhibit a large advantage at adult ages (with the largest advantage around age 45), and finally experience mortality convergence with natives at older ages. The explanation most consistent with this pattern is the "in-migration selection effects" explanation. By contrast, the "out-migration selection effects" explanation is poorly supported by the observed patterns. Our age disaggregation also shows that migrants at mid-adult ages experience mortality advantages that are often far greater than typically documented in this literature. Overall, these results reinforce the notion that migrants are a highly-selected population exhibiting mortality patterns that poorly reflect their living conditions in host countries.

International audience; Knowledge of the human visual system helps to develop better computational models of visual attention. State-of-the-art models have been developed to mimic the visual attention system of young adults that, however, largely ignore the variations that occur with age. In this paper, we investigated how visual scene processing changes with age and we propose an age-adapted framework that helps to develop a computational model that can predict saliency across different age groups. Our analysis uncovers how the explorativeness of an observer varies with age, how well saliency maps of an age group agree with fixation points of observers from the same or different age groups, and how age influences the center bias tendency. We analyzed the eye movement behavior of 82 observers belonging to four age groups while they explored visual scenes. Explorative-ness was quantified in terms of the entropy of a saliency map, and area under the curve (AUC) metrics was used to quantify the agreement analysis and the center bias tendency. Analysis results were used to develop age adapted saliency models. Our results suggest that the proposed age-adapted saliency model outperforms existing saliency models in predicting the regions of interest across age groups.

View at Publisher| Export | Download | Add to List| More... PLoS ONE Volume 12, Issue 1, January 2017, Article number e0169658 Open Access Vigi4Med scraper: A framework for web forum structured data extraction and semantic representation (Article) Audeh, B.a , Beigbeder, M.a, Zimmermann, A.a, Jaillon, P.b, Bousquet, C.c a University of Lyon, MINES Saint-Etienne, CNRS, Hubert Curien Laboratory, UMR 5516, Saint-Etienne, France b Ecole Nationale Superieure des Mines de Saint-Etienne, Saint-Etienne, France c INSERM, U1142, LIMICS, Paris, France View additional affiliations View references (36) Abstract The extraction of information from social media is an essential yet complicated step for data analysis in multiple domains. In this paper, we present Vigi4Med Scraper, a generic open source framework for extracting structured data from web forums. Our framework is highly configurable; using a configuration file, the user can freely choose the data to extract from any web forum. The extracted data are anonymized and represented in a semantic structure using Resource Description Framework (RDF) graphs. This representation enables efficient manipulation by data analysis algorithms and allows the collected data to be directly linked to any existing semantic resource. To avoid server overload, an integrated proxy with caching functionality imposes a minimal delay between sequential requests. Vigi4Med Scraper represents the first step of Vigi4Med, a project to detect adverse drug reactions (ADRs) from social networks founded by the French drug safety agency Agence Nationale de Securite du Medicament (ANSM). Vigi4Med Scraper has successfully extracted greater than 200 gigabytes of data from the web forums of over 20 different websites. © 2017 Audeh et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

International audience; In this paper we present the development and validation a comprehensive questionnaire to assess college students' knowledge about modern genetics and genomics, their belief in genetic determinism, and their attitudes towards applications of modern genetics and geno-mic-based technologies. Written in everyday language with minimal jargon, the Public Understanding and Attitudes towards Genetics and Genomics (PUGGS) questionnaire is intended for use in research on science education and public understanding of science, as a means to investigate relationships between knowledge, determinism and attitudes about modern genetics, which are to date little understood. We developed a set of core ideas and initial items from reviewing the scientific literature on genetics and previous studies on public and student knowledge and attitudes about genetics. Seventeen international experts from different fields (e.g., genetics, education, philosophy of science) reviewed the initial items and their feedback was used to revise the questionnaire. We validated the questionnaire in two pilot tests with samples of university freshmen students. The final questionnaire contains 45 items, including both multiple choice and Likert scale response formats. Cronbach alpha showed good reliability for each section of the questionnaire. In conclusion, the PUGGS questionnaire is a reliable tool for investigating public understanding and attitudes towards modern genetics and genomic-based technologies.

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) that recently caused outbreaks in the Americas. Over the past 60 years, this virus has been observed circulating among African, Asian, and Pacific Island populations, but little attention has been paid by the scientific community until the discovery that large-scale urban ZIKV outbreaks were associated with neurological complications such as microcephaly and several other neurological malformations in fetuses and newborns. This paper is a systematic review intended to list all mosquito species studied for ZIKV infection or for their vector competence. We discuss whether studies on ZIKV vectors have brought enough evidence to formally exclude other mosquitoes than Aedes species (and particularly Aedes aegypti) to be ZIKV vectors. From 1952 to August 15, 2017, ZIKV has been studied in 53 mosquito species, including 6 Anopheles, 26 Aedes, 11 Culex, 2 Lutzia, 3 Coquillettidia, 2 Mansonia, 2 Eretmapodites, and 1 Uranotaenia. Among those, ZIKV was isolated from 16 different Aedes species. The only species other than Aedes genus for which ZIKV was isolated were Anopheles coustani, Anopheles gambiae, Culex perfuscus, and Mansonia uniformis. Vector competence assays were performed on 22 different mosquito species, including 13 Aedes, 7 Culex, and 2 Anopheles species with, as a result, the discovery that A. aegypti and Aedes albopictus were competent for ZIKV, as well as some other Aedes species, and that there was a controversy surrounding Culex quinquefasciatus competence. Although Culex, Anopheles, and most of Aedes species were generally observed to be refractory to ZIKV infection, other potential vectors transmitting ZIKV should be explored., Author summary The first isolation of Zika virus (ZIKV) in mosquitoes was made in 1948 in Aedes africanus. Over the next years, knowledge about ZIKV increased, with detection of the virus in primates, including humans and several other mosquito species. Most of these species were collected in Africa during arbovirus surveillance studies and belong to the genus Aedes, and today, 20 mosquito species have been identified that can be naturally infected by ZIKV. Although field studies are essential to have an overview of potential mosquito vectors of ZIKV during outbreaks or involved in the maintenance of the sylvatic cycle, laboratory studies are needed to assess the capacity of a species to transmit the virus to a new host. Since 2015, corresponding to the beginning of the outbreak in Brazil, vector competence studies have multiplied and confirmed that the mosquito A. aegypti, known to transmit dengue fever and chikungunya viruses, was also the main vector of ZIKV. This review aims to highlight the studies conducted from several laboratories about mosquito species naturally infected or tested for their vector competence for ZIKV.

tex.pmcid: PMC5665517; International audience; The 16-item Vitamin D Status Predictor (VDSP) questionnaire helps to identify, without resorting to a blood test, older adults with low vitamin D concentrations. Our objective was to determine whether a self-administered VDSP was concordant with the VDSP administered by a physician, and to examine the concordance of every single item of the VDSP. Methods A total of 349 older in- and outpatients (mean, 83.2±7.2years; 59% female) were consecutively recruited in the geriatric ward of the University Hospital of Angers, France. All participants completed a self-administered VDSP questionnaire (self-VDSP) in paper format composed of 17 items exploring age, gender, general condition, nutrition, vision, mood, cognition, gait and falls, and osteoporosis. All participants underwent subsequently a full clinical examination by a physician exploring the same areas (rater-VDSP). Results The agreement between the self-VDSP and the rater-VDSP was almost perfect for the probability of having low vitamin D concentrations, regardless of the definition used (i.e., ≤25, ≤50 or ≤75 nmol/L). The agreements between physicians’ and patients’ responses were significant for every single VDSP item. The agreement was fair to perfect for all items, except for cognitive disorders, undernutrition and polymorbidity (poor agreement). Conclusions Older adults are able to evaluate their own probabilities of severe vitamin D deficiency, deficiency and insufficiency. A self-questionnaire may promote the use of the VDSP tool in this population, and help clinicians in decisions to supplement their patients in a reasoned way.

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.