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The fundamental trade-off between current and future reproduction has long been considered to result in a tendency for species that can grow large to begin reproduction at a larger size. Due to the prolonged time required to reach maturity, estimates of tree maturation size remain very rare and we lack a global view on the generality and the shape of this trade-off. Using seed production from five continents, we estimate tree maturation sizes for 486 tree species spanning tropical to boreal climates. Results show that a species' maturation size increases with maximum size, but in a non-proportional way: the largest species begin reproduction at smaller sizes than would be expected if maturation were simply proportional to maximum size. Furthermore, the decrease in relative maturation size is steepest in cold climates. These findings on maturation size drivers are key to accurately represent forests' responses to disturbance and climate change.

Abstract Background Vulnerable social groups have greater difficulty in accessing care and a lower quality of care. Health systems focused on primary care appear to be more effective, efficient and equitable. However, difficulties in accessing primary care are persisting. We focused on primary care screening for cervical cancer through Cervico-Uterine Smear (CUS), which has been shown to be effective in reducing disease incidence and mortality. In this study, we aimed to investigate the characteristics of women who undergo CUS according to the category of health professionals (general practitioners or gynaecologists) performing CUS and to analyse potential differences in access to care in terms of socioeconomic and geographical characteristics. Methods This was a retrospective observational study based on data from the main health insurance schemes in France, allowing analysis of health care consumption according to socioeconomic levels and proximity to health care services. We included women aged 25 to 64 years in 2012 for whom CUS would be a relevant procedure (695,694). The sociodemographic and territorial indicators were age, geographical area deprivation, and the availability of gynaecological care. The analysis was performed using multinomial logistic regression. Results A total of 202,271 (29%) patients underwent CUS; of whom 68% underwent CUS administered by gynaecologists and 28% were administered by general practitioners (GPs). However, inequalities in CUS screening rates were observed, with a decrease in the number of CUSs performed with increased age, a rural location, deprivation, and sparse health care provisions. Deprived people seemed less penalised by GPs. Conclusions Involvement of General Practitioners may improve cervical screening equality in France. The organisation of health systems around primary care may allow a better access to care and to account for the specific needs of deprived populations.

Vegetation phenology plays a key role in controlling the seasonality of ecosystem processes that modulate carbon, water and energy fluxes between the biosphere and atmosphere. Accurate modelling of vegetation phenology in the interplay of Earth's surface and the atmosphere is thus crucial to understand how the coupled system will respond to and shape climatic changes. Phenology is controlled by meteorological conditions at different timescales: on the one hand, changes in key meteorological variables (temperature, water, radiation) can have immediate effects on the vegetation development; on the other hand, phenological changes can be driven by past environmental conditions, known as memory effects. However, the processes governing meteorological memory effects on phenology are not completely understood, resulting in their limited performance of vegetation phenology represented in land surface models. A deep learning model, specifically a long short-term memory network (LSTM), has the potential to capture and model the meteorological memory effects on vegetation phenology. Here, we apply the LSTM to model the vegetation phenology using meteorological drivers and high-temporal-resolution canopy greenness observations through digital repeat photography by the PhenoCam network. We compare a multiple linear regression model, a no-memory-effect LSTM model and a full-memory-effect LSTM model to predict the whole seasonal greenness trajectory and the corresponding phenological transition dates across 50 sites and 317 site years during 2009–2018, covering deciduous broadleaf forests, evergreen needleleaf forests and grasslands. Results show that the deep learning model outperforms the multiple linear regression model, and the full-memory-effect LSTM model performs better than the no-memory-effect model for all three plant function types (median R2 of 0.878, 0.957 and 0.955 for broadleaf forests, evergreen needleleaf forests and grasslands). We also find that the full-memory-effect LSTM model is capable of predicting the seasonal dynamic variations of canopy greenness and reproducing trends in shifting phenological transition dates. We also performed a sensitivity analysis of the full-memory-effect LSTM model to assess its plausibility, revealing its coherence with established knowledge of vegetation phenology sensitivity to meteorological conditions, particularly changes in temperature. Our study highlights that (1) multi-variate meteorological memory effects play a crucial role in vegetation phenology, and (2) deep learning opens up new avenues for improving the representation of vegetation phenological processes in land surface models via a hybrid modelling approach.

In this paper, we present an innovative approach inspired by the Path-scan model to detect paths with k adjacent edges (k-path) exhibiting unusual behavior (synonymous with anomaly) within network communications. This work is motivated by the challenge of identifying malicious activities carried out in vulnerable k-path in a small to medium-sized computer network. Each observed edge (time series of the number of events or the number of packets exchanged between two computers in the network) is modeled using the three-state observed Markov model, as opposed to the Path-scan model which uses a two-state model (active state and inactive state), to establish baselines of behavior in order to detect anomalies. This model captures the typical behavior of network communications, as well as patterns of suspicious activity, such as those associated with brute force attacks. We take a perspective by analyzing each vulnerable k-path, enabling the accurate detection of anomalies on the k-path. Using this approach, our method aims to enhance the detection of suspicious activities in computer networks, thus providing a more robust and accurate solution to ensure the security of computer systems.

Abstract Background Like other countries in Europe and around the world, France was hit by the COVID-19 pandemic in 2020, although it had also experienced several social crises since 2017. This study assessed the evolution of self-reported health and activity limitations and explored the dynamics of their socio-territorial inequalities among the French population aged 18–75 years between 2017 and 2021. Methods Self-reported health (SRH) and global activity limitation indicator (GALI) were assessed in the same way in the four last editions of the French Health Barometer surveys conducted in the general population in 2017, 2019, 2020, and 2021, with between 9,200 and 24,500 subjects interviewed depending on the year. The prevalence of good or very good SRH and GALI (any limitation) and their evolution between 2017 and 2021 were studied according to sex, age, main socioeconomic positions (SEP), and regions. Poisson regression models were used to estimate adjusted prevalence ratios and potential modification effects of sociodemographic and geographic characteristics. Results Between 2017 and 2021, SRH and GALI deteriorated in adults in France in a continuous way. Very good or good SRH decreased from 75.2% (CI95% [74.5–75.9]) of subjects in 2017 to 68.5% (CI95% [67.7–69.3]) in 2021. In parallel, GALI increased from 21.5% (CI95% [21.0–22.2) in 2017 to 25.2% (CI95% [24.5–26.0]) in 2021.The deterioration of indicators affected both sexes, all age classes (except 65–75 years), especially younger age classes (18–24 and 25–34 years), all geographical regions, and all SEP variables, with groups with a higher SEP deteriorating more than others. Negative variations exceeding 20% (8–10 percentage points on the absolute scale of indicators) were observed in several population groups from 2019 onwards. Conclusion The previously observed deterioration of the SRH and GALI continued in France between 2017 and 2021, with narrowing socio-territorial gradients of inequalities. The impact of successive social and health crises on the poor evolution of self-reported health and activity limitations warrants further investigation over time and across locations using complementary and possibly more detailed indicators.

Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

Objective: To identify the articles in the existing literature that analyse healthcare costs according to the socioeconomic position (pre- or post-injury) for traumatic brain injury survivors. Secondary aims were to describe the types of costs and socioeconomic characteristics and to determine whether socioeconomic characteristics affect the risk of traumatic brain injury or whether the consequences of trauma alter living conditions post-injury. Methods: This scoping review followed the methods proposed by Arksey and O’Malley. The literature search was performed in 5 databases. Results: Twenty-two articles were included, published between 1988 and 2023. Only 2 articles (9%) followed the guidelines for economic evaluation of healthcare programmes and 2 articles (9%) evaluated socioeconomic position “completely” with 3 main individual measures of socioeconomic characteristics (i.e., education, income, and occupation). The relationship between costs and socioeconomic characteristics could vary in 2 ways in traumatic brain injury: socioeconomic disadvantage was mostly associated with higher healthcare costs, and the cost of healthcare reduced the survivors’ living conditions. Conclusion: This work highlights the need for a detailed and methodologically sound assessment of the relationship between socioeconomic characteristics and the costs associated with trauma. Modelling the care pathways of traumatic brain injury would make it possible to identify populations at risk of poor recovery or deterioration following a TBI, and to develop specific care pathways. The aim is to build more appropriate, effective, and equitable care programmes.

Abstract Background Health-Related Quality of life (HRQoL) in cancer survivors can be significantly affected in the long-term by various consequences resulting from differing levels of severity of cancer and its treatments. Our objective was to identify factors associated with HRQoL in breast cancer survivors (BCSs) and cancer-free women (CFWs). Methods We conducted a cross-sectional study in Seintinelles volunteers who answered online questionnaires between September 15, 2020 and February 5, 2021. HRQoL was measured using the World Health Organization Quality of Life–BREF questionnaire. We collected data on sociodemographic and health-related factors, lifestyle habits, coping mechanisms, locus of control, and health literacy. SAS version 9.4 statistical software was used for analyses. We performed descriptive analyses of the characteristics of the participants in each group and compared these characteristics between the two groups using the Chi2 test or the Student t-test. The adjusted means of the scores of different psychometric scales were calculated and compared using the method of least squares to fit general linear models (GLM) while adjusting for various factors. Multiple linear or multiple logistic regression models were used to assess the factors associated with WHOQOL-BREF scores, separately, in the two groups of participants. Results The study involved 722 BCSs and 1359 CFWs aged 26–75 years. BCSs had significantly lower physical health scores and were less likely to be satisfied with their health compared to CFWs (59.5 vs. 63.2, p 22) of internal locus of control); or inversely associated (neurological and sleep problems, over two medical consultations/year). In BCSs, treatment by mastectomy or radiation therapy/brachytherapy, a short-time since diagnosis, current cancer therapy, and presence of sequalae were inversely associated with physical health. BCSs’ health satisfaction was diminished with lower values of coping by positive thinking (≤ 14) and seeking social support (≤ 18). Conclusions HRQoL can be improved by developing strategies that increase internal locus of control and coping (positive thinking, problem-solving and seeking social support), and through health literacy.

Spring phenology is a key indicator of temperate and boreal ecosystems' response to climate change. To date, most phenological studies have analyzed the mean date of budburst in tree populations while overlooking the large variability of budburst among individual trees. The consequences of neglecting the within-population variability (WPV) of budburst when projecting the dynamics of tree communities are unknown. Here, we develop the first model designed to simulate the WPV of budburst in tree populations. We calibrated and evaluated the model on 48 442 budburst observations collected between 2000 and 2022 in three major temperate deciduous trees, namely, hornbeam (Carpinus betulus), oak (Quercus petraea) and chestnut (Castanea sativa). The WPV model received support for all three species, with a root mean square error of 5.7 ± 0.5 d for the prediction of unknown data. Retrospective simulations over 1961–2022 indicated earlier budburst as a consequence of ongoing climate warming. However, simulations revealed no significant change for the duration of budburst (DurBB, i.e., the time interval from BP20 to BP80 (with BP representing budburst percent), which respectively represent the date when 20 % and 80 % of trees in a population have reached budburst), due to a lack of significant temperature increase during DurBB in the past. This work can serve as a basis for the development of models targeting intra-population variability of other functional traits, which is of increasing interest in the context of climate change.

Abstract Background With the increase in the number of long-term survivors, interest is shifting from cancer survival to life and quality of life after cancer. These include consequences of long-term side effects of treatment, such as gonadotoxicity. Fertility preservation is becoming increasingly important in cancer management. International recommendations agree on the need to inform patients prior to treatments about the risk of fertility impairment and refer them to specialized centers to discuss fertility preservation. However, the literature reveals suboptimal access to fertility preservation on an international scale, and particularly in France, making information for patients and oncologists a potential lever for action. Our overall goal is to improve access to fertility preservation consultations for women with breast cancer through the development and evaluation of a combined intervention targeting the access and diffusion of information for these patients and brief training for oncologists. Methods Firstly, we will improve existing information tools and create brief training content for oncologists using a qualitative, iterative, user-centred and participatory approach (objective 1). We will then use these tools in a combined intervention to conduct a stepped-wedge cluster randomized trial (objective 2) including 750 women aged 18 to 40 newly treated with chemotherapy for breast cancer at one of the 6 participating centers. As the primary outcome of the trial will be the access to fertility preservation counselling before and after using the combined intervention (brochures and brief training for oncologists), we will compare the rate of fertility preservation consultations between the usual care and intervention phases using linear regression models. Finally, we will analyse our approach using a context-sensitive implementation analysis and provide key elements for transferability to other contexts in France (objective 3). Discussion We expect to observe an increase in access to fertility preservation consultations as a result of the combined intervention. Particular attention will be paid to the effect of this intervention on socially disadvantaged women, who are known to be at greater risk of inappropriate treatment. The user-centred design principles and participatory approaches used to optimize the acceptability, usability and feasibility of the combined intervention will likely enhance its impact, diffusion and sustainability. Trial registration Registry: ClinicalTrials.gov. Trial registration number: NCT05989776. Date of registration: 7th September 2023. URL: https://classic.clinicaltrials.gov/ct2/show/NCT05989776 . Protocol version Manuscript based on study protocol version 2.0, 21st may 2023.

Introduction Adolescence is a sensitive period for cardiometabolic health. Yet, it remains unknown if adolescent health behaviours, such as alcohol use, smoking, diet and physical activity, have differential effects across socioeconomic strata. Adopting a life-course perspective and a causal inference framework, we aim to assess whether the effects of adolescent health behaviours on adult cardiometabolic health differ by levels of neighbourhood deprivation, parental education and occupational class. Gaining a better understanding of these social disparities in susceptibility to health behaviours can inform policy initiatives that aim to improve population health and reduce socioeconomic inequalities in cardiometabolic health.Methods and analysis We will conduct a secondary analysis of the Young Finns Study, which is a longitudinal population-based cohort study. We will use measures of health behaviours—smoking, alcohol use, fruit and vegetable consumption, and physical activity—as exposure and parental education, occupational class and neighbourhood deprivation as effect modifiers during adolescence (ages 12–18 years). Eight biomarkers of cardiometabolic health (outcomes)—waist circumference, body mass index, blood pressure, low-density lipoprotein cholesterol, apolipoprotein B, plasma glucose and insulin resistance—will be measured when participants were aged 33–40. A descriptive analysis will investigate the clustering of health behaviours. Informed by this, we will conduct a causal analysis to estimate effects of single or clustered adolescent health behaviours on cardiometabolic health conditional on socioeconomic background. This analysis will be based on a causal model implemented via a directed acyclic graph and inverse probability-weighted marginal structural models to estimate effect modification.Ethics and dissemination The Young Finns study was conducted according to the guidelines of the Declaration of Helsinki, and the protocol was approved by ethics committees of University of Helsinki, Kuopio, Oulu, Tampere and Turku. We will disseminate findings at international conferences and a manuscript in an open-access peer-reviewed journal.

Objective Delineate the scope of teleconsultation services that can be effectively performed to provide women with comprehensive gynaecological and obstetrical care.Design Based on the literature and experts’ insights, we identified a list of gynaecological and obstetrical care practices suitable for teleconsultation. A three-round Delphi consensus survey was then conducted online among a panel of French experts. Experts using a 9-point Likert scale assessed the relevance of each teleconsultation practice in four key domains: prevention, gynaecology and antenatal and postnatal care. Consensus was determined by applying a dual-criteria approach: the median score on a 9-point Likert scale and the percentage of votes either below 5 or 5 and higher.Setting The study was conducted at a national level in France and involved multiple healthcare centres and professionals from various geographical locations.Participants The panel comprised 22 French experts with 19 healthcare professionals, including 12 midwives, 3 obstetricians-gynaecologists, 4 general practitioners and 3 healthcare system users. Participants were selected to include diverse practice settings encompassing hospital and private practices in both rural and urban areas.Primary and secondary outcome measures The study’s primary outcome was the identification of gynaecological and obstetrical care practices suitable for teleconsultation. Secondary outcomes included the level of professional consensus on these practices.Results In total, 71 practices were included in the Delphi survey. The practices approved for teleconsultation were distributed as follows: 92% in prevention (n=12/13), 55% in gynaecology (n=18/33), 31% in prenatal care (n=5/16) and 12% in postnatal care (n=1/9). Lastly, 10 practices remained under discussion: 7 in gynaecology, 2 in prenatal care and 1 in postnatal care.Conclusions Our consensus survey highlights both the advantages and limitations of teleconsultations for women’s gynaecological and obstetrical care, emphasising the need for careful consideration and tailored implementation.

Objective: Gender as the “sociocultural role of sex” is underrepresented in colorectal cancer incidence studies, potentially resulting in underestimated risk factors’ consequences and inequalities men/women. We aim to explore how literature focusing on differences between men and women in the incidence of colorectal cancer interprets these differences: through sex- or gender-related mechanisms, or both?Methods: We conducted a scoping review using PubMed and Google Scholar. We categorized studies based on their definitions of sex and/or gender variables.Results: We reviewed 99 studies, with 7 articles included in the analysis. All observed differences between men and women. Six articles examined colorectal cancer incidence by gender, but only 2 used the term “gender” to define exposure. One article defined its “sex” exposure variable as gender-related mechanisms, and two articles used “sex” and “gender” interchangeably to explain these inequalities. Gender mechanisms frequently manifest through health behaviors.Conclusion: Our results underscore the need for an explicit conceptual framework to disentangle sex and/or gender mechanisms in colorectal cancer incidence. Such understanding would contribute to the reduction and prevention of social health inequalities.

Lack of tree fecundity data across climatic gradients precludes the analysis of how seed supply contributes to global variation in forest regeneration and biotic interactions responsible for biodiversity. A global synthesis of raw seedproduction data shows a 250-fold increase in seed abundance from cold-dry to warm-wet climates, driven primarily by a 100-fold increase in seed production for a given tree size. The modest (threefold) increase in forest productivity across the same climate gradient cannot explain the magnitudes of these trends. The increase in seeds per tree can arise from adaptive evolution driven by intense species interactions or from the direct effects of a warm, moist climate on tree fecundity. Either way, the massive differences in seed supply ramify through food webs potentially explaining a disproportionate role for species interactions in the wet tropics.

The relationships that control seed production in trees are fundamental to understanding the evolution of forest species and their capacity to recover from increasing losses to drought, fire, and harvest. A synthesis of fecundity data from 714 species worldwide allowed us to examine hypotheses that are central to quantifying reproduction, a foundation for assessing fitness in forest trees. Four major findings emerged. First, seed production is not constrained by a strict trade-off between seed size and numbers. Instead, seed numbers vary over ten orders of magnitude, with species that invest in large seeds producing more seeds than expected from the 1:1 trade-off. Second, gymnosperms have lower seed production than angiosperms, potentially due to their extra investments in protective woody cones. Third, nutrient-demanding species, indicated by high foliar phosphorus concentrations, have low seed production. Finally, sensitivity of individual species to soil fertility varies widely, limiting the response of community seed production to fertility gradients. In combination, these findings can inform models of forest response that need to incorporate reproductive potential.

Abstract Background The aims of the “médecin traitant” or referring physician (RP) reform, introduced in France in 2004, were to improve the organisation and quality of care and to allow for greater equity, particularly in terms of prevention. The objective of our study was to evaluate the effect of having a declared RP on the uptake of screening for breast and cervical cancers, and to explore the mechanisms involved. Methods We used an existing dataset of 1,072,289 women, which combines data from the Health Insurance information systems, with census data. We built multivariable logistic regression models to study the effect of having a RP on the uptake of mammography and pap smear, adjusted for age, socio-economic level, health status and healthcare provision. We secondarily added to this model the variable “having consulted a General Practitioner (GP) within the year”. Finally, we evaluated the interaction between the effect of having a referring physician and the area of residence (metropolitan/urban/rural). Results Patients who had a declared RP had a significantly higher uptake of mammography and pap smear than those who did not. The strength of the association was particularly important in very urban areas. The effect of having visited a GP seemed to explain a part of the correlation between having a RP and uptake of screening. Conclusions Lower rates of gynaecological screening among women without an RP compared to those with an RP may partly reflect a specific behaviour pattern in women less adherent to the health care system. However, this result also shows the importance of the RP, who assumes the key role of relaying public health information in a more personalised and adapted way.

The extent of the potassium (K) limitation of forest productivity is probably more widespread than previously thought, and K limitation could influence the response of forests to future global changes. To understand the effects of K limitation on forest primary production, we have developed the first ecophysiological model simulating the K cycle and its interactions with the carbon (C) and water cycles. We focused on the limitation of the gross primary productivity (GPP) by K availability in tropical eucalypt plantations in Brazil. We used results from stand-scale fertilisation experiments as well as C flux measurements in two tropical eucalypt plantations to parameterise the model. The model was parameterised for fertilised conditions and then used to test for the effects of contrasting additions of K fertiliser. Simulations showed that K deficiency limits GPP by more than 50 % during a 6-year rotation, a value in agreement with estimations in K-limited eucalypt stands. Simulations showed a decrease of modelled canopy transpiration of around 50 % and a decrease in modelled water-use efficiency WUEGPP of 10 %. Through a sensitivity analysis, we used the model to identify the most critical processes to consider when studying K limitation of GPP. The inputs of K to the stands, such as the atmospheric deposition and weathering fluxes, and the regulation of the cycle of K within the ecosystem were critical for the response of the system to K deficiency. Litter leaching processes were of lower importance, since residence time of K in litter was low. The new forest K-cycle model developed in the present study includes multiple K processes interacting with the carbon and water cycles, and strong feedbacks on GPP were outlined. This is a first step in identifying the source or sink limitation of forest growth by K.

Potassium (K) availability constrains forest productivity. Brazilian eucalypt plantations are a good example of the K limitation of wood production. Here, we built upon a previously described model (CASTANEA-MAESPA-K) and used it to understand whether the simulated decline in C source under K deficiency was sufficient to explain the K limitation of wood productivity in Brazilian eucalypt plantations. We developed allocation schemes for both C and K and included these in CASTANEA-MAESPA-K. Neither direct limitations of the C-sink activity nor direct modifications of the C allocation by K availability were included in the model. Simulation results show that the model was successful in replicating the observed patterns of wood productivity limitation by K deficiency. Simulations also show that the response of net primary productivity (NPP) is not linear with increasing K fertilisation. Simulated stem carbon use and water use efficiencies decreased with decreasing levels of K availability. Simulating a direct stoichiometric limitation of NPP or wood growth was not necessary to reproduce the observed decline of productivity under K limitation, suggesting that K stoichiometric plasticity could be different to that of N and P. Confirming previous results from the literature, the model simulated an intense recirculation of K in the trees, suggesting that retranslocation processes were essential for tree functioning. Optimal K fertilisation levels calculated by the model were similar to nutritional recommendations currently applied in Brazilian eucalypt plantations, paving the way for validation of the model at a larger scale and of this approach for developing decision-making tools to improve fertilisation practices.

Abstract Context It is widely recognised that the COVID-19 pandemic has negatively impacted individuals’ mental health. However, little emphasis has been put on the possible influence of socio-economic factors in the relationship. In the context of the COVID-19 pandemic, our objectives were (i) to assess the relationship between education level and mental health in French adults, and (ii) to study the influence of the economic, social, health and the COVID-19-related factors in men and women respectively. Method Data are from 32,581 individuals representative of the French population who responded to the weekly survey “Baromètre COVID-19” between April 7th and May 31st 2020. Education level was self-reported (university degree, high school qualification, vocational certificate/qualification, no diploma). Anxiety-depressive state was derived from four items related to the frequency of occurrence of depressive and anxiety symptoms, and summarized in an overall validated anxiety-depressive score. Multivariate linear regression analyses were carried out with nested adjustments of variables related to economic, social, health and COVID-19 contexts to assess the relationship between education and anxiety-depressive state. Results In total, 45% of individuals reported symptoms of anxiety-depressive state (53% in women versus 36% in men). Among men, those with a vocational certificate/qualification and those with no diploma had a greater risk of having a higher anxiety-depressive state compared to those with a university degree (βVocational certificate/qualification = 0.16 [0.04; 0.27]; βNo diploma = 0.75 [0.43; 1.07]) while among women, the risk of anxiety-depressive state increased as education level decreased (βBaccalaureate = 0.37 [0.25; 0.49]; βVocational certificate/qualification = 0.41 [0.28; 0.54]; βNo diploma = 0.8 [0.49; 1.12]). For both men and women, economic, health, and COVID-19 factors partly attenuate these associations while social factors marginally modified the relationship. After accounting for confounders and intermediate variables, the absence of a diploma remained associated with anxiety-depressive state among men, while the whole educational gradient of anxiety-depressive state persisted among women. Conclusion In France, at the end of the first wave of COVID-19, individuals with a lower level of education had a higher risk of anxiety-depressive state. This association was more pronounced for women, highlighting a process of social inequality in health possibly related to gender. This should be considered in future prevention and public health interventions.

ContextAt least 40% of cancers are linked to environmental or behavioral factors, and dietary behavior appears to be a major lever. Epidaure Market is a prevention initiative developed using a method for co-constructing health promotion initiatives and prevention programs that stratifies evidence from the scientific literature and combines it with experiential knowledge (DEVA, TPB, BCT). It promotes a sustainable diet (i.e., healthy, ecological and ethical nutrition) among 5th and 4th grade students during the crucial period of adolescence, when these behaviors are often far from the recommendations.MethodThe protocol implemented was carried out in 72 middle school classes in the Montpellier and Dijon academies. The intervention included teaching sessions and a virtual supermarket game, integrated into the school curriculum and delivered by science teachers. Effectiveness is tested in a cluster randomized controlled trial with 3 evaluation times (pre- and post-intervention and 1 follow-up). The study also includes an implementation assessment, with process analysis and implementation elements, as well as a transferability assessment based on key functions (FIC model and Astaire grid).Expected outcomesThe study is still underway within the school. The primary expected outcome is a positive influence on the motives underlying food choices to move towards a sustainable diet. Secondary expectations involve changes in variables such as self-efficacy and perceived social norms, as well as an increase in knowledge about healthy eating. We also expect the qualitative approaches to provide information on the deployment process in the new territories.DiscussionThe study aims not only to demonstrate the effectiveness of Epidaure Market, but also to identify the optimal conditions for its nationwide implementation in France's middle schools. Ultimately, the initiative aims to help reduce the incidence of cancer by promoting healthier eating habits among teenagers.

IntroductionAntiretroviral therapy has improved life expectancy in HIV-infected patients. However, people living with HIV under antiretroviral therapy are at higher risks of developing chronic complications and acquiring multidrug resistant bacteria than healthy population. These factors have been associated with shifts in gut microbiome composition and immune activation. It is unclear how antiretroviral drugs affect gut microbiota composition, but it has been observed that antiretroviral treatment is not able to fully restore gut health after HIV infection. Additionally, some antiretroviral drugs have shown antibacterial activity suggesting that these drugs could have a direct impact on the human microbiome composition. MethodsWe determined the in vitro antibacterial activity of 16 antiretroviral drugs against a set of key clinically relevant and human commensal bacterial strains. ResultsOur results demonstrate that 5 antiretroviral drugs have in vitro antibacterial activity against gut and vaginal human commensal bacteria. Zidovudine has antibacterial activity against Escherichia coli, Klebsiella pneumoniae and Prevotella bivia, abacavir against Gardnerella vaginalis, efavirenz against G. vaginalis and P. bivia and bictegravir against Enterococcus spp. and G. vaginalis. Moreover, we describe for the first time that elvitegravir has antibacterial activity against G. vaginalis and P. bivia and, most importantly, against vancomycin-resistant Enterococcus spp. and methicillin-resistant Staphylococcus aureus strains with MIC values of 4-16 and 4 µg/mL, respectively showing high level of effectiveness against the tested multidrug-resistant bacteria.DiscussionOur results underscore that some antiretroviral drugs may influence the human microbiota composition. In addition, we report the potential use of elvitegravir to treat multidrug-resistant Gram-positive bacteria warranting the need of clinical studies to repurpose this antiretroviral drug.

BackgroundA sedentary lifestyle is commonly associated with a higher risk of chronic disease development. Among school-aged children from European countries, screen-time represents a significant portion of sedentary time with 39.8% of children spending more than 2h/day in front of a screen on average. Therefore, effective solutions to reduce sedentary behavior (SB) must be found. Multilevel interventions based on the socio-ecological model (SEM) are particularly relevant to take into account influences of the social environment on individuals' SB. Moreover, the trans-contextual model (TCM) can offer complementary levers for individuals' behavior change. The CIPRES study is a theory-based multilevel intervention designed to decrease the SB in French primary school children aged 8-10 years. The present paper describes the protocol of a randomized controlled study to evaluate the effectiveness of the CIPRES multilevel intervention on SB.MethodsThe CIPRES study is a cluster-randomized controlled trial comparing intervention vs control groups. A total of 700 children are targeted for inclusion, distributed in four municipalities considered as clusters. The study consists of two successive phases: 1) co-building of a SB prevention intervention by using a participatory approach involving representatives of each level of the SEM (e.g., children, parents, staff from municipalities, teachers) and 2) implementation and evaluation of the intervention. The intervention will last for 6 weeks in each involved class. Primary outcome will be the sedentary time of children per week, assessed by accelerometry. In addition, children and their parents will be asked to fill out questionnaires concerning children's physical activity level, screen time, quality-of-life and variables of the TCM.DiscussionThis study will give information on the effectiveness of a theory-based intervention, involving multiple levels of actors in the co-construction and the implementation of the intervention, that may interest schools and public health officers looking for innovative sedentary prevention programs.

We report the case of a 30-year-old female patient with sickle cell disease presenting with an acute chest syndrome and neurological deterioration. Cerebral magnetic resonance imaging revealed a handful of foci of diffusion restriction and numerous microbleeds with marked involvement of corpus callosum and subcortical white matter, with relative sparing of the cortex and deep white matter. Corpus callosum-predominant and juxtacortical microbleeds have been typically documented in cerebral fat embolism syndrome, but also in the so-called “critical-illness-associated cerebral microbleeds”, a recently described entity associated with respiratory failure. We discussed whether these 2 entities may coexist.

Introduction: Periodontal disease is an infectious syndrome presenting inflammatory aspects. Radiographic evaluation is an essential complement to clinical assessment but has limitations such as the impossibility of assessing tissue inflammation. It seems essential to consider new exploration methods in clinical practice. Ultrasound of periodontal tissues could make it possible to visualize periodontal structures and detect periodontal diseases (periodontal pocket measurement and the presence of intra-tissue inflammation). Clinical Innovation Report: An ultrasound probe has been specially developed to explore periodontal tissues. The objective of this clinical innovation report is to present this device and expose its potential. Discussion: Various immediate advantages favor using ultrasound: no pain, no bleeding, faster execution time, and an image recording that can be replayed without having to probe the patient again. Ultrasound measurements of pocket depth appear to be as reliable and reproducible as those obtained by manual probing, as do tissue thickness measurements and the detection of intra-tissue inflammation. Conclusions: Ultrasound seems to have a broad spectrum of indications. Given the major advances offered by ultrasound imaging as a complementary aid to diagnosis, additional studies are necessary to validate these elements and clarify the potential field of application of ultrasound imaging in dentistry.

Abstract Background The principal aim of this study was to explore if biological differences between men and women can be explained by gendered mechanisms. Methods We used data from the 1958 National Child Development Study, including all the living subjects of the cohort at the outcome collection wave (44–45 years). We explored several biomarkers as outcomes: systolic blood pressure, triglycerides, LDL cholesterol, HbA1c, CRP, and cortisol. Three conceptualizations of gender have been used to define methodological strategies: (a) Gender as an individual characteristic; (b) Gender as an effect of sex on socio-behavioural characteristics; (c) Gender as an interaction between sex and the social environment, here the early-life social environment. We estimated the total effect of sex and the proportion of total effect of sex at birth eliminated by gender, measured by 3 different ways according to these 3 concepts, using g-computation. Results The average level of each biomarker was significantly different according to sex at birth, higher in men for cardiometabolic biomarkers and higher in women for inflammatory and neuroendocrine biomarkers. The sizes of the differences were always smaller than one standard deviation but were larger than differences due to early-life deprivation, except for CRP. We observed gender mechanisms underlying these differences between men and women, even if the mediation effects were rarely statistically significant. These mechanisms were of three kinds: (1) mediation by socio-behavioural characteristics; (2) attenuation by gendered mechanisms; (3) interaction with early social environment. Indeed, we observed that being born into a deprived rather than non-deprived family increased metabolic and inflammatory biomarkers levels more strongly in females than in males. Conclusions The biological differences between men and women seem to not be purely explained by biological mechanisms. The exploration of gender mechanisms opens new perspectives, in terms of methodology, understanding and potential applications.

Abstract Background To promote improved coordination between general practice and hospital, the French clinical trial CREDO (“Concertation de REtour à DOmicile”) is testing an innovative experimental consultation for patients with metastatic cancer who are returning home. This consultation involves the patient, the patient’s referring GP (GPref) and a GP with specific skills in oncology (GPonc) in a specialized care center. The objective of our study is to explore the satisfaction of GPsref about this consultation, in the phase of interaction between GPonc and GPref. Methods This observational, cross-sectional, multicenter study explored the satisfaction of GPsref who had participated in this type of consultation, via a telephone survey. Results One Hundred GPsref responded to the questionnaire between April and September 2019 (overall response rate: 55%). 84.5% were satisfied with the consultation, and the majority were satisfied with its methods. Half of the GPsref learned new information during the consultation, three-quarters noted an impact on their practice, and 94.4% thought that this type of coordination between the GPref and the oncology specialist could improve general practice - hospital coordination. Conclusions For GPs, the CREDO consultation seems to be practical and effective in improving the coordination between general medicine and hospital. GPs would benefit from such coordination for all patients with cancer, several times during follow-up and at each occurrence of a medically significant event.

Abstract Background In France, we lack knowledge about factors influencing chiropractors’ use of French guideline for managing neck pain and associated disorders (NAD). In particular, we know little about how chiropractic interns use clinical practice guidelines during their training. Objectives We aimed to determine the feasibility of conducting a cross-sectional study of chiropractic interns to determine their utilization and conformity with clinical practice guidelines when managing patients with NAD in France. Method We developed a web-based questionnaire which included 3 sections: (1) clinical vignettes; (2) determinants of practice and (3) socio-demographic and current practice information. The study was conducted in two phases. The first phase included 2 groups: chiropractors and students (interns). Ten chiropractors reviewed and made recommendations on content (especially clinical vignettes), readability, and flow of the survey. Fifteen interns were invited to pretest the proposed recruitment strategy and determine time needed to survey completion, assess completeness of data collection, and evaluate its readability and flow in students. Due to the low participation of students during the first phase, 20 additional interns were invited to participate and pilot the revised recruitment strategy during the second phase. A group of 20 interns were invited to participate and pilot the revised recruitment strategy during the second phase. Qualitative feedbacks about the recruitment strategy, the content of the questionnaire and the survey process were collected by phone to improve all these steps if necessary. Results We collected data from November 2020 to February 2021. In phase 1, 70% of chiropractors (7/10) reviewed the survey and one intern responded (7% participation rate). A revised recruitment strategy was designed and 70% of interns agreed to participate in phase 2. Time to complete the questionnaire was on average 48 m:22 s. Interns evaluated survey content as relevant, comprehensive, covering the range of 4 grades of NAD, and adapted to an intern sample. Five main modifications were recommended by (1) Adjusting survey support; (2) Enhancing communication strategy; (3) Considering interns’ comments about the length of the questionnaire; (4) Modifying 2 determinants not adapted to a French context; (5) Adding a proposal when determinants deal with multidisciplinary management. Conclusion Conducting a web-based cross-sectional study of chiropractic interns to assess their utilization and conformity to clinical practice guideline is feasible.

IntroductionIn humans, adversity in childhood exerts enduring effects on brain and increases the vulnerability to psychiatric diseases. It also leads to a higher risk of eating disorders and obesity. Maternal separation (MS) in mice has been used as a proxy of stress during infancy. We hypothesized that MS in mice affects motivation to obtain palatable food in adulthood and changes gene expression in reward system.MethodsMale and female pups from C57Bl/6J and C3H/HeN mice strains were subjected to a daily MS protocol from postnatal day (PND) 2 to PND14. At adulthood, their motivation for palatable food reward was assessed in operant cages.ResultsCompared to control mice, male and female C3H/HeN mice exposed to MS increased their instrumental response for palatable food, especially when the effort required to obtain the reward was high. Importantly, this effect is shown in animals fed ad libitum. Transcriptional analysis revealed 375 genes differentially expressed in the nucleus accumbens of male MS C3H/HeN mice compared to the control group, some of these being associated with the regulation of the reward system (e.g., Gnas, Pnoc). Interestingly, C57Bl/6J mice exposed to MS did not show alterations in their motivation to obtain a palatable reward, nor significant changes in gene expression in the nucleus accumbens.ConclusionMS produces long-lasting changes in motivation for palatable food in C3H/HeN mice, but has no impact in C57Bl/6J mice. These behavioral alterations are accompanied by drastic changes in gene expression in the nucleus accumbens, a key structure in the regulation of motivational processes.

ObjectivesPreventive actions of sedentary behavior (SB) based on the socio-ecological model are needed among children and young adolescents. The aim of this systematic review is to ascertain the effectiveness of multilevel interventions (i.e., involving consideration of at least two interventional levels) in reducing sedentary time (ST) in children aged 5–12 years.MethodsAdhering to PRISMA guidelines, a systematic literature search was conducted in three databases (PsyInfo, PubMed and ERIC) until July 2021.Results30 trials met the eligibility criteria and were included. They showed acceptable (< 8, n = 18) and high (≥ 8, n = 12) methodological quality. Among studies targeting 2 (n = 2), 3 (n = 19) and 4 levels (n = 9), 1 (50%), 9 (47%) and 7 (78%) were effective and reported significant reduction of ST, respectively.ConclusionInterventions tend to be more effective when they involve 4 levels, using both agentic and structural strategies (targeting intrinsic determinants, in the organizational environment of the child). Findings underline the relevance of multilevel strategies to reduce ST in children, but also raise issues about operationalization of the socio-ecological perspective.Systematic review registrationPROSPERO, identifier: CRD42020209653.