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Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Numerous studies have shown a significant positive relationship between the mental representation of hands in young children and their calculation performance. The literature indicates that certain components of manual motor skills may be critical to the quality of this relationship. The main objective of this study is to measure the benefit of an explicit training and teaching device for finger use in mathematics by measuring the initial motor imitation abilities of young children. A protocol of pretest, training, and post-test type was proposed to 101 children with an average age of 5 years and 3 months. Measurements focused on manual motor skills and arithmetical skills. The 12-week classroom-based device was designed to develop manual motor skills and explicitly teach finger use in mathematics. The results indicate that significant progress was made in arithmetic for the students who benefited from the training. Interestingly this progress is modulated by the children's initial motor imitation skills. This contribution opens up new research and application perspectives on the relationships between mental motor imagery, fine motor skills, and arithmetic ability.

The process of teaching and learning handwriting is complex and laborious. A digital learning environment in the form of a tablet app could enhance teachers' knowledge of writer characteristics and their management of classroom diversity. This study aims to identify the needs of cursive writing teachers from a survey of 164 kindergarten teachers in France teaching writing skills for children aged 5 to 6 years. The results provide insights into teacher needs and, therefore, can be used to identify the acceptability criteria of a tool designed to scaffold the teaching of writing gestures. The results of needs analyses have been interpreted in the light of new scientific findings on reading and writing skills, and there is a discussion on the potential of such a digital learning environment for the classroom, particularly during the training and skills assessment phases. Questionnaire answers show that the teachers interviewed rarely use digital tools in the classroom and this prompts reflection on the value and meaning that preschool children give to the digital trace.

Abstract Background In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination. Methods A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression. Results Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05–2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17–7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71–4.04), reporting an “unsafe” opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50–10.26), reporting an “unsupportive” opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77–6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16–0.48) and trust in the government’s actions (aOR = 0.50; 95% CI, 0.34–0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake. Conclusions Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of “reaching out” vaccination strategy that specifically targets the most vulnerable fringe of older adult population.

Abstract Accurately mapping the evolving bathymetry under energetic wave breaking is challenging, yet critical for improving our understanding of sandy beach morphodynamics. Though remote sensing is one of the most promising opportunities for reaching this goal, existing depth‐inversion algorithms using linear approaches face major theoretical and/or technical issues in the surf zone, limiting their accuracy over this region. Here, we present a new depth‐inversion approach relying on Boussinesq theory for quantifying nonlinear dispersion effects in nearshore waves. Using high‐resolution datasets collected in the laboratory under diverse wave conditions and beach morphologies, we demonstrate that this approach results in enhanced levels of accuracy in the surf zone (errors typically within 10%) and presents a major improvement over linear methods. The new nonlinear depth‐inversion approach provides significant prospects for future practical applications in the field using existing remote sensing technologies, including continuous lidar scanners and stereo‐imaging systems.

What constitutes effective teaching of arithmetical skills in early school years is still uncertain. Finger use could play a crucial role in this acquisition, but some children do not use them spontaneously and studies would be necessary to know if it is possible to teach them. This research assesses the impact of a teacher-implemented intervention program to teach 5-year- to 6-year-old children to use their fingers in numerical tasks. Participants were 36 kindergarten pupils (16 girls, 20 boys; mean age 5 years, 5 months) from two classrooms. The research compares a program in which motor training and explicit teaching of finger use are promoted to represent numbers and to act on them, with a "business as usual" contrast group. Children were tested before and after the intervention with problem-solving. After the experimental training program, finger counting appears to be a good strategy because its frequency is positively linked to the scores in the problem-solving tasks. We showed a greater improvement in problem-solving following the finger use intervention, compared to the contrast group. Our results support the explicit teaching of finger use to build numerical representation and enhance the calculation skills of kindergarten students (age 5) in French schools.

The French health authorities extended vaccination against COVID-19 to adolescents in June 2021, during the epidemic resurgence linked to the delta variant and because of insufficient vaccination coverage to ensure collective protection. In May 2021, we conducted a national online cross-sectional survey of 2533 adults in France to study their attitudes toward COVID-19 vaccines and their acceptance of child/adolescent vaccination according to targeted age groups (

Abstract Background Bacterial vaginosis (BV) is associated with a higher risk of preterm delivery and spontaneous abortion. Yet little data on BV prevalence exist for sub-Saharan countries. The aim of this study was to estimate the prevalence of bacterial vaginosis and associated risk factors among pregnant women in Senegal. Methods From October 2013 to December 2018, pregnant women in their third trimester were recruited in two primary health centers (one suburban, one rural) in Senegal. Healthcare workers interviewed women and collected a lower vaginal swab and a blood sample. Vaginal flora were classified into four categories using vaginal smear microscopic examination and Gram’s coloration. In our study, BV was defined as vaginal flora with no Lactobacillus spp. Variables associated with BV were analyzed using STATA® through univariate and multivariate analysis. Results A total of 457 women provided a vaginal sample for analysis. Overall, BV prevalence was 18.6% (85/457) [95% CI 15.4–22.6]) and was similar in suburban and rural areas (18.9% versus 18.1%, p = 0.843). Multivariate analysis showed that primigravidity was the only factor independently associated with a lower risk of BV (aOR 0.35 [95% CI 0.17–0.72]). Conclusions Our study showed significant BV prevalence among pregnant women in Senegal. Although the literature has underscored the potential consequences of BV for obstetric outcomes, data are scarce on BV prevalence in sub-Saharan African countries. Before authorities consider systematic BV screening for pregnant women, a larger study would be useful in documenting prevalence, risk factors and the impact of BV on pregnancy outcomes.

In May 2021, while the immunization campaign was in progress, the emergence of new SARS-CoV-2 variants led us to assess attitudes toward participation in a COVID-19 vaccine clinical trial (VCT) in France. Between the 10th and the 23rd of May 2021, we conducted a cross-sectional online survey among a representative sample of the French population aged 18 and over and a specific sample of the French population over 65. Among the 3,056 respondents, 28.0% (856) would consider participation in a COVID-19 VCT. Factors independently negatively associated with willingness to participate in a COVID-19 VCT were female gender with an adjusted odd ratio (aOR) 0.42 and 95% confidence interval (95% CI) 0.35–0.51, and mistrust in health actors (in their own physician and pharmacists, health ministry, government, scientists in medias, medias and pharmaceutical companies) with aOR 0.86 (95% CI 0.84–0.88) by one-point increase in mistrust in health actors score. Factors positively associated with willingness to participate in a COVID-19 VCT were COVID-19 vaccination or intention to get vaccinated with aOR 4.89 (95% CI 3.15–7.61), being a healthcare worker with aOR 2.051 (95% CI 1.51–2.80), being at risk for severe COVID-19 with aOR 1.39 (95% CI 1.14–1.69) and altruism as the main reason for getting vaccination with aOR 1.56 (95% CI 1.29–1.88). In May 2021, despite COVID 19 vaccine availability, 28% of the French population would agree to participate in a COVID-19 VCT. Mistrust in health actors contributes to a reduction in the intention to participate. Attitudes toward COVID-19 vaccination predict attitudes toward participation in a COVID-19 VCT.

During the Covid-19 pandemic, the urgent need for safe and effective vaccines has led to many vaccine trials, implying fast and extensive recruitment of volunteers. In France, until 2020, vaccine clinical research participants were usually recruited locally, through center-based pools of volunteers, and local communication plans. Covireivac is a French public online platform launched on 10/01/2020 that enables national, large-scale recruitment of volunteers for Covid-19 vaccine studies. On the Covireivac website, all adult participants registered online, gave their informed consent, and filled out two online forms with information on their identity, health status (comorbidities, treatments), and known exposure to SARS-CoV-2. Since July 2021, volunteers could mention if their children are interested in participating in a Covid-19 vaccine trial. The objective of this work is to describe Covireivac’s volunteer characteristics registered from 10/01/2020 to 11/02/2022. To identify independent volunteer characteristics associated with a period of registration we performed a multivariate logistic regression. Among 54,424 registrations, 52,391 (96%) were analysed; 61% were male (n = 31,893), median age was 50 y; 13% (n = 6586) were healthcare workers. At registration, 15,879 volunteers (33%) reported at least one comorbidity, among whom 16% (n = 7349) were obese and 17% (n = 8346) had hypertension. Most volunteers registered during the first month (n = 35,876, 66%). The Covireivac platform allowed quick and large recruitment of potential volunteers for Covid-19 vaccine trials and could be used on a larger scale for vaccine trials in France. It could facilitate recruitment in vaccine trials and provide sponsors with better visibility of the recruitment capacities of clinical research centers.

Handwriting is a determining factor for academic success and autonomy for all children. Making knowledge accessible to all is a challenge in the context of inclusive education. Given the neurodevelopmental diversity within a classroom of children, ensuring that the handwriting of all pupils progresses is very demanding for education professionals. The development of tools that can take into account the variability of the profiles and learning abilities of children with handwriting difficulties offers a new potential for the development of specific and adapted remediation strategies. This narrative review aims to present and discuss the challenges of handwriting learning and the opportunities offered by new technologies involving AI for school and health professionals to successfully improve the handwriting skills of all children.

We examined the understanding of emotional speech by deaf children with cochlear implant (CI). Thirty deaf children with CI and 60 typically developing controls (matched on chronological age or hearing age) performed a computerized task featuring emotional prosody, either embedded in a discrepant context or without any context at all. Across the task conditions, the deaf participants with CI scored lower on the prosody-bases responses than their peers matched on chronological age or hearing age. Additionally, we analyzed the effect of age on determining correct prosody-based responses and we found that hearing age was a predictor of the accuracy of prosody-based responses. We discuss these findings with respect to delay in prosody and intermodal processing. Future research should aim to specify the nature of the cognitive processes that would be required to process prosody.

The objective of this study was to confirm the existence of knowledge relating to the cursive writing movement for French pupils in 3rd year of kindergarten, 2nd grade and 5th grade of elementary school. 141 pupils were asked to watch a visual presentation of cursive handwriting to determine whether they were able to detect violations of two rules of handwriting: continuity and sequentiality of the cursive handwriting movement. Our results showed progressive development of the understanding of characteristics of the cursive handwriting movement, with different developmental trajectories of knowledge for the different rules. The ability to detect continuity of the cursive writing movement developed earlier than the ability to detect sequentiality. Correct decisions were not always accompanied by correct justifications, which developed more slowly than detection of rule violations.

Synthetic progesterone and 5α/β-pregnane-3,20-dione derivatives were evaluated as in vitro and in vivo modulators of multidrug-resistance (MDR) using two P-gp-expressing human cell lines, the non-steroidogenic K562/R7 erythroleukaemia cells and the steroidogenic NCI-H295R adrenocortical carcinoma cells, both resistant to doxorubicin. The maximal effect in both cell lines was observed for 7α-O-benzoyloxy,11α(R)-O-tetrahydropyranyloxy-5β-pregnane-3,20-dione 4. This modulator co-injected with doxorubicin significantly decreased the tumour size and increased the survival time of immunodeficient mice xenografted with NCI-H295R or K562/R7 cells.

Background: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool. The objective of this study is to evaluate the use of NGS in children with cholestasis. Methods: Children presenting cholestasis were included between 2015 and 2020. Molecular sequencing was performed by targeted capture of a panel of 34 genes involved in cholestasis and jaundice. Patients were classified into three categories: certain diagnosis; suggested diagnosis (when genotype was consistent with phenotype for conditions without any available OMIM or ORPHANET-number); uncertain diagnosis (when clinical and para-clinical findings were not consistent enough with molecular findings). Results: A certain diagnosis was established in 169 patients among the 602 included (28.1%). Molecular studies led to a suggested diagnosis in 40 patients (6.6%) and to an uncertain diagnosis in 21 patients (3.5%). In 372 children (61.7%), no molecular defect was identified. Conclusions: NGS is a useful diagnostic tool in pediatric cholestasis, providing a certain diagnosis in 28.1% of the patients included in this study. In the remaining patients, especially those with variants of uncertain significance, the imputability of the variants requires further investigations.

Abstract Background Having conquered water surfaces worldwide, the semi-aquatic bugs occupy ponds, streams, lakes, mangroves, and even open oceans. The diversity of this group has inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders our ability to more thoroughly investigate the molecular mechanisms underlying the processes of adaptation and diversification within this group. Results Here we report the sequencing and manual annotation of the Gerris buenoi (G. buenoi) genome; the first water strider genome to be sequenced thus far. The size of the G. buenoi genome is approximately 1,000 Mb, and this sequencing effort has recovered 20,949 predicted protein-coding genes. Manual annotation uncovered a number of local (tandem and proximal) gene duplications and expansions of gene families known for their importance in a variety of processes associated with morphological and physiological adaptations to a water surface lifestyle. These expansions may affect key processes associated with growth, vision, desiccation resistance, detoxification, olfaction and epigenetic regulation. Strikingly, the G. buenoi genome contains three insulin receptors, suggesting key changes in the rewiring and function of the insulin pathway. Other genomic changes affecting with opsin genes may be associated with wavelength sensitivity shifts in opsins, which is likely to be key in facilitating specific adaptations in vision for diverse water habitats. Conclusions Our findings suggest that local gene duplications might have played an important role during the evolution of water striders. Along with these findings, the sequencing of the G. buenoi genome now provides us the opportunity to pursue exciting research opportunities to further understand the genomic underpinnings of traits associated with the extreme body plan and life history of water striders.

Signal-to-noise ratio (SNR) time series acquired by a geodetic antenna were analyzed to retrieve water heights during asymmetric tides on a narrow river using the Interference Pattern Technique (IPT) from Global Navigation Satellite System Reflectometry (GNSS-R). The dynamic SNR method was selected because the elevation rate of the reflecting surface during rising tides is high in the Garonne River with macro tidal conditions. A new process was developed to filter out the noise introduced by the environmental conditions on the reflected signal due to the narrowness of the river compared to the size of the Fresnel areas, the presence of vegetation on the river banks, and the presence of boats causing multiple reflections. This process involved the removal of multipeaks in the Lomb-Scargle Periodogram (LSP) output and an iterative least square estimation (LSE) of the output heights. Evaluation of the results was performed against pressure-derived water heights. The best results were obtained using all GNSS bands (L1, L2, and L5) simultaneously: R = 0.99, ubRMSD = 0.31 m. We showed that the quality of the retrieved heights was consistent, whatever the vertical velocity of the reflecting surface, and was highly dependent on the number of satellites visible. The sampling period of our solution was 1 min with a 5-min moving window, and no tide models or fit were used in the inversion process. This highlights the potential of the dynamic SNR method to detect and monitor extreme events with GNSS-R, including those affecting inland waters such as flash floods.

A XBeach surfbeat model is used to explore the dynamics of natural headland rip circulation under a broad range of incident wave conditions and tide level. The model was calibrated and extensively validated against measurements collected in the vicinity of a 500-m rocky headland. Modelled bulk hydrodynamic quantities were in good agreement with measurements for two wave events during which deflection rips were captured. In particular, the model was able to reproduce the tidal modulation and very-low-frequency fluctuations (≈1 h period) of the deflection rip during the 4-m wave event. For that event, the synoptic flow behaviour shows the large spatial coverage of the rip which extended 1600 m offshore at low tide, when the surf zone limit extends beyond the headland tip. These results emphasize a deflection mechanism different from conceptualised deflection mechanisms based on the boundary length to surf zone width ratio. Further simulations indicate that the adjacent embayment is responsible for the seaward extent of the rip under energetic wave conditions. The present study shows that the circulation patterns along natural rugged coastlines are strongly controlled by the natural variability of the coastal morphology, including headland shape and adjacent embayments, which has implications on headland bypassing expressions.

This paper examines the potential of an optical flow video-based technique to estimate wave-filtered surface currents in the nearshore where wave-breaking induced foam is present. This approach uses the drifting foam, left after the passage of breaking waves, as a quasi-passive tracer and tracks it to estimate the surface water flow. The optical signature associated with sea-swell waves is first removed from the image sequence to avoid capturing propagating waves instead of the desired foam motion. Waves are removed by applying a temporal Fourier low-pass filter to each pixel of the image. The low-pass filtered images are then fed into an optical flow algorithm to estimate the foam displacement and to produce mean velocity fields (i.e., wave-filtered surface currents). We use one week of consecutive 1-Hz sampled frames collected during daylight hours from a single fixed camera located at La Petite Chambre d’Amour beach (Anglet, SW France) under high-energy conditions with significant wave height ranging from 0.8 to 3.3 m. Optical flow-computed velocities are compared against time-averaged in situ measurements retrieved from one current profiler installed on a submerged reef. The computed circulation patterns are also compared against surf-zone drifter trajectories under different field conditions. Optical flow time-averaged velocities show a good agreement with current profiler measurements: coefficient of determination (r2)= 0.5–0.8; root mean square error (RMSE) = 0.12–0.24 m/s; mean error (bias) =−0.09 to −0.17 m/s; regression slope =1±0.15; coherence2 = 0.4–0.6. Despite an underestimation of offshore-directed velocities under persistent wave breaking across the reef, the optical flow was able to correctly reproduce the mean flow patterns depicted by drifter trajectories. Such patterns include rip-cell circulation, dominant onshore-directed surface flow and energetic longshore current. Our study suggests that open-source optical flow algorithms are a promising technique for coastal imaging applications, particularly under high-energy wave conditions when in situ instrument deployment can be challenging.

Headland rips, sometimes referred to as boundary rips, are rip currents flowing against natural or artificial obstructions extending seaward from the beach, such as headland or groynes. They can be driven either by the deflection of the longshore current against the obstacle or by alongshore variation in breaking wave height due to wave shadowing in the lee of the obstacle. The driving mechanism therefore essentially depends on the angle of wave incidence with respect to the natural or artificial obstruction. We analyze 42 days of velocity profile measurements against a natural headland at the high-energy meso-macrotidal beach of Anglet, southwest France. Measurements were collected in 6.5–10.5-m depth as tide elevation varied, during the autumn–winter period with offshore significant wave height and period ranging 0.9–6 m and 8–16 s, respectively, and the angle of wave incidence ranging from −20 ∘ to 20 ∘ . Here we analyze deflection rip configurations, corresponding to approximately 24 days of measurements, for which the current meter was alternatively located in the rip neck, rip head or away from the rip as wave and tide conditions changed. Deflection rips were associated with large offshore-directed velocities (up to 0.6 m/s depth-averaged velocities) and tide modulation for low- to moderate-energy waves. The vertical profile of deflection rips was found to vary from depth-uniform in the rip neck to strongly depth-varying further offshore in the rip head with maximum velocities near the surface. Very low frequency motions of the rip were dramatic, ranging 10–60 min with a dominant peak period of approximately 40 min, i.e., with longer periods than commonly reported. The strong offshore-directed velocities measured well beyond the surf zone edge provide new insight into deflection rips as a dominant mechanism for water and sediment exchanges between embayed (or structurally-controlled) beaches and the inner-shelf and/or the adjacent embayments.

In this study, three months of records (January–March 2010) that were acquired by a geodetic Global Navigation Satellite Systems (GNSS) station from the permanent network of RGP (Réseau GNSS Permanent), which was deployed by the French Geographic Institute (IGNF), located in Socoa, in the south of the Bay of Biscay, were used to determine the tide components and identify the signature of storms on the signal to noise ratio (SNR) during winter 2010. The Xynthia storm hit the French Atlantic coast on the 28th of February 2010, causing large floods and damages from the Gironde to the Loire estuaries. Blind separation of the tide components and of the storm signature was achieved while using both a singular spectrum analysis (SSA) and a continuous wavelet transform (CWT). A correlation of 0.98/0.97 and root mean square error (RMSE) of 0.21/0.28 m between the tide gauge records of Socoa and our estimates of the sea surface height (SSH) using the SSA and the CWT, respectively, were found. Correlations of 0.76 and 0.7 were also obtained between one of the modes from the SSA and atmospheric pressure from a meteorological station and a mode of the SSA. Particularly, a correlation reaches to 0.76 when using both the tide residual that is associated to surges and atmospheric pressure variation.

The secondary wave field associated with undular tidal bores (known as whelps) has been barely studied in field conditions: the wave field can be strongly non-hydrostatic, and the turbidity is generally high. In situ measurements based on pressure or acoustic signals can therefore be limited or inadequate. The intermittent nature of this process in the field and the complications encountered in the downscaling to laboratory conditions also render its study difficult. Here, we present a new methodology based on LiDAR technology to provide high spatial and temporal resolution measurements of the free surface of an undular tidal bore. A wave-by-wave analysis is performed on the whelps, and comparisons between LiDAR, acoustic and pressure-derived measurements are used to quantify the non-hydrostatic nature of this phenomenon. A correction based on linear wave theory applied on individual wave properties improves the results from the pressure transducer (Root mean square error, R M S E of 0 . 19 m against 0 . 38 m); however, more robust data is obtained from an upwards-looking acoustic sensor despite high turbidity during the passage of the whelps ( R M S E of 0 . 05 m). Finally, the LiDAR scanner provides the unique possibility to study the wave geometry: the distribution of measured wave height, period, celerity, steepness and wavelength are presented. It is found that the highest wave from the whelps can be steeper than the bore front, explaining why breaking events are sometimes observed in the secondary wave field of undular tidal bores.