Diabolo, une simulation pour l'apprentissage des métabolismes

International audienceThis paper presents an interactive web simulation (SimDiabolo), designed by education and computer education researchers. The activity, proposed to students from 15 to 17 years old, is about designing an experimental procedure to highlight alcoholic fermentation in biology. In order to help students in this complex task, fixed and adaptive scaffolds have been designed and implemented in the simulation. The anthropological theory of the didactic has been used for modeling errors and designing scaffolds. The simulation can also be connected to present software FORMID, which can modify the actual script implemented in SimDiabolo and offer different scripts with different scaffolds. Experimentations will take place this year in biology class in high school (France).Nous proposons dans cette communication le résultat de la co-construction entre didacticiens des sciences et informaticiens, d'une simulation web interactive (SimDiabolo) à destination d'élèves de 15-17 ans. Elle propose actuellement une activité de conception expérimentale sur le thème de la fermentation alcoolique. Pour aider les élèves dans cette tâche complexe nous avons intégré des étayages fixes et adaptatifs. Les différentes aides ont été conçues à partir d'une analyse didactique de l'erreur selon le cadre de la théorie anthropologique du didactique. Grâce à la connexion avec la suite logicielle FORMID, il est possible de scénariser différentes situations d'utilisation de SimDiabolo et notamment de proposer des niveaux d'étayage différenciés. Les différents scénarios seront testés in situ dans des classes de lycée en France cette année

Contrôle de la variabilité interannuelle de la composition du phytoplancton de la Baie de Calvi (Corse) par les facteurs environnementaux

Le but de la présentation est de synthétiser les connaissances sur le contrôle de la dynamique du phytoplancton par les contraintes environnementales dans un site de référence méditerranéen. L’étude est réalisée en Baie de Calvi (Corse) à la station PHYTOCLY (42°34.85'N, 08°43.71'E) où des séries temporelles haute fréquence de données physiques, chimiques et biologiques sont réalisées depuis 1979. Depuis 2006, l’acquisition des données de subsurface et le traitement des échantillons, qui inclut des analyses HPLC de contenu pigmentaire du phytoplancton et des comptages de flore totale, sont réalisés grâce au soutien de la DCE. En Baie de Calvi, l’intensité de la rigueur hivernale, identifiée par deux proxys, la température de l’eau et le nombre de jours de vent fort, contrôle le réapprovisionnement en sels nutritifs des couches de surface et le développement du bloom phytoplanctonique (détails dans Goffart et al., 2015, Progress in Oceanography). Lors des années caractérisées par un hiver rigoureux (e.g. 2010), le bloom phytoplanctonique hivernal se développe pendant la période d’eau froide (eau de subsurface ≤13.5°C). Il est dominé par les diatomées et les cryptophycées, deux groupes qui montrent une préférence marquée pour les eaux froides et riches en sels nutritifs. Lorsque l’hiver est très doux (e.g. 2007), la disponibilité en sels nutritifs est réduite et le bloom ne se développe pas. Les diatomées et les cryptophycées sont absentes, et les communautés phytoplanctoniques sont dominées par les prymnesiophycées pico- et nanoplanctoniques et les cyanobactéries. Les résultats de l’étude permettent aussi : • de fixer les limites de la variabilité naturelle du phytoplancton dans un site de référence méditerranéen, • d’expliquer les variations interannuelles de biomasse et de composition phytoplanctonique, • de définir les préférences écologiques des différents groupes phytoplanctoniques, • d’établir des courbes d’évolution saisonnière des principaux groupes phytoplanctoniques qui intègrent la variabilité interannuelle liée aux variations climatiques. La connaissance acquise au cours de cette étude permet de contribuer au développement d’indices de qualité intégrant la composition du phytoplancton (e.g. indice de composition I C MEDIT) et de tester des méthodes de surveillance à grande échelle (e.g. croisement des suivis pigmentaires réalisés à haute fréquence et de l’imagerie satellitaire), contribuant ainsi à la mise en œuvre des politiques publiques (DCE, DCSMM)

Real-life management of neovascular age-related macular degeneration (nAMD) in France: a nationwide observational study using retrospective claims data

AIMS: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is standard care for neovascular age-related macular degeneration (nAMD), but the recommended monthly injection regimen is burdensome. Evidence suggests low injection/monitoring frequencies in clinical practice and suboptimal vision outcomes. This observational cohort study uses administrative claims data from the French national healthcare system to assess anti-VEGF treatment patterns and nAMD-specific healthcare resource demands and costs. PATIENTS AND METHODS: nAMD patients ≥50 years initiating intravitreal ranibizumab, aflibercept or bevacizumab treatment (2014‒2015), and propensity score-matched non-nAMD patients (controls), were identified from the Echantillon Généraliste de Bénéficiaires database. Outcomes of interest included anti-VEGF treatment patterns, and healthcare resource utilization and associated costs of patients vis-à-vis controls over 24 months. RESULTS: Study patients (n = 355) received (mean) 5.2 and 2.4 anti-VEGF injections over 0‒12 and 12‒24 months, respectively. Most patients (79.0%) remained on their initial anti-VEGF agent; among treatment switchers the most common transition was from ranibizumab to aflibercept. During follow-up, nAMD patients were more likely than controls to require ophthalmology visits (99.7% vs 44.8%), ocular procedures (optical coherence tomography/angiography/fundoscopy) (96.9% vs 27.2%), cataract surgery (13.0% vs 6.7%), and medical transports (38.0% vs 31.9%). Mean numbers of ophthalmology visits (25.1 vs 1.2) and medical transports (6.0 vs 3.5) were higher (p<.01) among nAMD patients. Total reimbursed costs were two-fold higher for nAMD patients than controls (mean €16,799 vs €8255) due to higher treatment costs (€6847 vs €1156), medical fees (€1858 vs €295), hospital fees (€6396 vs €5235), and transport costs (€358 vs €259). Excess total healthcare cost was (mean) €5279 and €7918 over the first 12 and 24 months of treatment, respectively. CONCLUSIONS: Current intravitreal anti-VEGF treatment and monitoring requirements place considerable economic burden on the French healthcare system. New intravitreal therapies with extended dosing intervals and predictable efficacy might reduce demand on ophthalmology services

Snow accumulation and ablation measurements in a midlatitude mountain coniferous forest (Col de Porte, France, 1325&thinsp;m altitude): the Snow Under Forest (SnoUF) field campaign data set

Forests strongly modify the accumulation, metamorphism and melting of snow in midlatitude and high-latitude regions. Recently, snow routines in hydrological and land surface models were improved to incorporate more accurate representations of forest snow processes, but model intercomparison projects have identified deficiencies, partly due to incomplete knowledge of the processes controlling snow cover in forests. The Snow Under Forest (SnoUF) project was initiated to enhance knowledge of the complex interactions between snow and vegetation. Two field campaigns, during the winters 2016–2017 and 2017–2018, were conducted in a coniferous forest bordering the snow study at Col de Porte (1325 m a.s.l., French Alps) to document the snow accumulation and ablation processes. This paper presents the field site, the instrumentation and the collection and postprocessing methods. The observations include distributed forest characteristics (tree inventory, lidar measurements of forest structure, subcanopy hemispherical photographs), meteorology (automatic weather station and an array of radiometers), snow cover and depth (snow pole transect and laser scan) and snow interception by the canopy during precipitation events. The weather station installed under dense canopy during the first campaign has been maintained since then and has provided continuous measurements throughout the year since 2018. Data are publicly available from the repository of the Observatoire des Sciences de l'Univers de Grenoble (OSUG) data center at https://doi.org/10.17178/SNOUF.2022 (Sicart et al., 2022).</p

Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response

Simple Summary Triple-negative breast cancer (TNBC) is currently in the clinical research spotlight because of the tumor's aggressive and invasive nature and the scarcity of therapeutic targets. Despite recent advances in identifying reliable prognostic biomarkers in the tumor microenvironment (TME), rigorous evaluation of their predictive capacity remains challenging. We describe the immune cellular and genetic profile of the residual tumor of TNBC that does not achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). A high concentration of lymphocytes and dendritic cells, as well as genetic TME markers such as MUC-1 and CXCL13 in the residual tumor, are valuable prognostic factors of survival and relapse in TNBC patients. From a clinical health perspective, a thorough understanding of the composition of the TME and its prognostic implications might yield relevant immunological information and reveal key predictive biomarkers. This could ultimately help substantially improve the outcomes of residual cancer-burdened TNBC patients after NAC. With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling

Does the availability of positron emission tomography modify diagnostic strategies for solitary pulmonary nodules? An observational study in France

International audienceBACKGROUND: Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization. METHODS: In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002-2003, and 20,075 in an after-PET period, 2004-2005. Patients were followed through their physician, who was responsible for diagnostic management. RESULTS: We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups. CONCLUSION: In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches

Evaluation du risque malarique avec utilisation de l'imagerie satellite et des arbres de regression "boostés" dans la région de l'Amazone au Pérou

This is the first study to assess the risk of co-endemic Plasmodium vivax and Plasmodium falciparum transmission in the Peruvian Amazon using boosted regression tree (BRT) models based on social and environmental predictors derived from satellite imagery and data. Yearly cross-validated BRT models were created to discriminate high-risk (annual parasite index API > 10 cases/1000 people) and veryhigh-risk for malaria (API > 50 cases/1000 people) in 2766 georeferenced villages of Loreto department, between 2010–2017 as other parts in the article (graphs, tables, and texts). Predictors were cumulative annual rainfall, forest coverage, annual forest loss, annual mean land surface temperature, normalized difference vegetation index (NDVI), normalized difference water index (NDWI), shortest distance to rivers, time to populated villages, and population density. BRT models built with predictor data of a given year efficiently discriminated the malaria risk for that year in villages (area under the ROC curve (AUC) > 0.80), and most models also effectively predicted malaria risk in the following year. Cumulative rainfall, population density and time to populated villages were consistently the top three predictors for both P. vivax and P. falciparum incidence. Maps created using the BRT models characterize the spatial distribution of the malaria incidence in Loreto and should contribute to malaria-related decision making in the area.PR

Protein-enriched meal replacements do not adversely affect liver, kidney or bone density: an outpatient randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is concern that recommending protein-enriched meal replacements as part of a weight management program could lead to changes in biomarkers of liver or renal function and reductions in bone density. This study was designed as a placebo-controlled clinical trial utilizing two isocaloric meal plans utilizing either a high protein-enriched (HP) or a standard protein (SP) meal replacement in an outpatient weight loss program.</p> <p>Subjects/methods</p> <p>100 obese men and women over 30 years of age with a body mass index (BMI) between 27 to 40 kg/m²were randomized to one of two isocaloric weight loss meal plans 1). HP group: providing 2.2 g protein/kg of lean body mass (LBM)/day or 2). SP group: providing 1.1 g protein/kg LBM/day. Meal replacement (MR) was used twice daily (one meal, one snack) for 3 months and then once a day for 9 months. Body weight, lipid profiles, liver function, renal function and bone density were measured at baseline and 12 months.</p> <p>Results</p> <p>Seventy subjects completed the study. Both groups lost weight (HP -4.29 ± 5.90 kg vs. SP -4.66 ± 6.91 kg, p < 0.01) and there was no difference in weight loss observed between the groups at one year. There was no significant change noted in liver function [AST (HP -2.07 ± 10.32 U/L, p = 0.28; SP 0.27 ± 6.67 U/L, p = 0.820), ALT (HP -1.03 ± 10.08 U/L, p = 0.34; SP -2.6 ± 12.51 U/L, p = 0.24), bilirubin (HP 0.007 ± 0.33, U/L, p = 0.91; SP 0.07 ± 0.24 U/L, p = 0.120), alkaline phosphatase (HP 2.00 ± 9.07 U/L, p = 0.240; SP -2.12 ± 11.01 U/L, p = 0.280)], renal function [serum creatinine (HP 0.31 ± 1.89 mg/dL, p = 0.380; SP -0.05 ± 0.15 mg/dL, p = 0.060), urea nitrogen (HP 1.33 ± 4.68 mg/dL, p = 0.130; SP -0.24 ± 3.03 mg/dL, p = 0.650), 24 hour urine creatinine clearance (HP -0.02 ± 0.16 mL/min, p = 0.480; SP 1.18 ± 7.53 mL/min, p = 0.400), and calcium excretion (HP -0.41 ± 9.48 mg/24 hours, p = 0.830; SP -0.007 ± 6.76 mg/24 hours, p = 0.990)] or in bone mineral density by DEXA (HP 0.04 ± 0.19 g/cm², p = 0.210; SP -0.03 ± 0.17 g/cm², p = 0.320) in either group over one year.</p> <p>Conclusions</p> <p>These studies demonstrate that protein-enriched meals replacements as compared to standard meal replacements recommended for weight management do not have adverse effects on routine measures of liver function, renal function or bone density at one year. Clinicaltrial.gov: NCT01030354.</p

Use of 2,6-diaminopurine as a potent suppressor of UGA premature stop codons in cystic fibrosis

Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can correct a nonsense mutation in the Cftr gene in vivo in a new CF mouse model, in utero, and through breastfeeding, thanks, notably, to adequate pharmacokinetic properties. DAP turns out to be very stable in plasma and is distributed throughout the body. The ability of DAP to correct various endogenous UGA nonsense mutations in the CFTR gene and to restore its function in mice, in organoids derived from murine or patient cells, and in cells from patients with cystic fibrosis reveals the potential of such readthrough-stimulating molecules in developing a therapeutic approach. The fact that correction by DAP of certain nonsense mutations reaches a clinically relevant level, as judged from previous studies, makes the use of this compound all the more attractive

The GenTree Dendroecological Collection, tree-ring and wood density data from seven tree species across Europe

The dataset presented here was collected by the GenTree project (EU-Horizon 2020), which aims to improve the use of forest genetic resources across Europe by better understanding how trees adapt to their local environment. This dataset of individual tree-core characteristics including ring-width series and whole-core wood density was collected for seven ecologically and economically important European tree species: silver birch (Betula pendula), European beech (Fagus sylvatica), Norway spruce (Picea abies), European black poplar (Populus nigra), maritime pine (Pinus pinaster), Scots pine (Pinus sylvestris), and sessile oak (Quercus petraea). Tree-ring width measurements were obtained from 3600 trees in 142 populations and whole-core wood density was measured for 3098 trees in 125 populations. This dataset covers most of the geographical and climatic range occupied by the selected species. The potential use of it will be highly valuable for assessing ecological and evolutionary responses to environmental conditions as well as for model development and parameterization, to predict adaptability under climate change scenarios