Les stratégies de recherche et de traitement de l’information des futurs enseignants dans des environnements informatiques

L’article porte sur les stratégies de recherche et de traitement de l’information des futurs enseignants utilisant des environnements informatiques. Dix étudiantes terminant leur programme de formation à l’enseignement dans une université québécoise ont réalisé neuf activités de recherche et de traitement d’information dans des environnements informatiques. Les données recueillies renseignent sur les stratégies utilisées. Les résultats montrent que les participants utilisent des stratégies diversifiées à chacune des étapes du processus de recherche et de traitement de l’information, mais que ces stratégies ne sont pas toujours pertinentes.This paper presents a study focusing on student teachers’ information searching and information processing strategies in Web-based environments. Ten student teachers completing their program performed nine information searching and processing tasks. Data collected through observation, thinking aloud process and interview showed a wide range of strategies throughout the completion of these tasks, but the study also highlights some shortfalls and limitations related to those strategies

Les stratégies de recherche et de traitement de l’information des futurs enseignants dans des environnements informatiques

L’article porte sur les stratégies de recherche et de traitement de l’information des futurs enseignants utilisant des environnements informatiques. Dix étudiantes terminant leur programme de formation à l’enseignement dans une université québécoise ont réalisé neuf activités de recherche et de traitement d’information dans des environnements informatiques. Les données recueillies renseignent sur les stratégies utilisées. Les résultats montrent que les participants utilisent des stratégies diversifiées à chacune des étapes du processus de recherche et de traitement de l’information, mais que ces stratégies ne sont pas toujours pertinentes

Les habitudes de recherche et de traitement de l’information des étudiants universitaires utilisant des environnements d’apprentissage informatisés

Les étudiants universitaires sont de plus en plus appelés à utiliser des environnements électroniques (sites Web, cédéroms, cours en ligne) pour rechercher de l’information dans le cadre de projets ou d’activités de résolution de problèmes. Une enquête a été réalisée afin de mieux connaître les habitudes et les besoins de ces étudiants en ce qui a trait à la recherche et au traitement de l’information dans de tels environnements électroniques. Cette enquête révèle que les étudiants se considèrent compétents dans ce domaine mais indique également des limites chez plusieurs dans les stratégies utilisées pour rechercher l’information et en vérifier la validité. University students are more frequently required to use information technology such as Web sites, CD-ROMs, and on-line courses in order to find information for projects or for problem solving. An enquiry has been conducted in order to better understand the practices and the needs of students when it comes to research and information processing within computerized environments. This inquest has determined that students considerer themselves competent in this area; however, it shows that several students are limited with reference to their ability to research information and verify its validity

Development of predictive risk models for major adverse cardiovascular events among patients with type 2 diabetes mellitus using health insurance claims data

Abstract Background There exist several predictive risk models for cardiovascular disease (CVD), including some developed specifically for patients with type 2 diabetes mellitus (T2DM). However, the models developed for a diabetic population are based on information derived from medical records or laboratory results, which are not typically available to entities like payers or quality of care organizations. The objective of this study is to develop and validate models predicting the risk of cardiovascular events in patients with T2DM based on medical insurance claims data. Methods Patients with T2DM aged 50 years or older were identified from the Optum™ Integrated Real World Evidence Electronic Health Records and Claims de-identified database (10/01/2006–09/30/2016). Risk factors were assessed over a 12-month baseline period and cardiovascular events were monitored from the end of the baseline period until end of data availability, continuous enrollment, or death. Risk models were developed using logistic regressions separately for patients with and without prior CVD, and for each outcome: (1) major adverse cardiovascular events (MACE; i.e., non-fatal myocardial infarction, non-fatal stroke, CVD-related death); (2) any MACE, hospitalization for unstable angina, or hospitalization for congestive heart failure; (3) CVD-related death. Models were developed and validated on 70% and 30% of the sample, respectively. Model performance was assessed using C-statistics. Results A total of 181,619 patients were identified, including 136,544 (75.2%) without prior CVD and 45,075 (24.8%) with a history of CVD. Age, diabetes-related hospitalizations, prior CVD diagnoses and chronic pulmonary disease were the most important predictors across all models. C-statistics ranged from 0.70 to 0.81, indicating that the models performed well. The additional inclusion of risk factors derived from pharmacy claims (e.g., use of antihypertensive, and use of antihyperglycemic) or from medical records and laboratory measures (e.g., hemoglobin A1c, urine albumin to creatinine ratio) only marginally improved the performance of the models. Conclusion The claims-based models developed could reliably predict the risk of cardiovascular events in T2DM patients, without requiring pharmacy claims or laboratory measures. These models could be relevant for providers and payers and help implement approaches to prevent cardiovascular events in high-risk diabetic patients

Pathogenic monoallelic variants in GLIS3 increase type 2 diabetes risk and identify a subgroup of patients sensitive to sulfonylureas

International audienceAims/hypothesis: GLIS3 encodes a transcription factor involved in pancreatic beta cell development and function. Rare pathogenic, bi-allelic mutations in GLIS3 cause syndromic neonatal diabetes whereas frequent SNPs at this locus associate with common type 2 diabetes risk. Because rare, functional variants located in other susceptibility genes for type 2 diabetes have already been shown to strongly increase individual risk for common type 2 diabetes, we aimed to investigate the contribution of rare pathogenic GLIS3 variants to type 2 diabetes. Methods: GLIS3 was sequenced in 5471 individuals from the Rare Variants Involved in Diabetes and Obesity (RaDiO) study. Variant pathogenicity was assessed following the criteria established by the American College of Medical Genetics and Genomics (ACMG). To address the pathogenic strong criterion number 3 (PS3), we conducted functional investigations of these variants using luciferase assays, focusing on capacity of GLIS family zinc finger 3 (GLIS3) to bind to and activate the INS promoter. The association between rare pathogenic or likely pathogenic (P/LP) variants and type 2 diabetes risk (and other metabolic traits) was then evaluated. A meta-analysis combining association results from RaDiO, the 52K study (43,125 individuals) and the TOPMed study (44,083 individuals) was finally performed. Results: Through targeted resequencing of GLIS3, we identified 105 rare variants that were carried by 395 participants from RaDiO. Among them, 49 variants decreased the activation of the INS promoter. Following ACMG criteria, 18 rare variants were classified as P/LP, showing an enrichment in the last two exons compared with the remaining exons (p3.5). The burden of these P/LP variants was strongly higher in individuals with type 2 diabetes (p=3.0×10−3; OR 3.9 [95% CI 1.4, 12]), whereas adiposity, age at type 2 diabetes diagnosis and cholesterol levels were similar between variant carriers and non-carriers with type 2 diabetes. Interestingly, all carriers with type 2 diabetes were sensitive to oral sulfonylureas. A total of 7 P/LP variants were identified in both 52K and TOPMed studies. The meta-analysis of association studies obtained from RaDiO, 52K and TOPMed showed an enrichment of P/LP GLIS3 variants in individuals with type 2 diabetes (p=5.6×10−5; OR 2.1 [95% CI 1.4, 2.9]). Conclusions/interpretation: Rare P/LP GLIS3 variants do contribute to type 2 diabetes risk. The variants located in the distal part of the protein could have a direct effect on its functional activity by impacting its transactivation domain, by homology with the mouse GLIS3 protein. Furthermore, rare P/LP GLIS3 variants seem to have a direct clinical effect on beta cell function, which could be improved by increasing insulin secretion via the use of sulfonylureas. Graphical Abstract: [Figure not available: see fulltext.

Contribution of heterozygous PCSK1 variants to obesity and implications for precision medicine: a case-control study

International audienceBackground: Rare biallelic pathogenic mutations in PCSK1 (encoding proprotein convertase subtilisin/kexin type 1 [PC1/3]) cause early-onset obesity associated with various endocrinopathies. Setmelanotide has been approved for carriers of these biallelic mutations in the past 3 years. We aimed to perform a large-scale functional genomic study focusing on rare heterozygous variants of PCSK1 to decipher their putative impact on obesity risk. Methods: This case-control study included all participants with overweight and obesity (ie, cases) or healthy weight (ie, controls) from the RaDiO study of three community-based and one hospital-based cohort in France recruited between Jan 1, 1995, and Dec 31, 2000. In adults older than 18 years, healthy weight was defined as BMI of less than 25·0 kg/m2, overweight as 25·0–29·9 kg/m2, and obesity as 30·0 kg/m2 or higher. Participants with type 2 diabetes had fasting glucose of 7·0 mmol/L or higher or used treatment for hyperglycaemia (or both) and were negative for islet or insulin autoantibodies. Functional assessment of rare missense variants of PCSK1 was performed. Pathogenicity clusters of variants were determined with machine learning. The effect of each cluster of PCSK1 variants on obesity was assessed using the adjusted mixed-effects score test. Findings: All 13 coding exons of PCSK1 were sequenced in 9320 participants (including 7260 adults and 2060 children and adolescents) recruited from the RaDiO study. We detected 65 rare heterozygous PCSK1 variants, including four null variants and 61 missense variants that were analysed in vitro and clustered into five groups (A–E), according to enzymatic activity. Compared with the wild-type, 15 missense variants led to complete PC1/3 loss of function (group A; reference) and rare exome variant ensemble learner (REVEL) led to 15 (25%) false positives and four (7%) false negatives. Carrying complete loss-of-function or null PCSK1 variants was significantly associated with obesity (six [86%] of seven carriers vs 1518 [35%] of 4395 non-carriers; OR 9·3 [95% CI 1·5–177·4]; p=0·014) and higher BMI (32·0 kg/m2 [SD 9·3] in carriers vs 27·3 kg/m2 [6·5] in non-carriers; mean effect π 6·94 [SE 1·95]; p=0·00029). Clusters of PCSK1 variants with partial or neutral effect on PC1/3 activity did not have an effect on obesity or overweight and on BMI. Interpretation: Only carriers of heterozygous, null, or complete loss-of-function PCSK1 variants cause monogenic obesity and, therefore, might be eligible for setmelanotide. In silico tests were unable to accurately detect these variants, which suggests that in vitro assays are necessary to determine the variant pathogenicity for genetic diagnosis and precision medicine purposes. Funding: Agence Nationale de la Recherche, European Research Council, National Center for Precision Diabetic Medicine, European Regional Development Fund, Hauts-de-France Regional Council, and the European Metropolis of Lille

Functional genetics reveals the contribution of delta opioid receptor to type 2 diabetes and beta-cell function

International audienceFunctional genetics has identified drug targets for metabolic disorders. Opioid use impacts metabolic homeostasis, although mechanisms remain elusive. Here, we explore the OPRD1 gene (encoding delta opioid receptor, DOP) to understand its impact on type 2 diabetes. Large-scale sequencing of OPRD1 and in vitro analysis reveal that loss-of-function variants are associated with higher adiposity and lower hyperglycemia risk, whereas gain-of-function variants are associated with lower adiposity and higher type 2 diabetes risk. These findings align with studies of opium addicts. OPRD1 is expressed in human islets and beta cells, with decreased expression under type 2 diabetes conditions. DOP inhibition by an antagonist enhances insulin secretion from human beta cells and islets. RNA-sequencing identifies pathways regulated by DOP antagonism, including nerve growth factor, circadian clock, and nuclear receptor pathways. Our study highlights DOP as a key player between opioids and metabolic homeostasis, suggesting its potential as a therapeutic target for type 2 diabetes

Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension

International audienceThe G-protein-coupled receptor accessory protein MRAP2 is implicated in energy control in rodents, notably via the melanocortin-4 receptor1. Although some MRAP2 mutations have been described in people with obesity1-3, their functional consequences on adiposity remain elusive. Using large-scale sequencing of MRAP2 in 9,418 people, we identified 23 rare heterozygous variants associated with increased obesity risk in both adults and children. Functional assessment of each variant shows that loss-of-function MRAP2 variants are pathogenic for monogenic hyperphagic obesity, hyperglycemia and hypertension. This contrasts with other monogenic forms of obesity characterized by excessive hunger, including melanocortin-4 receptor deficiency, that present with low blood pressure and normal glucose tolerance4. The pleiotropic metabolic effect of loss-of-function mutations in MRAP2 might be due to the failure of different MRAP2-regulated G-protein-coupled receptors in various tissues including pancreatic islets