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Fostering flexibility using comparing solution methods and classroom discussions: Effects of two professional development programs
No full textThis article shows that enabling teachers to integrate comparing solution strategies into their teaching fosters student flexibility in algebra. We designed two professional development (PD) programs that either focused exclusively on comparing solution strategies, or additionally introduced the accountable talk approach to guiding productive classroom discussions. The effects of both PD programs were investigated in an experimental field study (N = 39 teachers, 739 students). In both experimental groups, student posttest gains in strategy flexibility and procedural knowledge were greater than in the control group. The accountable talk group also increased conceptual knowledge. Significant effects in strategy flexibility were still observed 2.5 months later. We discuss recommendations for PD programs to foster flexibility in algebra using comparing
Inhibition of de novo ceramide synthesis by sirtuin-1 improves beta-cell function and glucose metabolism in type 2 diabetes
No full textAims
Obesity and type 2 diabetes (T2D) are major risk factors for cardiovascular (CV) diseases. Dysregulated pro-apoptotic ceramide synthesis reduces β-cell insulin secretion, thereby promoting hyperglycaemic states that may manifest as T2D. Pro-apoptotic ceramides modulate insulin sensitivity and glucose tolerance while being linked to poor CV outcomes. Sirtuin-1 (SIRT1) is a NAD + -dependent deacetylase that protects against pancreatic β-cell dysfunction; however, systemic levels are decreased in obese–T2D mice and may promote pro-apoptotic ceramide synthesis and hyperglycaemia. Herein, we aimed to assess the effects of restoring circulating SIRT1 levels to prevent metabolic imbalance in obese and diabetic mice.
Methods and results
Circulating SIRT1 levels were reduced in obese–diabetic mice (db/db) as compared to age-matched non-diabetic db/+ controls. Restoration of SIRT1 plasma levels with recombinant murine SIRT1 for 4 weeks prevented body weight gain and improved glucose tolerance, insulin sensitivity, and vascular function in mice models of obesity and T2D. Untargeted lipidomics revealed that SIRT1 restored insulin secretory function of β-cells by reducing synthesis and accumulation of pro-apoptotic ceramides. Molecular mechanisms involved direct binding to and deacetylation of Toll-like receptor 4 (TLR4) by SIRT1 in β-cells, thereby decreasing the rate-limiting enzymes of sphingolipid synthesis SPTLC1/2 via AKT/NF-κB. Among patients with T2D, those with high baseline plasma levels of SIRT1 prior to metabolic surgery displayed restored β-cell function (HOMA2-β) and were more likely to have T2D remission during follow-up.
Conclusion
Acetylation of TLR4 promotes β-cell dysfunction via ceramide synthesis in T2D, which is blunted by systemic SIRT1 replenishment. Hence, restoration of systemic SIRT1 may provide a novel therapeutic strategy to counteract toxic ceramide synthesis and mitigate CV complications of T2D
Viral and Immune Risk Factors of HIV Rebound after Interruption of Antiretroviral Therapy
No full textBACKGROUND
Identifying risk factors for HIV rebound after treatment interruption is crucial for designing effective remission strategies.
METHODS
Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, N=73) and ACTG study A5345 (N=44) were analyzed before ART interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene). Immune phenotyping was conducted by flow cytometry. Cox proportional hazards (PH) models and penalized Cox PH models with an adaptive LASSO penalty identified risk factors for time to rebound (HIV RNA >1,000 copies/mL).
RESULTS
Late ART initiation was associated with higher rebound risk (shorter time to rebound), as compared to early ART. Higher pre-ART HIV RNA, total HIV DNA, and increased cellular HIV transcription at the time of ART interruption were associated with higher rebound risk. Higher proviral diversity was associated with higher rebound risk but only among male participants and those enrolled in the ZPHI cohort. Less CD4+ T cells at ART interruption, higher proportions of effector and terminally differentiated T cells, and more activated and exhausted T cells were associated with higher rebound risk, primarily in early treated participants. No significant immunological risk factors were found in participants treated during chronic HIV. In the combined cohort, total HIV DNA and terminally differentiated CD8+ T Cells appeared to be the most relevant risk factors for time to rebound.
CONCLUSION
These findings underscore the importance of early ART initiation and suggest that tailored interventions based on virologic, immunologic, and demographic factors may help achieve sustained viral suppression
External Validation of the ARISE Prediction Models for Aneurysmal Rebleeding After Aneurysmal Subarachnoid Hemorrhage
No full textBACKGROUND AND OBJECTIVES: To externally validate the Aneurysmal RebleedIng after Subarachnoid hEmorrhage (ARISE) prediction models that predict preinterventional aneurysmal rebleeding within 24 and 72 hours after aneurysmal subarachnoid hemorrhage (aSAH).
METHODS: We pooled data from two international hospital registries from University Hospital Oslo, Norway, and University Hospital Rotterdam, The Netherlands, to validate the ARISE base model (including patient age, sex, hypertension, World Federation of Neurological Surgeons grade, Fisher grade, aneurysm size, and cerebrospinal fluid diversion) and the ARISE extended model (adding aneurysm irregularity to the base model). Model performance was assessed with discrimination (Harrell c-statistic, model-based c-statistic) and calibration (calibration-in-the-large, calibration slope, and calibration plots). After validation, we updated the ARISE models as appropriate.
RESULTS: The combined cohort consisted of 1467 patients, of whom 143 (10%) suffered preinterventional rebleeding. In the University Hospital Oslo, Norway cohort, the externally validated c-statistics were 0.75 (95% CI: 0.71-0.80) for the ARISE base model and 0.71 (0.66-0.76) for the ARISE extended model. In the University Hospital Rotterdam, The Netherlands cohort, the c-statistics were 0.70 (0.64-0.76) for the ARISE base model and 0.64 (0.57-0.72) for the ARISE extended model. Calibration-in-the-large was poor; the average predicted risks were lower than the average observed risk for both models in both centers. After updating the baseline hazard, the base model calibrated excellently over the range of clinically relevant probabilities of rebleeding.
CONCLUSION: The ARISE base model had good discriminative ability for the prediction of preinterventional rebleeding in patients suffering from aSAH. Updating the baseline hazard for each center was needed to improve calibration. After local validation and adjustment of the baseline hazard if required, the ARISE baseline model may well be used for risk prediction in patients with aSAH in other settings. The ARISE extended model needs further modification before reliable application can take place
Hunderttausend gültige: Eine qualitative Analyse der Unterschriftensammlung für Volksinitiativen in der Schweiz und ihrer Erfolgsfaktoren
No full textLa traduction latine du Codi de Richard de Pise: entre tradition(s) discursive(s) et romanisation
No full textL’objectif de cet article est de caractériser le latin de Richard de Pise dans sa traduction du Codi, une somme occitane contenant le Code de Justinien. L’accent est mis sur la romanisation du latin et sur les éléments discursifs du ‘latin juridique’ et de ‘l’occitan juridique’. Nous avons abordé les questions concernant les éléments discursifs par une approche déductive sur la base de descriptions correspondantes et les éléments de romanisation par la comparaison entre le texte latin et occitan, tout en prenant en compte la source du Codi, la Summa Trecensis. Les résultats montrent que les traits de ‘latin juridique’ ne sont quasiment plus repérables à quelques exceptions près, e. a. les constructions postquam + futur I/futur II tout comme les propositions conditionnelles du type fuerit – erit, tandis que les éléments discursifs de ‘l’occitan juridique’ dominent le texte. La grammaticalisation de ibi et inde d’après le modèle roman constitue un exemple frappant de romanisation
Ultrasound-assisted catheter-directed thrombolysis versus surgical pulmonary embolectomy for intermediate-high or high-risk pulmonary embolism: a randomized phase II non-inferiority trial
No full textOBJECTIVES: We hypothesized that ultrasound-assisted thrombolysis (USAT) is non-inferior to surgical pulmonary embolectomy (SPE) to improve right ventricular (RV) function in patients with acute pulmonary embolism (PE). METHODS: In a single-centre, non-inferiority trial, we randomly assigned 27 patients with intermediate-high or high-risk acute PE to undergo either USAT or SPE stratified by PE risk. Primary and secondary outcomes were the baseline-to-72-h difference in right-to-left ventricular (RV/LV) ratio and the Qanadli pulmonary occlusion score, respectively, by contrast-enhanced chest-computed tomography assessed by a blinded CoreLab. RESULTS: The trial was prematurely terminated due to slow enrolment. Mean age was 62.6 (SD 12.4) years, 26% were women, and 15% had high-risk PE. Mean change in RV/LV ratio was -0.34 (95% CI -0.50 to -0.18) in the USAT and -0.53 (95% CI -0.68 to -0.38) in the SPE group (mean difference: 0.152; 95% CI 0.032-0.271; P = 0.80; P = 0.013). Mean change in Qanadli pulmonary occlusion score was -7.23 (95% CI -9.58 to -4.88) in the USAT and -11.36 (95% CI -15.27 to -7.44) in the SPE group (mean difference: 5.00; 95% CI 0.44-9.56, P = 0.032). Clinical and functional outcomes were similar between the 2 groups up to 12 months. CONCLUSIONS: In patients with intermediate-high and high-risk acute PE, USAT was not non-inferior when compared with SPE in reducing RV/LV ratio within the first 72 h. In a post hoc superiority analysis, SPE resulted in greater improvement of RV overload and reduction of thrombus burden
