Learning from erroneous models using SCYDynamics

Dynamic phenomena are common in science education. Students can learn about such system dynamic processes through model based learning activities. This paper describes a study on the effects of a learning from erroneous models approach using the learning environment SCYDynamics. The study compared three conditions. Two experimental conditions where students had to correct errors in a model were contrasted to working with a correct model. The experimental conditions differed on whether or not the students had to detect the errors before correcting them. Results indicate that this approach enhanced students’ model testing and revising activities. Furthermore this approach was found to have a beneficial effect on learning common errors. Contrary to expectations this approach showed no learning effect on domain knowledge acquisition. The discussion further elaborates on improvements that might enhance this learning from erroneous model approac

Finding out how they find it out: an empirical analysis of inquiry learners' need for support

Inquiry learning environments increasingly incorporate modelling facilities for students to articulate their research hypotheses and (acquired) domain knowledge. This study compared performance success and scientific reasoning of university students with high prior knowledge (n=11), students from senior high-school (n=10), and junior high-school (n=10) with intermediate and low prior knowledge respectively, in order to reveal domain novice's need for support in such environments. Results indicated that the scientific reasoning of both groups of high-school students was comparable to that of the experts. As high-school students achieved significantly lower performance success scores, their expert-like behaviour was rather ineffective; qualitative analyses substantiated this conclusion. Based on these findings, implications for supporting domain novices in inquiry learning environments are advanced

Scaffolding learning by modelling: The effects of partially worked-out models

Creating executable computer models is a potentially powerful approach to science learning. Learning by modelling is also challenging because students can easily get overwhelmed by the inherent complexities of the task. This study investigated whether offering partially worked-out models can facilitate students’ modelling practices and promote learning. Partially worked-out models were expected to aid model construction by revealing the overall structure of the model, and thus enabling student to create better models and learn from the experience. This assumption was tested in high school biology classes where students modelled the human glucose-insulin regulatory system. Students either received support in the form of a partial model that outlined the basic structure of the glucose-insulin system (PM condition; n = 26), an extended partial model that also contained a set of variables students could use to complete the model (PM+ condition; n = 21), or no support (control condition; n = 23). Results showed a significant knowledge increase from pretest to posttest in all conditions. Consistent with expectations, knowledge gains were higher in the two partial model conditions than in the control condition. Students in both partial model conditions also ran their model more often to check its accuracy, and eventually built better models than students from the control condition. Comparison between the PM and PM+ conditions showed that more extensive support further increased knowledge acquisition, model quality, and model testing activities. Based on these findings, it was concluded that partial solutions can support learning by modelling, and that offering both a structure of a model and a list of variables yields the best result

Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-beta and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-beta and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-beta were found especially in MFS patients with aortic root dilatation (124 pg/ml), when compared to MFS patients with normal aorta (10 pg/ml; p = 8x10(-6), 95% CI: 70-159 pg/ml). Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR) = 0%), ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC) = 1.8; 1.4; 1.5, FDR = 0%) and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%). Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF) in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02) and increased number of CD8+ T-cells (p = 0.003) in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients

Genome-Wide Association Study Identifies Single Nucleotide Polymorphism in DYRK1A Associated with Replication of HIV-1 in Monocyte-Derived Macrophages

Background: HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART), macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages. Methodology/Principal Findings: Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96) or high (n = 96) p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16×10-5). While the association was not genome-wide significant (p<1×10-7), we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034). Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84×10-6). In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048). Conclusions/Significance: These findings suggest that the kinase DYRK1A is involved in the replication of HIV-1, in vitro in macrophages as well as in vivo. © 2011 Bol et al

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Using heuristic worked examples to promote inquiry-based learning

Inquiry learning can be facilitated by having students investigate the domain through a computer simulation and express their acquired understanding in a runnable computer model. This study investigated whether heuristic worked examples can further enhance students' inquiry behaviour, the quality of the models they create, and their domain knowledge. High-school students were offered a simulation of an electrical circuit and a modelling tool. Students in the experimental condition (n = 46) could consult heuristic worked examples that explained what activities were needed and how they should be performed. Students in the control condition (n = 36) did not receive this support. Cross-condition comparisons confirmed that heuristic worked examples improved students' inquiry behaviour and enhanced the quality of their models. However, few students created a model that reflected full understanding of the electrical circuit, and the expected between-group difference in posttest scores failed to appear. Based on these findings, improvements to the design of heuristic worked examples are proposed

Risk Factors for Diabetes Mellitus Type 2 and Metabolic Syndrome Are Comparable for Previously Growth Hormone-Treated Young Adults Born Small for Gestational Age (SGA) and Untreated Short SGA Controls

Context: Low birth weight might increase risk of diabetes mellitus type 2 and metabolic syndrome (MS). GH has insulin-antagonistic properties. Therefore, long-term follow-up of GH-treated children born small for gestational age (SGA) is important. Objective and Patients: The objective of the study was to evaluate insulin sensitivity (Si) and disposition index (DI), all components of the MS and IGF-I and IGF binding protein (IGFBP)-3 levels in 37 previously GH-treated young SGA adults in comparison with 25 untreated short SGA controls. Results: GH-treated subjects were 22.3 (1.7) yr old. Mean duration of GH treatment had been 7.3 (1.3) yr. Mean period after discontinuation was 6.5 (1.4) yr. Si and DI were comparable for GH-treated and untreated SGA subjects. Fasting glucose and insulin levels increased during GH treatment but recovered after discontinuation. Body mass index, waist circumference, high-density lipoprotein cholesterol levels, and triglycerides were equivalent. Systolic and diastolic blood pressure and cholesterol were significantly lower in GH-treated subjects. Thirty-two percent of untreated controls vs. none of the GHtreated subjects had an increased blood pressure. GH-induced rises in IGF-I and IGFBP-3 levels had completely recovered after GH stop. Conclusion: At 6.5 yr after discontinuation of long-term GH treatment, Si, DI, fasting levels of glucose and insulin, body mass index, waist circumference, and IGF-I and IGFBP-3 levels were equivalent for GH-treated and untreated young SGA adults. Systolic and diastolic blood pressure and serum cholesterol were even lower in GHtreated subjects. These data are reassuring because they suggest that long-term GH treatment does not increase the risk for diabetes mellitus type 2 and MS in young adults. (J Clin Endocrinol Metab 92: 160 -165, 2007