How and Why Do Students Use Learning Strategies? A Mixed Methods Study on Learning Strategies and Desirable Difficulties With Effective Strategy Users

In order to ensure long-term retention of information students must move from relying on surface-level approaches that are seemingly effective in the short-term to “building in” so called “desirable difficulties,” with the aim of achieving understanding and long-term retention of the subject matter. But how can this level of self-regulation be achieved by students when learning? Traditionally, research on learning strategy use is performed using self-report questionnaires. As this method is accompanied by several drawbacks, we chose a qualitative, in-depth approach to inquire about students' strategies and to investigate how students successfully self-regulate their learning. In order to paint a picture of effective learning strategy use, focus groups were organized in which previously identified, effectively self-regulating students (N = 26) were asked to explain how they approach their learning. Using a constructivist grounded theory methodology, a model was constructed describing how effective strategy users manage their learning. In this model, students are driven by a personal learning goal, adopting a predominantly qualitative, or quantitative approach to learning. While learning, students are continually engaged in active processing and self-monitoring. This process is guided by a constant balancing between adhering to established study habits, while maintaining a sufficient degree of flexibility to adapt to changes in the learning environment, assessment demands, and time limitations. Indeed, students reported using several strategies, some of which are traditionally regarded as “ineffective” (highlighting, rereading etc.). However, they used them in a way that fit their learning situation. Implications are discussed for the incorporation of desirable difficulties in higher education

A Qualitative Study of the Feasibility and Acceptability of Implementing 'Sit-To-Stand' Desks in Vocational Education and Training

While it has been shown that interrupting a person’s sedentary behaviour has the potentialto improve cognitive, physical and mental health, a large part of time that students spend in schoolis sedentary. As research has shown that approximately 80% of vocational education and training(VET) students have an unhealthy sedentary lifestyle, implementing “sit-to-stand” (StS) desks couldinterrupt sedentary behaviour and promote healthier behaviour. Therefore, the acceptability andfeasibility of using such desks in the VET setting should be investigated. Using semi-structuredfocus group interviews analysed via deductive content analysis, the opinions of 33 students for thefollowing topics were assessed: (1) usage of the standing option of the desks (2) reasons for standingin class (3) experienced effect of standing behind the desk, and (4) fostering future StS desks usage.Although VET students are aware of the potential benefits of using StS desks, they need to be activelystimulated and motivated by teachers to use them. In addition, time is needed to get into the habit ofstanding. Thus, for successful implementation of StS desks in the VET setting, all stakeholders (i.e.,students, teachers, schoolboards) should be actively involved in stimulating the healthy behaviour ofVET students

Granularity matters:comparing different ways of measuring self-regulated learning

Although self-regulated learning (SRL) is becoming increasingly important in modern educational contexts, disagreements exist regarding its measurement. One particularly important issue is whether self-reports represent valid ways to measure this process. Several researchers have advocated the use of behavioral indicators of SRL instead. An outstanding research debate concerns the extent to which it is possible to compare behavioral measures of SRL to traditional ways of measuring SRL using self-report questionnaire data, and which of these methods provides the most valid and reliable indicator of SRL. The current review investigates this question. It was found that granularity is an important concept in the comparison of SRL measurements, influencing the degree to which students can accurately report on their use of SRL strategies. The results show that self-report questionnaires may give a relatively accurate insight into students' global level of self-regulation, giving them their own value in educational research and remediation. In contrast, when students are asked to report on specific SRL strategies, behavioral measures give a more accurate account. First and foremost, researchers and practitioners must have a clear idea about their research question or problem statement, before choosing or combining either form of measurement

Loss-of-Function Mutations in the WNT Co-receptor LRP6 Cause Autosomal-Dominant Oligodontia

Tooth agenesis is one of the most common developmental anomalies in man. Oligodontia, a severe form of tooth agenesis, occurs both as an isolated anomaly and as a syndromal feature. We performed exome sequencing on 20 unrelated individuals with apparent non-syndromic oligodontia and failed to detect mutations in genes previously associated with oligodontia. In three of the probands, we detected heterozygous variants in LRP6, and sequencing of additional oligodontia-affected individuals yielded one additional mutation in LRP6. Three mutations (c.1144_1145dupAG [p.Ala383Glyfs*8], c.1779dupT [p.Glu594*], and c.2224_2225dupTT [p.Leu742Phefs*7]) are predicted to truncate the protein, whereas the fourth (c.56C>T [p.Ala19Val]) is a missense variant of a conserved residue located at the cleavage site of the protein's signal peptide. All four affected individuals harboring a LRP6 mutation had a family history of tooth agenesis. LRP6 encodes a transmembrane cell-surface protein that functions as a co-receptor with members from the Frizzled protein family in the canonical Wnt/β-catenin signaling cascade. In this same pathway, WNT10A was recently identified as a major contributor in the etiology of non-syndromic oligodontia. We show that the LRP6 missense variant (c.56C>T) results in altered glycosylation and improper subcellular localization of the protein, resulting in abrogated activation of the Wnt pathway. Our results identify LRP6 variants as contributing to the etiology of non-syndromic autosomal-dominant oligodontia and suggest that this gene is a candidate for screening in DNA diagnostics

Pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency in zebrafish results in fatal seizures and metabolic aberrations

Pyridox(am)ine 5'-phosphate oxidase (PNPO) catalyzes oxidation of pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP) to pyridoxal 5'-phosphate (PLP), the active form of vitamin B6. PNPO deficiency results in neonatal/infantile seizures and neurodevelopmental delay. To gain insight into this disorder we generated Pnpo deficient (pnpo-/-) zebrafish (CRISPR/Cas9 gene editing). Locomotion analysis showed that pnpo-/- zebrafish develop seizures resulting in only 38% of pnpo-/- zebrafish surviving beyond 20 days post fertilization (dpf). The age of seizure onset varied and survival after the onset was brief. Biochemical profiling at 20 dpf revealed a reduction of PLP and pyridoxal (PL) and accumulation of PMP and pyridoxamine (PM). Amino acids involved in neurotransmission including glutamate, γ-aminobutyric acid (GABA) and glycine were decreased. Concentrations of several, mostly essential, amino acids were increased in pnpo-/- zebrafish suggesting impaired activity of PLP-dependent transaminases involved in their degradation. PLP treatment increased survival at 20 dpf and led to complete normalization of PLP, PL, glutamate, GABA and glycine. However, amino acid profiles only partially normalized and accumulation of PMP and PM persisted. Taken together, our data indicate that not only decreased PLP but also accumulation of PMP may play a role in the clinical phenotype of PNPO deficiency

Pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency in zebrafish results in fatal seizures and metabolic aberrations

Pyridox(am)ine 5'-phosphate oxidase (PNPO) catalyzes oxidation of pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP) to pyridoxal 5'-phosphate (PLP), the active form of vitamin B6. PNPO deficiency results in neonatal/infantile seizures and neurodevelopmental delay. To gain insight into this disorder we generated Pnpo deficient (pnpo-/-) zebrafish (CRISPR/Cas9 gene editing). Locomotion analysis showed that pnpo-/- zebrafish develop seizures resulting in only 38% of pnpo-/- zebrafish surviving beyond 20 days post fertilization (dpf). The age of seizure onset varied and survival after the onset was brief. Biochemical profiling at 20 dpf revealed a reduction of PLP and pyridoxal (PL) and accumulation of PMP and pyridoxamine (PM). Amino acids involved in neurotransmission including glutamate, γ-aminobutyric acid (GABA) and glycine were decreased. Concentrations of several, mostly essential, amino acids were increased in pnpo-/- zebrafish suggesting impaired activity of PLP-dependent transaminases involved in their degradation. PLP treatment increased survival at 20 dpf and led to complete normalization of PLP, PL, glutamate, GABA and glycine. However, amino acid profiles only partially normalized and accumulation of PMP and PM persisted. Taken together, our data indicate that not only decreased PLP but also accumulation of PMP may play a role in the clinical phenotype of PNPO deficiency

Assessment of parental mosaicism in SCN1A -related epilepsy by single-molecule molecular inversion probes and next-generation sequencing

Background: Dravet syndrome is a severe genetic encephalopathy, caused by pathogenic variants in SCN1A. Low-grade parental mosaicism occurs in a substantial proportion of families (7%-13%) and has important implications for recurrence risks. However, parental mosaicism can remain undetected by methods regularly used in diagnostics. In this study, we use single-molecule molecular inversion probes (smMIP), a technique with high sensitivity for detecting low-grade mosaic variants and high cost-effectiveness, to investigate the incidence of parental mosaicism of SCN1A variants in a cohort of 90 families and assess the feasibility of this technique. Methods: Deep sequencing of SCN1A was performed using smMIPs. False positive rates for each of the proband's pathogenic variants were determined in 145 unrelated samples. If parents showed corresponding variant alleles at a significantly higher rate than the established noise ratio, mosaicism was confirmed by droplet digital PCR (ddPCR). Results: Sequence coverage of at least 100× at the location of the corresponding pathogenic variant was reached for 80 parent couples. The variant ratio was significantly higher than the established noise ratio in eight parent couples, of which four (5%) were regarded as true mosaics, based on ddPCR results. The false positive rate of smMIP analysis without ddPCR was therefore 50%. Three of these variants had previously been considered de novo in the proband by Sanger sequencing. Conclusion: smMIP technology combined withnext generation sequencing (NGS) performs better than Sanger sequencing in the detection of parental mosaicism. Because parental mosaicism has important implications for genetic counselling and recurrence risks, we stress the importance of implementing high-sensitivity NGS-based assays in standard diagnostics

Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

PURPOSE: This study investigated whole-exome sequencing (WES) yield in a subset of intellectually disabled patients referred to our clinical diagnostic center and calculated the total costs of these patients' diagnostic trajectory in order to evaluate early WES implementation. METHODS: We compared 17 patients' trio-WES yield with the retrospective costs of diagnostic procedures by comprehensively examining patient records and collecting resource use information for each patient, beginning with patient admittance and concluding with WES initiation. We calculated cost savings using scenario analyses to evaluate the costs replaced by WES when used as a first diagnostic tool. RESULTS: WES resulted in diagnostically useful outcomes in 29.4% of patients. The entire traditional diagnostic trajectory average cost was $16,409 per patient, substantially higher than the$3,972 trio-WES cost. WES resulted in average cost savings of $3,547 for genetic and metabolic investigations in diagnosed patients and$1,727 for genetic investigations in undiagnosed patients. CONCLUSION: The increased causal variant detection yield by WES and the relatively high costs of the entire traditional diagnostic trajectory suggest that early implementation of WES is a relevant and cost-efficient option in patient diagnostics. This information is crucial for centers considering implementation of WES and serves as input for future value-based research into diagnostics

Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity

We identified de novo nonsense variants in KIDINS220/ARMS in three unrelated patients with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO). KIDINS220 is an essential scaffold protein coordinating neurotrophin signal pathways in neurites and is spatially and temporally regulated in the brain. Molecular analysis of patients' variants confirmed expression and translation of truncated transcripts similar to recently characterized alternative terminal exon splice isoforms of KIDINS220 KIDINS220 undergoes extensive alternative splicing in specific neuronal populations and developmental time points, reflecting its complex role in neuronal maturation. In mice and humans, KIDINS220 is alternative spliced in the middle region as well as in the last exon. These full-length and KIDINS220 splice variants occur at precise moments in cortical, hippocampal, and motor neuron development, with splice variants similar to the variants seen in our patients and lacking the last exon of KIDINS220 occurring in adult rather than in embryonic brain. We conducted tissue-specific expression studies in zebrafish that resulted in spasms, confirming a functional link with disruption of the KIDINS220 levels in developing neurites. This work reveals a crucial physiological role of KIDINS220 in development and provides insight into how perturbation of the complex interplay of KIDINS220 isoforms and their relative expression can affect neuron control and human metabolism. Altogether, we here show that de novo protein-truncating KIDINS220 variants cause a new syndrome, SINO. This is the first report of KIDINS220 variants causing a human disease