COVID and Curriculum: Elementary Teachers Report on the Challenges of Teaching and Learning Mathematics Remotely

This article reports on findings from a survey administered to 524 elementary teachers across 46 states that asked about their experiences with mathematics teaching, learning, and curriculum use before and during the COVID-19 pandemic. The purpose of this article is to report on the challenges teachers experienced with mathematics teaching, learning, and curriculum use during the pandemic and to explore educational inequities faced by students of families with lower income backgrounds. In particular, we discuss differences across high- and low-income schools regarding teachers’ perceived preparedness for online teaching, teachers’ use and decisions about mathematics curriculum, and their students’ remote resources (i.e., internet, computer, and workspace). We also share statements from teachers that illustrate challenges they experienced in engaging students, assessing learning outcomes, and building relationships. We found that students and teachers in schools from all socioeconomic levels faced hardship. However, lower income schools generally faced greater challenges in terms of access to computers, internet, and adequate workspaces. This often resulted in decreased access to teachers and decreased engagement. The exacerbation of educational inequities experienced by students from low income backgrounds during the pandemic suggests that we may see further widening of gaps in learning growth between students of low- and high-socioeconomic backgrounds. This has implications for policy makers, teacher educators, and other stakeholders seeking to advance equity and justice for less wealthy students

The effects of an aerobic training intervention on cognition, grey matter volumes and white matter microstructure

While there is strong evidence from observational studies that physical activity is associated with reduced risk of cognitive decline and dementia, the extent to which aerobic training interventions impact on cognitive health and brain structure remains subject to debate. In a pilot study of 46 healthy older adults (66.6 years ± 5.2 years, 63% female), we compared the effects of a twelve-week aerobic training programme to a waitlist control condition on cardiorespiratory fitness, cognition and magnetic resonance imaging (MRI) outcomes. Cardiorespiratory fitness was assessed by VO2 max testing. Cognitive assessments spanned executive function, memory and processing speed. Structural MRI analysis included examination of hippocampal volume, and voxel-wise assessment of grey matter volumes using voxel-based morphometry. Diffusion tensor imaging analysis of fractional anisotropy, axial diffusivity and radial diffusivity was performed using tract-based spatial statistics. While the intervention successfully increased cardiorespiratory fitness, there was no evidence that the aerobic training programme led to changes in cognitive functioning or measures of brain structure in older adults. Interventions that are longer lasting, multi-factorial, or targeted at specific high-risk populations, may yield more encouraging results

Genome sequencing with gene panel-based analysis for rare inherited conditions in a publicly funded healthcare system: implications for future testing

Acknowledgements This study would not be possible without the families, patients, clinicians, nurses, research scientists, laboratory staff, informaticians and the wider Scottish Genomes Partnership team to whom we give grateful thanks. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health). The Scottish Genomes Partnership was funded by the Chief Scientist Office of the Scottish Government Health Directorates (SGP/1) and The Medical Research Council Whole Genome Sequencing for Health and Wealth Initiative (MC/PC/15080). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure.Peer reviewedPublisher PD

A case series of familial ARID1B variants illustrating variable expression and suggestions to update the ACMG criteria

ARID1B is one of the most frequently mutated genes in intellectual disability (~1%). Most variants are readily classified, since they are de novo and are predicted to lead to loss of function, and therefore classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines for the interpretation of sequence variants. However, familial loss-of-function variants can also occur and can be challenging to interpret. Such variants may be pathogenic with variable expression, causing only a mild phenotype in a parent. Alternatively, since some regions of the ARID1B gene seem to be lacking pathogenic variants, loss-of-function variants in those regions may not lead to ARID1B haploinsufficiency and may therefore be benign. We describe 12 families with potential loss-of-function variants, which were either familial or with unknown inheritance and were in regions where pathogenic variants have not been described or are otherwise challenging to interpret. We performed detailed clinical and DNA methylation studies, which allowed us to confidently classify most variants. In five families we observed transmission of pathogenic variants, confirming their highly variable expression. Our findings provide further evidence for an alternative translational start site and we suggest updates for the ACMG guidelines for the interpretation of sequence variants to incorporate DNA methylation studies and facial analyses

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Association of cardiovascular risk factors with MRI indices of cerebrovascular structure and function and white matter hyperintensities in young adults

Importance: Risk of stroke and brain atrophy in later life relate to levels of cardiovascular risk in early adulthood. However, it is unknown whether cerebrovascular changes are already present in young adults. Objective: To examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function and white matter integrity in young adults. Design, Setting, and Participants: A cross-sectional observational study completed between August 2014 and May 2016 at the University of Oxford, United Kingdom. Participants recruited through active and passive recruitment from the local community, including invitation from the Oxford University Hospitals Hypertension Service. Exposures: Clinic and ambulatory blood pressure (mmHg), body mass index (kg/m2), objective physical activity (hours/week), alcohol intake (drinks/week), smoking (pack years), peak oxygen uptake (ml/kg/min), peak exercise blood 65 pressure (mmHg), lipid profile (mg/dL), insulin resistance and use of anti-66 hypertension medication. 67 Main Outcomes and Measures: Cerebral vessel density (vessels/cm3), caliber (μm) and tortuosity, brain white matter hyperintensity lesion count (number), and in a subgroup (n=52) brain blood arrival time (seconds) and cerebral blood flow (ml/100g/min) assessed by brain magnetic resonance. Results: 125 participants (mean age 25±5 years, 49% female) were recruited. Cerebrovascular morphology and white matter hyperintensity count correlated with cardiovascular risk factors in univariable and multivariable models. In a risk score, for each healthier modifiable risk factor, characterised as: ambulatory blood pressure ; BMI < 25kg/m2; top tertile of cardiovascular fitness; non-smoker; <8 alcoholic drinks/week; normotensive exercise blood pressure response; cholesterol <200mg/dL; and fasting glucose <100mg/dL, vessel density increased by 0.3 vessels/cm3 (95%CI 0.1 to 0.5, p=0.003), vessel caliber by 8μm (95%CI 3 to 13, p=0.01) and white matter hyperintensity lesions reduced by 1.6 lesions (95%CI 0.6 to 2.8, p=0.006). In subgroup analysis, cerebral blood flow varied with vessel density and increased by 2.5ml/min/100g per risk score (95%CI 0.05 to 4.98, p=0.05). Conclusions and Relevance: In this preliminary study, involving young adults without clinical evidence of cerebrovascular disease, modifiable cardiovascular risk factors were associated with MR indices of cerebral vessel structure and function, and white matter hyperintensities. Further research is needed to determine the clinical importance of these findings for the primordial prevention of cerebrovascular disease

Genome-Wide Association Study of Circadian Rhythmicity in 71,500 UK Biobank Participants and Polygenic Association with Mood Instability

Background: Circadian rhythms are fundamental to health and are particularly important for mental wellbeing. Disrupted rhythms of rest and activity are recognised as risk factors for major depressive disorder and bipolar disorder. Methods: We conducted a genome-wide association study (GWAS) of low relative amplitude (RA), an objective measure of rest-activity cycles derived from the accelerometer data of 71,500 UK Biobank participants. Polygenic risk scores (PRS) for low RA were used to investigate potential associations with psychiatric phenotypes. Outcomes: Two independent genetic loci were associated with low RA, within genomic regions for Neurofascin (NFASC) and Solute Carrier Family 25 Member 17 (SLC25A17). A secondary GWAS of RA as a continuous measure identified a locus within Meis Homeobox 1 (MEIS1). There were no significant genetic correlations between low RA and any of the psychiatric phenotypes assessed. However, PRS for low RA was significantly associated with mood instability across multiple PRS thresholds (at PRS threshold 0·05: OR = 1·02, 95% CI = 1·01–1·02, p = 9·6 × 10−5), and with major depressive disorder (at PRS threshold 0·1: OR = 1·03, 95% CI = 1·01–1·05, p = 0·025) and neuroticism (at PRS threshold 0·5: Beta = 0·02, 95% CI = 0·007–0·04, p = 0·021). Interpretation: Overall, our findings contribute new knowledge on the complex genetic architecture of circadian rhythmicity and suggest a putative biological link between disrupted circadian function and mood disorder phenotypes, particularly mood instability, but also major depressive disorder and neuroticism. Funding: Medical Research Council (MR/K501335/1)

Identification of novel epithelial ovarian cancer loci in women of African ancestry.

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry

Identification and Molecular Characterization of a New Ovarian Cancer Susceptibility Locus at 17q21.31

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3 ′ untranslated region at putative microRNA (miRNA) binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA binding site single nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (OR=1.12, P =10−8 ) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion ( P =10−10 ). Variation at 17q21.31 associates with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes