Linear/Nonlinear Relations of Activity and Fitness with Children’s Academic Achievement

This is an an accepted manuscript and not the final published version.ABSTRACT: A growing research base suggests the benefits of physical activity (PA) and aerobic fitness for children extend beyond overall health/well-being to include academic achievement (AA). The majority of research studies on relations of PA and fitness with AA have utilized linear-only analytic approaches, thereby precluding the possibility that PA and fitness could have a differing impact on AA for those more/less active or fit. OBJECTIVE: Evaluate both linear and non-linear associations of PA and aerobic fitness with children’s AA among a sample of 687 2nd and 3rd grade students from 17 Midwest schools. STUDY DESIGN: Using baseline data (fall 2011) from a larger 3-year intervention trial, multi-level regression analyses examined the linear and non-linear associations of AA with PA and with PACER laps (i.e., aerobic fitness), controlling for relevant covariates. RESULTS: Fitness, but not PA, had a significant quadratic association with both spelling and math achievement. Results indicate that 22–28 laps on the PACER was the point at which the associated increase in achievement per lap plateaued for spelling and math. CONCLUSIONS: Increasing fitness could potentially have the greatest impact on children’s AA for those below the 50th fitness percentile on the PACER

Indirect and direct relations between aerobic fitness, physical activity, and academic achievement in elementary school students

BACKGROUND: There is evidence to suggest that increasing physical activity (PA) improves academic achievement (AA) in children and that aerobic fitness is associated with both cognitive function and AA. However, it is not known how these variables are interrelated and analyses with adequate control for socioeconomic variables are needed. It was hypothesized that PA would not directly affect AA but would have an indirect effect on AA through its effect on aerobic fitness. The purpose of this study was to test this hypothesized mediation using path analysis. METHODS: Cross-sectional data including AA, aerobic fitness, and daily PA assessed through accelerometry were collected from a large sample (N = 687) of 2nd and 3rd grade students. Demographic data were assessed via parent self-report. RESULTS: A total of 401 students wore the accelerometer for at least 10 hours on 3 days or more and were included in the final path analysis to evaluate potential relations among PA (predictor), aerobic fitness (mediator), and WIAT-III subtest standard scores (outcomes; i.e., reading, spelling, and mathematics). Findings showed a direct effect of PA on aerobic fitness (b = 0.009, p < 0.001) and an indirect effect (mediation) of PA via fitness on math achievement (b = 0.003, p < 0.01) after controlling for student’s grade, gender, body mass index, mother’s education level, and household income, as well as intraclass correlations among classes and schools. Neither PA nor aerobic fitness were correlated with WIAT-III reading or spelling scores. CONCLUSIONS: Mediation analysis indicated that PA exerted an influence on math achievement through its effects on aerobic fitness but was not associated with reading or spelling achievement scores

Reintroduction of elective cardiac interventions in the era of COVID-19: the Barts experience.

BACKGROUND: The response to COVID-19 has required cancellation of all but the most urgent procedures; there is therefore a need for the reintroduction of a safe elective pathway. METHODS: This was a study of a pilot pathway performed at Barts Heart Centre for the admission of patients requiring elective coronary and structural procedures during the COVID-19 pandemic (April-June 2020). All patients on coronary and structural waiting lists were screened for procedural indications, urgency and adverse features for COVID-19 prognosis and discussed at dedicated multidisciplinary teams. Dedicated admission pathways involving preadmission isolation, additional consent, COVID-19 PCR testing and dedicated clean areas were used. RESULTS: 143 patients (101 coronary and 42 structural) underwent procedures (coronary angiography, percutaneous coronary intervention, transcatheter aortic valve intervention and MitralClip) during the study period. The average age was 68.2; 74% were male; and over 93% had one or more moderate COVID-19 risk factors. All patients were COVID-19 PCR negative on admission with (8.1%) COVID-19 antibody positive (swab negative). All procedures were performed successfully with low rates of procedural complications (9.8%). At 2-week follow-up, no patients had symptoms or confirmed COVID-19 infection with significant improvements in quality if life and symptoms. CONCLUSION: We demonstrated that patients undergoing coronary and structural procedures can be safely admitted during the COVID-19 pandemic, with no patients contracting COVID-19 during their admission. Reassuringly, patients reflective of typical practice, that is, those at moderate or higher risk, were treated successfully. This pilot provides important information applicable to other settings, specialties and areas to reintroduce services safely

Report and recommendations on multimedia materials for teaching and learning electricity and magnetism

This paper presents the results of a peer review of multimedia materials for teaching and learning electricity and magnetism prepared as a part of the annual activities undertaken by an international group of scientists associated with Multimedia Physics in Teaching and Learning. The work promotes the use of valuable and freely accessible information technology materials for different levels of teaching, mostly higher education. The authors discuss the process of selecting resources and the rubrics used in the rating process. The reviews of high-quality learning resources are presented along with descriptions of valuable didactical feature

Distinct amyloid-beta and tau-associated microglia profiles in Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by abnormal extracellular aggregates of amyloid-beta and intraneuronal hyperphosphorylated tau tangles and neuropil threads. Microglia, the tissue-resident macrophages of the central nervous system (CNS), are important for CNS homeostasis and implicated in AD pathology. In amyloid mouse models, a phagocytic/activated microglia phenotype has been identified. How increasing levels of amyloid-beta and tau pathology affect human microglia transcriptional profiles is unknown. Here, we performed snRNAseq on 482,472 nuclei from non-demented control brains and AD brains containing only amyloid-beta plaques or both amyloid-beta plaques and tau pathology. Within the microglia population, distinct expression profiles were identified of which two were AD pathology-associated. The phagocytic/activated AD1-microglia population abundance strongly correlated with tissue amyloid-beta load and localized to amyloid-beta plaques. The AD2-microglia abundance strongly correlated with tissue phospho-tau load and these microglia were more abundant in samples with overt tau pathology. This full characterization of human disease-associated microglia phenotypes provides new insights in the pathophysiological role of microglia in AD and offers new targets for microglia-state-specific therapeutic strategies

Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection

BACKGROUND: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity. METHODS: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements. FINDINGS: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p<0.0001) but only anti-S1 measurements correlated with near-contemporary pseudovirus neutralising antibody titres (measured at 16-18 weeks, r = 0.57, p<0.0001). By 21 weeks' follow-up, 31/143 (21.7%) anti-S1 and 6/150 (4.0%) anti-NP measurements reverted to negative. Mathematical modelling revealed faster clearance of anti-S1 compared to anti-NP (median half-life of 2.5 weeks versus 4.0 weeks), earlier transition to lower levels of antibody production (median of 8 versus 13 weeks), and greater reductions in relative antibody production rate after the transition (median of 35% versus 50%). INTERPRETATION: Mild SARS-CoV-2 infection is associated with heterogeneous serological responses in Euroimmun anti-S1 and Roche anti-NP assays. Anti-S1 responses showed faster rates of clearance, more rapid transition from high to low level production rate and greater reduction in production rate after this transition. In mild infection, anti-S1 serology alone may underestimate incident infections. The mechanisms that underpin faster clearance and lower rates of sustained anti-S1 production may impact on the longevity of humoral immunity. FUNDING: Charitable donations via Barts Charity, Wellcome Trust, NIHR

Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection.

BACKGROUND: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity. METHODS: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements. FINDINGS: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p<0.0001) but only anti-S1 measurements correlated with near-contemporary pseudovirus neutralising antibody titres (measured at 16-18 weeks, r = 0.57, p<0.0001). By 21 weeks' follow-up, 31/143 (21.7%) anti-S1 and 6/150 (4.0%) anti-NP measurements reverted to negative. Mathematical modelling revealed faster clearance of anti-S1 compared to anti-NP (median half-life of 2.5 weeks versus 4.0 weeks), earlier transition to lower levels of antibody production (median of 8 versus 13 weeks), and greater reductions in relative antibody production rate after the transition (median of 35% versus 50%). INTERPRETATION: Mild SARS-CoV-2 infection is associated with heterogeneous serological responses in Euroimmun anti-S1 and Roche anti-NP assays. Anti-S1 responses showed faster rates of clearance, more rapid transition from high to low level production rate and greater reduction in production rate after this transition. In mild infection, anti-S1 serology alone may underestimate incident infections. The mechanisms that underpin faster clearance and lower rates of sustained anti-S1 production may impact on the longevity of humoral immunity. FUNDING: Charitable donations via Barts Charity, Wellcome Trust, NIHR

Physical activity and academic achievement across the curriculum (A + PAAC): rationale and design of a 3-year, cluster-randomized trial

Abstract Background Improving academic achievement and reducing the rates of obesity in elementary school students are both of considerable interest. Increased physical activity during academic instruction time during school offers a potential intervention to address both issues. A program titled &#8220;Physical Activity Across the Curriculum&#8221; (PAAC) was developed in which classroom teachers in 22 elementary schools were trained to deliver academic instruction using physical activity with a primary aim of preventing increased BMI. A secondary analysis of data assessed the impact of PAAC on academic achievement using the Weschler Individual Achievement Test-II and significant improvements were shown for reading, math and spelling in students who participated in PAAC. Based on the results from PAAC, an adequately powered trial will be conducted to assess differences in academic achievement between intervention and control schools called, &#8220;Academic Achievement and Physical Activity Across the Curriculum (A&#8201;+&#8201;PAAC).&#8221; Methods/design Seventeen elementary schools were cluster randomized to A&#8201;+&#8201;PAAC or control for a 3-year trial. Classroom teachers were trained to deliver academic instruction through moderate-to-vigorous physical activity with a target of 100+ minutes of A&#8201;+&#8201;PAAC activities per week. The primary outcome measure is academic achievement measured by the Weschler Individual Achievement Test-III, which was administered at baseline (Fall 2011) and will be repeated in the spring of each year by assessors blinded to condition. Potential mediators of any association between A&#8201;+&#8201;PAAC and academic achievement will be examined on the same schedule and include changes in cognitive function, cardiovascular fitness, daily physical activity, BMI, and attention-to-task. An extensive process analysis will be conducted to document the fidelity of the intervention. School and student recruitment/randomization, teacher training, and baseline testing for A&#8201;+&#8201;PAAC have been completed. Nine schools were randomized to the intervention and 8 to control. A random sample of students in each school, stratified by gender and grade (A&#8201;+&#8201;PAAC&#8201;=&#8201;370, Control&#8201;=&#8201;317), was selected for outcome assessments from those who provided parental consent/child assent. Baseline data by intervention group are presented. Discussion If successful, the A&#8201;+&#8201;PAAC approach could be easily and inexpensively scaled and disseminated across elementary schools to improve both educational quality and health. Funding source: R01- DK85317. Trial registration: US NIH Clinical Trials, http://NCT01699295.Peer Reviewe