Designing 'Embodied' Science Learning Experiences for Young Children

Research in embodied cognition emphasises the importance of meaningful ‘bodily’ experience, or congruent action, in learning and development. This highlights the need for evidence-based design guidelines for sensorimotor interactions that meaningfully exploit action-based experiences, that are instrumental in shaping the way we conceptualise the world. These sensorimotor experiences are particularly important for young children as they can provide them with an embodied toolkit of resources (independent of language skills or subject specific vocabulary) that they can draw upon to support science ‘think’ and ‘talk’, using their own bodies to develop and express ideas through gesture, that are grounded on sensorimotoric representations from action experiences. Taking an iterative design-based research (DBR) approach, this paper reports the design, development and deployment of a programme of outdoor activities for children aged 4–6 years, that drew on embodied cognition theory to foster meaningful action in relation to ideas of air resistance. This research is relevant to researchers, practitioners and designers. It makes a contribution to learning experience design by making explicit the process of applying key components of embodied cognition theory to the design of science learning activities for early years, and how this can effectively inform digital design

The Prevalence and Psychopathological Correlates of Sibling Bullying in Children with and without Autism Spectrum Disorder

Using data from a prospective population based study, the prevalence and psychopathological correlates of sibling bullying in children with and without autism spectrum disorder (ASD) were estimated. There were 475 children with ASD and 13,702 children without ASD aged 11 years. Children with ASD were more likely to be bullied by their siblings compared to those without ASD. They were also more likely than those without ASD to both bully and be bullied by their siblings, which was associated with lower prosocial skills as well as more internalizing and externalizing problems compared to those not involved in any sibling bullying. Interventions to improve social and emotional outcomes in children with ASD should focus on both the affected and the unaffected sibling

Combining Independent, Weighted P-Values: Achieving Computational Stability by a Systematic Expansion with Controllable Accuracy

Given the expanding availability of scientific data and tools to analyze them, combining different assessments of the same piece of information has become increasingly important for social, biological, and even physical sciences. This task demands, to begin with, a method-independent standard, such as the -value, that can be used to assess the reliability of a piece of information. Good's formula and Fisher's method combine independent -values with respectively unequal and equal weights. Both approaches may be regarded as limiting instances of a general case of combining -values from groups; -values within each group are weighted equally, while weight varies by group. When some of the weights become nearly degenerate, as cautioned by Good, numeric instability occurs in computation of the combined -values. We deal explicitly with this difficulty by deriving a controlled expansion, in powers of differences in inverse weights, that provides both accurate statistics and stable numerics. We illustrate the utility of this systematic approach with a few examples. In addition, we also provide here an alternative derivation for the probability distribution function of the general case and show how the analytic formula obtained reduces to both Good's and Fisher's methods as special cases. A C++ program, which computes the combined -values with equal numerical stability regardless of whether weights are (nearly) degenerate or not, is available for download at our group website http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads/CoinedPValues.html

Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) As Determinants of Habitual Caffeine Consumption

We report the first genome-wide association study of habitual caffeine intake. We included 47,341 individuals of European descent based on five population-based studies within the United States. In a meta-analysis adjusted for age, sex, smoking, and eigenvectors of population variation, two loci achieved genome-wide significance: 7p21 (P = 2.4×10−19), near AHR, and 15q24 (P = 5.2×10−14), between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2

Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability

A phase Ib/II study of ivosidenib with venetoclax plus /- azacitidine in IDH1-mutated myeloid malignancies

Background: Isocitrate dehydrogenase-1 (IDH1+) mutations are present in 5-15% of myeloid malignancies, promoting leukemogenesis through production of the oncometabolite 2-hydroxyglutarate resulting in arrested myeloid differentiation. IDH1+ malignancies demonstrate increased reliance on the anti-apoptotic protein BCL-2, enhancing susceptibility to the BCL-2 inhibitor venetoclax (VEN). We report an interim safety and efficacy analysis of the IDH1 inhibitor ivosidenib (IVO; 500 mg PO daily D15-continuous) combined with VEN (D1-14) +/- azacitidine (AZA; 75mg/m2 D1-7 every 28 days). Methods: Eligible patients age ≥18 with IDH1+ MDS, newly diagnosed AML (ND: treatment naïve [TN] or secondary/treated secondary AML [sAML]), or relapsed/refractory (R/R) AML enrolled into three dose levels (DL): DL1 (IVO+VEN 400 mg), DL2 (IVO+VEN 800 mg), DL3 (IVO+VEN 400 mg+AZA). Primary objectives included safety and tolerability, and IWG defined overall response (ORR: CR+CRi+CRh+PR+MLFS). Prior receipt of IVO or VEN was exclusionary. Results: 25 evaluable patients (DL1: 6, DL2: 6, DL3: 13) enrolled with a median follow-up of 16.1 months. Median age was 67 (range: 44-84). 84% (N=21) of patients had AML (ND: N=13 [TN: 8, sAML: 5], R/R: N=8), while 16% (N=4) had MDS. ELN risk was intermediate and adverse in 16% (N=4) and 56% (N=14). Median IDH1 VAF at enrollment was 22.7% (range: 5.1%-47.8%). Two patients had received a prior IDH1 inhibitor. The ORR was 92% (DL1: 67%, DL2: 100%, DL3: 100%). Composite CR (CRc: CR+CRi+CRh) was 84% (DL1: 67%, DL2: 100%, DL3: 85%) including 92% (TN: 100%, sAML: 80%), 63%, and 100% of patients with ND-AML, R/R-AML, or MDS. Median number of cycles received was 4 (DL1: 8.5, DL2: 6, DL3: 4) with ongoing responses in 62% (DL1: 33%, DL2: 50%, DL3: 82%) at 1-year. 8 patients transitioned to SCT (DL1: 0, DL2: 2, DL3: 6), and 8 patients remain on study (DL1: 2, DL2: 1, DL3: 5). 1-year OS was 68% for the entire study population (DL1: 50%, DL2: 67%, DL3: 78%), 71% in ND-AML (TN: 86%, sAML: 60%), 50% in R/R-AML, and 100% in MDS. Measurable residual disease negative CRc by multiparameter flow cytometry was attained in 60% (ND-AML: 67%, R/R-AML: 60%, MDS: 33%) correlating with improved OS (median OS: NR vs. 8.5 months, p-value: 0.038). Common grade 3/4 adverse events included febrile neutropenia (28%) and pneumonia (24%). Tumor lysis and differentiation syndrome occurred in two and four patients; all cases resolved with medical management. Conclusions: IVO+VEN +/- AZA is an effective treatment regimen in patients with IDH1+myeloid malignancies. The combination therapy is associated with an acceptable and expected toxicity profile with notable efficacy and high rates of MRD-negative CRc in AML. Enrollment into the study continues. Clinical trial information: NCT03471260.</p