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It is not known whether early intervention can improve long-term autism symptom outcomes. We aimed to follow-up the Preschool Autism Communication Trial (PACT), to investigate whether the PACT intervention had a long-term effect on autism symptoms and continued effects on parent and child social interaction. PACT was a randomised controlled trial of a parent-mediated social communication intervention for children aged 2–4 years with core autism. Follow-up ascertainment was done at three specialised clinical services centres in the UK (London, Manchester, and Newcastle) at a median of 5·75 years (IQR 5·42–5·92) from the original trial endpoint. The main blinded outcomes were the comparative severity score (CSS) from the Autism Diagnostic Observation Schedule (ADOS), the Dyadic Communication Assessment Measure (DCMA) of the proportion of child initiatiations when interacting with the parent, and an expressive-receptive language composite. All analyses followed the intention-to-treat principle. PACT is registered with the ISRCTN registry, number ISRCTN58133827. 121 (80%) of the 152 trial participants (59 [77%] of 77 assigned to PACT intervention vs 62 [83%] of 75 assigned to treatment as usual) were traced and consented to be assessed between July, 2013, and September, 2014. Mean age at follow-up was 10·5 years (SD 0·8). Group difference in favour of the PACT intervention based on ADOS CSS of log-odds effect size (ES) was 0·64 (95% CI 0·07 to 1·20) at treatment endpoint and ES 0·70 (95% CI −0·05 to 1·47) at follow-up, giving an overall reduction in symptom severity over the course of the whole trial and follow-up period (ES 0·55, 95% CI 0·14 to 0·91, p=0·004). Group difference in DCMA child initiations at follow-up showed a Cohen's d ES of 0·29 (95% CI −0.02 to 0.57) and was significant over the course of the study (ES 0·33, 95% CI 0·11 to 0·57, p=0·004). There were no group differences in the language composite at follow-up (ES 0·15, 95% CI −0·23 to 0·53). The results are the first to show long-term symptom reduction after a randomised controlled trial of early intervention in autism spectrum disorder. They support the clinical value of the PACT intervention and have implications for developmental theory. Medical Research Council.

To investigate the relationships between handheld dynamometer (HHD), isokinetic and Nordic hamstrings exercise (NHE) measurements of knee flexor strength and their association with sprinting performance. Cross-sectional. The relationships between HHD (prone isometric, prone break and supine break knee flexor strength tests), isokinetic and NHE peak knee flexor strength measures were examined using Pearson product correlations on 38 female footballers. A linear regression analysis was also performed for each pair of dependent variables (10 and 30 metre sprint times) and independent predictor variables (average relative peak torque for HHD, isokinetic and NHE testing). There were good correlations between HHD tests (r = 0.81-0.90, p < 0.001, R2 = 0.65-0.82), moderate correlations between HHD and isokinetic peak torque, (r = 0.61-0.67, p < 0.001, R2 = 0.37-0.44) and poor association between the HHD peak torques and isokinetic work (r = 0.44-0.46, p = 0.005-0.007, R2 = 0.20-0.21) and average power (r = 0.39-0.45, n = 36, p = 0.006-0.019, R2 = 0.15-0.22). There was a poor association between NHE peak torque and isokinetic total work (r = 0.34, p = 0.04, R2 = 0.12). No associations between knee flexor strength and sprint times were observed (p = 0.12-0.79, r2 = 0.002-0.086). Moderate to good correlations within HHD testing and poor to moderate correlations between HHD and isokinetic testing were observed. HHD knee flexor torque assessment may be useful to regularly chart the progress of hamstring rehabilitation for female footballers. Knee flexor strength assessments were not associated with sprint times in female footballers. Other aspects of knee flexor strength and sprint performance should be investigated to assist clinicians in making return to running and sprinting decisions in this population.

Purpose Research suggests that cancer-related cognitive impairment (CRCI) can occur before breast cancer (BC) treatment. The limited extant evidence suggests the underlying mechanisms could be stress-related. Potential psychological and biological predictors of CRCI prior to any BC treatment were examined. Methods 112 treatment-naïve women with BC and 67 healthy controls (HC) completed a neuropsychological test battery to assess cognitive impairment and a self-report battery to assess cognitive complaints, cancer-related stress, depressive and anxiety symptoms. Morning and evening cortisol and α-amylase were collected from saliva. Multilinear regressions were conducted. Results Treatment-naïve BC patients were more frequently impaired in verbal memory and processing speed and reported more cognitive complaints (all p  < .001) than HC. BC patients and HC did not differ in overall cognitive impairment ( p  = .21). Steeper α-amylase, lower cancer-related stress and younger age was associated with better overall cognitive function in treatment-naïve BC patients. Higher depressive symptoms predicted higher levels of cognitive complaints in BC patients. Conclusion Overall, these findings suggest that stress plays a role in CRCI. This study is the first to associate α-amylase with cognitive function in cancer patients, informing future research. The findings on impairment in processing speed and verbal memory among treatment-naïve BC highlight the need to screen for such impairments among BC patients and indicate that future studies on CRCI should include baseline assessments prior to BC treatment. If replicated, these findings could inform the development and testing of appropriate interventions to decrease CRCI among cancer patients. Clinical trials registration number NCT04418856, date of registration: 06.05.2020.

Background Despite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism. Methods We analysed data from n  = 194 children aged 4–16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires. Results There was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire. Conclusions There is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD.

Background Cancer‐related cognitive impairment (CRCI), for example, impairments in reaction time, processing speed, memory and executive function, may be associated with breast cancer (BC) surgery which can disrupt biological and psychological stress markers. Evidence suggests that light therapy may ameliorate cognitive impairment and stress. In this double‐blind, randomized controlled trial, we investigated the efficacy of light therapy on mitigating the impact of BC surgery on CRCI in a national Icelandic cohort of women with BC. Methods Participants were randomly allocated to receive circadian‐effective blue light (BL, N = 60) or circadian‐ineffective dim light (DL, N = 57) for 4 weeks after surgery. The primary outcome was overall cognitive performance (assessed via global composite score), and secondary outcomes were specific cognitive domains, cognitive complaints, psychological (depressive symptoms, overall cancer‐related stress and its symptoms: hyperarousal, avoidance, and intrusive thoughts) and biological (cortisol and α‐amylase) stress markers. Linear regression and path analyses within structural equation modeling frameworks were conducted, adjusted for baseline cognitive performance, age, education, subsequent cancer treatment, cancer stage, and treatment credibility. Results No group differences were found in overall cognitive performance or in specific cognitive domains, except for a non‐significant trend for faster reaction times in the BL group (p < 0.11). Additionally, the BL group reported significantly fewer cognitive complaints compared with the DL group (p < 0.05), as well as a non‐significant trend for less intrusive thoughts (p < 0.11). No group differences were observed in the biological stress markers. Conclusion Overall, these findings suggest that light therapy may help mitigate the adverse effects associated with BC surgery on CRCI and intrusive thoughts, although further research is warranted. Trial Registration: NCT04418856

We examined predictors of mental health difficulties and wellbeing in caregivers of children with autism in the Pre-school Autism Communication Trial cohort in middle childhood (N = 104). Child’s intellectual disability, daily living skills impairment, elevated emotional and behavioural difficulties, high educational level of caregiver and household income below the median significantly predicted caregivers’ mental health difficulties, but autism severity, child communication skills and family circumstances did not. Lower caregiver mental wellbeing was predicted by elevated child emotional and behavioural difficulties. The need to support the mental health and wellbeing of caregivers of children with autism is discussed in light of the results.

There is a lack of measures that reflect the intervention priorities of parents of children with autism spectrum disorder (ASD) and that assess the impact of interventions on family experience and quality of life. The Autism Family Experience Questionnaire (AFEQ) was developed through focus groups and online consultation with parents, and reflected parental priorities. It was then administered to the parents of children enrolled in the Pre-school Autism Communication Trial and its 6-year follow-up study. The AFEQ showed good convergent validity with well-established measures of child adaptive functioning, parental mental health and parental wellbeing. It was sensitive to change in response to a parent-mediated intervention for young children with autism, showing treatment effect at treatment endpoint which increased at six-year follow-up.

This study presents the first longitudinal data on American Jewish children's thoughts and feelings about Israel, highlighting children's development between kindergarten and second grade. Drawing upon interviews and photo and music elicitation exercises with Jewish elementary school students, the research examines both children's conceptual understandings of Israel—what they imagine it to be—and their feelings toward Israel. The research finds that throughout the early elementary grades, children think of Israel as a place where both good and bad can happen—a duality that remains relatively stable over time. Yet their feelings about Israel change over time, as consistently happy emotions give way to a wider range of affective responses to Israel, including worry, fear, and sadness. This manuscript examines both children's static conceptions of Israel and their changing feelings about the Jewish state, addressing the implications of these findings for elementary school Israel education and Jewish communal policy toward youth engagement with Israel.

Background Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA ( t (12) = − 2.12, p  = .055), GABA/Glx ratio ( t (12) = − 2.78, p  = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p  < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p  < 0.01). Machine-learning classification of imaging outcomes achieved 79% ( p  < .05) accuracy differentiating groups at endpoint against chance level (64%, p  = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met ‘clinical responder’ criteria for behavioural outcome. Conclusions We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration EU Clinical Trial Register (EudraCT) 2012-005742-38 ( www.clinicaltrialsregister.eu )