Successful Crizotinib-targeted Therapy of Pediatric Unresectable ERC1::ALK Fusion Sarcoma.

Anaplastic lymphoma kinase ( ALK )-fusion sarcomas are rare part of the emerging theoretically targetable tyrosine kinase RAS::MAPK pathway fusion myopericytic-ovoid sarcomas. We report our clinicopathologic and treatment experience with an ALK fusion sarcoma. A novel ELKS/RAB6-interacting/CAST family member 1 - unaligned ALK fusion infiltrative nonmetastatic low-grade sarcoma of the right hand of a 15-month-old male was treated with crizotinib, an ALK tyrosine kinase inhibitor as oral monotherapy, inducing complete radiographic and clinical resolution by 10 months and sustained response now over 12 months after elective discontinuation. Crizotinib can successfully be used to treat unresectable novel ALK fusion sarcomas.

Risk of not being in employment, education or training (NEET) in late adolescence is signalled by school readiness measures at 4-5 years.

BACKGROUND: Not being in employment, education, or training (NEET) is associated with poor health (physical and mental) and social exclusion. We investigated whether England's statutory school readiness measure conducted at 4-5 years provides a risk signal for NEET in late adolescence. METHODS: We identified 8,118 individuals with school readiness measures at 4-5 years and NEET records at 16-17 years using Connected Bradford, a bank of linked routinely collected datasets. Children were categorised as 'school ready' if they reached a 'Good Level of Development' on the Early Years Foundation Stage Profile. We used probit regression and structural equation modelling to investigate the relationship between school readiness and NEET status and whether it primarily relates to academic attainment. RESULTS: School readiness was significantly associated with NEET status. A larger proportion of young people who were not school ready were later NEET (11%) compared to those who were school ready (4%). Most of this effect was attributable to shared relationships with academic attainment, but there was also a direct effect. Measures of deprivation and Special Educational Needs were also strong predictors of NEET status. CONCLUSIONS: NEET risk factors occur early in life. School readiness measures could be used as early indicators of risk, with interventions targeted to prevent the long-term physical and mental health problems associated with NEET, especially in disadvantaged areas. Primary schools are therefore well placed to be public health partners in early intervention strategies.

The relationship between 'school readiness' and later persistent absenteeism.

Post-pandemic school absence is an increasing concern for governments worldwide. Absence is associated with poor academic outcomes and long-term illness (physical and mental). Absenteeism increases the risk of financial difficulties in adulthood and involvement in the criminal justice system. We hypothesized that early childhood problems might be an antecedent of absenteeism. We tested this hypothesis by investigating the pre-pandemic association between school readiness and persistent absenteeism using a population-linked dataset. Analyses included 62,598 children aged 5-13 years from the Connected Bradford database (spanning academic years 2012/13 to 2019/20). Special educational needs status, English as an Additional Language status, socioeconomic status, sex and ethnicity were covariates significantly associated with persistent absenteeism. Children who were not 'school ready' had increased odds of being persistently absent later in their education journey after controlling for these covariates. School readiness was associated with even greater odds of being persistently absent over two or more years. These findings show (i) the seeds of absenteeism are sown early in childhood; (ii) absenteeism shows the hallmark of structural inequities; and (iii) the potential of 'school readiness' measures to identify children at risk of long-term disengagement from the education system.

Immunometabolic Blood Biomarkers of Developmental Trajectories of Depressive Symptoms: Findings From the ALSPAC Birth Cohort.

Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiologic mechanism, heterogeneity and origin of common cardiometabolic comorbidities for depression. Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n=7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%). We examined associations of these trajectories with: i) anthropometric, cardiometabolic and psychiatric phenotypes using multivariable regression (n=1709-3410); ii) 67 blood immunological proteins and 57 metabolomic features using empirical Bayes moderated linear models (n=2059 and n=2240 respectively); and iii) 28 blood cell counts and biochemical measures using multivariable regression (n=2256). Relative to the low-stable group, risk of depression and anxiety in adulthood was higher for all other groups, especially in the adolescent-persistent (ORdepression=22.80, 95% CI 15.25-34.37; ORGAD=19.32, 95% CI 12.86-29.22) and adulthood-onset (ORdepression=7.68, 95% CI 5.31-11.17; ORGAD=5.39, 95% CI 3.65-7.94) groups. The three depression-related trajectories vary in their immunometabolic profile, with evidence of little or no alterations in the adolescent-limited group. The adulthood-onset group shows widespread classical immunometabolic changes (e.g., increased immune cell counts and insulin resistance), while the adolescent-persistent group is characterised by higher BMI both in childhood and adulthood with few other immunometabolic changes. These findings point to distinct mechanisms and intervention opportunities for adverse cardiometabolic profile in different groups of young people with depression.