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 association between state-based provisional attendance periods and adolescent middle school-entry vaccination coverage.

The rise of vaccine-preventable disease outbreaks calls for a deeper understanding of the impact of policy on school-entry vaccine compliance. Provisional attendance policies vary by state but permit under-vaccinated students a limited period to attend school while receiving their immunizations. The primary objective of this study was to clarify the relationship between annual immunization coverage and state provisional policies for a single-dose of school-entry-required adolescent vaccinations: tetanus, diphtheria, pertussis (Tdap), meningococcal conjugate (MCV4), and human papillomavirus (HPV). From June 22, 2020 to August 20, 2020, the Immunization Action Coalition and state-level Department of Health (DOH) webpages were reviewed with email confirmation with a DOH representative to determine provisional period policy. Vaccination coverage for Tdap, MCV4, and HPV were obtained from the Center for Disease Control's National Immunization Survey. Overall, 49 states and D.C. legally mandate exclusion of vaccine noncompliant adolescents, and the majority of jurisdictions assign responsibility for exclusion to local school officials (84%). Complete provisional period data was obtained for 46/51 jurisdictions. The effect of provisional period length categorized as 0 days (18 jurisdictions, 35.3%), 1 to 30 days (18 jurisdictions, 35.3%), 31+ days (10 jurisdictions, 19.6%), and "unclear" (5 jurisdictions with incomplete data, 9.8%) had no significant association with annual adolescent vaccination coverage for Tdap (p = 0.82), MCV4 (p = 0.08), and HPV (p = 0.76). Provisional policies may not increase vaccination coverage as anticipated. Unintended consequences, such as increased nonmedical exemptions and increased demands on clinical providers, are additional factors to consider.

A systematic review of randomized and case-controlled trials investigating the effectiveness of school-based motor skill interventions in 3- to 12-year-old children.

BACKGROUND: Research suggests that children identified with impaired motor skills can respond well to intensive therapeutic interventions delivered via occupational and physical therapy services. There is, however, a need to explore alternative approaches to delivering interventions outside traditional referral-based clinic settings because limited resources mean such health services often struggle to meet demand. This review sets out to systematically assess the evidence for and against school-based interventions targeted at improving the motor skills of children aged between 3 and 12 years old. METHOD: Five electronic databases were searched systematically (AMED, CINAHL, Cochrane, Medline, and PsycINFO) for peer-reviewed articles published between January 2012 and July 2018. Studies were eligible if they implemented a school-based motor skill intervention with a randomized or case-controlled trial design that objectively measured motor skills as an outcome, which were not specific to an athletic or sporting skill. Participants had to be aged between 3 and 12 years old and free from neurological disorders known to affect muscle function. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: Twenty-three studies met the inclusion criteria. These studies encompassed interventions targeted at training: fundamental movement skills, handwriting, fine, and global motor skills. The majority of these studies reported beneficial impact on motor function specifically, but some interventions also assessed subsequent impacts on activity and participation (but not well-being). A number of the studies had methodological shortcomings that means these results need to be interpreted with caution. CONCLUSIONS: Schools appear to be an effective setting for motor skill interventions, but the extent of benefit likely depends on the type of intervention. Moreover, confirmation is needed as to whether benefits extend beyond motor function into everyday activities, participation, and well-being. Future research should include follow-up measures to assess the longer term efficacy of school-based interventions.

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.

Potential for England's statutory school entry assessment to identify special educational needs and reveal structural inequalities: a population-based study.

OBJECTIVE: To investigate at a population level whether England's universal assessment of 'school readiness' is associated with later identification of special educational needs (SEN). Also, whether ethnic differences exist in SEN identification (white British versus ethnic minority) and whether this varies as a function of school readiness. METHOD: Analysis included 53 229 individuals aged 5-12 years from the Connected Bradford Database (2012/2013-2019/2020). Logistic regression analyses examined: (1) whether reaching a 'good level of development' on England's 'school readiness' assessment was associated with later SEN identification; and (2) whether interactions exist between school readiness and ethnicity. RESULTS: 32 515 of 53 229 children reached a good level of development, of which 3036 (9.3%) were identified as having SEN. In contrast, 10 171 of 20 714 (49.1%) of children who did not reach a good level of development were later identified as having SEN. Children not reaching a good level of development had increased odds of being later identified as having SEN after controlling for covariates (OR: 8.50, 95% CI: 8.10 to 8.91). In children who did not reach a good level of development, white British children had higher odds of being identified as having SEN compared with ethnic minority peers (OR: 1.22, 95% CI: 1.11 to 1.34). No ethnic differences of having SEN were observed in children reaching a good level of development (OR: 1.04, 95% CI: 0.93 to 1.16). CONCLUSIONS: School readiness assessments are associated with later SEN identification. Structural inequalities may exist in SEN identification in children not entering formal education 'school ready'. Such assessments could facilitate earlier identification of SEN and reduce structural inequalities in its identification.

Exclusion of Reproductive-aged Women in COVID-19 Vaccination and Clinical Trials.

INTRODUCTION: We analyzed the exclusion of pregnant and breastfeeding individuals and those capable of pregnancy in COVID-19 vaccine and clinical treatment trials. METHODS: Inclusion and exclusion criteria were extracted from all listed COVID-19 vaccine and treatment clinical trials from May 1, 2020, to October 31, 2020, using the U.S. National Library of Medicine database. We report rates of rates of exclusion for pregnant and lactating individuals and requirements for contraception for pregnancy-capable participants in COVID-19 vaccine and treatment clinical trials. The analysis included the association between clinical trial exclusion and vaccine and treatment type, study location, sponsor, and phase. RESULTS: Pregnant and lactating individuals were explicitly excluded from most COVID-19 vaccine and treatment clinical trials. Of the 90 vaccine trials, 88 (97.8%) excluded pregnant individuals, 73 (81.1%) excluded lactating individuals, and 56 (62.2%) required contraception use. Of the 495 treatment trials, 350 (70.7%) excluded pregnant individuals, 269 (54.3%) excluded lactating individuals, and 91 (18.4%) required contraception use. Although vaccine type was not associated with pregnancy exclusion, it was associated with lactation exclusion (p = .01) and contraception requirement (p < .001). Treatment type was associated with pregnancy exclusion, lactation exclusion, and contraception requirement (all p < .001). CONCLUSIONS: COVID-19 vaccination and treatment clinical trials mirrored historical trends restricting participation owing to pregnancy, lactation, and contraception nonuse, despite known safety profiles. People of childbearing potential should be considered for and afforded the same opportunity as males to make informed decisions on study participation, particularly in the setting of a global pandemic.

Large-scale assessment of 7-11-year-olds' cognitive and sensorimotor function within the Born in Bradford longitudinal birth cohort study.

Background: Cognitive ability and sensorimotor function are crucial aspects of children's development, and are associated with physical and mental health outcomes and educational attainment. This paper describes cross-sectional sensorimotor and cognitive function data collected on over 15,000 children aged 7-10 years, collected as part of the Born in Bradford (BiB) longitudinal birth-cohort study. Methodological details of the large-scale data collection process are described, along with initial analyses of the data involving the relationship between cognition/sensorimotor ability and age and task difficulty, and associations between tasks. Method: Data collection was completed in 86 schools between May 2016 and July 2019. Children were tested at school, individually, using a tablet computer with a digital stylus or finger touch for input. Assessments comprised a battery of three sensorimotor tasks (Tracking, Aiming, & Steering) and five cognitive tasks (three Working Memory tasks, Inhibition, and Processing Speed), which took approximately 40 minutes. Results: Performance improved with increasing age and decreasing task difficulty, for each task. Performance on all three sensorimotor tasks was correlated, as was performance on the three working memory tasks. In addition, performance on a composite working memory score correlated with performance on both inhibition and processing speed. Interestingly, within age-group variation was much larger than between age-group variation. Conclusions: The current project collected computerised measures of a range of cognitive and sensorimotor functions at 7-10 years of age in over 15,000 children. Performance varied as expected by age and task difficulty, and showed the predicted correlations between related tasks. Large within-age group variation highlights the need to consider the profile of individual children in studying cognitive and sensorimotor development. These data can be linked to the wider BiB dataset including measures of physical and mental health, biomarkers and genome-wide data, socio-demographic information, and routine data from local health and education services.

Laparoscopic Motor Learning and Workspace Exploration.

BACKGROUND: Laparoscopic surgery requires operators to learn novel complex movement patterns. However, our understanding of how best to train surgeons' motor skills is inadequate, and research is needed to determine optimal laparoscopic training regimes. This difficulty is confounded by variables inherent in surgical practice, for example, the increasing prevalence of morbidly obese patients presents additional challenges related to restriction of movement because of abdominal wall resistance and reduced intra-abdominal space. The aim of this study was to assess learning of a surgery-related task in constrained and unconstrained conditions using a novel system linking a commercially available robotic arm with specialised software creating the novel kinematic assessment tool (Omni-KAT). METHODS: We created an experimental tool that records motor performance by linking a commercially available robotic arm with specialized software that presents visual stimuli and objectively measures movement outcome (kinematics). Participants were given the task of generating aiming movements along a horizontal plane to move a visual cursor on a vertical screen. One group received training that constrained movements to the correct plane, whereas the other group was unconstrained and could explore the entire "action space." RESULTS: The tool successfully generated the requisite force fields and precisely recorded the aiming movements. Consistent with predictions from structural learning theory, the unconstrained group produced better performance after training as indexed by movement duration (p < 0.05). CONCLUSION: The data showed improved performance for participants who explored the entire action space, highlighting the importance of learning the full dynamics of laparoscopic instruments. These findings, alongside the development of the Omni-KAT, open up exciting prospects for better understanding of the learning processes behind surgical training and investigate ways in which learning can be optimized.