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Background: Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including 'Not in Education, Employment or Training' (NEET) status., Methods: We took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model , meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms., Results: Our analysis sample included participants with full information on NEET status ( N = 3951), and the results supported the accumulation of risk model , showing that the odds of NEET increase by 1.015 (95% CI 1.012-1.019) for an increase of 1 unit in depression at any age between 11 and 24 years., Conclusions: Given the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.

We examined whether inaccurate teacher judgements of primary school student achievement correlate with students' gender and whether such bias contributes to gender achievement gaps in language and mathematics. Our study used ex-post harmonised longitudinal data from England, Germany, and the US. We observed domain-specific teacher judgement bias with a positive bias for girls in the language domain and for boys in mathematics. Furthermore, biased teacher judgements partly mediated the effect of gender on later achievement. Despite these common findings, cross-country differences emerged in the extent of teacher judgement bias as well as its mediation of gender achievement gaps. We conclude that this is a topic of relevance across national contexts and where the institutional and societal setting needs more attention in future research., Competing Interests: Declarations of competing interest Authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are significant cross-country differences in socio-economic gradients in later childhood and adulthood overweight/obesity; few studies assess whether this cross-national variation is evident from early childhood. Furthermore, the role of childcare in explaining overweight/obesity gradients might vary across countries, given differences in access, quality and heterogeneity within. Additionally, childcare is linked to parental characteristics such as maternal employment. The interplay between childcare and employment in producing early overweight/obesity gradients has received little attention, and might vary cross-nationally., Methods: Using harmonized data from six high-quality, large datasets, we explore the variation in gradients in early overweight/obesity (at age 3-4 years old) by parental education across several high-income countries (USA, UK, France, the Netherlands, Germany and Japan). We then assess whether differential formal group care use attenuates some of these gradients, and whether this varies across maternal employment., Results: Gradients in early childhood overweight/obesity by parental education are evident across several developed countries. Countries with higher overall prevalence of early overweight/obesity did not have the largest inequalities across education groups. The contribution of formal group care to producing these gradients varied across countries and across maternal employment status., Conclusion: Early childhood inequalities in overweight/obesity are pervasive across developed countries, as noted for older children and adults. However, mechanisms producing these gradients vary across national contexts. Our study shows that, given the right context, quality childcare and maternal employment can successfully support healthy weight trajectories and not contribute (or even reduce) social inequalities in early overweight/obesity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Socioeconomic inequalities in childhood Body Mass Index (BMI) are becoming increasingly more pronounced across the world. Although countries differ in the direction and strength of these inequalities, cross-national comparative research on this topic is rare. This paper draws on harmonized longitudinal cohort data from four wealthy countries-Germany, the Netherlands, the United Kingdom (UK), and the United States (US)-to 1) map cross-country differences in the magnitude of socioeconomic inequalities in childhood BMI, and 2) to examine cross-country differences in the role of three energy-balance-related behaviors-physical activity, screen time, and breakfast consumption-in explaining these inequalities. Children were aged 5-7 at our first timepoint and were followed up at age 8-11. We used data from the German National Educational Panel Study, the Dutch Generation R study, the UK Millennium Cohort Study and the US Early Childhood Longitudinal-Kindergarten Study. All countries revealed significant inequalities in childhood BMI. The US stood out in having the largest inequalities. Overall, inequalities between children with low versus medium educated parents were smaller than those between children with high versus medium educated parents. The role of energy-balance-related behaviors in explaining inequalities in BMI was surprisingly consistent. Across countries, physical activity did not, while screen time and breakfast consumption did play a role. The only exception was that breakfast consumption did not play a role in the US. Cross-country differences emerged in the relative contribution of each behavior in explaining inequalities in BMI: Breakfast consumption was most important in the UK, screen time explained most in Germany and the US, and breakfast consumption and screen time were equally important in the Netherlands. Our findings suggest that what constitutes the most effective policy intervention differs across countries and that these should target both children from medium as well as low educated families., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Depressive symptoms show different trajectories throughout childhood and adolescence that may have different consequences for adult outcomes., Aims: To examine trajectories of childhood depressive symptoms and their association with education and employment outcomes in early adulthood., Method: We estimated latent trajectory classes from participants with repeated measures of self-reported depressive symptoms between 11 and 24 years of age and examined their association with two distal outcomes: university degree and those not in employment, education or training at age 24., Results: Our main analyses (n = 9399) yielded five heterogenous trajectories of depressive symptoms. The largest group found (70.5% of participants) had a stable trajectory of low depressive symptoms (stable-low). The other four groups had symptom profiles that reached full-threshold levels at different developmental stages and for different durations. We identified the following groups: childhood-limited (5.1% of participants) with full-threshold symptoms at ages 11-13; childhood-persistent (3.5%) with full-threshold symptoms at ages 13-24; adolescent onset (9.4%) with full-threshold symptoms at ages 17-19; and early-adult onset (11.6%) with full-threshold symptoms at ages 22-24. Relative to the majority 'stable-low' group, the other four groups all exhibited higher risks of one or both adult outcomes., Conclusions: Accurate identification of depressive symptom trajectories requires data spanning the period from early adolescence to early adulthood. Consideration of changes in, as well as levels of, depressive symptoms could improve the targeting of preventative interventions in early-to-mid adolescence.

Previous research has documented significantly larger income-related gaps in children's early cognitive development in the United States than in the United Kingdom, Canada, and Australia. In this study, we investigate the extent to which this is a result of a more unequal income distribution in the United States. We show that although incomes are more unequal in the United States than elsewhere, a given difference in real income is associated with larger gaps in child test scores there than in the three other countries. In particular, high-income families in the United States appear to translate the same amount of financial resources into greater cognitive advantages relative to the middle-income group than those in the other countries studied. We compare inequalities in other kinds of family characteristics and show that higher income levels are disproportionately concentrated among families with advantageous demographic characteristics in the United States. Our results underline the fact that the same degree of income inequality can translate into different disparities in child development, depending on the distribution of other family resources.

Objective: To investigate the impact of increasing levels of inattention, hyperactivity/impulsivity, and oppositional/defiant behaviors at age 7 years on academic achievement at age 16 years., Method: In a population-based sample of 7-year-old children in England, information was obtained about inattention, hyperactivity/impulsivity, and oppositional/defiant behaviors (using parent and teacher ratings) and the presence of attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs). After adjusting for confounder variables, their associations with academic achievement in national General Certificate of Secondary Education (GCSE) examinations (using scores and minimum expected school-leaving qualification level [5 "good" GCSEs]) at age 16 years were investigated (N = 11,640)., Results: In adjusted analyses, there was a linear association between each 1-point increase in inattention symptoms and worse outcomes (2- to 3-point reduction in GCSE scores and 6% to 7% (10%-12% with teacher ratings) increased likelihood of not achieving 5 good GCSEs). ADHD was associated with a 27- to 32-point reduction in GCSE scores and, in boys, a more than 2-fold increased likelihood of not achieving 5 good GCSEs. In boys, oppositional/defiant behaviors were also independently associated with worse outcomes, and DBDs were associated with a 19-point reduction in GCSE scores and a 1.83-increased likelihood of not achieving 5 good GCSEs., Conclusion: Across the full range of scores at a population level, each 1-point increase in inattention at age 7 years is associated with worse academic outcomes at age 16. The findings highlight long-term academic risk associated with ADHD, particularly inattentive symptoms. After adjusting for inattention and ADHD respectively, oppositional/defiant behaviors and DBDs are also independently associated with worse academic outcomes., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

This study examines fertility variation by residential context in Britain. While there is a large literature on fertility trends and determinants in industrialised countries, to date longitudinal research on spatial fertility variation has been restricted to the Nordic countries. We study fertility variation across regions of different sizes, and within urban regions by distinguishing between central cities and suburbs. We use vital statistics and longitudinal data and apply event history analysis. We investigate the extent to which the socio-economic characteristics of couples and selective migrations explain fertility variation between residential contexts, and the extent to which contextual factors potentially play a role. Our analysis shows that fertility levels decline as the size of an urban area increases; within urban regions suburbs have significantly higher fertility levels than city centres. Differences in fertility by residential context persist when we control for the effect of population composition and selective migrations., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: High levels of attentional and hyperactivity problems in school-aged children, even if subthreshold for attention-deficit hyperactivity disorder (ADHD), are associated with academic under-achievement. Few large-scale, community-based studies have investigated the relationship between pre-school and adolescence., Aims: To investigate whether pre-school hyperactivity/inattention and conduct problems are independently associated with academic outcomes at age 16., Method: Data from the prospective, population-based Avon Longitudinal Study of Parents and Children (ALSPAC) were used. After adjusting for a broad range of confounder variables, the associations between parent-rated hyperactivity/inattention and conduct problems measured at age 3 and academic outcomes at age 16 (national General Certificate of Secondary Education (GCSE) examination results) were investigated (n = 11 640)., Results: Both early hyperactivity/inattention and conduct problems had negative effects on academic outcomes. In adjusted analyses, abnormal hyperactivity/inattention scores were associated with reductions of ten GCSE points in boys. Borderline and abnormal conduct problem scores were associated with reductions of 9-10 and 12-15 points respectively., Conclusions: Pre-school hyperactivity/inattention and conduct problems carry risk of worse academic outcomes at 16.

In spite of important differences in some of the resources immigrant parents have to invest in their children, and in immigrant selection rules and settlement policies, there are significant similarities in the relative positions of 4- and 5-year-old children of immigrants in Australia, Canada, the United Kingdom, and the United States. Children of immigrants underperform their counterparts with native-born parents in vocabulary tests, particularly if a language other than the official language is spoken at home, but are not generally disadvantaged in nonverbal cognitive domains, nor are there notable behavioral differences. These findings suggest that the cross-country differences in cognitive outcomes during the teen years documented in the existing literature are much less evident during the early years., (© 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.)

Economic models of investment in human capital sometimes refer to neuroscience as a means to support their underlying assumptions regarding human development. These assumptions have a crucial influence on the policy implications the models generate. We review the extent to which the neuroscience of development can be used to support a "learning begets learning" principle of human capital accumulation. We conclude that, although early neural development can be considered as foundational, it cannot be considered as a unitary phenomenon that proceeds in continuous fashion. Furthermore, the concept of the sensitive period, which is often used associated with the principle, suggests benefits of investment depend upon an individual's circumstances and developmental history, and particularly whether this can be classified as normal. A more recent model of investment has involved two different types of abilities, with outcomes demonstrating the value of including more sophisticated assumptions about human development. We conclude that, while current discussions of policy would benefit from a more careful interpretation of existing models, the potential for future work combining modern neuroscientific understanding with economic theory is considerable., (Copyright © 2011. Published by Elsevier Ltd.)

In this paper, we analyze the role that early years policy might play in narrowing educational attainment gaps. We begin by examining gaps in school readiness between low-, middle-, and high-income children, drawing on data from new large and nationally representative birth cohort studies in the US and UK. We find that sizable income-related gaps in school readiness are present in both countries before children enter school and then decompose these gaps to identify the factors that account for the poorer scores of low-income children. We then consider what role early years policy could play in tackling these gaps, drawing on the best available evidence to identify promising programs.

Estrogen receptor alpha (ERalpha) is a transcription factor that regulates expression of target genes in a ligand-dependent manner. Activation of gene expression is mediated by two transcription activation functions AF-1 and AF-2, which act in a promoter- and cell-specific manner. Whilst AF-2 activity is regulated by estrogen (E2) binding, the activity of AF-1 is additionally modulated by phosphorylation at several sites. One of these phosphorylation sites, serine 118 (S118) is of particular interest as its mutation significantly reduces ERalpha activity. Previous studies have shown that S118 can be phosphorylated by the ERK1/2 mitogen activated protein kinases (MAPK) and by the cyclin-dependent protein kinase Cdk7. In this study we use antisera that specifically recognize ERalpha phosphorylated at S118 to demonstrate that MAPK phosphorylates S118 in a ligand-independent manner, whereas Cdk7 mediates E2-induced phosphorylation of S118. E2 stimulation of S118 phosphorylation was observed within 10 min of its addition and was maximal at 10(-7) M E2. S118 phosphorylation was maximal at 30 min but then declined, such that by 180 min following E2 addition little S118 phosphorylation was evident. S118 phosphorylation was also induced by the partial estrogen antagonist 4-hydroxytamoxifen, but not by the complete antagonist ICI 182, 780. S118 phosphorylation upon addition of the MAPK inducers EGF or PMA followed the expected time courses. Finally, we show that ERalpha is phosphorylated at S118 in vivo using immunoblotting of extracts prepared from a series of ERalpha-positive breast tumours.

Phosphorylation of the estrogen receptor alpha (ERalpha) N-terminal transcription activation function AF1 at serine 118 (S118) modulates its activity. We show here that human ERalpha is phosphorylated by the TFIIH cyclin-dependent kinase in a ligand-dependent manner. Furthermore, the efficient phosphorylation of S118 requires a ligand-regulated interaction of TFIIH with AF2, the activation function located in the ligand binding domain (LBD) of ERalpha. This interaction involves (1) the integrity of helix 12 of the LBD/AF2 and (2) p62 and XPD, two subunits of the core TFIIH. These findings are suggestive of a novel mechanism by which nuclear receptor activity can be regulated by ligand-dependent recruitment of modifying activities, such as kinases.

We have examined the formation of alternate strand triple-helices at the target sequence A11(TC)6.(GA)6T11 using the oligonucleotides T11(AG)6 and T11(TG)6, by DNase I footprinting. These third strands were designed so as to form parallel T.AT triplets together with antiparallel G.GC and A.AT or T.AT triplets. We find that, although both oligonucleotides yield clear footprints at similar concentrations (0.3 microM) in the presence of manganese, only T11(TG)6 forms a stable complex in magnesium-containing buffers, albeit at a higher concentration (10-30 microM). Examination of the interaction of (AG)6 and (TG)6 with half the target site confirmed that the complex containing A.AT triplets was only stable in the presence of manganese. In contrast no binding of (TG)6 was detected in the presence of either metal ion, suggesting that the reverse-Hoogsteen T.AT triplet is less stable that G.GC. We suggest that, within the context of G.GC triplets, the rank order of antiparallel triplet stability is A.AT (Mn2+) > T.AT (Mn2+) > T.AT (Mg2+) > A.AT (Mg2+). Third strands containing a single base substitution in the centre of either the parallel or antiparallel portion showed a (10-fold) weaker interaction in manganese-containing buffers, and no interaction in the presence of magnesium.