Education is one strategy to reduce cycle-related accidents, and many countries have training courses for children. In the UK, the National Cycle Proficiency Scheme (NCPS) was first introduced in 1947. A typical course takes place during the final years of primary school and 40% of children participate by their twelfth birthday. Despite the significant resources invested in child cycle training both in the UK and elsewhere, there has been little scientific evaluation of their outcomes.

Refractive error (e.g. myopia) is an important public health concern worldwide, as the most common cause of impaired vision. There is increasing interest in the affect of social position on visual health, considering the whole range of severity including those with mild impairment. ALSPAC is included in our programme of work within CLOSER (Cohort & Longitudinal Studies Enhancement Resource) which is investigating visual function and refractive error, making comparisons both within and across UK-based cohort and longitudinal studies. We will apply life course epidemiological approaches to investigate biological, environmental and lifestyle factors influencing the development of refractive error and the biological and social factors that influence visual health. We will also investigate the health and social outcomes associated with impaired visual health and with refractive error. Using several studies, which started recruitment at different times, we will assess any changes over time in both risk factors and outcomes which may help to identify modifiable risk factors.

Skin pigmentation differs between the sexes. In most populations, women exhibit lighter skin than men, which could be a consequence of requiring greater quantities of vitamin D to support pregnancy and lactation, of having more subcutaneous adipose tissue with less melanogenesis-stimulating androgens than men, and/or of a preference of males for fairer females(1,2). Among pre-pubertal children, however, girls are usually darker than boys, but this appears to reverse at the onset of puberty(1,3). We propose to use genetic variants strongly associated with age at menarche and Tanner stage (a measurement of pubertal development in adolescents)(4,5) to examine the relationship between puberty initiation and pigmentation changes, with particular emphasis on the consequences that these changes bring to sun exposure patterns and vitamin D levels, in ALSPAC children. Additionally, we will assess the role that androgens and estrogens play in eliciting gender pigmentation differences, using a similar framework.

Human social interaction plays an important role in social success, adjustment and development. This involves also altruistic and prosocial behaviour1, which supports creating and maintaining social bonds, an important quality of functioning societies2. Prosocial behaviour is one of the most heritable social skills with twin heritabilities rising from 0.32 during early childhood to 0.61 during middle childhood3. It is strongly associated with social cognition and intelligence, and prosocial motivation is one of the three major cognitive components, which have been hypothesized to underlie empathyADDIN ZOTERO_ITEM CSL_CITATION{"citationID":"16tvof0ais","properties":{"formattedCitation":"{\rtf\super4\nosupersub{}}","plainCitation":"4"},"citationItems":[{"id":3140,"uris":["http://zotero.org/users/8513/items/9AICVEX6"],"uri":["http://zotero.org/users/8513/items/9AICVEX6"],"itemData":{"id":3140,"type":"article-journal","title":"Theneuroscience of empathy: progress, pitfalls andpromise","container-title":"Nature Neuroscience","page":"675-680","volume":"15","issue":"5","source":"www.nature.com","abstract":"Thelast decade has witnessed enormous growth in the neuroscience of empathy. Here,we survey research in this domain with an eye toward evaluating its strengthsand weaknesses. First, we take stock of the notable progress made by earlyresearch in characterizing the neural systems supporting two empathicsub-processes: sharing others' internal states and explicitly considering thosestates. Second, we describe methodological and conceptual pitfalls into whichthis work has sometimes fallen, which can limit its validity. These include theuse of relatively artificial stimuli that differ qualitatively from the socialcues people typically encounter and a lack of focus on the relationship betweenbrain activity and social behavior. Finally, we describe current researchtrends that are overcoming these pitfalls through simple but importantadjustments in focus, and the future promise of empathy research if thesetrends continue and expand.
View fulltext","DOI":"10.1038/nn.3085","ISSN":"1097-6256","shortTitle":"Theneuroscience of empathy","journalAbbreviation":"NatNeurosci","language":"en","author":[{"family":"Zaki","given":"Jamil"},{"family":"Ochsner","given":"KevinN."}],"issued":{"date-parts":[["2012",5]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}4. The neurobiological basis of pro-social behaviour and empathy is complex. Empathic cognition has been linked to multiple subcortical regions such as the limbic system, the putative mirror system, a proposed mentalising network 5,6, as well as the septal area, which has also been associated with prosocial motivation e.g. ADDIN ZOTERO_ITEM CSL_CITATION{"citationID":"XIZroMmB","properties":{"formattedCitation":"{\rtf\super7,8\nosupersub{}}","plainCitation":"7,8"},"citationItems":[{"id":3151,"uris":["http://zotero.org/users/8513/items/W9689QEU"],"uri":["http://zotero.org/users/8513/items/W9689QEU"],"itemData":{"id":3151,"type":"article-journal","title":"Neuralcorrelates of giving support to a lovedone","container-title":"PsychosomaticMedicine","page":"3-7","volume":"74","issue":"1","source":"PubMed","abstract":"OBJECTIVE:Social support may benefit mental and physical well-being, but most researchhas focused on the receipt, rather than the provision, of social support. Weexplored the potentially beneficial effects of support giving by examining theneural substrates of giving support to a loved one. We focused on a prioriregions of interest in the ventral striatum and septal area (SA) because oftheir role in maternal caregiving behavior in animals.
METHODS: Twentyromantic couples completed a functional magnetic resonance imaging session inwhich the female partner underwent a scan while her partner stood just outsidethe scanner and received unpleasant electric shocks.
RESULTS: Support giving(holding a partner's arm while they experienced physical pain), compared withother control conditions, led to significantly more activity in the ventralstriatum, a reward-related region also involved in maternal behavior (p valuesless than .05). Similar effects were observed for the SA, a region involved in bothmaternal behavior and fear attenuation. Greater activity in each of theseregions during support giving was associated with greater self-reported supportgiving effectiveness and social connection (r values = 0.55-0.64, p values less than .05). In addition, in line with the SA's role in fear attenuation (presumablyto facilitate caregiving during stress), increased SA activity during supportgiving was associated with reduced left (r = -0.44, p less than .05) and right (r =-0.42, p less than .05) amygdala activity.
CONCLUSIONS: Results suggest thatsupport giving may be beneficial not only for the receiver but also for thegiver. Implications for the possible stress-reducing effects of support givingare discussed.","DOI":"10.1097/PSY.0b013e3182359335","ISSN":"1534-7796","note":"PMID:22071630","journalAbbreviation":"PsychosomMed","language":"eng","author":[{"family":"Inagaki","given":"TristenK."},{"family":"Eisenberger","given":"NaomiI."}],"issued":{"date-parts":[["2012",1]]},"PMID":"22071630"}},{"id":3177,"uris":["http://zotero.org/users/1947403/items/PSZ5IXEX"],"uri":["http://zotero.org/users/1947403/items/PSZ5IXEX"],"itemData":{"id":3177,"type":"article-journal","title":"Impairmentof prosocial sentiments is associated with frontopolar and septal damage infrontotemporaldementia","container-title":"NeuroImage","page":"1735-1742","volume":"54","issue":"2","source":"PubMedCentral","abstract":"Poets and philosophers have longacknowledged moral sentiments as key motivators of human social behavior.Prosocial sentiments, which include guilt, pity and embarrassment, enable us tocare about others and to be concerned about our mistakes. Functional imagingstudies have implicated frontopolar, ventromedial frontal and basal forebrainregions in the experience of prosocial sentiments. Patients with lesions of thefrontopolar and ventromedial frontal areas were observed to behaveinappropriately and less prosocially, which could be attributed to ageneralized emotional blunting. Direct experimental evidence for brain regionsdistinctively associated with moral sentiment impairments is lacking, however.We investigated this issue in patients with the behavioral variant offrontotemporal dementia, a disorder in which early and selective impairments ofsocial conduct are consistently observed. Using a novel moral sentiment task,we show that the degree of impairment of prosocial sentiments is associatedwith the degree of damage to frontopolar cortex and septal area, as assessedwith 18-Fluoro-Deoxy-Glucose-Positron Emission Tomography, an establishedmeasure of neurodegenerative damage. This effect was dissociable fromimpairment of other-critical feelings (anger and disgust), which was in turnassociated with dorsomedial prefrontal and amygdala dysfunction. Our findingssuggest a critical role of the frontopolar cortex and septal region in enablingprosocial sentiments, a fundamental component of moralconscience.","DOI":"10.1016/j.neuroimage.2010.08.026","ISSN":"1053-8119","note":"PMID:20728544
PMCID:PMC2997153","journalAbbreviation":"Neuroimage","author":[{"family":"Moll","given":"Jorge"},{"family":"Zahn","given":"Roland"},{"family":"deOliveira-Souza","given":"Ricardo"},{"family":"Bramati","given":"IvaneiE."},{"family":"Krueger","given":"Frank"},{"family":"Tura","given":"Bernardo"},{"family":"Cavanagh","given":"AlysonL."},{"family":"Grafman","given":"Jordan"}],"issued":{"date-parts":[["2011",1,15]]},"PMID":"20728544","PMCID":"PMC2997153"}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}7,8. In addition, several neuropsychiatric disorders show abnormal social functioning. Understanding the neural basis of prosocial behaviour has remained however challenging due to the diversity of cognitive assessments, developmental changes in genetic architecture of prosocial and cognitive skills and the wide range of often costly neuroimaging technologies.

Impulsive aggression is a key feature of a number of psychiatric disorders including schizophrenia, bipolar disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder, and conduct disorder. It has a deep impact on the patient, as well as society. Acts of aggression account for 1.5 million deaths annually worldwide, yet effective treatments for impulsive aggression are very limited. A better understanding of the development of aggressive behavior and the underlying neural circuits will allow for the development of interventions and targeted treatments for excessive aggression found in psychiatric disorders. From recent basic science research, using a novel transgenic mouse model we recently identified a developmental sensitive period for the effect of 5-HT1BR on aggression. Specifically, alterations in 5-HT1BR signaling during the peri-pubertal period lead to increased impulsive aggression in mice throughout life. Now, through epidemiological analysis of longitudinal studies, we will investigate the presence of a similar sensitive period for the development of aggression in humans.

The purpose of this research is to examine how prenatal behavioral, clinical, and biological risk factors and risks in the early childhood social environment independently and jointly contribute to the development of temperament and personality from early childhood through adolescence.

A gene (DMRT1) was found to be associated with asthma in a Dutch study. This failed to replicate in ALSPAC; the effects were in the opposite direction to those found in the discovery cohorts and other replication samples. We are investigating the reasons for this by doing some further analyses of the genetic variants in his region.

Anorexia nerovsa is a severe mental illness most often affecting adolescent girls. The etiology of the disorder is complex and involves genetics as well as environmental aspects. We have shown that epigenetic factors can contribute to the disorder. In the current Project, we have already measured epigenetic marks (i.e. DNA methylation) on a genome-wide level in girls participating in a psychotherapy-trial for anorexia nervosa. We want to compare our findings to the data from girls participating in the ALSPAC study that show no signs of an eating disorder.

Lipoproteins such as high density lipoprotein (HDL) and low density lipoprotein (LDL) are commonly studied in both epidemiological and genetic studies. However, their simple classification undermines the complexity of these lipoproteins with respect to size, composition and roles in metabolic pathways. For example, results for the association between HDL and coronary heart disease (CHD) are mixed with regards to the direction of effect. Conversely, the association between genetic variants associated with LDL and CHD appear to be much more uniform. Therefore, If HDL is to be regarded as a valid biomarker for drug targets, all genetic variants associated with HDL should have a corresponding consistent effect.
To date, studies may lack power to determine the effect of HDL on CHD. In addition, HDL-C as conventionally measured may not be sufficient biomarker to allow associations to be revealed. Therefore, before discarding the potential of the HDL to CHD, it is worth considering additional biomarkers that better characterise the full complexity of the pathway.
This new project is based on using genetic variants residing in genes associated with HDL-C (as reported by the Global Lipid Consortium) and testing their association with HDL related NMR metabolites. In addition, we are extending our analyses to test the association between HDL related genetic variants and scores developed from HDL metabolites which were generated using factor analysis, in order to determine whether any consistencies exist between the direction of effect and factors of HDL metabolites.