Human adolescent brain similarity development is different for paralimbic versus neocortical zones.

Adolescent development of human brain structural and functional networks is increasingly recognized as fundamental to emergence of typical and atypical adult cognitive and emotional proodal magnetic resonance imaging (MRI) data collected from N [Formula: see text] 300 healthy adolescents (51%; female; 14 to 26 y) each scanned repeatedly in an accelerated longitudinal design, to provide an analyzable dataset of 469 structural scans and 448 functional MRI scans. We estimated the morphometric similarity between each possible pair of 358 cortical areas on a feature vector comprising six macro- and microstructural MRI metrics, resulting in a morphometric similarity network (MSN) for each scan. Over the course of adolescence, we found that morphometric similarity increased in paralimbic cortical areas, e.g., insula and cingulate cortex, but generally decreased in neocortical areas, and these results were replicated in an independent developmental MRI cohort (N [Formula: see text] 304). Increasing hubness of paralimbic nodes in MSNs was associated with increased strength of coupling between their morphometric similarity and functional connectivity. Decreasing hubness of neocortical nodes in MSNs was associated with reduced strength of structure-function coupling and increasingly diverse functional connections in the corresponding fMRI networks. Neocortical areas became more structurally differentiated and more functionally integrative in a metabolically expensive process linked to cortical thinning and myelination, whereas paralimbic areas specialized for affective and interoceptive functions became less differentiated, as hypothetically predicted by a developmental transition from periallocortical to proisocortical organization of the cortex. Cytoarchitectonically distinct zones of the human cortex undergo distinct neurodevelopmental programs during typical adolescence.

Neuroinflammation is linked to dementia risk in Parkinson's disease.

The development of dementia is a devastating aspect of Parkinson's disease (PD), affecting nearly half of patients within 10 years post-diagnosis. For effective therapies to prevent and slow progression to PD dementia (PDD), the key mechanisms that determine why some people with PD develop early dementia, while others remain cognitively unaffected, need to be understood. Neuroinflammation and tau protein accumulation have been demonstrated in post-mortem PD brains, and in many other neurodegenerative disorders leading to dementia. However, whether these processes mediate dementia risk early on in the PD disease course is not established. To this end, we used PET neuroimaging with 11C-PK11195 to index neuroinflammation and 18F-AV-1451 for misfolded tau in early PD patients, stratified according to dementia risk in our 'Neuroinflammation and Tau Accumulation in Parkinson's Disease Dementia' (NET-PDD) study. The NET-PDD study longitudinally assesses newly-diagnosed PD patients in two subgroups at low and high dementia risk (stratified based on pentagon copying, semantic fluency, MAPT genotype), with comparison to age- and sex-matched controls. Non-displaceable binding potential (BPND) in 43 brain regions (Hammers' parcellation) was compared between groups (pairwise t-tests), and associations between BPND of the tracers tested (linear-mixed-effect models). We hypothesized that people with higher dementia risk have greater inflammation and/or tau accumulation in advance of significant cognitive decline. We found significantly elevated neuroinflammation (11C-PK11195 BPND) in multiple subcortical and restricted cortical regions in the high dementia risk group compared with controls, while in the low-risk group this was limited to two cortical areas. The high dementia risk group also showed significantly greater neuroinflammation than the low-risk group concentrated on subcortical and basal ganglia regions. Neuroinflammation in most of these regions was associated with worse cognitive performance (Addenbrooke's Cognitive Examination-III score). Overall neuroinflammation burden also correlated with serum levels of pro-inflammatory cytokines. In contrast, increases in 18F-AV-1451 (tau) BPND in PD versus controls were restricted to subcortical regions where off-target binding is typically seen, with no relationship to cognition found. Whole-brain 18F-AV-1451 burden correlated with serum phosphorylated tau181 levels. Although there was minimal regional tau accumulation in PD, regional neuroinflammation and tau burden correlated in PD participants, with the strongest association in the high dementia risk group, suggesting possible co-localization of these pathologies. In conclusion, our findings suggest that significant regional neuroinflammation in early PD might underpin higher risk for PDD development, indicating neuroinflammation as a putative early modifiable aetiopathological disease factor to prevent or slow dementia development using immunomodulatory strategies.

Mental health in the COVID-19 pandemic: A longitudinal analysis of the CLoCk cohort study.

BACKGROUND: Little is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP's mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP's mental health trajectories. METHODS AND FINDINGS: A matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (B = 0.11 (per month), 95% CI = 0.09 to 0.12, p < 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (B = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; pinteraction = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias. CONCLUSIONS: Overall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.

Review of weighted exponential random graph models frameworks applied to neuroimaging.

Neuro-imaging data can often be represented as statistical networks, especially for functional magnetic resonance imaging (fMRI) data, where brain regions are defined as nodes and the functional interactions between those regions are taken as edges. Such networks are commonly divided into classes depending on the type of edges, namely binary or weighted. A binary network means edges can either be present or absent. Whereas the edges of a weighted network are associated with weight values, and fMRI networks belong to weighted networks. Statistical methods are often adopted to analyse such networks, among which, the exponential random graph model (ERGM) is an important network analysis approach. Typically ERGMs are applied to binary networks, and weighted networks often need to be binarised by arbitrarily selecting a threshold value to define the presence of the edges, which can lead to non-robustness and loss of valuable edge weight information representing the strength of fMRI interaction in fMRI networks. While it is therefore important to gain deeper insight in adopting ERGM on weighted networks, there only exists a few different ERGM frameworks for weighted networks; some of these are not directly implementable on fMRI networks based on their original proposal. We systematically review, implement, analyse and compare five such frameworks via a simulation study and provide guidelines on each modelling framework as well as conclude the suitability of them on fMRI networks based on a range of criteria. We concluded that Multi-Layered ERGM is currently the most suitable framework.

Risk of new onset and persistent psychopathology in children with long-term physical health conditions: a population-based cohort study.

Children and young people (CYP) with long-term physical health conditions (pLTCs) have increased risk of psychopathology compared to physically healthier peers. We explored risk factors for new onset and persistent psychiatric disorders in CYP with pLTCs compared to CYP without pLTCs. This 3-year follow-up study involved a UK representative sample of CYP from the British Child and Adolescent Mental Health Surveys (N = 7804). We examined potential baseline predictors of new onset and persistent psychiatric disorders at follow-up in four groups of children based on the presence of any physical and/or any psychiatric conditions at baseline. Psychiatric disorders were assessed using standardised multi-informant diagnostic assessment. Separate multivariable binary logistic regressions were conducted for each group. In CYP with pLTCs, rented housing (aOR = 1.42, 95% CI 1.01 to 1.99), non-traditional family structure (aOR = 2.08, 95% CI 1.42 to 3.05), increased parental distress (aOR = 1.09, 95% CI 1.04 to 1.14), and greater peer relationship difficulties (aOR = 1.29, 95% CI 1.19 to 1.39) predicted future psychiatric disorder. Only peer relationship difficulties predicted persistent disorder (aOR = 1.27, 95% CI 1.17 to 1.38) in this group. A greater number of factors predicted the onset of psychiatric disorder in CYP with pLTCs compared to physically healthier peers and similarly, a higher number of factors predicted persistent disorder in CYP without pLTCs. CYP with pLTCs might comprise a group with different vulnerabilities, some of which are potentially tractable and may be useful indicators of patients who require preventable or management interventions.

Brain Growth Charts for Quantitative Analysis of Pediatric Clinical Brain MRI Scans with Limited Imaging Pathology.

Background Clinically acquired brain MRI scans represent a valuable but underused resource for investigating neurodevelopment due to their technical heterogeneity and lack of appropriate controls. These barriers have curtailed retrospective studies of clinical brain MRI scans compared with more costly prospectively acquired research-quality brain MRI scans. Purpose To provide a benchmark for neuroanatomic variability in clinically acquired brain MRI scans with limited imaging pathology (SLIPs) and to evaluate if growth charts from curated clinical MRI scans differed from research-quality MRI scans or were influenced by clinical indication for the scan. Materials and Methods In this secondary analysis of preexisting data, clinical brain MRI SLIPs from an urban pediatric health care system (individuals aged ≤22 years) were scanned across nine 3.0-T MRI scanners. The curation process included manual review of signed radiology reports and automated and manual quality review of images without gross pathology. Global and regional volumetric imaging phenotypes were measured using two image segmentation pipelines, and clinical brain growth charts were quantitatively compared with charts derived from a large set of research controls in the same age range by means of Pearson correlation and age at peak volume. Results The curated clinical data set included 532 patients (277 male; median age, 10 years [IQR, 5-14 years]; age range, 28 days after birth to 22 years) scanned between 2005 and 2020. Clinical brain growth charts were highly correlated with growth charts derived from research data sets (22 studies, 8346 individuals [4947 male]; age range, 152 days after birth to 22 years) in terms of normative developmental trajectories predicted by the models (median r = 0.979). Conclusion The clinical indication of the scans did not significantly bias the output of clinical brain charts. Brain growth charts derived from clinical controls with limited imaging pathology were highly correlated with brain charts from research controls, suggesting the potential of curated clinical MRI scans to supplement research data sets. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ertl-Wagner and Pai in this issue.

Modelling count, bounded and skewed continuous outcomes in physical activity research: beyond linear regression models.

BACKGROUND: Inference using standard linear regression models (LMs) relies on assumptions that are rarely satisfied in practice. Substantial departures, if not addressed, have serious impacts on any inference and conclusions; potentially rendering them invalid and misleading. Count, bounded and skewed outcomes, common in physical activity research, can substantially violate LM assumptions. A common approach to handle these is to transform the outcome and apply a LM. However, a transformation may not suffice. METHODS: In this paper, we introduce the generalized linear model (GLM), a generalization of the LM, as an approach for the appropriate modelling of count and non-normally distributed (i.e., bounded and skewed) outcomes. Using data from a study of physical activity among older adults, we demonstrate appropriate methods to analyse count, bounded and skewed outcomes. RESULTS: We show how fitting an LM when inappropriate, especially for the type of outcomes commonly encountered in physical activity research, substantially impacts the analysis, inference, and conclusions compared to a GLM. CONCLUSIONS: GLMs which more appropriately model non-normally distributed response variables should be considered as more suitable approaches for managing count, bounded and skewed outcomes rather than simply relying on transformations. We recommend that physical activity researchers add the GLM to their statistical toolboxes and become aware of situations when GLMs are a better method than traditional approaches for modeling count, bounded and skewed outcomes.

Trends in comorbid physical and mental health conditions in children from 1999 to 2017 in England.

INTRODUCTION: Children with long-term physical health conditions (pLTCs) are at increased risk of mental health conditions but less is known about time trends in the mental health of this group of children. METHODS: We used data from three comparable, population-based surveys of children conducted in 1999, 2004, and 2017. We examined whether the proportion of children aged 5-15 years old with comorbid mental health conditions (measured using the multi-informant Development and Well-being Assessment tool) and pLTCs (measured using parental report) in England increased from 1999 to 2017 using linear regression analysis. RESULTS: Our analysis used data from 8662 (1999), 6401 (2004) and 6219 (2017) children, respectively. The proportion of children with comorbid pLTCs and psychiatric disorders was 0.050 (95% CI = 0.045, 0.055) in 1999, 0.054 (95% CI = 0.049, 0.060) in 2004, and 0.059 (95% CI = 0.053, 0.065) in 2017. The linear regression model revealed a non-significant effect of time on the proportion of children with comorbid pLTCs and psychiatric disorders from 1999 to 2017 (B = 0.0004785; SE = 0.0001256; p = 0.163). CONCLUSION: The estimated prevalence of school-aged children with comorbid pLTCs and mental health conditions in England remained stable since 1999, highlighting the need to prioritize mental health resources for children with physical health comorbidities.

Predictors of contact with services for mental health problems among children with comorbid long-term physical health conditions: a follow-up study.

Children with long-term physical health conditions (pLTCs) are at increased risk of developing mental health comorbidities, although most do not access services for their mental health. No previous studies have examined the determinants of contact with services for mental health concerns among this group of children. This 3-year longitudinal study involved a population-based sample of children aged 5-16 years from the British Child and Adolescent Mental Health Surveys conducted in 1999 and 2004. In children with comorbid pLTCs and mental health disorders at baseline (N = 397), we examined associations between several child-, family- and service-related factors and (a) contact with primary health care, (b) contact with paediatrics and (c) contact with child and adolescent mental health services over 3-year follow-up (2002 and 2007). Separate multivariable binary logistic regressions were conducted for each service. The impact of mental health difficulties on the child and contact with the teacher predicted contact with all three services. Adolescent age, female gender, larger family size, some or marked academic difficulties, and having parents with educational qualification(s) were specific predictors of contact with primary health care. Male gender, stressful life events, and contact with primary health care were specific predictors of contact with child and adolescent mental health services. No other factors predicted contact with paediatrics. Our findings highlight the role of child-, family-, and service-related factors in accessing mental health care in children with comorbid pLTCs and mental health disorders which could inform planning and provision of services to reduce unmet mental health needs.

The use and misuse of ratio and proportion exposure measures in food environment research.

BACKGROUND: The food stores within residential environments are increasingly investigated as a possible mechanism driving food behaviours and health outcomes. Whilst increased emphasis is being placed on the type of study designs used and how we measure the outcomes, surprisingly little attention gets diverted to the measures of the food environment beyond calls for standardised approaches for food store coding and geographic scales of exposure. Food environments are a challenging concept to measure and model and the use of ratio and proportion measures are becoming more common in food environment research. Whilst these are seemingly an advance on single store type indicators, such as simply counting the number of supermarkets or fast food restaurants present, they have several limitations that do not appear to have been fully considered. MAIN BODY: In this article we report on five issues related to the use of ratio and proportion food environment measures: 1) binary categorisation of food stores; 2) whether they truly reflect a more or less healthy food environment; 3) issues with these measures not reflecting the quantity of food stores; 4) difficulties when no stores are present; and 5) complications in statistical treatment and interpretation of ratio and proportion measures. Each of these issues are underappreciated in the literature to date and highlight that ratio and proportion measures need to be treated with caution. CONCLUSION: Calls for the broader adoption of relative food environment measures may be misguided. Whilst we should continue to search for better ways to represent the complexity of food environments, ratio and proportion measures are unlikely to be the answer.

Methods for accounting for neighbourhood self-selection in physical activity and dietary behaviour research: a systematic review.

BACKGROUND: Self-selection into residential neighbourhoods is a widely acknowledged, but under-studied problem in research investigating neighbourhood influences on physical activity and diet. Failure to handle neighbourhood self-selection can lead to biased estimates of the association between the neighbourhood environment and behaviour. This means that effects could be over- or under-estimated, both of which have implications for public health policies related to neighbourhood (re)design. Therefore, it is important that methods to deal with neighbourhood self-selection are identified and reviewed. The aim of this review was to assess how neighbourhood self-selection is conceived and accounted for in the literature. METHODS: Articles from a systematic search undertaken in 2017 were included if they examined associations between neighbourhood environment exposures and adult physical activity or dietary behaviour. Exposures could include any objective measurement of the built (e.g., supermarkets), natural (e.g., parks) or social (e.g., crime) environment. Articles had to explicitly state that a given method was used to account for neighbourhood self-selection. The systematic review was registered with the PROSPERO International Prospective Register of Systematic Reviews (number CRD42018083593) and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Of 31 eligible articles, almost all considered physical activity (30/31); few examined diet (2/31). Methods used to address neighbourhood self-selection varied. Most studies (23/31) accounted for items relating to participants' neighbourhood preferences or reasons for moving to the neighbourhood using multi-variable adjustment in regression models (20/23) or propensity scores (3/23). Of 11 longitudinal studies, three controlled for neighbourhood self-selection as an unmeasured confounder using fixed effects regression. CONCLUSIONS: Most studies accounted for neighbourhood self-selection by adjusting for measured attributes of neighbourhood preference. However, commonly the impact of adjustment could not be assessed. Future studies using adjustment should provide estimates of associations with and without adjustment for self-selection; consider temporality in the measurement of self-selection variables relative to the timing of the environmental exposure and outcome behaviours; and consider the theoretical plausibility of presumed pathways in cross-sectional research where causal direction is impossible to establish.

Waves of Maturation and Senescence in Micro-structural MRI Markers of Human Cortical Myelination over the Lifespan.

Seminal human brain histology work has demonstrated developmental waves of myelination. Here, using a micro-structural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle. In 484 participants, aged 8-85 years, we fitted smooth growth curves to T1- to T2-weighted ratio in each of 360 regions from one of seven cytoarchitectonic classes. From the first derivatives of these generally inverted-U trajectories, we defined three milestones: the age at peak growth; the age at onset of a stable plateau; and the age at the onset of decline. Age at peak growth had a bimodal distribution comprising an early (pre-pubertal) wave of primary sensory and motor cortices and a later (post-pubertal) wave of association, insular and limbic cortices. Most regions reached stability in the 30-s but there was a second wave reaching stability in the 50-s. Age at onset of decline was also bimodal: in some right hemisphere regions, the curve declined from the 60-s, but in other left hemisphere regions, there was no significant decline from the stable plateau. These results are consistent with regionally heterogeneous waves of intracortical myelinogenesis and age-related demyelination.

Long-term cognitive outcome in adult survivors of an early childhood posterior fossa brain tumour.

PURPOSE: Posterior fossa brain tumours (PFT) and their treatment in young children are often associated with subsequent cognitive impairment. However, reported follow-up periods rarely exceed 10 years. This study reports very long-term cognitive consequences of surviving an early childhood PFT. METHODS: 62 adult survivors of a PFT, ascertained from a national register, diagnosed before 5 years of age, and a sibling control, received a single IQ assessment an average of 32 years (range 18-53) after initial diagnosis, using the Weschler Abbreviated Scale of Intelligence. Regression models were fitted to survivor-sibling pair differences on verbal and performance IQ (VIQ and PIQ) scores to investigate whether increasing time between PFT diagnosis and follow-up IQ assessment contributed to survivor-sibling IQ differences. RESULTS: At follow-up, survivors had, on average, VIQ 15 points and PIQ 19 points lower than their siblings. There was no significant effect of time since diagnosis on survivor-sibling VIQ difference. Survivors who received radiotherapy showed no significant effect of time since diagnosis on survivor-sibling PIQ difference. Survivors who did not receive radiotherapy demonstrated a trend for it to reduce. CONCLUSIONS: VIQ and PIQ deficits persist in adulthood, suggesting the effect of a fixed injury imposing on cognitive development, rather than an ongoing pathological process. IMPLICATIONS FOR CANCER SURVIVORS: The findings will help parents and others supporting survivors of an early life PFT to identify and plan for possible cognitive outcomes, and highlight the importance of early interventions to optimize cognitive function during the developmental period.

Modeling the initiation of others into injection drug use, using data from 2,500 injectors surveyed in Scotland during 2008-2009.

The prevalence of injection drug use has been of especial interest for assessment of the impact of blood-borne viruses. However, the incidence of injection drug use has been underresearched. Our 2-fold aim in this study was to estimate 1) how many other persons, per annum, an injection drug user (IDU) has the equivalent of full responsibility (EFR) for initiating into injection drug use and 2) the consequences for IDUs' replacement rate. EFR initiation rates are strongly associated with incarceration history, so that our analysis of IDUs' replacement rate must incorporate when, in their injecting career, IDUs were first incarcerated. To do so, we have first to estimate piecewise constant incarceration rates in conjunction with EFR initiation rates, which are then combined with rates of cessation from injecting to model IDUs' replacement rate over their injecting career, analogous to the reproduction number of an epidemic model. We apply our approach to Scotland's IDUs, using over 2,500 anonymous injector participants who were interviewed in Scotland's Needle Exchange Surveillance Initiative during 2008-2009. Our approach was made possible by the inclusion of key questions about initiations. Finally, we extend our model to include an immediate quit rate, as a reasoned compensation for higher-than-expected replacement rates, and we estimate how high initiates' quit rate should be for IDUs' replacement rate to be 1.

Categorisation of built environment characteristics: the trouble with tertiles.

BACKGROUND: In the analysis of the effect of built environment features on health, it is common for researchers to categorise built environment exposure variables based on arbitrary percentile cut-points, such as median or tertile splits. This arbitrary categorisation leads to a loss of information and a lack of comparability between studies since the choice of cut-point is based on the sample distribution. DISCUSSION: In this paper, we highlight the various drawbacks of adopting percentile categorisation of exposure variables. Using data from the SocioEconomic Status and Activity in Women (SESAW) study from Melbourne, Australia, we highlight alternative approaches which may be used instead of percentile categorisation in order to assess built environment effects on health. We discuss these approaches using an example which examines the association between the number of accessible supermarkets and body mass index. We show that alternative approaches to percentile categorisation, such as transformations of the exposure variable or factorial polynomials, can be implemented easily using standard statistical software packages. These procedures utilise all of the available information available in the data, avoiding a loss of power as experienced when categorisation is adopted.We argue that researchers should retain all available information by using the continuous exposure, adopting transformations where necessary.

Same sex-attraction as a predictor of suicide and self-harm behaviours: The role of bullying and social support.

Sexual minority youth are at higher risk of self-harming than heterosexual adolescents. Understanding why sexual minority youth are more vulnerable to poor mental health and identifying factors that might buffer against this risk is important for developing targeted interventions. We used the Millennium Cohort Study to investigate whether same-sex attraction at age 14 is associated with suicide attempts and self-harm at age 17. Additionally, we tested whether bullying victimisation might mediate any observed associations, and whether social support might protect against any increased risk. Sexual minority youth were 2.44 times more likely to attempt suicide and 2.59 times more likely to self-harm aged 17. There was no evidence for an association between greater social support and lower levels of self-harm. However, greater social support in sexual minority youth is associated with reduced risk for suicide attempt. Bullying partially mediated the relationship between same-sex attraction and mental health. Greater levels in bullying in sexual minority youth were associated with 1.32 times higher risk for suicide and 1.30 times higher risk for self-harm. Social support was not associated with reduced risk of suicide attempt or self-harm among bullied sexual minority youth. Sexual minority youth in the UK are at higher risk for suicide attempt and self-harm. To address this disparity, health and educational practitioners should understand this heightened risk for poor mental health, and address bullying as one risk factor. Further interventions are needed to assist sexual minority youth beyond social support provision through friends and family.

Bayesian profile regression for clustering analysis involving a longitudinal response and explanatory variables.

The identification of sets of co-regulated genes that share a common function is a key question of modern genomics. Bayesian profile regression is a semi-supervised mixture modelling approach that makes use of a response to guide inference toward relevant clusterings. Previous applications of profile regression have considered univariate continuous, categorical, and count outcomes. In this work, we extend Bayesian profile regression to cases where the outcome is longitudinal (or multivariate continuous) and provide PReMiuMlongi, an updated version of PReMiuM, the R package for profile regression. We consider multivariate normal and Gaussian process regression response models and provide proof of principle applications to four simulation studies. The model is applied on budding yeast data to identify groups of genes co-regulated during the Saccharomyces cerevisiae cell cycle. We identify 4 distinct groups of genes associated with specific patterns of gene expression trajectories, along with the bound transcriptional factors, likely involved in their co-regulation process.

Accelerating the domestication of a bioenergy crop: identifying and modelling morphological targets for sustainable yield increase in Miscanthus.

To accelerate domestication of Miscanthus, an important energy crop, 244 replicated genotypes, including two different species and their hybrids, were analysed for morphological traits and biomass yield over three growing seasons following an establishment phase of 2 years in the largest Miscanthus diversity trial described to date. Stem and leaf traits were selected that contributed both directly and indirectly to total harvested biomass yield, and there was variation in all traits measured. Morphological diversity within the population was correlated with dry matter yield (DMY) both as individual traits and in combination, in order to determine the respective contributions of the traits to biomass accumulation and to identify breeding targets for yield improvement. Predictive morphometric analysis was possible at year 3 within Miscanthus sinensis genotypes but not between M. sinensis, Miscanthus sacchariflorus, and interspecific hybrids. Yield is a complex trait, and no single simple trait explained more than 33% of DMY, which varied from 1 to 5297 g among genotypes within this trial. Associating simple traits increased the power of the morphological data to predict yield to 60%. Trait variety, in combination, enabled multiple ideotypes, thereby increasing the potential diversity of the crop for multiple growth locations and end uses. Both triploids and interspecific hybrids produced the highest mature yields, indicating that there is significant heterosis to be exploited within Miscanthus that might be overlooked in early selection screens within years 1-3. The potential for optimizing biomass yield by selecting on the basis of morphology is discussed.

Fetal alcohol syndrome in the UK.

OBJECTIVE: To determine the incidence of fetal alcohol syndrome (FAS) in the UK in children aged 0-16 years. DESIGN: Active surveillance was undertaken through the British Paediatric Surveillance Unit between October 2018 and October 2019 inclusive. Data were collected from reporting clinicians using standardised questionnaires. PATIENTS: Children aged 0-16 years in the UK and Ireland with a diagnosis of FAS seen in the previous month. This study did not include children with fetal alcohol spectrum disorder. MAIN OUTCOME MEASURES: Demographic details (including age and ethnicity), details of exposure, growth parameters, neurological and cognitive diagnoses, and service usage. RESULTS: 148 notifications were received. After exclusions and withdrawals, there were 10 confirmed and 37 probable cases (analysed together). Just 24 of these children were newly diagnosed with FAS during the surveillance period, giving an estimated incidence rate of 3.4/100 000 live births (95% CI 2.2 to 5.0); their median age at diagnosis was just over 5 years and they were diagnosed between 3 months and 14 years 3 months of age. CONCLUSIONS: The estimated incidence rate of FAS is lower than reported by similar studies and there was a wide variation in the age that cases were diagnosed. This, combined with the fact that many cases were notified and then withdrawn or excluded, suggests that in the UK there is a lack of consistency and certainty in diagnosing FAS. The study findings strongly support the need to educate key professionals involved in the care of infants and children at risk of FAS.

Does Having a Sibling Affect Autistic People's Empathy?

This study examined whether autistic people with siblings score higher on measures of empathy than those without siblings. Cohorts of autistic children (n = 939; mean age = 7.35 years (SD = 2.15)) and autistic adults (n = 736; mean age = 37 years (SD = 12.39)) from the Cambridge Autism Research Database (CARD) were each divided into two groups: with or without siblings. Empathy was measured using the children version of the Empathy Quotient (EQ) (parent-report) for children. For adults, the EQ (self-report version) and the Reading the Mind in the Eyes Test (RMET) were used. Contrary to the hypothesis, autistic children without siblings scored higher on EQ than those with siblings (t(283.70) = 4.20, p < .001; d = 0.50). In adults, there was no difference between autistic adults with and without siblings on both measures, but there was an interaction effect between sex and group on the RMET (f(1732) = 4.10, p = 0.04): whilst autistic males without siblings on average scored lower than females, autistic males with siblings on average performed similarly to females. Future research should investigate the possible effect of siblings on autistic males' empathy performance in a larger cohort of autistic individuals. Children's empathic abilities may be underestimated by their parents when they have siblings due to a contrast effect.