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Autism spectrum disorder (ASD) is a heterogeneous group of early-onset neurodevelopmental disorders known to be highly heritable with a complex genetic architecture. Abnormal brain developmental trajectories that impact synaptic functioning, excitation-inhibition balance and brain connectivity are now understood to play a central role in ASD. Ongoing efforts to identify the genetic underpinnings still prove challenging, in part due to phenotypic and genetic heterogeneity.This review focuses on parent-of-origin effects (POEs), where the phenotypic effect of an allele depends on its parental origin. POEs include genomic imprinting, transgenerational effects, mitochondrial DNA, sex chromosomes and mutational transmission bias. The motivation for investigating these mechanisms in ASD has been driven by their known impacts on early brain development and brain functioning, in particular for the most well-documented POE, genomic imprinting. Moreover, imprinting is implicated in syndromes such as Angelman and Prader-Willi, which frequently share comorbid symptoms with ASD. In addition to other regions in the genome, this comprehensive review highlights the 15q11-q13 and 7q chromosomal regions as well as the mitochondrial DNA as harbouring the majority of currently identified POEs in ASD.

Nanophotonic materials offer spectral and directional control over thermal emission, but in high-temperature oxidizing environments, their stability remains low. This limits their applications in technologies such as solid-state energy conversion and thermal barrier coatings. Here we show an epitaxial heterostructure of perovskite BaZr

Background Physical inactivity increases the risk of chronic disease and mortality. The high prevalence of physical inactivity in the UK is likely to increase financial pressure on the National Health Service. The UK Biobank Study offered an opportunity to assess the impact of physical inactivity on healthcare use and spending using individual-level data and objective measures of physical activity. The objective of this study was to assess the associations between objectively measured physical activity levels and future inpatient days and costs in adults in the UK Biobank study. Methods We conducted an econometric analysis of the UK Biobank study, a large prospective cohort study. The participants (n = 86,066) were UK adults aged 43–79 who had provided sufficient valid accelerometer data. Hospital inpatient days and costs were discounted and standardised to mean monthly values per person to adjust for the variation in follow-up times. Econometric models adjusted for BMI, long-standing illness, and other sociodemographic factors. Results Mean follow-up time for the sample was 28.11 (SD 7.65) months. Adults in the most active group experienced 0.037 fewer days per month (0.059–0.016) and 14.1% lower inpatient costs ( – £3.81 [ – £6.71 to – £0.91] monthly inpatient costs) compared to adults in the least active group. The relationship between physical activity and inpatient costs was stronger in women compared to men and amongst those in the lowest income group compared to others. The findings remained significant across various sensitivity analyses. Conclusions Increasing physical activity levels in the UK may reduce inpatient hospitalisations and costs, especially in women and lower-income groups.

Indigenous ways of caring for the environment have long been marginalised through research methodologies that are blind to a range of ways of knowing the world. Co-production of knowledge across Indigenous knowledge systems and Western scientific approaches is receiving attention both internationally and within the science system in Aotearoa New Zealand. Addressing power asymmetries as part of the co-production process is also slowly gaining recognition. Those involved in knowledge co-production initiatives must support learning about different world views, ways of knowing and accounting for the environment, while also enabling learning of the many biases and assumptions built into methodologies. This deliberation is needed, so non-Indigenous researchers can form enduring trustworthy partnerships and contribute to co-production initiatives. Presented here are insights shared by a cohort of environment research practitioners who have been deliberating on co-production occurring across knowledge systems in Aotearoa New Zealand. Originating from analysis of interviews undertaken about relationships recreational groups have with Te Urewera (forested hill country in the North Island of Aotearoa New Zealand), this paper depicts a layered reflection on how non-Māori (primarily but not exclusively) across Aotearoa New Zealand are learning to be manuhiri (those being welcomed on arrival to a place by the Indigenous people of that place). As a contribution to this collective learning, a set of methodological sensitivities are proposed as support for research amidst changing relationships with places. Doing so we aim to contribute to reflexive and decolonising encounters with Indigenous approaches to environmental care.

Musculoskeletal conditions, including fractures, can have severe and long-lasting consequences. Higher body mass index in adulthood is widely acknowledged to be protective for most fracture sites. However, sources of bias induced by confounding factors may have distorted previous findings. Employing a lifecourse Mendelian randomisation (MR) approach by using genetic instruments to separate effects at different life stages, this investigation aims to explore how prepubertal and adult body size independently influence fracture risk in later life.Using data from a large prospective cohort, univariable and multivariable MR were conducted to simultaneously estimate the effects of age-specific genetic proxies for body size (n = 453,169) on fracture risk (n = 416,795). A two-step MR framework was additionally applied to elucidate potential mediators. Univariable and multivariable MR indicated strong evidence that higher body size in childhood reduced fracture risk (OR, 95% CI: 0.89, 0.82 to 0.96, P = 0.005 and 0.76, 0.69 to 0.85, P = 1 × 10− 6, respectively). Conversely, higher body size in adulthood increased fracture risk (OR, 95% CI: 1.08, 1.01 to 1.16, P = 0.023 and 1.26, 1.14 to 1.38, P = 2 × 10− 6, respectively). Two-step MR analyses suggested that the effect of higher body size in childhood on reduced fracture risk was mediated by its influence on higher estimated bone mineral density (eBMD) in adulthood.This investigation provides novel evidence that higher body size in childhood reduces fracture risk in later life through its influence on increased eBMD. From a public health perspective, this relationship is complex since obesity in adulthood remains a major risk factor for co-morbidities. Results additionally indicate that higher body size in adulthood is a risk factor for fractures. Protective effect estimates previously observed are likely attributed to childhood effects.

Ceramic objects account for over 90% of the cultural material recovered from archaeological sites in the Caribbean. However, little research has been conducted on molecular evidence for past food production from these same vessels. Forty ceramic sherds from Isla de Mona have been analysed by GC–MS and GC-C-IRMS in order to address questions surrounding foodways in the Greater Antilles prior to and post European arrival. We evaluate evidence for dietary changes to illuminate aspects of cultural exchange between Indigenous populations and the first generations of Spanish colonists. Here, we show that plant residues are found in a variety of pottery forms, with some evidence for non-ruminant and ruminant fats. The dearth of marine biomarkers is curious given the volume of fish bones found in archaeological contexts on Isla de Mona and may offer evidence for spit-roasting, pit-roasting, or the use of a ‘barbacoa’ to cook fish on the island. The ubiquity of plant residues in a variety of pottery forms may relate to the large-scale cultivation and export of cassava (Manihot esculenta) from the island. A Spanish olive jar revealed evidence of wine residues, which may constitute the earliest detection of wine residues in pottery found in the Americas.

Quantitative measures are available for adult videofluoroscopic swallow study (VFSS) analysis but are yet to be seen routinely in clinical practice. This study explores agreement between traditional observational analysis and quantitative analysis, and the impact of analytical approaches on subsequent diagnosis and recommendations. One hundred adults referred for VFSSs with swallowing concerns were administered a standardised VFSS protocol. All VFSSs were analysed using three approaches: (1) a traditional observational analysis typically used by treating speech-language pathologists (SLPs), (2) quantitative analysis by two independent raters, and (3) binary subjective analysis by 11 independent raters. Three metrics were focussed on; pharyngeal constriction (PC), hyoid displacement (Hmax) and pharyngoesophageal segment opening (PESmax). All raters were blinded to others’ ratings. Treating SLPs using traditional observational analysis were provided with no instructions. Quantitative analysis used published Leonard and Kendall digital displacement measures. Binary subjective analysis involved rating each VFSS as normal versus impaired for the three metrics above. Treating SLPs using traditional observational analysis and quantitative analysis raters independently provided diagnostics and treatment plans. PC, Hmax and PESmax achieved fair agreement (Kappa = 0.33–0.36) between binary subjective analysis compared to substantial agreement (ICC = 0.77–0.94) for quantitative analysis. Reports of impairment were significantly lower in the traditional observational and binary subjective analyses compared with studies rated using the quantitative analysis (p

Background Minimising the effects of unconscious bias in selection for clinical academic training is essential to ensure that allocation of training posts is based on merit. We looked at the effect of anonymising applications to a training programme for junior doctors on the scores of the applications and on gender balance; and whether female candidates were more likely to seek gender-concordant mentors. Methods Applications to the training programme were reviewed and scored independently by reviewers who received either an anonymised or named copy. Scores were compared using a paired t-test, and differences in scores compared by gender. The gender of named supervisors for male and female candidates was compared. Results Scores of 101 applications were reviewed. When their identity was known, male candidates scored 1.72% higher and female candidates scored 0.74% higher, but these findings were not statistically significant (p value = 0.279 and 0.579). Following introduction of anonymisation, the proportion of successful female candidates increased from 27 to 46%. Female candidates were more likely to name a female supervisor compared to male (41% vs. 25% of supervisors). Conclusions Anonymising applications did not significantly change scores, although gender balance improved. Gender-concordant mentoring initiatives should consider effects on mentors as well as mentees.

This work introduces a scaling analysis of sub-aerial axisymmetric column collapses of glass beads and Newtonian glycerol-water solutions mimicking some of the behaviours of debris flows. The beads were in a size range where their inertia partly decouples their collapse behaviour from the water column. Experiments explored a range of viscous, surface tension and particle inertia effects through systematic variation of particle size and fluid viscosity. Crucially a geotechnical centrifuge was used to access elevated effective gravitational accelerations driving the collapse, allowing field-scale viscous and surface tension effects to be replicated. Temporal pore pressure and run out front position evolution data was extracted using a pressure transducer and high speed imaging, respectively. A least-squares fitted scale analysis demonstrated that all characteristic dimensionless quantities of the acceleration phase could be described as a function of the column-scale Bond number $$\text{ Bo }$$ Bo , the Capillary number $$\text{ Ca }$$ Ca , the system size $$r^*$$ r ∗ , and the grain-fluid density ratio $$\rho ^*$$ ρ ∗ . This analysis demonstrated that collapses as characterised by pore pressure evolution and front positions were controlled by the ratio of $$\text{ Bo}/\text{Ca}$$ Bo / Ca . This indicates that grain-scale surface tension effects are negligible in such inertial column collapses where they may dominate laboratory-scale granular-fluid flow behaviour where geometric similarity between grain and system size is preserved. Graphical abstract

Emotional/behaviour problems and exposure to stressful life events are thought to contribute to new onset of urinary incontinence (UI) amongst children who have attained bladder control. However, very few prospective studies have examined these associations. We assessed whether mental health problems and stressful life events were associated with subsequent new onset in UI using multivariable logistic regression in a prospective UK cohort (n = 6408). Mothers provided information on their child’s symptoms of common mental disorders (Development and Wellbeing Assessment, 7 years), stressful life events (7–8 years) and wetting (day and night, 9 years). There was strong evidence that separation anxiety symptoms were associated with new-onset UI in the fully adjusted model (OR (95% CI) = 2.08 (1.39, 3.13), p p = 0.065), such that females experiencing more stressful life events were at higher risk of new-onset UI (fully adjusted model OR (95% CI) = 1.66 (1.05, 2.61), p = 0.029), but there was no association in males (fully adjusted model OR (95% CI) = 0.87 (0.52, 1.47), p = 0.608). These results suggest that separation anxiety and stressful life events in girls may lead to an increase in UI.