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Abstract Background Cerebrospinal fluid (CSF) dynamics are increasingly studied in aging and neurological disorders. Models of CSF-mediated waste clearance suggest that altered CSF dynamics could play a role in the accumulation of toxic waste in the CNS, with implications for Alzheimer’s disease and other proteinopathies. Therefore, approaches that enable quantitative and volumetric assessment of CSF flow velocities could be of value. In this study we demonstrate the feasibility of 4D flow MRI for simultaneous assessment of CSF dynamics throughout the ventricular system, and evaluate associations to arterial pulsatility, ventricular volumes, and age. Methods In a cognitively unimpaired cohort (N = 43; age 41–83 years), cardiac-resolved 4D flow MRI CSF velocities were obtained in the lateral ventricles (LV), foramens of Monro, third and fourth ventricles (V3 and V4), the cerebral aqueduct (CA) and the spinal canal (SC), using a velocity encoding (venc) of 5 cm/s. Cerebral blood flow pulsatility was also assessed with 4D flow (venc = 80 cm/s), and CSF volumes were obtained from T1- and T2-weighted MRI. Multiple linear regression was used to assess effects of age, ventricular volumes, and arterial pulsatility on CSF velocities. Results Cardiac-driven CSF dynamics were observed in all CSF spaces, with region-averaged velocity range and root-mean-square (RMS) velocity encompassing from very low in the LVs (RMS 0.25 ± 0.08; range 0.85 ± 0.28 mm/s) to relatively high in the CA (RMS 6.29 ± 2.87; range 18.6 ± 15.2 mm/s). In the regression models, CSF velocity was significantly related to age in 5/6 regions, to CSF space volume in 2/3 regions, and to arterial pulsatility in 3/6 regions. Group-averaged waveforms indicated distinct CSF flow propagation delays throughout CSF spaces, particularly between the SC and LVs. Conclusions Our findings show that 4D flow MRI enables assessment of CSF dynamics throughout the ventricular system, and captures independent effects of age, CSF space morphology, and arterial pulsatility on CSF motion.

Summary: Background: Early childcare attendance may be related to children's internalizing and externalizing symptoms throughout childhood and young adolescence, however evidence from Europe is limited. We aimed to assess this association across multiple population-based birth cohorts of children recruited in different European countries. Methods: Data come from six parent-offspring prospective birth cohort studies across five European countries within the EU Child Cohort Network. A total of 87,208 parent-child dyads were included in the study. To test associations between childcare attendance (centre-based or informal) anytime between ages 0 and 4 years and children's internalizing and externalizing symptoms in middle childhood and young adolescence (measured at: 5–6 years, 7–9 years, and 10–13 years) a two-stage individual participant data meta-analysis was implemented. Linear regression models were performed in each cohort separately; combined random-effects meta-analysis was then used to obtain overall association estimates. In secondary analyses, we tested interactions between childcare attendance and mother's post-partum depression, low education status, and the child's sex. Findings: Compared to children who were exclusively cared for by their parents prior to school entry, those who attended centre-based childcare had lower levels of internalizing symptoms in all age groups [5–6 years: β: −1.78 (95% CI: −3.39, −0.16); 7–9 years: β: −0.55 (95% CI: −0.88, −0.73); 10–13 years: β: −0.76 (95% CI: −1.15, −0.37)]. Children who attended informal childcare appeared to have elevated levels of internalizing symptoms between 7–9 and 10–13 years, respectively [β: 1.65 (95% CI: 1.25, 2.06); β: 1.25 (95% CI: 0.96, 1.54)]. Informal childcare attendance was also associated with increased levels of children's externalizing symptoms between 7–9 and 10–13 years, respectively [β: 2.84 (95% CI: 1.41, 4.26); β: 2.19 (95% CI: 0.54, 3.84)]. Interpretation: Early centre-based childcare is associated with decreased levels of children's internalizing symptoms compared to exclusive parental care. For informal childcare, opposite associations were observed. Overall, our results suggest that centre-based childcare attendance may be associated with slight positive impacts on children's emotional development and should be encouraged by public policies. In addition, children from socioeconomically disadvantaged families require special attention, as they may not sufficiently benefit from universal early childhood education and care (ECEC). Funding: This research was funded by the ERC Consolidator grant RESEDA (Horizon Europe, 101001420).

Summary: Background: Gut L-type enteroendocrine cells (EECs) are intestinal chemosensory cells that secrete satiety hormones GLP-1 and PYY in response to activation of G-protein coupled receptors (GPCRs) by luminal components of nutrient digestion and microbial fermentation. Regulator of G-protein Signaling (RGS) proteins are negative regulators of GPCR signaling. The expression profile of RGS in EECs, and their potential role in satiety hormone secretion and obesity is unknown. Methods: Transcriptomic profiling of RGS was completed in native colonic EECs was completed using single-cell RNA sequencing (scRNA-Seq) in lean and obesity, and human jejunal EECs with data obtained from a publicly available RNAseq dataset (GSE114853). RGS validation studies were completed using whole mucosal intestinal tissue obtained during endoscopy in 61 patients (n = 42 OB, n = 19 Lean); a subset of patients’ postprandial plasma was assayed for GLP-1 and PYY. Ex vivo human intestinal cultures and in vitro NCI–H716 cells overexpressing RGS9 were exposed to GLP-1 secretagogues in conjunction with a nonselective RGS-inhibitor and assayed for GLP-1 secretion. Findings: Transcriptomic profiling of colonic and jejunal enteroendocrine cells revealed a unique RGS expression profile in EECs, and further within GLP-1+ L-type EECs. In obesity the RGS expression profile was altered in colonic EECs. Human gut RGS9 expression correlated positively with BMI and negatively with postprandial GLP-1 and PYY. RGS inhibition in human intestinal cultures increased GLP-1 release from EECs ex vivo. NCI–H716 cells overexpressing RGS9 displayed defective nutrient-stimulated GLP-1 secretion. Interpretation: This study introduces the expression profile of RGS in human EECs, alterations in obesity, and suggests a role for RGS proteins as modulators of GLP-1 and PYY secretion from intestinal EECs. Funding: AA is supported by the NIH(C-Sig P30DK84567, K23 DK114460), a Pilot Award from the Mayo Clinic Center for Biomedical Discovery, and a Translational Product Development Fund from The Mayo Clinic Center for Clinical and Translational Science Office of Translational Practice in partnership with the University of Minnesota Clinical and Translational Science Institute.

Studies evaluating the benefits and risks of green spaces on children’s health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (β = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p

Background & aimsThere are limited prospective data on patients with type 2 diabetes mellitus (T2DM) specifically enrolled and systematically assessed for advanced fibrosis or cirrhosis due to non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to evaluate the prevalence of advanced fibrosis and cirrhosis in a prospectively recruited cohort of adults with T2DM.MethodsThis prospective study enrolled adults aged ≥50 years with T2DM, recruited from primary care or endocrinology clinics. Participants underwent a standardized clinical research visit with MRI-proton density fat fraction (MRI-PDFF), magnetic resonance elastography (MRE), vibration-controlled transient elastography (VCTE) and controlled-attenuation parameter. NAFLD was defined as MRI-PDFF ≥5% after exclusion of other liver diseases. Advanced fibrosis and cirrhosis were defined by established liver stiffness cut-off points on MRE or VCTE if MRE was not available.ResultsOf 524 patients screened, 501 adults (63% female) with T2DM met eligibility. The mean age and BMI were 64.6 (±8.1) years and 31.4 (±5.9) kg/m2, respectively. The prevalence of NAFLD, advanced fibrosis and cirrhosis was 65%, 14% and 6%, respectively. In multivariable adjusted models, adjusted for age and sex, obesity and insulin use were associated with increased odds of advanced fibrosis (odds ratio 2.50; 95% CI 1.38-4.54; p = 0.003 and odds ratio 2.71; 95% CI 1.33-5.50; p = 0.006, respectively). Among 29 patients with cirrhosis, two were found to have hepatocellular carcinoma and one patient had gallbladder adenocarcinoma.ConclusionUtilizing a uniquely well-phenotyped prospective cohort of patients aged ≥50 years with T2DM, we found that the prevalence of advanced fibrosis was 14% and that of cirrhosis was 6%. These data underscore the high risk of advanced fibrosis/cirrhosis in adults aged ≥50 years with T2DM.Impact and implicationsNon-alcoholic fatty liver disease (NAFLD) is common in patients with type 2 diabetes (T2DM), however, there are limited prospective data characterizing the prevalence of advanced fibrosis and cirrhosis using the most accurate non-invasive biomarkers of liver fat and fibrosis. We show that 14% of older adults with T2DM have advanced fibrosis and 6% have cirrhosis, which places them at risk for liver failure and liver cancer. Accurate prevalence rates and comparative analysis regarding the diagnostic accuracy of non-invasive tests in this population will guide the optimal screening strategy and future cost-effectiveness analyses. These results will inform future Hepatology and Endocrinology practice guidelines regarding NAFLD screening programs in older adults with T2DM.

There is considerable variability in developmental outcomes of children whose mothers experience depression. Few longitudinal studies have examined contributions of paternal involvement in the association between maternal postnatal depression (PND) and offspring development. We examined pathways from maternal PND at 8 weeks (Edinburgh Postnatal Depression Scale; total score) to offspring emotional and behavioral development at 7 years (Strengths and Difficulties Questionnaire; total score) through behavioral, affective, and cognitive dimensions of paternal involvement in a U.K.-based birth cohort (Avon Longitudinal Study of Parents and Children; n = 3,434). Analyses were adjusted for baseline confounders and paternal PND (Edinburgh Postnatal Depression Scale; total score) as an intermediate confounder. Maternal PND was strongly associated with offspring development, but this association was not mediated by the combination of all indirect pathways through various dimensions of paternal involvement. Only father--child conflict emerged as a risk factor for adverse offspring development and as a mediator in the association between maternal PND and offspring development (albeit the effect size was small). If found causal, interventions that reduce father-child conflict may reduce the risk of adverse development in offspring of mothers with PND.

The fruit surface is a critical first line of defense against environmental stress. Overlaying the fruit epidermis is the cuticle, comprising a matrix of cutin monomers and waxes that provides protection and mechanical support throughout development. The epidermal layer of the cucumber (Cucumis sativus L.) fruit also contains prominent lipid droplets, which have recently been recognized as dynamic organelles involved in lipid storage and metabolism, stress response, and the accumulation of specialized metabolites. Our objective was to genetically characterize natural variations for traits associated with the cuticle and lipid droplets in cucumber fruit. Phenotypic characterization and genome-wide association studies (GWAS) were performed using a resequenced cucumber core collection accounting for >96% of the allelic diversity present in the U.S. National Plant Germplasm System collection. The collection was grown in the field, and fruit were harvested at 16–20 days post-anthesis, an age when the cuticle thickness and the number and size of lipid droplets have stabilized. Fresh fruit tissue sections were prepared to measure cuticle thickness and lipid droplet size and number. The collection showed extensive variation for the measured traits. GWAS identified several QTLs corresponding with genes previously implicated in cuticle or lipid biosynthesis, including the transcription factor SHINE1/WIN1, as well as suggesting new candidate genes, including a potential lipid-transfer domain containing protein found in association with isolated lipid droplets.

Background: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). Objectives: We investigated associations between urban environment exposures during pregnancy and PPD. Methods: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686–30,716 depending on exposure; representing 26–46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3–18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. Results: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs.

Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusion: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Abstract Background Manuscript preparation and the (re)submission of articles can create a significant workload in academic jobs. In this exploratory analysis, we estimate the time and costs needed to meet the diverse formatting requirements for manuscript submissions in biomedical publishing. Methods We reviewed 302 leading biomedical journals’ submission guidelines and extracted information on the components that tend to vary the most among submission guidelines (the length of the title, the running title, the abstract, and the manuscript; the structure of the abstract and the manuscript, number of items and references allowed, whether the journal has a template). We estimated annual research funding lost due to manuscript formatting by calculating hourly academic salaries, the time lost to reformatting articles, and quantifying the total number of resubmissions per year. We interviewed several researchers and senior journal editors and editors-in-chief to contextualize our findings and develop guidelines that could help both biomedical journals and researchers work more efficiently. Results Among the analyzed journals, we found a huge diversity in submission requirements. By calculating average researcher salaries in the European Union and the USA, and the time spent on reformatting articles, we estimated that ~ 230 million USD were lost in 2021 alone due to reformatting articles. Should the current practice remain unchanged within this decade, we estimate ~ 2.5 billion USD could be lost between 2022 and 2030—solely due to reformatting articles after a first editorial desk rejection. In our interviews, we found alignment between researchers and editors; researchers would like the submission process to be as straightforward and simple as possible, and editors want to easily identify strong, suitable articles and not waste researchers’ time. Conclusions Based on the findings from our quantitative analysis and contextualized by the qualitative interviews, we conclude that free-format submission guidelines would benefit both researchers and editors. However, a minimum set of requirements is necessary to avoid manuscript submissions that lack structure. We developed our guidelines to improve the status quo, and we urge the publishers and the editorial-advisory boards of biomedical journals to adopt them. This may also require support from publishers and major international organizations that govern the work of editors.

Abstract Background Isolated ACL reconstructions (ACLR) demonstrate limitations in restoring native knee kinematics. This study investigates the knee mechanics of ACLR plus various anterolateral augmentations using a patient-specific musculoskeletal knee model. Materials and methods A patient-specific knee model was developed in OpenSim using contact surfaces and ligament details derived from MRI and CT data. The contact geometry and ligament parameters were varied until the predicted knee angles for intact and ACL-sectioned models were validated against cadaveric test data for that same specimen. Musculoskeletal models of the ACLR combined with various anterolateral augmentations were then simulated. Knee angles were compared between these reconstruction models to determine which technique best matched the intact kinematics. Also, ligament strains calculated by the validated knee model were compared to those of the OpenSim model driven by experimental data. The accuracy of the results was assessed by calculating the normalised RMS error (NRMSE); an NRMSE 60%). Similar errors were observed between ACL strain results (NRMSE > 60%). Other ligament comparisons were acceptable. All ACLR plus anterolateral augmentation models restored kinematics toward the intact state, with ACLR plus anterolateral ligament reconstruction (ACLR + ALLR) achieving the best match and the greatest strain reduction in ACL, PCL, MCL, and DMCL. Conclusion The intact and ACL-sectioned models were validated against cadaveric experimental results for all rotations. It is acknowledged that the validation criteria are very lenient; further refinement is required for improved validation. The results indicate that anterolateral augmentation moves the kinematics closer to the intact knee state; combined ACLR and ALLR provide the best outcome for this specimen.

With Inuit organizations leading the way, there is a growing opportunity for meaningful partnerships between Inuit and visiting researchers to create impactful research programs and policy initiatives that reflect Inuit priorities. Collaborative research methods, where Inuit and visiting researchers work together to meet community needs, offer a potential avenue for braiding knowledge systems, and therefore have become an increasingly popular way to conduct research in the Arctic. In this paper, we outline our use of the data analysis method known as the “Framework Method” during the Imappivut Knowledge Study, a participatory mapping project led by the Nunatsiavut Government. We reflect on both the method's applicability and its usefulness for future research conducted in collaboration between Inuit and non-Inuit researchers. We find that the Framework Method allowed us to work in an iterative and adaptive manner, resulting in comprehensive findings for marine spatial planning. The method also supported data sovereignty for the Nunatsiavut Government. The Framework Method can be used to allow Nunatsiavut greater control over the data internally and self-determining access to external researchers.

Abstract Background Common pregnancy and perinatal complications are associated with offspring cardiometabolic risk factors. These complications may influence multiple metabolic traits in the offspring and these associations might differ with offspring age. Methods We used data from eight population-based cohort studies to examine and compare associations of pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes (GD), preterm birth (PTB), small (SGA) and large (LGA) for gestational age (vs. appropriate size for gestational age (AGA)) with up to 167 plasma/serum-based nuclear magnetic resonance-derived metabolic traits encompassing lipids, lipoproteins, fatty acids, amino acids, ketones, glycerides/phospholipids, glycolysis, fluid balance, and inflammation. Confounder-adjusted regression models were used to examine associations (adjusted for maternal education, parity age at pregnancy, ethnicity, pre/early pregnancy body mass index and smoking, and offspring sex and age at metabolic trait assessment), and results were combined using meta-analysis by five age categories representing different periods of the offspring life course: neonates (cord blood), infancy (mean ages: 1.1–1.6 years), childhood (4.2–7.5 years); adolescence (12.0–16.0 years), and adulthood (22.0–67.8 years). Results Offspring numbers for each age category/analysis varied from 8925 adults (441 PTB) to 1181 infants (135 GD); 48.4% to 60.0% were females. Pregnancy complications (PE, GH, GD) were each associated with up to three metabolic traits in neonates (P≤0.001) with some evidence of persistence to older ages. PTB and SGA were associated with 32 and 12 metabolic traits in neonates respectively, which included an adjusted standardised mean difference of −0.89 standard deviation (SD) units for albumin with PTB (95% CI: −1.10 to −0.69, P=1.3×10−17) and −0.41 SD for total lipids in medium HDL with SGA (95% CI: −0.56 to −0.25, P=2.6×10−7), with some evidence of persistence to older ages. LGA was inversely associated with 19 metabolic traits including lower levels of cholesterol, lipoproteins, fatty acids, and amino acids, with associations emerging in adolescence, (e.g. −0.11 SD total fatty acids, 95% CI: −0.18 to −0.05, P=0.0009), and attenuating with older age across adulthood. Conclusions These reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications.

This paper investigates the views of multi-stakeholders on the governance quality of existing forest management strategies for red panda (Ailurus fulgens) protection in Nepal, focusing on forest governance in general, red panda conservation programmes and natural habitat protection in particular. The study deployed two surveys in August and September 2020. The first survey was conducted online for the stakeholders with internet access; for those without, it was conducted over the phone. While the results reveal almost similar perspectives among the stakeholders regarding the effectiveness of the red panda management approaches, they differ significantly between the online survey and telephonic survey, in terms of the relative scores given to these initiatives. In depth, follow-up interviews revealed that marginalised groups had little access to income generation from conservation activities and few capacity-building opportunities. These findings indicate that while management strategies for red panda conservation were generally considered effective by online survey participants which are generally more privileged, this is less effective for marginalised people. Local people, who are typically resource-poor and reliant on the forest, continue to endure inequitable resource distribution and benefit sharing. Consequently, greater attention should be paid to balancing the conservation needs and basic needs of forest-dependent communities through capacity building, income generation and alternative sources of livelihood.

Plain English summary Many people with eating disorders (EDs) either do not access treatment, access it well after symptoms first start, or drop out of treatment. This study evaluated ways to improve early access to the best treatments for those with EDs in regional Australia. Links were formed between general medical practitioners and treatment providers (such as psychologists and dietitians) who received ongoing training, feedback and support. This approach achieved completion rates and outcomes equivalent to those found in specialised clinical trials of ED treatments. A key finding was the benefit of a care coordinator to connect users to services and help navigate barriers to ongoing treatment.

Abstract Volumetric laser endomicroscopy (VLE) is an advanced endoscopic imaging tool that can improve dysplasia detection in Barrett’s esophagus (BE). However, VLE scans generate 1200 cross-sectional images that can make interpretation difficult. The impact of a new VLE artificial intelligence algorithm called Intelligent Real-time Image Segmentation (IRIS) is not well-characterized. This is a randomized prospective cross-over study of BE patients undergoing endoscopy who were randomized to IRIS-enhanced or unenhanced VLE first followed by the other (IRIS-VLE vs. VLE-IRIS, respectively) at expert BE centers. The primary outcome was image interpretation time, which served as a surrogate measure for ease of interpretation. The secondary outcome was diagnostic yield of dysplasia for each imaging modality. 133 patients were enrolled. 67 patients were randomized to VLE-IRIS and 66 to IRIS-VLE. Total interpretation time did not differ significantly between groups (7.8 min VLE-IRIS vs. 7 min IRIS-VLE, P = 0.1), however unenhanced VLE interpretation time was significantly shorter in the IRIS-VLE group (2.4 min vs. 3.8 min, P

Futures thinking is an increasingly popular approach to solving complex environmental problems because it offers a framework to consider potential and desirable futures. It is also possible to create highly participatory future planning processes that incorporate the perspectives, beliefs, and values of resource users. In 2019, a group of fisheries stakeholders in Nunatsiavut, an Inuit land claim region in northern Labrador, began a target seeking scenario planning process to help them create a vision for the future of commercial fisheries in the region. Through this process, the group hoped to not only create a vision of Inuit-led fisheries but also to advance communication, collaboration, and learning for the group. In this paper, we reflect on the process we underwent over the past few years, including the research design, data collection and analysis, and the results of the project to broadly consider the strengths and weaknesses of participatory scenario planning for Indigenous governance. Reflecting on the process that we undertook provides important, experience-based knowledge for future projects. The elevation of Inuit voices makes this vision specific to the region and reframes fisheries as a tool for cultural and political rejuvenation in the region.

Farm animals can form preferential associations within their social group. Research has shown that the presence of familiar conspecifics can help to cope with stressful situations. Nonetheless, whether the strength of the relationship matters is largely unknown. Our aim was to investigate the influence of the strength of the social relationship between familiar partners during a stressful event. Pigs (n = 116) were observed pre-weaning for their social interactions and spatial proximity with littermates. From this, preferential associations were calculated based on sociality indices of non-agonistic social behaviours (SIsoc) and spatial proximity (SIprox). Pigs were weaned into groups of unfamiliar pigs together with one littermate. The partner was selected based on the strength of their relationship pre-weaning, with pairs from across the SIsoc and SIprox distribution. SIprox and non-agonistic social behaviour (SIsoc) were included in the statistical analysis as measures of relationship strength. Focal pigs were observed postweaning for their social behaviour and spatial proximity, skin lesions and growth, and salivary cortisol concentration pre-weaning and at 4 h and 48 h postweaning. The strength of the social relationship pre-weaning did not significantly influence the behaviour or proximity towards the familiar partner postweaning, or the amount of skin lesions or weight gain. Pigs who were weaned with a littermate with whom they were strongly affiliated based on active social behaviour (SIsoc) tended to have a lower proportional increase in their cortisol concentration after weaning (P = 0.07). Pigs differed in their behaviour towards the familiar partner as compared to the unfamiliar pigs, by directing more aggression towards unfamiliar pigs (P

[This corrects the article DOI: 10.1371/journal.pmed.1004036.].

Investigative interviews by police are socially and cognitively demanding encounters, likely presenting significant challenges to those on the autism spectrum. Behavioral and communication differences mean that autistic people may also be more likely to be perceived as deceptive in the context of an investigative interview. In the present study, 32 autistic and 33 (age and IQ-matched) non-autistic adults took part in a novel virtual burglary scenario in either an ‘innocent’ or ‘guilty’ condition. In a subsequent mock-police interview, innocent suspects were instructed to tell the truth about what they did, while guilty suspects were instructed to lie in order to convince the interviewer of their innocence. In the mock-interviews, innocent autistic mock-suspects reported fewer details that would support their innocence than non-autistic mock-suspects, although both innocent and guilty autistic and non-autistic mock-suspects reported similar levels of investigation-relevant information and had similar levels of statement-evidence consistency. In post-interview questionnaires, innocent and guilty autistic mock-suspects self-reported greater difficulty in understanding interview questions, higher anxiety and perceived the interview as less supportive than non-autistic participants. Implications for investigative interviewing with autistic suspects and cues to deception are discussed.

BackgroundPreterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.Methods and findingsWe conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.ConclusionsThis study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.

Despite widespread use of Pegylated forms of Inteferon in the management of Myeloproliferative Neoplasms (MPN), most clinicians have experience predominantly with peginterferon alfa-2a (Pegasys). Third generation pegylated IFNα, ropeginterferon alfa-2b (ropegIFN; Besremi), was recommended by the European Medicine Authority (EMA) for treatment of Polycythaemia Vera (PV) following a Phase III trial (PROUD-PV / CONTINUATION-PV). FDA approval for PV, regardless of treatment history, was subsequently granted in November 2021. We hereby demonstrate the safety and tolerability of ropegIFN in a series of MPN patients at variable doses. It corroborates reports of efficacy of ropegIFN in patients with PV and use in pregnancy.

BackgroundInsecure attachment in infancy is associated with a range of later socioemotional problems; therefore, it is important to identify at-risk children so that support can be provided. However, there are currently no well-validated brief measures of infant attachment. The aim of this study is to create a brief version of the Attachment Q-Sort (AQS), one of the gold-standard measures of attachment.MethodData was used from the National Institute of Child Health and Development Study of Child Care and Youth Development (N = 1,364). The factor structure of the AQS was explored, and Item Response Theory was used to select a reduced number of items. Convergent validity of the shortened measure was assessed through associations with the Strange Situation Procedure. Correlations with sensitivity, externalising, and social competence were also examined.ResultsThe Brief Attachment Scale (BAS-16) was created consisting of two scales of eight items, relating to (a) harmonious interaction with the caregiver and (b) proximity-seeking behaviours. The BAS-16 showed comparable convergent, discriminant, and concurrent validity to the full AQS.ConclusionThis brief version of the AQS shows potential as a screening measure for insecure attachment in infancy. Further development and validation is required in separate samples.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.

Introduction: Prior research examining the impact of parenting on adolescent mental health has been limited by the use of cross-sectional designs and small or clinical samples. Methods: We used data (N = 6,212) from the Avon Longitudinal Study of Parents and Children, a UK-based birth cohort study. Results: We found longitudinal evidence that parental monitoring in late childhood/early adolescence (ages 9.5–13.5), but not the emotional quality of the parent-child relationship, reduces the likelihood of offspring major depressive disorder (Odds Ratio (OR) = 0.64, 95% Confidence Interval (CI) = 0.56 – 0.76), anxiety disorder (OR = 0.60, 95% CI = 0.53 – 0.69), and self-harm (OR = 0.65, 95% CI = 0.57 – 0.75) at age 18. Associations did not vary according to adolescent sex. Discussion: Findings indicate that parenting monitoring may be important for later adolescent mental health. Future research is needed to understand why this aspect of parenting is associated with better adolescent outcomes.