Analysis of the Arabidopsis Polyadenylation Factors PAP1, CstF64 and CstF77 and their characteristic inter-relationship

3’-end modification by polyadenylation is a ubiquitous feature of almost all eukaryotic mRNA species and is catalyzed by a consortium of enzymes, the polyadenylation factors. Poly(A) polymerase (PAP), the enzyme catalyzing the addition of adenosine residues during the polyadenylation stage, exists in four isoforms within Arabidopsis. In silico and yeast two-hybrid studies showed that PAP1 has unique expression and interaction pattern in Arabidopsis, suggesting non-canonical functions of PAP1. Its exclusive interaction with PAP4 has not been reported in other living systems until now and hints at a difference in polyadenylation in plants with respect to mammals and yeast. Cleavage Stimulation Factor (CstF), a heterotrimeric complex of the polyadenylation factors CstF50, CstF64 and CstF77, plays a role largely in cleavage of pre-mRNA. This study highlights some aspects of the Arabidopsis homologs of CstF64 and CstF77, central to various cellular processes other than nuclear polyadenylation. In silico studies showed an elevated expression of CstF64 in the pollen while that of CstF77 remained fairly low. Yeast two-hybrid assays indicated a novel kind of interaction of CstF64 with Fip1(V). It is also speculated from sub-cellular localization techniques by agroinfiltration in tobacco leaves that CstF64 localizes in the cytoplasm and CstF77 in the nucleus, as found for the orthologs of CstF77 in other systems

The Effect COVID Has Had on the Wants and Needs of Children in Terms of Play: Text Mining the Qualitative Response of the Happen Primary School Survey with 20,000 Children in Wales, UK between 2016 and 2021

Play is central to children’s physical and social development. This study examines changes in children’s response to questions on play opportunities between 2016 and 2021. Primary school children aged 8–11 in Wales participated in the HAPPEN survey between 2016 and 2021. The survey captures a range of information about children’s health and wellbeing, including open-ended questions about what could make them happier. Text mining methods were used to examine how open-ended responses have changed over time in relation to play, before and, after the COVID enforced school closures. A total of 20,488 participant responses were analysed, 14,200 pre-school closures (2016 to pre-March 2020) and 6248 after initial school closures (September 2020–December 2021). Five themes were identified based on children’s open-ended responses; (a) space to play (35%), (b) their recommendations on play (31%), (c) having permission to play (20%), (d) their feelings on health and wellbeing and play (10%) and (e) having time to play (4%). Despite differences due to mitigation measures, the predominant recommendation from children after COVID is that they would like more space to play (outside homes, including gardens), more time with friends and protected time to play with friends in school and at home

Association of asthma severity and educational attainment at age 6-7 years in a birth cohort : Population based record-linkage study

Acknowledgments: We are very grateful to David Fone for help in the concept of the study. SP received a Translational Health Research Platform Award from the National Institute for Social Care and Health Research (grant reference: TPR08- 15 006) for the development of WECC.JD was supported by The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer), a UKCRC Public Health Research: Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council (RES-590-28-0005), Medical Research Council, the Welsh Government and the Wellcome Trust (WT087640MA), under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. SP was an applicant in the Centre for the Improvement of Population Health through E-records Research (CIPHER), one of four UK e-health Informatics Research Centres funded by a joint investment from: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Chief Scientist Office (Scottish Government Health Directorates), the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council,the National Institute for Health Research, the National Institute for Social Care and Health Research (Welsh Government) and the Wellcome Trust (Grant reference: 7 MR/K006525/1).Peer reviewe

Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification

Background: Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters. Methods: This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims’ health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome. Findings: After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71·8%) were female. Within a year of a domestic abuse incident, 3650 (41·9%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1·183 [95% CI 1·053–1·329], p=0·0048), further PPN submissions after the initial referral (1·383 [1·295–1·476]; p<0·0001), injury at the scene (1·484 [1·368–1·609]; p<0·0001), assessed high risk (1·600 [1·444–1·773]; p<0·0001), referral to other agencies (1·518 [1·358–1·697]; p<0·0001), history of violence (1·229 [1·134–1·333]; p<0·0001), attempted strangulation (1·311 [1·148–1·497]; p<0·0001), and pregnancy (1·372 [1·142–1·648]; p=0·0007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident. Interpretation: The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals

Breastfeeding initiation and duration through the COVID-19 pandemic, a linked population-level routine data study: the Born in Wales Cohort 2018–2021

Objectives: The WHO recommends exclusive breastfeeding for the first 6 months of life. This study aimed to examine the impact the pandemic had on breastfeeding uptake and duration, and whether intention to breastfeed is associated with longer duration of exclusive breastfeeding. Methods: A cohort study using routinely collected, linked healthcare data from the Secure Anonymised Information Linkage databank. All women who gave birth in Wales between 2018 and 2021 recorded in the Maternal Indicators dataset were asked about intention to breastfeed. These data were linked with the National Community Child Health Births and Breastfeeding dataset to examine breastfeeding rates. Results: Intention to breastfeed was associated with being 27.6 times more likely to continue to exclusively breastfeed for 6 months compared with those who did not intend to breastfeed (OR 27.6, 95% CI 24.9 to 30.7). Breastfeeding rates at 6 months were 16.6% prepandemic and 20.5% in 2020. When compared with a survey population, the initial intention to breastfeed/not breastfeed only changes for about 10% of women. Conclusion: Women were more likely to exclusively breastfeed for 6 months during the pandemic compared with before or after the pandemic. Arguably, interventions which enable families to spend more time with their baby such as maternal and paternal leave may help improve breastfeeding duration. The biggest predictor of breastfeeding at 6 months was intention to breastfeed. Therefore, targeted interventions during pregnancy to encourage motivation to breastfeed could improve duration of breastfeeding

Adverse childhood experiences and child mental health : an electronic birth cohort study

Acknowledgement We thank the SAIL databank for assisting in the statistical disclosure process. Declarations and Funding Data is collected routinely and access to this was granted via the SAIL databank. The corresponding author had full access to all the data in the study and final responsibility for the decision to submit for publication. The data sets generated and analysed during the current study are available in the SAIL databank repository, https://saildatabank.com/. This work was supported by funds from the Economic and Social Research Council, the Medical Research Council, and Alcohol Research UK to the ELAStiC Project (ESL015471/1) and Public Health Wales. The views expressed are those of the authors and should not be assumed to be of the funding body. The research was also supported by The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement, a UK Clinical Research Collaboration Public Health Research Centre of Excellence. This work was supported by Health Data Research UK, which receives its funding from HDR UK Ltd (HDR-9006) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust. The funders had no role in designing the study, data collection, analysis, or interpretation, or in writing the report; MAB’s role in the design, analysis, and writing was independent of the funding from Public Health Wales. SP, SL and MAB had the original idea for this study. SP, AE, RA, EL and RD designed the study and developed the analysis plan. AJ provided advice on the mental health codes used in this analysis. AB extracted the data and prepared data sets for analysis. EM, AE and RA analysed the data. EM and RA wrote the first draft of the paper. All authors were involved in interpreting the findings, revising drafts and agreeing the final version.Peer reviewedPublisher PD

The role of health and social factors in education outcome: A record-linked electronic birth cohort analysis

Background and objectiveHealth status in childhood is correlated with educational outcomes. Emergency hospital admissions during childhood are common but it is not known how these unplanned breaks from schooling impact on education outcomes. We hypothesised that children who had emergency hospital admissions had an increased risk of lower educational attainment, in addition to the increased risks associated with other health, social and school factors.MethodsThis record-linked electronic birth cohort, included children born in Wales between 1 January 1998 and 31 August 2001. We fitted multilevel logistic regression models grouped by schools, to determine whether emergency hospital inpatient admission before age 7 years was associated with the educational outcome of not attaining the expected level in a teacher-based assessment at age 7 years (KS1). We adjusted for pregnancy, perinatal, socio-economic, neighbourhood, pupil mobility and school-level factors.ResultsThe cohort comprised 64 934 children. Overall, 4680 (7.2%) did not attain the expected educational level. Emergency admission to hospital was associated with poor educational attainment (OR 1.12 95% Credible Interval (CI) 1.05, 1.20 for all causes during childhood, OR 1.19 95%CI 1.07, 1.32 for injuries and external causes and OR 1.31 95%CI 1.04, 1.22 for admissions during infancy), after adjusting for known determinants of education outcomes such as extreme prematurity, being small for gestational age and socio-economic indicators, such as eligibility for free school meals.ConclusionEmergency inpatient hospital admission during childhood, particularly during infancy or for injuries and external causes was associated with an increased risk of lower education attainment at age 7 years, in addition to the effects of pregnancy factors (gestational age, birthweight) and social deprivation. These findings support the need for injury prevention measures and additional support in school for affected children to help them to achieve their potential

Childhood asthma prevalence: cross-sectional record linkage study comparing parent-reported wheeze with general practitioner-recorded asthma diagnoses from primary care electronic health records in Wales

Introduction Electronic health records (EHRs) are increasingly used to estimate the prevalence of childhood asthma. The relation of these estimates to those obtained from parent-reported wheezing suggestive of asthma is unclear. We hypothesised that parent-reported wheezing would be more prevalent than general practitioner (GP)-recorded asthma diagnoses in preschool-aged children. Methods 1529 of 1840 (83%) Millennium Cohort Study children registered with GPs in the Welsh Secure Anonymised Information Linkage databank were linked. Prevalences of parent-reported wheezing and GP-recorded asthma diagnoses in the previous 12 months were estimated, respectively, from parent report at ages 3, 5, 7 and 11 years, and from Read codes for asthma diagnoses and prescriptions based on GP EHRs over the same time period. Prevalences were weighted to account for clustered survey design and non-response. Cohen’s kappa statistics were used to assess agreement. Results Parent-reported wheezing was more prevalent than GP-recorded asthma diagnoses at 3 and 5 years. Both diminished with age: by age 11, prevalences of parent-reported wheezing and GP-recorded asthma diagnosis were 12.9% (95% CI 10.6 to 15.4) and 10.9% (8.8 to 13.3), respectively (difference: 2% (−0.5 to 4.5)). Other GP-recorded respiratory diagnoses accounted for 45.7% (95% CI 37.7 to 53.9) and 44.8% (33.9 to 56.2) of the excess in parent-reported wheezing at ages 3 and 5 years, respectively. Conclusion Parent-reported wheezing is more prevalent than GP-recorded asthma diagnoses in the preschool years, and this difference diminishes in primary school aged children. Further research is needed to evaluate the implications of these differences for the characterisation of longitudinal childhood asthma phenotypes from EHRs