Socio-demographic patterns in hospital admissions and accident and emergency attendances among young people using linkage to NHS Hospital Episode Statistics:results from the Avon Longitudinal Study of Parents and Children

Abstract Background In England emergency hospital admissions among children are increasing and the under 25s are the most frequent attenders of A&E departments. Children of lower socio-economic status (SES) have poorer health outcomes and higher hospital admission rates. NHS Hospital Episode Statistics (HES) are increasingly being used for research but lack detailed data on individual characteristics such as SES. We report the results of an Avon Longitudinal Study of Parents and Children (ALSPAC) study that linked the data of 3,189 consenting participants to HES. We describe rates of hospital admission, emergency readmissions, and A&E attendances and examine socio-demographic correlates of these. Methods Subjects were singletons and twins enrolled in ALSPAC who had provided consent for linkage to their health records by the study cut-off date (31.02.12). Linkage was carried out by the Health and Social Care Information Centre (now NHS Digital). We examined rates of admissions between birth and age 20 and A&E attendances between 14 and 20 years. Socio-demographic information collected in ALSPAC questionnaires during pregnancy were used to examine factors associated with admissions, emergency readmissions (an emergency admission within 30 days of discharge) and A&E attendances. Results Excluding birth records, we found at least one admission for 1,792/3,189 (56.2%) participants and 4,305 admissions in total. Admission rates were highest in the first year of life. Among males, admissions declined until about age 5 and then remained relatively stable; conversely, among females, they increased sharply from the age of 15. ICD 10 chapters for diseases of the digestive system and injury and poisoning accounted for the largest proportions of admissions (15.8 and 14.5%, respectively). Tooth decay was the highest single cause of admission for those aged 5–9 years. Overall, 1,518/3,189 (47.6%) of participants attended A&E at least once, with a total of 3,613 attendances between age 14 and 20 years. Individuals from more deprived backgrounds had higher rates of admissions, readmissions and A&E attendances. Conclusions Linkage between cohort studies such as ALSPAC and HES data provides unique opportunities for detailed insights into socio-demographic and other determinants of hospital activity, which can inform secondary care demand management in the NHS

Removal of Human Leukemic Cells from Peripheral Blood Mononuclear Cells by Cell Recognition Chromatography with Size Matched Particle Imprints

We report a cell recognition chromatography approach for blood cancer cell separation from healthy peripheral blood mononuclear cells (PBMCs) based on sizematched functionalized particle imprints. Negative imprints were prepared from layers of 15 μm polymeric microbeads closely matching the size of cultured human leukemic cells (HL60). We replicated these imprints on a large scale with UV curable polyurethane resin using nanoimprinting lithography. The imprints were functionalized with branched polyethylene imine (bPEI) and passivated by Poloxamer 407 to promote a weak attraction toward cells. When a matching cell fits into an imprint cavity, its contact area with the imprint is maximized, which amplifies the attraction and the binding selectivity. We tested these imprints specificity for depleting myeloblasts from a mixture with healthy human PBMCs in a cell recognition chromatography setup hosting the imprint. The mixture of fixed HL60/PBMCs ratio was circulated over the imprint and at each step the selectivity toward HL60 was assessed by flow cytometry. The role of the imprint length, flow rate, channel depth, and the bPEI coating concentration were examined. The results show that HL60 cells, closely matching the imprint cavities, get trapped on the imprint, while the smaller PBMCs are carried away by the drag force of the flow. Lower flow rates, longer imprints, and interim channel depth favor HL60 specific retention. The bPEI concentration higher than 1 wt % on the imprint made it less selective toward the HL60 because of indiscriminate attraction with all cells. Particle imprint based cell recognition chromatography was able to achieve selective myeloblast depletion from initial 11.7% HL60 (88.3% PBMC) to less than 1.3% HL60 for 3 h of circulation. The cell recognition chromatography with size-matched microbead imprints can be employed as an efficient cell separation technique and potentially lead to alternative therapies for myeloblasts removal from peripheral blood of patients with acute myeloid leukemia

Representing the majority and not the minority: the importance of the individual in communicating climate change

This research presents three case studies, through which a creative approach to developing dialogue around climate change is outlined. By working with three distinct communities and encouraging them to discuss and write poetry about how climate change affects them, we demonstrate how such an approach might be adopted at this level. By analysing the discussions and poetry that arose out of these workshops we show how this community-level approach to communicating climate change is an essential counterpart to wider-scale quantitative research. The engagement of each community with climate change is dependent on the lived experiences of their members; a failure to recognize this results in less effective communications and can also cause communities to feel isolated and helpless. By considering the individual needs and aspirations of these communities we can support effective dialogue around the topic of climate change, and in doing so can better engender positive action against the negative effects of anthropogenic climate change

Using an internet intervention to support self-management of low back pain in primary care:Findings from a randomised controlled feasibility trial (SupportBack)

Introduction Low back pain (LBP) is a prevalent and costly condition. The majority of patients experiencing LBP are managed in primary care, where first-line care recommendations consist of advice to self-manage and remain active. Internet interventions present a potential means of providing patients with tailored self-management advice and evidence-based support for increasing physical activity.Methods/analysis This protocol describes a single-blind, randomised controlled feasibility trial of an internet intervention developed to support the self-management of LBP in primary care. Patients are being randomised to 1 of 3 groups receiving either usual primary care, usual primary care with the addition of an internet intervention or an internet intervention with physiotherapist telephone support. Patients are followed up at 3 months. Primary outcomes are the feasibility of (1) the trial design/methods, (2) the delivery of the internet intervention and (3) the provision of telephone support by physiotherapists. Secondary outcomes will include exploratory analysis of estimates and variation in clinical outcomes of pain and disability, in order to inform a future main trial.Ethics/dissemination This feasibility trial has undergone ethical scrutiny and been approved by the National Health Service (NHS) Research Ethics Committee, REC Reference 13/SC/0202. The feasibility findings will be disseminated to the research community through presentations at conferences and publication in peer review journals. Broader dissemination will come following a definitive trial

COVID-19-related social support service closures and mental well-being in older adults and those affected by dementia: a UK longitudinal survey

Background: The COVID-19 pandemic has had a major impact on delivery of social support services. This might be expected to particularly affect older adults and people living with dementia (PLWD), and to reduce their well-being. Aims: To explore how social support service use by older adults, carers and PLWD, and their mental well-being changed over the first 3 months since the pandemic outbreak. Methods: Unpaid dementia carers, PLWD and older adults took part in a longitudinal online or telephone survey collected between April and May 2020, and at two subsequent timepoints 6 and 12 weeks after baseline. Participants were asked about their social support service usage in a typical week prior to the pandemic (at baseline), and in the past week at each of the three timepoints. They also completed measures of levels of depression, anxiety and mental well-being. Results: 377 participants had complete data at all three timepoints. Social support service usage dropped shortly after lockdown measures were imposed at timepoint 1 (T1), to then increase again by T3. The access to paid care was least affected by COVID-19. Cases of anxiety dropped significantly across the study period, while cases of depression rose. Well-being increased significantly for older adults and PLWD from T1 to T3. Conclusions: Access to social support services has been significantly affected by the pandemic, which is starting to recover slowly. With mental well-being differently affected across groups, support needs to be put in place to maintain better well-being across those vulnerable groups during the ongoing pandemic

DNAAF1 links heart laterality with the AAA+ ATPase RUVBL1 and ciliary intraflagellar transport

DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p.Leu191Phe, as causative for heterotaxy in this family. Genetic complementation in dnaaf1-null zebrafish embryos demonstrated the rescue of normal heart looping with wild-type human DNAAF1, but not the p.Leu191Phe variant, supporting the conserved pathogenicity of this DNAAF1 missense mutation. This observation points to a phenotypic continuum between CHD and PCD, providing new insights into the pathogenesis of isolated CHD. In further investigations of the function of DNAAF1 in dynein arm assembly, we identified interactions with members of a putative dynein arm assembly complex. These include the ciliary intraflagellar transport protein IFT88 and the AAA+ (ATPases Associated with various cellular Activities) family proteins RUVBL1 (Pontin) and RUVBL2 (Reptin). Co-localization studies support these findings, with the loss of RUVBL1 perturbing the co-localization of DNAAF1 with IFT88. We show that RUVBL1 orthologues have an asymmetric left-sided distribution at both the mouse embryonic node and the Kupffer’s vesicle in zebrafish embryos, with the latter asymmetry dependent on DNAAF1. These results suggest that DNAAF1-RUVBL1 biochemical and genetic interactions have a novel functional role in symmetry breaking and cardiac development

Extensive field evidence for the release of HONO from the photolysis of nitrate aerosols

Particulate nitrate ([Formula: see text]) has long been considered a permanent sink for NO(x) (NO and NO(2)), removing a gaseous pollutant that is central to air quality and that influences the global self-cleansing capacity of the atmosphere. Evidence is emerging that photolysis of [Formula: see text] can recycle HONO and NO(x) back to the gas phase with potentially important implications for tropospheric ozone and OH budgets; however, there are substantial discrepancies in “renoxification” photolysis rate constants. Using aircraft and ground-based HONO observations in the remote Atlantic troposphere, we show evidence for renoxification occurring on mixed marine aerosols with an efficiency that increases with relative humidity and decreases with the concentration of [Formula: see text] , thus largely reconciling the very large discrepancies in renoxification photolysis rate constants found across multiple laboratory and field studies. Active release of HONO from aerosol has important implications for atmospheric oxidants such as OH and O(3) in both polluted and clean environments

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Adolescents' experience of receiving internet-delivered cognitive therapy for social anxiety disorder

Background: Social anxiety disorder (SAD) is a debilitating condition that usually begins in adolescence. We recently demonstrated preliminary efficacy of an internet-delivered therapist-assisted version of Cognitive Therapy for Social Anxiety Disorder (SAD) for adolescents called Online Social anxiety Cognitive therapy for Adolescents (OSCA). Here we report on the helpfulness, support, and overall acceptability of OSCA from the perspective of trial participants. Methods: Participants were 17 young people aged 15–18 years who had participated in a trial of OSCA. Post-treatment, participants completed an online treatment acceptability questionnaire and took part in a semi-structured interview to gain an understanding of their experience of OSCA. Results: Overall, there was a very high rate of treatment satisfaction. Core aspects of the treatment were viewed as most helpful, including behavioural experiments even though participants found them challenging. Participants found the online nature of the treatment helpful, allowing for easier communication with the therapist, regular encouragement from the therapist, and the ability to go back to their treatment and view their progress. Challenges were, for some, the quantity of content and practical issues around scheduling the short weekly calls with their therapist. Conclusions: This study suggests that young people felt helped and supported by OSCA