Neuropsychiatric differences among adolescents with early and late onset conduct, and externalizing and internalizing disorders presenting to a specialist service

Objective: The two papers presented investigate whether disorders in childhood are distinctive in their etiology and development and then extends to broader domains of child and adolescent mental disorders. The first paper focuses on psychiatric illness, neuropsychological and psychosocial dysfunction within the domain of externalizing disorders, examining differences between early and late onset conduct disordered (CD) youth. The second paper examines differences in neuropsychological and psychosocial function between externalizing and internalizing youth. Method: Paper one compares the psychiatric, neuropsychological and psychosocial function of 43 subjects with either childhood-onset or adolescent-onset CD. Paper two examines the neuropsychological and psychosocial function of 148 subjects across the two domains of externalizing and internalizing disorders. Participants were compared with normative scores from control samples in each study. Results: The first study shows differences between childhood-onset and adolescent onset CD youth for verbal learning and memory function, psychosis, childhood maltreatment and violent behavior with childhood onset youth performing worse on these measures. Both childhood and adolescent onset CD youth were impaired in executive function. The second study found significant differences between the externalizing disordered youth and both the internalizing and comorbid youth on executive function, with the externalizing youth exhibiting severe impairment in this area or cognitive function. Conclusion: Childhood onset CD is associated with more severe cognitive impairment, more psychiatric symptoms and childhood adversity than adolescent-onset youth. They were also more likely to commit serious, violent offences. When CD youth were included in a larger externalizing sample and compared with internalizing and comorbid youth, distinctiveness between the domains remained for some cognitive functions, specifically executive function

Neuropsychiatric differences among adolescents with early and late onset conduct, and externalizing and internalizing disorders presenting to a specialist service

Objective: The two papers presented investigate whether disorders in childhood are distinctive in their etiology and development and then extends to broader domains of child and adolescent mental disorders. The first paper focuses on psychiatric illness, neuropsychological and psychosocial dysfunction within the domain of externalizing disorders, examining differences between early and late onset conduct disordered (CD) youth. The second paper examines differences in neuropsychological and psychosocial function between externalizing and internalizing youth. Method: Paper one compares the psychiatric, neuropsychological and psychosocial function of 43 subjects with either childhood-onset or adolescent-onset CD. Paper two examines the neuropsychological and psychosocial function of 148 subjects across the two domains of externalizing and internalizing disorders. Participants were compared with normative scores from control samples in each study. Results: The first study shows differences between childhood-onset and adolescent onset CD youth for verbal learning and memory function, psychosis, childhood maltreatment and violent behavior with childhood onset youth performing worse on these measures. Both childhood and adolescent onset CD youth were impaired in executive function. The second study found significant differences between the externalizing disordered youth and both the internalizing and comorbid youth on executive function, with the externalizing youth exhibiting severe impairment in this area or cognitive function. Conclusion: Childhood onset CD is associated with more severe cognitive impairment, more psychiatric symptoms and childhood adversity than adolescent-onset youth. They were also more likely to commit serious, violent offences. When CD youth were included in a larger externalizing sample and compared with internalizing and comorbid youth, distinctiveness between the domains remained for some cognitive functions, specifically executive function

Integrating Process with Outcome Data in a Randomized Controlled Trial of Sex Education

Integration of process with outcome evaluations has been recommended as a way of addressing some of the criticisms of Randomized Controlled Trials (RCTs) for evaluating social interventions. This is the second of two articles (the first was published in issue 10(4) of this journal) discussing the design, implementation and analysis of a process evaluation as an integral part of the RIPPLE (Randomized Intervention of Pupil Peer-Led sex Education) Study. The methods for integrating process and outcome data are outlined and findings are presented to illustrate how integration of process and outcome data enabled exploration of: 1) variation between schools in the extent and quality of the intervention implemented, and any impact of this on outcomes; 2) the processes by which the intervention might affect outcomes; and 3) the extent to which different subgroups of students or schools may have responded differently to the intervention. The article concludes with a discussion of the methodological issues arising from this attempt at integrating process and outcome evaluations within the design of an RCT

The long-term effects of a peer-led sex education programme (RIPPLE): a cluster randomised trial in schools in England.

BACKGROUND: Peer-led sex education is widely believed to be an effective approach to reducing unsafe sex among young people, but reliable evidence from long-term studies is lacking. To assess the effectiveness of one form of school-based peer-led sex education in reducing unintended teenage pregnancy, we did a cluster (school) randomised trial with 7 y of follow-up. METHODS AND FINDINGS: Twenty-seven representative schools in England, with over 9,000 pupils aged 13-14 y at baseline, took part in the trial. Schools were randomised to either peer-led sex education (intervention) or to continue their usual teacher-led sex education (control). Peer educators, aged 16-17 y, were trained to deliver three 1-h classroom sessions of sex education to 13- to 14-y-old pupils from the same schools. The sessions used participatory learning methods designed to improve the younger pupils' skills in sexual communication and condom use and their knowledge about pregnancy, sexually transmitted infections (STIs), contraception, and local sexual health services. Main outcome measures were abortion and live births by age 20 y, determined by anonymised linkage of girls to routine (statutory) data. Assessment of these outcomes was blind to sex education allocation. The proportion of girls who had one or more abortions before age 20 y was the same in each arm (intervention, 5.0% [95% confidence interval (CI) 4.0%-6.3%]; control, 5.0% [95% CI 4.0%-6.4%]). The odds ratio (OR) adjusted for randomisation strata was 1.07 (95% CI 0.80-1.42, p = 0.64, intervention versus control). The proportion of girls with one or more live births by 20.5 y was 7.5% (95% CI 5.9%-9.6%) in the intervention arm and 10.6% (95% CI 6.8%-16.1%) in the control arm, adjusted OR 0.77 (0.51-1.15). Fewer girls in the peer-led arm self-reported a pregnancy by age 18 y (7.2% intervention versus 11.2% control, adjusted OR 0.62 [95% CI 0.42-0.91], weighted for non-response; response rate 61% intervention, 45% control). There were no significant differences for girls or boys in self-reported unprotected first sex, regretted or pressured sex, quality of current sexual relationship, diagnosed sexually transmitted diseases, or ability to identify local sexual health services. CONCLUSION: Compared with conventional school sex education at age 13-14 y, this form of peer-led sex education was not associated with change in teenage abortions, but may have led to fewer teenage births and was popular with pupils. It merits consideration within broader teenage pregnancy prevention strategies

The Long-Term Effects of a Peer-Led Sex Education Programme (RIPPLE): A Cluster Randomised Trial in Schools in England

Judith Stephenson and colleagues report on a cluster randomized trial in London of school-based peer-led sex education and whether it reduced unintended teenage pregnancy

PET and polyolefin plastics supply chains in Michigan: present and future systems analysis of environmental and socio-economic impacts

Many actions are underway at global, national, and local levels to increase plastics circularity. However, studies evaluating the environmental and socio-economic impacts of such a transition are lacking at regional levels in the United States. In this work, the existing polyethylene terephthalate and polyolefin plastics supply chains in Michigan were compared to a potential future (‘NextCycle’) scenario that looks at increasing Michigan’s overall recycling rate to 45%. Material flow analysis data was combined with environmental and socio-economic metrics to evaluate the sustainability of these supply chains for the modeled scenarios. Overall, the NextCycle scenario for these supply chains achieved a net 14% and 34% savings of greenhouse gas (GHG) emissions and energy impacts, when compared with their respective baseline values. Additionally, the NextCycle scenario showed a net gain in employment and wages, however, it showed a net loss of revenue generation outside of Michigan due to the avoided use of virgin resins in Michigan

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research