Understanding the genetic and environmental specificity and overlap between well-being and internalizing symptoms in adolescence

Moderate inverse correlations are typically found between well-being and mental illness. We aimed to investigate the role of genes and environments in explaining the relationships between two aspects of well-being and two measures of internalizing symptoms. Altogether, 4700 pairs of 16-year-old twins contributed data on subjective happiness and life satisfaction, as well as symptoms of depression and emotional problems. Well-being was moderately correlated with internalizing symptoms (range = 0.45, 0.58). Multivariate twin model-fitting indicated both genetic and environmental overlap. Life satisfaction and happiness demonstrated different patterns of overlap, with stronger genetic links between life satisfaction and depression. Non-shared environmental influences were largely specific to each trait. This study supports the theory of mental health and illness being partly (but not entirely) correlated dimensions. There are also significant genetic and environmental factors to identify for well-being that go beyond the absence of mental illness. It is therefore possible that different interventions are needed for treating mental illness and promoting mental health

Multiple breath washout in bronchiectasis clinical trials:is it feasible?

Background: Evaluation of Multiple Breath Washout (MBW) set-up including staff training, certification and central “over-reading” for data quality control is essential to determine the feasibility of MBW in future bronchiectasis studies. Aims: To assess the outcomes of a MBW training, certification and central over-reading programme. Methods: MBW training and certification was conducted in European sites collecting LCI data in the BronchUK clinimetrics and/or i-BEST-1 studies. The blended training programme included the use of an eLearning tool and a 1-day face-to-face session. Sites submitted MBW data to trained central over-readers who determined validity and quality. Results: Thirteen training days were delivered to 56 participants from 22 sites. 18/22 (82%) were MBW naïve. Participant knowledge and confidence increased significantly (p<0.001). By the end of the study recruitment, 15/22 sites (68%) had completed certification with a mean (range) time since training of 6.2 (3-14) months. In the BronchUK clinimetrics study, 468/589 (79%) tests met45 the quality criteria following central over-reading, compared with 137/236 (58%) tests in the i-BEST-1 study. Conclusions: LCI is feasible in a bronchiectasis multicentre clinical trial setting however, consideration of site experience in terms of training as well as assessment of skill drift and the need for re-training may be important to reduce time to certification and optimise data quality. Longer times to certification, a higher percentage of naive sites and patients with worse lung function may have contributed to the lower success rate in the i-BEST-1 study

Added Value Measures in Education Show Genetic as Well as Environmental Influence

Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%). The pervasiveness of genetic influence in how and how much children learn is compatible with an active view of learning in which children create their own educational experiences in part on the basis of their genetic propensities

US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with preexisting inflammatory lung disease such as cystic fibrosis(CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered ‘good’ agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition

Do MZ twins have discordant experiences of friendship? : A qualitative hypothesis-generating MZ twin differences study

[This corrects the article DOI: 10.1371/journal.pone.0180521.]

A comparison of stomatal traits between contemporary and fossil leaves of Melaleuca quinquenervia: Do they reflect climate variation?

© 2019 Stomatal traits have been shown to vary in predictable ways in response to environmental change in many plant species. As a consequence, stomatal traits in fossil leaves are sometimes used as proxies for past CO2 and climate. Here we investigate the influence of temperature, rainfall and CO2 on stomatal traits in plant cuticle fine details of Melaleuca quinquenervia. We use both modern and fossil leaves deposited over the last c. 7500 years to evaluate the effect of CO2, and modern leaves for climate variables. We found a significant negative relationship between stomatal size and density across both modern and fossil leaves of M. quinquenervia. However, we were unable to find any relationship between stomatal traits and CO2 across a range from 260 to 380 ppm. We were unable to find any robust relationships between stomatal traits and either evaporation or temperature using the modern dataset. Apogeotropic roots account for the lack of stomatal anatomy response to evaporation in sites that experiences inundation. We conclude that stomatal size is a highly plastic trait in this species and changes do not necessarily reflect functional changes in the leaves

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a

Background Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. Methods and Findings We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Conclusions Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge

Person-Specific Non-shared Environmental Influences in Intra-individual Variability : A Preliminary Case of Daily School Feelings in Monozygotic Twins

Most behavioural genetic studies focus on genetic and environmental influences on inter-individual phenotypic differences at the population level. The growing collection of intensive longitudinal data in social and behavioural science offers a unique opportunity to examine genetic and environmental influences on intra-individual phenotypic variability at the individual level. The current study introduces a novel idiographic approach and one novel method to investigate genetic and environmental influences on intra-individual variability by a simple empirical demonstration. Person-specific non-shared environmental influences on intra-individual variability of daily school feelings were estimated using time series data from twenty-one pairs of monozygotic twins (age = 10 years, 16 female pairs) over two consecutive weeks. Results showed substantial inter-individual heterogeneity in person-specific non-shared environmental influences. The current study represents a first step in investigating environmental influences on intra-individual variability with an idiographic approach, and provides implications for future behavioural genetic studies to examine developmental processes from a microscopic angle

From classroom environment to mathematics achievement: The mediating role of self-perceived ability and subject interest

Drawing on Bandura's triadic reciprocal causation model, perceived classroom environment and three intrapersonal factors (mathematics self-efficacy, maths interest and academic self-concept) were considered as predictors of test performance in two correlated mathematics assessments: a public examination (GCSE) and an on-line test, both taken by UK pupils at age 16 (n = 6689). Intrapersonal factors were significantly associated with both test scores, even when the alternative score was taken into account. Classroom environment did not correlate with mathematics achievement once intrapersonal factors and alternative test performance were included in the model, but was associated with subject interest and academic self-concept. Perceptions of classroom environment may exercise an indirect influence on achievement by boosting interest and self-concept. In turn, these intrapersonal factors have direct relationships with achievement and were found to mediate the relationship between perceived classroom environment and maths performance. Findings and their implications for mathematics education are discussed

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden