The effect of a one-year vigorous physical activity intervention on fitness, cognitive performance and mental health in young adolescents: the Fit to Study cluster randomised controlled trial.

BACKGROUND: Physical activity (PA) may positively stimulate the brain, cognition and mental health during adolescence, a period of dynamic neurobiological development. High-intensity interval training (HIIT) or vigorous PA interventions are time-efficient, scalable and can be easily implemented in existing school curricula, yet their effects on cognitive, academic and mental health outcomes are unclear. The primary aim of the Fit to Study trial was to investigate whether a pragmatic and scalable HIIT-style VPA intervention delivered during school physical education (PE) could improve attainment in maths. The primary outcome has previously been reported and was null. Here, we report the effect of the intervention on prespecified secondary outcomes, including cardiorespiratory fitness, cognitive performance, and mental health in young adolescents. METHODS: The Fit to Study cluster randomised controlled trial included Year 8 pupils (n = 18,261, aged 12-13) from 104 secondary state schools in South/Mid-England. Schools were randomised into an intervention condition (n = 52), in which PE teachers delivered an additional 10 min of VPA per PE lesson for one academic year (2017-2018), or into a "PE as usual" control condition. Secondary outcomes included assessments of cardiorespiratory fitness (20-m shuttle run), cognitive performance (executive functions, relational memory and processing speed) and mental health (Strength and Difficulties Questionnaire and self-esteem measures). The primary intention-to-treat (ITT) analysis used linear models and structural equation models with cluster-robust standard errors to test for intervention effects. A complier-average causal effect (CACE) was estimated using a two-stage least squares procedure. RESULTS: The HIIT-style VPA intervention did not significantly improve cardiorespiratory fitness, cognitive performance (executive functions, relational memory or processed speed), or mental health (all p > 0.05). Subgroup analyses showed no significant moderation of intervention effects by sex, socioeconomic status or baseline fitness levels. Changes in cardiorespiratory fitness were not significantly related to changes in cognitive or mental health outcomes. The trial was marked by high drop-out and low intervention compliance. Findings from the CACE analysis were in line with those from the ITT analysis. CONCLUSION: The one-academic year HIIT-style VPA intervention delivered during regular school PE did not significantly improve fitness, cognitive performance or mental health, but these findings should be interpreted with caution given low implementation fidelity and high drop-out. Well-controlled, large-scale, school-based trials that examine the effectiveness of HIIT-style interventions to enhance cognitive and mental health outcomes are warranted. TRIAL REGISTRATION: ISRCTN registry, 15,730,512 . Trial protocol and analysis plan for primary outcome prospectively registered on 30th March 2017. ClinicalTrials.gov , NCT03286725 . Secondary measures (focus of current manuscript) retrospectively registered on 18 September 2017.

Effects of a programme of vigorous physical activity during secondary school physical education on academic performance, fitness, cognition, mental health and the brain of adolescents (Fit to Study): study protocol for a cluster-randomised trial.

BACKGROUND: Early adolescence is a period of dynamic neurobiological change. Converging lines of research suggest that regular physical activity (PA) and improved aerobic fitness have the potential to stimulate positive brain changes, improve cognitive function and boost academic attainment in this age group, but high-quality studies are needed to substantiate these findings. The primary aim of the Fit to Study trial is to investigate whether short infusions of vigorous PA (VPA) delivered during secondary school physical education (PE) can improve attainment in maths, as described in a protocol published by NatCen Social Research. The present protocol concerns the trial's secondary outcome measures, which are variables thought to moderate or mediate the relationship between PA and attainment, including the effect of the intervention on cardiorespiratory fitness, cognitive performance, mental health and brain structure and function. METHOD: The Fit to Study project is a cluster-randomised controlled trial that includes Year 8 pupils (aged 12-13) from secondary state schools in South/Mid-England. Schools were randomised into an intervention condition in which PE teachers delivered an additional 10 min of VPA per PE lesson for one academic year, or a 'PE as usual' control condition. Intervention and control groups were stratified according to whether schools were single-sex or co-educational. Assessments take place at baseline (end of Year 7, aged 11-12) and after 12 months (Year 8). Secondary outcomes are cardiorespiratory fitness, objective PA during PE, cognitive performance and mental health. The study also includes exploratory measures of daytime sleepiness, attitudes towards daily PA and PE enjoyment. A sub-set of pupils from a sub-set of schools will also take part in a brain imaging sub-study, which is embedded in the trial. DISCUSSION: The Fit to Study trial could advance our understanding of the complex relationships between PA and aerobic fitness, the brain, cognitive performance, mental health and academic attainment during adolescence. Further, it will add to our understanding of whether school PE is an effective setting to increase VPA and fitness, which could inform future PA interventions and education policy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03286725 . Retrospectively registered on 18 September 2017. ClinicalTrials.gov, NCT03593863 . Retrospectively registered on 19 July 2018.

An experimental study on the manufacture and characterization of in-plane fibre-waviness defects in composites.

A new method has been developed for creating localized in-plane fibre waviness in composite coupons and used to create a large batch of specimens. This method could be used by manufacturers to experimentally explore the effect of fibre waviness on composite structures both directly and indirectly to develop and validate computational models. The specimens were assessed using ultrasound, digital image correlation and a novel inspection technique capable of measuring residual strain fields. To explore how the defect affects the performance of composite structures, the specimens were then loaded to failure. Predictions of remnant strength were made using a simple ultrasound damage metric and a new residual strain-based damage metric. The predictions made using residual strain measurements were found to be substantially more effective at characterizing ultimate strength than ultrasound measurements. This suggests that residual strains have a significant effect on the failure of laminates containing fibre waviness and that these strains could be incorporated into computational models to improve their ability to simulate the defect.

Understanding the information needs of people with haematological cancers. A meta-ethnography of quantitative and qualitative research.

Clinical practice in haematological oncology often involves difficult diagnostic and treatment decisions. In this context, understanding patients' information needs and the functions that information serves for them is particularly important. We systematically reviewed qualitative and quantitative evidence on haematological oncology patients' information needs to inform how these needs can best be addressed in clinical practice. PsycINFO, Medline and CINAHL Plus electronic databases were searched for relevant empirical papers published from January 2003 to July 2016. Synthesis of the findings drew on meta-ethnography and meta-study. Most quantitative studies used a survey design and indicated that patients are largely content with the information they receive from physicians, however much or little they actually receive, although a minority of patients are not content with information. Qualitative studies suggest that a sense of being in a caring relationship with a physician allows patients to feel content with the information they have been given, whereas patients who lack such a relationship want more information. The qualitative evidence can help explain the lack of association between the amount of information received and contentment with it in the quantitative research. Trusting relationships are integral to helping patients feel that their information needs have been met.

Maternal smoking in pregnancy, adult adiposity and other risk factors for cardiovascular disease.

OBJECTIVE: To establish whether maternal smoking in pregnancy is associated with risk factors for cardiovascular disease (CVD) in mid-adulthood and whether associations are explained by postnatal influences. METHODS: Participants were 8815 men and women in the 1958 British birth cohort, with data on CVD risk factors measured at 45 y. Maternal smoking was recorded at birth. RESULTS: Offspring of smokers had a higher adult BMI, waist circumference, blood pressure, HbA1c and triglycerides on average than offspring of non-smokers; females had lower HDL cholesterol levels. Total cholesterol was unrelated to maternal smoking. Associations were abolished after adjustment for postnatal influences across life, except for BMI and waist circumference: offspring of smokers had a BMI greater by 0.83 kg/m(2) on average than offspring of non-smokers and a 1.8 cm larger waist circumference. Mean BMI and waist circumference increased with number of cigarettes that the mother smoked, but were not elevated in offspring whose mother had quit smoking before or early in pregnancy. CONCLUSIONS: Adults exposed to tobacco in utero had a more adverse CVD risk profile in mid-adulthood which appeared to reflect a lifetime accumulation of postnatal influences; whereas their higher BMI and central adiposity may be due in part to intrauterine mechanisms.

The influence of socioeconomic status on the reporting of regional and widespread musculoskeletal pain: results from the 1958 British Birth Cohort Study.

OBJECTIVE: This study aims to determine to what extent the reporting of pain in adulthood varies by adult socioeconomic status, whether there are additional long-term effects of socioeconomic status in childhood and whether any such relationships are mediated through adult psychological ill health. METHODS: A prospective cohort study (the 1958 British Birth Cohort Study) was conducted. Participants were recruited, at birth, in 1958 and were followed-up throughout childhood and adulthood, most recently at 45 years when information was collected on regional and widespread pain, and various potential mediating factors. RESULTS: The prevalence of shoulder, forearm, low back, knee and chronic widespread pain at 45 years generally increased with lower adult social class. Persons in the lowest social class (compared to the highest) experienced nearly a threefold increase in the risk of chronic widespread pain: relative risk: 2.9 (95% CI 1.8 to 4.6). The strength of association varied between 1.5 and 2.0 for regional pains. Childhood social class also demonstrated a relationship with most regional pains and chronic widespread pain. With the exception of forearm pain, the magnitude of effect of childhood social status on reporting of pain in adulthood was less than that of adult social status. On multivariable analysis these relationships were partly explained by poor adult mental health, psychological distress, adverse life events and lifestyle factors. CONCLUSIONS: These results emphasise the importance and potential impact of measures to reduce social adversity, which will have the effect of improving musculoskeletal health in adult life and other major causes of morbidity.

Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional population survey.

BACKGROUND: Identified aetiological factors for chronic widespread pain (CWP) are largely related to emotional and behavioural factors, but current management leads to modest improvement in symptoms. Vitamin D deficiency has been suggested as a new modifiable risk factor for CWP. OBJECTIVE: To examine the association between vitamin D status (measured by 25-hydroxyvitamin D (25(OH)D)) and CWP in a nationwide population sample of white British adults, accounting for potential mediating and confounding lifestyle factors. METHODS: 9377 participants born 1 week in March 1958, in England, Scotland or Wales and completing a biomedical assessment at age 45; 6824 eligible participants had data on 25(OH)D and completed pain manikins. RESULTS: Prevalence of CWP varied by 25(OH)D concentration in women but not in men, with the lowest prevalence observed for women with 75-99 nmol/l (14.4% for <25 nmol/l, 14.8% for 25-49 nmol/l, 11.6% for 50-74 nmo/l, 8.2% for 75-99 nmol/l and 9.8% for participants with > or =100 nmol/l). There was an interaction between 25(OH)D concentration and gender in relation to CWP (interaction, p = 0.006), which was not fully explained by differences in lifestyle or social factors (adjusted interaction, p = 0.03). For women, the association between 25(OH)D concentration and CWP persisted after full adjustment (odds ratio (OR) for <75 nmol/l vs 75-99 nmol/l 1.57, 95% CI 1.09 to 2.26), while no evidence for an association was apparent in men (OR = 1.03, 95% CI 0.75 to 1.43). CONCLUSION: Current vitamin D status was associated with CWP in women but not in men. Follow-up studies are needed to evaluate whether higher vitamin D intake might have beneficial effects on the risk of CWP.

Co-occurrence of risk factors for cardiovascular disease by social class: 1958 British birth cohort.

AIM: To establish whether social differences in multiple risk factors for cardiovascular disease are due to a greater strength of association (higher correlation) between risk factors in less advantaged groups. METHODS: Co-occurrence of five risk factors (smoking, hypertension, low high-density lipoprotein cholesterol, obesity, diabetes) in 3614 British 45-year-old men and 3560 women in the manual and non-manual social groups. RESULTS: 4.0% of women in manual groups had >or=3 risk factors compared with 1.7% in non-manual groups: 6.2% and 3.4% respectively for men. There was a higher than expected percentage of the population, overall, with >or=3 risk factors assuming independence between risk factors; correspondingly, there was a slightly lower than expected proportion with one factor. However, patterns of observed to expected ratios were consistent in manual and non-manual groups and did not differ by the number of risk factors. CONCLUSIONS: Higher prevalence of multiple risk factors in manual groups was due to the higher prevalence of individual factors rather than a greater tendency of those with an individual risk factor to have additional risks. Strategies to reduce multiple risk factors in less advantaged groups would help to lessen their health burden.

Loss and representativeness in a biomedical survey at age 45 years: 1958 British birth cohort.

OBJECTIVE: A biomedical survey of the 1958 British birth cohort at age 45 years provides a baseline for future studies of chronic disease. The extent and nature of bias in this sample was examined. METHODS: Follow-up of all births in Great Britain in one week in March 1958. At 45 years the sample was compared with the surviving cohort on characteristics recorded at birth and seven years, and in adulthood (42 years). RESULTS: Sample attrition to age 45 years was chiefly through avoidable (35.8%) than unavoidable loss through death or emigration (13.7%). 11 971 individuals were invited to participate at 45 years. Of 9377 participants (78.3%), most consented to, and had valid values for, physical and mental measurements, survey questionnaires, and blood and saliva sampling; 8302 (88.5%) provided a blood sample. Groups moderately underrepresented in the 45-year sample included those with externalizing or internalizing behaviours, poor reading or math scores, and shorter stature. For example, 8.8% of the 45-year sample had been poor readers at age seven years compared with 11.1% of the total surviving cohort; for shorter stature the figures were 7.2% versus 8.4%, respectively. There was also underrepresentation of some minority groups (non-whites, births in households with no male head and children in social care). Most bias was present before the 45-year survey. CONCLUSION: The 45-year sample remains broadly representative of the surviving cohort, but specific biases may need to be taken into account in future research. Renewed efforts to re-engage all cohort members will improve the representativeness and value of the study.

Predictors of persistent neck pain after whiplash injury.

OBJECTIVE: To establish the aetiological influences of persistent neck pain following a motor vehicle collision and to construct a model for use in the emergency department for identifying patients at high risk of persistent symptoms. DESIGN: Prospective cohort study. Patients recruited from hospital emergency departments were sent a questionnaire to gather information on various exposures. They were followed up at 1, 3, and 12 months to identify those with persistent symptoms. MAIN OUTCOME MEASURE: Persistent neck pain (pain at 1, 3, and 12 months after collision). RESULTS: The baseline survey included 765 patients. Subsequently, 480 completed a questionnaire at each follow up time point, of whom 128 (27%) reported neck pain on each occasion. Few collision specific factors predicted persistent neck pain. In contrast, a high level of general psychological distress, pre-collision history of widespread body pain, type of vehicle, whiplash associated symptoms, and initial neck disability best predicted the persistence of symptoms. Furthermore, these factors, in combination, accounted for more than a fivefold increase in the risk of persistent neck pain. CONCLUSION: The greatest predictors of persistent neck pain following a motor vehicle collision relate to psychological distress and aspects of pre-collision health rather than to various attributes of the collision itself. With these factors, and those relating to initial injury severity, it is possible to identify a subgroup of patients presenting with neck pain with the highest risk of persistent symptoms. Thus, it is possible to identify whiplash patients with a poor prognosis and to provide closer follow up and specific attention to management in these individuals.

Role of glutathione S-transferase P1, P-glycoprotein and multidrug resistance-associated protein 1 in acquired doxorubicin resistance.

While P-glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) are known to be important in acquired doxorubicin resistance, the role of glutathione S-transferases (GST) remains unclear. Our study assessed roles of these 3 factors in a human drug-sensitive carcinoma cell line (HEp2), a subclone made resistant by prolonged incubation in doxorubicin (HEp2A), and HEp2 cells stably transfected with human GSTP1. Drug-resistant HEp2A cells showed greater total GST activity, GSTP class enzyme expression, Pgp expression, MRP1 transcript expression, drug efflux and at least 13-fold greater resistance to doxorubicin than the parent HEp2 cell line. GSTM class enzyme expression was similar in both cell types, while GSTA class enzymes were not detected. In the resistant HEp2A cells, cytotoxicity was markedly enhanced by the Pgp/MRP inhibitor verapamil at low doxorubicin concentrations. The GST inhibitor curcumin also enhanced cytotoxicity in HEp2A cells when the Pgp/MRP efflux barrier had been reversed by verapamil or overcome by high doxorubicin concentrations. In addition, curcumin had a chemosensitising effect at low doxorubicin concentrations in HEp2 cells. Stable transfection of HEp2 cells with human GSTP1 increases doxorubicin resistance 3-fold over control cells. Our study indicates involvement of GSTP enzymes as well as efflux mechanisms in the acquired doxorubicin-resistance phenotype.

Expression of a chemically synthesized human alpha 1 interferon gene.

Cells of Escherichia coli containing a chemically synthesized human alpha 1 interferon (IFN-alpha 1) gene, under control of the lac promoter, make a product with biological properties indistinguishable from those of the natural IFN-alpha 1 [antiviral activity, acid stability, species crossreactivity, inactivation by antisera directed against leukocyte or Namalwa cell interferon, and stimulation of (2'-5')oligoadenylate synthetase activity]. Similar levels of IFN synthesis were obtained when the expression unit (lac promoter plus synthetic IFN-alpha 1 gene) was transplanted into the obligate methylotroph Methylophilus methylotrophus.

Improved conversion of methanol to single-cell protein by Methylophilus methylotrophus.

The glutamate dehydrogenase gene of Escherichia coli has been cloned into broad host-range plasmids and can complement glutamate synthase mutants of Methylophilus methylotrophus. Assimilation of ammonia via glutamate dehydrogenase is more energy-efficient than via glutamate synthase, thus the recombinant organism converts more growth substrate, methanol, into cellular carbon.

The effects of some different metabolic inhibitors on interferon superinduction.

Three different inhibitors of RNA synthesis, actinomycin, alpha-amanitin and camptothecin, and five different inhibitors of protein synthesis were able to superinduce interferon production in human diploid fibroblasts treated with poly(rI).poly(rC). Camptothecin was shown to be a reversible inhibitor of virus induced interferon formation. It also substantially reduced the interferon yield from human diploid fibroblasts which had been superinduced with actinomycin D and cycloheximide. This suggests that the previously reported failure of camptothecin to inhibit interferon production in human diploid cells after induction with poly(rI).poly(rC) is the result of two mutually opposing effects: a marked inhibition of interferon messenger RNA synthesis, but a stimulation of the activity of the interferon messenger RNA that is formed.

The binding of poly(rI) - poly(rC) to human fibroblasts and the induction of interferon.

Human embryonic fibroblasts produce interferon when incubated at 37 degrees C after being treated at 4 degrees C with poly(rI) - poly(rC), either by addition of the double-stranded duplex or by sequential addition of the constitutent single-stranded polynucleotides. Cells which have been incubated with double-stranded poly(rI) - poly(rC) can be prevented from forming interferon by washing the cells with high concentrations of salt, immediately after adsorption of polynucleotides, or by incubation of the cells with single-stranded polynucleotides. The inhibition is probably due to displacement of the inducing molecule from the cell surface. Interferon production by cells treated sequentially with poly(rI) and poly(rC) is not inhibited by either of these treatments and the polynucleotides are not easily displaced from the cell surface.

Interferon induction by viruses and polynucleotides: a differential effect of comptothecin.

The plant alkaloid comptothecin inhibits interferon production induced by Newcastle disease virus (NDV) or ultraviolet-irradiated NDV in chick and human cells, and by Sindbis virus in chick cells. It has no effect on interferon production induced by poly (rI).poly(rC) in chick and human cells. No effect of comptothecin could be detected on the multiplication of NDV, and it is concluded that the inhibition reflects a difference between interferon induction by viruses and by polynucleotides.