A pilot telephone intervention to increase uptake of breast cancer screening in socially deprived areas in Scotland (TELBRECS):study protocol for a randomised controlled trial

BACKGROUND Breast cancer accounts for almost 30% of all cancers and is the second leading cause of cancer deaths in women in Scotland. Screening is key to early detection. The Scottish Breast Screening Programme is a nationwide, free at point of delivery screening service, to which all women aged between 50 and 70 years are invited to attend every 3 years. Currently over three-quarters of invited women regularly attend screening. However, women from more deprived areas are much less likely to attend: for example in the 3 years from 2010-2012 only 63% of women in the most deprived area attended the East of Scotland Breast Screening programme versus 81% in the least deprived. Research has suggested that reminders (telephone or letter) and brief, personalised interventions addressing barriers to attendance may be helpful in increasing uptake in low-income women. METHODS/DESIGN We will employ a brief telephone reminder and support intervention, whose purpose is to elicit and address any mistaken beliefs women have about breast screening, with the aim that the perceived benefits of screening come to outweigh any perceived barriers for individuals. We will test whether this intervention, plus a simple anticipated regret manipulation, will lead to an increase in the uptake of breast cancer screening amongst low-income women who have failed to attend a first appointment, in a randomised controlled trial with 600 women. Participants will be randomly allocated to one of four treatment arms i.e. 1) Letter reminder (i.e. Treatment as usual: CONTROL); 2) Telephone reminder (TEL), 3) Telephone reminder plus telephone support (TEL-SUPP) and 4) Telephone reminder plus support plus AR (TEL-SUPP-AR). The primary outcome will be attendance at breast screening within 3 months of the reminder letter. DISCUSSION If this simple telephone support intervention (with or without AR intervention) leads to a significant increase in breast screening attendance, this would represent a rare example of a theoretically-driven, relatively simple psychological intervention that could result in earlier detection of breast cancer amongst an under-served group of lower socio-economic women. TRIAL REGISTRATION Current Controlled trials: ISRCTN06039270. Registered 16th January 2014

Differential expression analysis for sequence count data

*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.

*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. 

*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from "http://www-huber.embl.de/users/anders/DESeq":http://www-huber.embl.de/users/anders/DESeq

Change in maternal body mass index is associated with offspring body mass index: a 21-year prospective study

High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012

Validation of a digital photographic method for assessment of dietary quality of school lunch sandwiches brought from home.

Background: It is a challenge to assess children's dietary intake. The digital photographic method (DPM) may be an objective method that can overcome some of these challenges. Objective: The aim of this study was to evaluate the validity and reliability of a DPM to assess the quality of dietary intake from school lunch sandwiches brought from home among children aged 7–13 years. Design: School lunch sandwiches (n=191) were prepared to represent randomly selected school lunch sandwiches from a large database. All components were weighed to provide an objective measure of the composition. The lunches were photographed using a standardised DPM. From the digital images, the dietary components were estimated by a trained image analyst using weights or household measures and the dietary quality was assessed using a validated Meal Index of Dietary Quality (Meal IQ). The dietary components and the Meal IQ obtained from the digital images were validated against the objective weighed foods of the school lunch sandwiches. To determine interrater reliability, the digital images were evaluated by a second image analyst. Results: Correlation coefficients between the DPM and the weighed foods ranged from 0.89 to 0.97. The proportion of meals classified in the same or an adjacent quartile ranged from 98% (starch) to 100% (fruits, vegetables, fish, whole grain, and Meal IQ). There was no statistical difference between fish, fat, starch, whole grains, and Meal IQ using the two methods. Differences were found for fruits and vegetables; Bland–Altman analyses showed a tendency to underestimate high amounts of these variables using the DPM. For interrater reliability, kappa statistics ranged from 0.59 to 0.82 across the dietary components and Meal IQ. Conclusions: The standardised DPM is a valid and reliable method for assessing the dietary quality of school lunch sandwiches brought from home

Lunar exploration: opening a window into the history and evolution of the inner Solar System

The lunar geological record contains a rich archive of the history of the inner Solar System, including information relevant to understanding the origin and evolution of the Earth-Moon system, the geological evolution of rocky planets, and our local cosmic environment. This paper provides a brief review of lunar exploration to-date, and describes how future exploration initiatives will further advance our understanding of the origin and evolution of the Moon, the Earth-Moon system, and of the Solar System more generally. It is concluded that further advances will require the placing of new scientific instruments on, and the return of additional samples from, the lunar surface. Some of these scientific objectives can be achieved robotically, for example by in situ geochemical and geophysical measurements and through carefully targeted sample return missions. However, in the longer term, we argue that lunar science would greatly benefit from renewed human operations on the surface of the Moon, such as would be facilitated by implementing the recently proposed Global Exploration Roadmap

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Gram Negative Wound Infection in Hospitalised Adult Burn Patients-Systematic Review and Metanalysis-

BACKGROUND: Gram negative infection is a major determinant of morbidity and survival. Traditional teaching suggests that burn wound infections in different centres are caused by differing sets of causative organisms. This study established whether Gram-negative burn wound isolates associated to clinical wound infection differ between burn centres. METHODS: Studies investigating adult hospitalised patients (2000-2010) were critically appraised and qualified to a levels of evidence hierarchy. The contribution of bacterial pathogen type, and burn centre to the variance in standardised incidence of Gram-negative burn wound infection was analysed using two-way analysis of variance. PRIMARY FINDINGS: Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanni, Enterobacter spp., Proteus spp. and Escherichia coli emerged as the commonest Gram-negative burn wound pathogens. Individual pathogens' incidence did not differ significantly between burn centres (F (4, 20) = 1.1, p = 0.3797; r2 = 9.84). INTERPRETATION: Gram-negative infections predominate in burn surgery. This study is the first to establish that burn wound infections do not differ significantly between burn centres. It is the first study to report the pathogens responsible for the majority of Gram-negative infections in these patients. Whilst burn wound infection is not exclusive to these bacteria, it is hoped that reporting the presence of this group of common Gram-negative "target organisms" facilitate clinical practice and target research towards a defined clinical demand.peer-reviewe

Effectiveness of an implementation optimisation intervention aimed at increasing parent engagement in HENRY, a childhood obesity prevention programme - the Optimising Family Engagement in HENRY (OFTEN) trial: study protocol for a randomised controlled trial

Background: Family-based interventions to prevent childhood obesity depend upon parents’ taking action to improve diet and other lifestyle behaviours in their families. Programmes that attract and retain high numbers of parents provide an enhanced opportunity to improve public health and are also likely to be more cost-effective than those that do not. We have developed a theory-informed optimisation intervention to promote parent engagement within an existing childhood obesity prevention group programme, HENRY (Health Exercise Nutrition for the Really Young). Here, we describe a proposal to evaluate the effectiveness of this optimisation intervention in regard to the engagement of parents and cost-effectiveness. Methods/design: The Optimising Family Engagement in HENRY (OFTEN) trial is a cluster randomised controlled trial being conducted across 24 local authorities (approximately 144 children’s centres) which currently deliver HENRY programmes. The primary outcome will be parental enrolment and attendance at the HENRY programme, assessed using routinely collected process data. Cost-effectiveness will be presented in terms of primary outcomes using acceptability curves and through eliciting the willingness to pay for the optimisation from HENRY commissioners. Secondary outcomes include the longitudinal impact of the optimisation, parent-reported infant intake of fruits and vegetables (as a proxy to compliance) and other parent-reported family habits and lifestyle. Discussion: This innovative trial will provide evidence on the implementation of a theory-informed optimisation intervention to promote parent engagement in HENRY, a community-based childhood obesity prevention programme. The findings will be generalisable to other interventions delivered to parents in other community-based environments. This research meets the expressed needs of commissioners, children’s centres and parents to optimise the potential impact that HENRY has on obesity prevention. A subsequent cluster randomised controlled pilot trial is planned to determine the practicality of undertaking a definitive trial to robustly evaluate the effectiveness and cost-effectiveness of the optimised intervention on childhood obesity prevention

Effects of early feeding on growth velocity and overweight/obesity in a cohort of HIV unexposed South African infants and children

BACKGROUND: South Africa has the highest prevalence of overweight/obesity in Sub-Saharan Africa. Assessing the effect of modifiable factors such as early infant feeding on growth velocity and overweight/obesity is therefore important. This paper aimed to assess the effect of infant feeding in the transitional period (12 weeks) on 12–24 week growth velocity amongst HIV unexposed children using WHO growth velocity standards and on the age and sex adjusted body mass index (BMI) Z-score distribution at 2 years. METHODS: Data were from 3 sites in South Africa participating in the PROMISE-EBF trial. We calculated growth velocity Z-scores using the WHO growth standards and assessed feeding practices using 24-hour and 7-day recall data. We used quantile regression to study the associations between 12 week infant feeding and 12–24 week weight velocity (WVZ) with BMI-for-age Z-score at 2 years. We included the internal sample quantiles (70th and 90th centiles) that approximated the reference cut-offs of +2 (corresponding to overweight) and +3 (corresponding to obesity) of the 2 year BMI-for-age Z-scores. RESULTS: At the 2-year visit, 641 children were analysed (median age 22 months, IQR: 17–26 months). Thirty percent were overweight while 8.7% were obese. Children not breastfed at 12 weeks had higher 12–24 week mean WVZ and were more overweight and obese at 2 years. In the quantile regression, children not breastfed at 12 weeks had a 0.37 (95% CI 0.07, 0.66) increment in BMI-for-age Z-score at the 50th sample quantile compared to breast-fed children. This difference in BMI-for-age Z-score increased to 0.46 (95% CI 0.18, 0.74) at the 70th quantile and 0.68 (95% CI 0.41, 0.94) at the 90th quantile . The 12–24 week WVZ had a uniform independent effect across the same quantiles. CONCLUSIONS: This study demonstrates that the first 6 months of life is a critical period in the development of childhood overweight and obesity. Interventions targeted at modifiable factors such as early infant feeding practices may reduce the risks of rapid weight gain and subsequent childhood overweight/obesity.Scopu

Family and Early Life Factors Associated With Changes in Overweight Status Between Ages 5 and 14 Years: Findings From The Mater University Study Of Pregnancy and its Outcomes

Objective To describe different patterns of overweight status between ages 5 and 14 y and examine the role of modifiable family and early life characteristics in explaining different patterns of change between these two ages. Design A population-based prospective birth cohort. Subjects A total of 2934 children (52% males) who were participants in the Mater-University study of pregnancy, Brisbane, and who were examined at ages 5 and 14 y. Main outcome measures Four patterns of change in overweight/obesity status between ages 5 and 14 y: (i) normal at both ages; (ii) normal at 5 y and overweight/obese at 14 y; (iii) overweight/obese at 5 y and normal at 14 y; (iv) overweight/obese at both ages. Results Of the 2934 participants, 2018 (68.8%) had a normal body mass index (BMI) at ages 5 and 14 y, 425 (14.5%) changed from a normal BMI at age 5 y to overweight or obese at age 14 y, 175 (6.0%) changed from being overweight or obese at age 5 y to normal weight at age 14 y and 316 (10.8%) were overweight or obese at both ages 5 and 14 y. Girls were more likely to make the transition from overweight or obese at age 5 y to normal at 14 y than their boy counterparts. Children whose parents were overweight or obese were more likely to change from having a normal BMI at age 5 y to being overweight at 14 y (fully adjusted RR: 6.17 (95% CI: 3.97, 9.59)) and were more likely to be overweight at both ages (7.44 (95% CI: 4.60, 12.02)). Birth weight and increase in weight over the first 6 months of life were both positively associated with being overweight at both ages. Other explanatory factors were not associated with the different overweight status transitions. Conclusions Parental overweight status is an important determinant of whether a child is overweight at either stage or changes from being not overweight at 5 y to becoming so at 14 y