Multiple-instance-learning-based detection of coeliac disease in histological whole-slide images.

We present a multiple-instance-learning-based scheme for detecting coeliac disease, an autoimmune disorder affecting the intestine, in histological whole-slide images (WSIs) of duodenal biopsies. We train our model to detect 2 distinct classes, normal tissue and coeliac disease, on the patch-level, and in turn leverage slide-level classifications. Using 5-fold cross-validation in a training set of 1841 (1163 normal; 680 coeliac disease) WSIs, our model classifies slides as normal with accuracy (96.7±0.6)%, precision (98.0±1.7)%, and recall (96.8±2.5)%, and as coeliac disease with accuracy (96.7±0.5)%, precision (94.9±3.7)%, and recall (96.5±2.9)% where the error bars are the cross-validation standard deviation. We apply our model to 2 test sets: one containing 191 WSIs (126 normal; 65 coeliac) from the same sources as the training data, and another from a completely independent source, containing 34 WSIs (17 normal; 17 coeliac), obtained with a scanner model not represented in the training data. Using the same-source test data, our model classifies slides as normal with accuracy 96.5%, precision 98.4% and recall 96.1%, and positive for coeliac disease with accuracy 96.5%, precision 93.5%, and recall 97.3%. Using the different-source test data the model classifies slides as normal with accuracy 94.1% (32/34), precision 89.5%, and recall 100%, and as positive for coeliac disease with accuracy 94.1%, precision 100%, and recall 88.2%. We discuss generalising our approach to screen for a range of pathologies.

Nutrition, growth, and other factors associated with early cognitive and motor development in Sub-Saharan Africa: a scoping review.

BACKGROUND: Food insecurity, poverty and exposure to infectious disease are well-established drivers of malnutrition in children in Sub-Saharan Africa. Early development of cognitive and motor skills - the foundations for learning - may also be compromised by the same or additional factors that restrict physical growth. However, little is known about factors associated with early child development in this region, which limits the scope to intervene effectively. To address this knowledge gap, we compared studies that have examined factors associated with early cognitive and/or motor development within this population. METHODS: Predetermined criteria were used to examine four publication databases (PsycInfo, Embase, Web of Science and Medline) and identify studies considering the determinants of cognitive and motor development in children aged 0-8 years in Sub-Saharan Africa. RESULTS: In total, 51 quantitative studies met the inclusion criteria, reporting on 30% of countries across the region. Within these papers, factors associated with early child development were grouped into five themes: Nutrition, Growth and Anthropometry, Maternal Health, Malaria and HIV, and Household. Food security and dietary diversity were associated with positive developmental outcomes, whereas exposure to HIV, malaria, poor maternal mental health, poor sanitation, maternal alcohol abuse and stunting were indicators of poor cognitive and motor development. DISCUSSION: In this synthesis of research findings obtained across Sub-Saharan Africa, factors that restrict physical growth are also shown to hinder the development of early cognitive and motor skills, although additional factors also influence early developmental outcomes. The study also reviews the methodological limitations of conducting research using Western methods in sub-Saharan Africa.

Impact of early exposure to a cafeteria diet on prefrontal cortex monoamines and novel object recognition in adolescent rats.

The prefrontal cortex (PFC) undergoes protracted postnatal development such that its structure and behavioural function may be profoundly altered by environmental factors. Here we investigate the effect of lactational dietary manipulations on novel object recognition (NOR) learning and PFC monoamine neurotransmitter metabolism in early adolescent rats. To this end, Wistar rat dams were fed a high caloric cafeteria diet (CD) during lactation and resultant 24-26 day old offspring exposed to NOR testing and simultaneous PFC dopamine and serotonin metabolism measurement. In the second NOR choice trial where one familiar and one novel object were presented controls explored the novel preferentially to the familiar object both after a 5 min (P < 0.001) or 30 min (P < 0.05) inter-trial intervals (ITI). By contrast, offspring from dams fed on lactational CD failed to show any significant preference for the novel object at either time point. Compared with chow fed controls, their average exploration ratio of the novel object was lower after the 5 min ITI (P < 0.05). Following a 60 min ITI, neither CD nor control offspring showed a preference for the novel object. PFC dopamine metabolism was significantly reduced in the CD group (P < 0.001), whereas serotonin metabolism was increased (P < 0.001). These results suggest that an obesogenic lactational diet can have a detrimental impact on cognition in adolescent offspring associated with aberrant PFC serotonin and dopamine metabolism.

A holistic approach to healthy ageing: how can people live longer, healthier lives?

BACKGROUND: Although lifespan is increasing, there is no evidence to suggest that older people are experiencing better health in their later years than previous generations. Nutrition, at all stages of life, plays an important role in determining health and wellbeing. METHODS: A roundtable meeting of UK experts on nutrition and ageing considered key aspects of the diet-ageing relationship and developed a consensus position on the main priorities for research and public health actions that are required to help people live healthier lives as they age. RESULTS: The group consensus highlighted the requirement for a life course approach, recognising the multifactorial nature of the impact of ageing. Environmental and lifestyle influences at any life stage are modified by genetic factors and early development. The response to the environment at each stage of life can determine the impact of lifestyle later on. There are no key factors that act in isolation to determine patterns of ageing and it is a combination of environmental and social factors that drives healthy or unhealthy ageing. Too little is known about how contemporary dietary patterns and sedentary lifestyles will impact upon healthy ageing in future generations and this is a priority for future research. CONCLUSIONS: There is good evidence to support change to lifestyle (i.e. diet, nutrition and physical) activity in relation to maintaining or improving body composition, cognitive health and emotional intelligence, immune function and vascular health. Lifestyle change at any stage of life may extend healthy lifespan, although the impact of early changes appears to be greatest.

Exposure to maternal cafeteria diets during the suckling period has greater effects on fat deposition and Sterol Regulatory Element Binding Protein-1c (SREBP-1c) gene expression in rodent offspring compared to exposure before birth.

BACKGROUND: While the adverse metabolic effects of exposure to obesogenic diets during both the prenatal and early postnatal period are well established, the relative impact of exposure during these separate developmental windows remains unclear. This study aimed to assess the relative contribution of exposure to a maternal cafeteria diet during pregnancy and lactation on body weight, fat mass and expression of lipogenic and adipokine genes in the offspring. METHODS: Wistar rats were fed either a control chow (Control, n = 14) or obesogenic cafeteria diet (CAF, n = 12) during pregnancy and lactation. Pups were cross-fostered to another dam in either the same or different dietary group within 24 h of birth. Body weight, body fat mass and expression of lipogenic and adipokine genes in subcutaneous and visceral adipose tissues were determined in offspring at weaning and 3 weeks post-weaning. RESULTS: Offspring suckled by CAF dams had a lower body weight (P < 0.05), but ~ 2-fold higher percentage body fat at weaning than offspring suckled by Control dams (P < 0.01), independent of whether they were born to a Control or CAF dam. At 6 weeks of age, after all offspring were weaned onto standard chow, males and females suckled by CAF dams remained lighter (P < 0.05) than offspring suckled by Control dams, but the percentage fat mass was no longer different between groups. Sterol Regulatory Element Binding Protein-1c (SREBP-1c) mRNA expression was ~ 25% lower in offspring suckled by cafeteria dams in males at weaning (P < 0.05) and in females at 6 weeks of age (P < 0.05). Exposure to a cafeteria diet during the suckling period alone also resulted in increased adipocyte Peroxisome Proliferator Activated Receptor-γ (PPAR-γ) mRNA expression in females, and adiponectin and leptin mRNA expression in both sexes at weaning. CONCLUSIONS: The findings from this study point to the critical role of the suckling period for deposition of adipose tissue in rodents, and the potential role of altered adipocyte gene expression in mediating these effects.

A novel technique to optimise the length of a linear accelerator treatment room maze without compromising radiation protection.

Simulations with the FLUktuierende KAskade (FLUKA) Monte Carlo code were used to establish the possibility of introducing lead to cover the existing concrete walls of a linear accelerator treatment room maze, in order to reduce the dose of the scattered photons at the maze entrance. In the present work, a pilot study performed at Singleton Hospital in Swansea was used to pioneer the use of lead sheets of various thicknesses to absorb scattered low energy photons in the maze. The dose reduction was considered to be due to the strong effect of the photoelectric interaction in lead resulting in attenuation of the back-scattered photons. Calculations using FLUKA with mono-energetic photons were used to represent the main components of the x-ray spectrum up to 10 MV. Mono-energetic photons were used to enable the study of the behaviour of each energy component from the associated interaction processes. The results showed that adding lead of 1 to 4 mm thickness to the walls and floor of the maze reduced the dose at the maze entrance by up to 80%. Subsequent scatter dose measurements performed at the maze entrance of an existing treatment room with lead sheet of 1.3 mm thickness added to the maze walls and floor supported the results from the simulations. The dose reduction at the maze entrance with the lead in place was up to 50%. The variation between simulation and measurement was attributed to the fact that insufficient lead was available to completely cover the maze walls and floor. This novel proposal of partly, or entirely, covering the maze walls with lead a few millimetres in thickness has implications for the design of linear accelerator treatment rooms since it has the potential to provide savings, in terms of space and costs, when an existing maze requires upgrading in an environment where space is limited and the maze length cannot be extended sufficiently to reduce the dose.

Not re-inventing the wheel: the adaptive implementation of the meeting centres support programme in four European countries.

OBJECTIVES: The implementation of new health services is a complex process. This study investigated the first phase of the adaptive implementation of the Dutch Meeting Centres Support Programme (MCSP) for people with dementia and their carers in three European countries (Italy, Poland, the UK) within the JPND-MEETINGDEM project. Anticipated and experienced factors influencing the implementation, and the efficacy of the implementation process, were investigated. Findings were compared with previous research in the Netherlands. METHOD: A qualitative multiple case study design was applied. Checklist on anticipated facilitators and barriers to the implementation and semi-structured interview were completed by stakeholders, respectively at the end and at the beginning of the preparation phase. RESULTS: Overall, few differences between countries were founded. Facilitators for all countries were: added value of MCSP matching needs of the target group, evidence of effectiveness of MCSP, enthusiasm of stakeholders. General barriers were: competition with existing care and welfare organizations and scarce funding. Some countries experienced improved collaborations, others had difficulties finding a socially integrated location for MCSP. The step-by-step implementation method proved efficacious. CONCLUSION: These insights into factors influencing the implementation of MCSP in three European countries and the efficacy of the step-by-step preparation may aid further implementation of MCSP in Europe.

Antenatal Weight Management: Women's Experiences, Behaviours, and Expectations of Weighing in Early Pregnancy.

The current emphasis on obstetric risk management helps to frame gestational weight gain as problematic and encourages intervention by healthcare professionals. However pregnant women have reported confusion, distrust, and negative effects associated with antenatal weight management interactions. The MAGIC study (MAnaging weiGht In pregnanCy) sought to examine women's self-reported experiences of usual-care antenatal weight management in early pregnancy and consider these alongside weight monitoring behaviours and future expectations. 193 women (18 yrs+) were recruited from routine antenatal clinics at the Nottingham University Hospital NHS Trust. Self-reported gestation was 10-27 weeks, with 41.5% (n = 80) between 12 and 14 and 43.0% (n = 83) between 20 and 22 weeks. At recruitment 50.3% of participants (n = 97) could be classified as overweight or obese. 69.4% of highest weight women (≥30 kg/m2) did not report receiving advice about weight, although they were significantly more likely compared to women with BMI < 30 kg/m2. The majority of women (regardless of BMI) did not express any barriers to being weighed and 40.8% reported weighing themselves at home. Women across the BMI categories expressed a desire for more engagement from healthcare professionals on the issue of bodyweight. Women are clearly not being served appropriately in the current situation which simultaneously problematizes and fails to offer constructive dialogue.

Setting targets leads to greater long-term weight losses and 'unrealistic' targets increase the effect in a large community-based commercial weight management group.

BACKGROUND: Setting personal targets is an important behavioural component in weight management programmes. Normal practice is to encourage 'realistic' weight loss, although the underlying evidence base for this is limited and controversial. The present study investigates the effect of number and size of weight-loss targets on long-term weight loss in a large community sample of adults. METHODS: Weight change, attendance and target weight data for all new UK members, joining from January to March 2012, were extracted from a commercial slimming organisation's electronic database. RESULTS: Of the 35 380 members who had weight data available at 12 months after joining, 69.1% (n = 24 447) had a starting body mass index (BMI) ≥30 kg m-2 . Their mean (SD) weight loss was 12.9% (7.8%) and, for both sexes, weight loss at 12 months was greater for those who set targets (P < 0.001). Those that set ≥4 targets achieved the greatest loss (P < 0.001). The odds ratio for weight loss ≥10% at 12 months was 10.3 (95% confidence interval = 9.7-11.1, P < 0.001) where targets had been set compared to none. At the highest quintile of target size, the size of the first target explained 47.2% (P < 0.001) of the variance in weight loss achieved at 12 months. The mean (SD) BMI reduction in those with a target >25% was 7.6 (4.0) kg m-2 . A higher percentage of obese members did not set targets (P < 0.001) compared to those with a BMI <30 kg m-2 . CONCLUSIONS: Much of the variance in weight loss achieved in this population was explained by the number of targets set and the size of the first target. Although obese people were less likely to set targets, doing so increased the likelihood of achieving clinically significant weight loss and, for some 'unrealistic' targets, improved the results.

Maternal high-fat feeding in pregnancy programs atherosclerotic lesion size in the ApoE*3 Leiden mouse.

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R 2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.

Body composition and behaviour in adult rats are influenced by maternal diet, maternal age and high-fat feeding.

Fetal exposure to maternal undernutrition has lifelong consequences for physiological and metabolic function. Maternal low-protein diet is associated with an age-related phenotype in rats, characterised by a period of resistance to development of obesity in early adulthood, giving way to an obesity-prone, insulin-resistant state in later adulthood. Offspring of rats fed a control (18 % casein) or low-protein (9 % casein; LP) diet in pregnancy were challenged with a high-fat diet at 9 months of age. To assess whether other maternal factors modulated the programming effects of nutrition, offspring were studied from young (2-4 months old) and older (6-9 months old) mothers. Weight gain with a high-fat diet was attenuated in male offspring of older mothers fed LP (interaction of maternal age and diet; P = 0·011) and adipose tissue deposition was lower with LP feeding in both males and females (P < 0·05). Although the resistance to weight gain and adiposity was partially explained by lower energy intake in offspring of LP mothers (P < 0·001 males only), it was apparent that energy expenditure must be influenced by maternal diet and age. Assessment of locomotor activity indicated that energy expenditure associated with physical activity was unlikely to explain resistance to weight gain, but showed that offspring of older mothers were more anxious than those of younger mothers, with more rearing observed in a novel environment and on the elevated plus-maze. The data showed that in addition to maternal undernutrition, greater maternal age may influence development and long-term body composition in the rat.

Nutrition in early life and the programming of adult disease: a review.

Foetal development and infancy are life stages that are characterised by rapid growth, development and maturation of organs and systems. Variation in the quality or quantity of nutrients consumed by mothers during pregnancy, or infants during the first year of life, can exert permanent and powerful effects upon developing tissues. These effects are termed 'programming' and represent an important risk factor for noncommunicable diseases of adulthood, including the metabolic syndrome and coronary heart disease. This narrative review provides an overview of the evidence-base showing that indicators of nutritional deficit in pregnancy are associated with a greater risk of type-2 diabetes and cardiovascular mortality. There is also a limited evidence-base that suggests some relationship between breastfeeding and the timing and type of foods used in weaning, and disease in later life. Many of the associations reported between indicators of early growth and adult disease appear to interact with specific genotypes. This supports the idea that programming is one of several cumulative influences upon health and disease acting across the lifespan. Experimental studies have provided important clues to the mechanisms that link nutritional challenges in early life to disease in adulthood. It is suggested that nutritional programming is a product of the altered expression of genes that regulate the cell cycle, resulting in effective remodelling of tissue structure and functionality. The observation that traits programmed by nutritional exposures in foetal life can be transmitted to further generations adds weight the argument that heritable epigenetic modifications play a critical role in nutritional programming.

Limiting antenatal weight gain improves maternal health outcomes in severely obese pregnant women: findings of a pragmatic evaluation of a midwife-led intervention.

BACKGROUND: Antenatal obesity in pregnancy is associated with complications of pregnancy and poor obstetric outcomes. Although most guidance on pregnancy weight is focused on the prepregnancy period, pregnancy is widely viewed as a period where women are open to lifestyle change to optimise their health. METHODS: The hospital-based Bumps and Beyond intervention invited all pregnant women with a body mass index (BMI) >35 kg m(-2) to take part in a programme of health education around diet and exercise, accompanied by one-to-one guidance and monitoring of dietary change. This service evaluation compares 89 women who completed at a programme of seven sessions with healthy lifestyle midwives and advisors (intervention) versus a group of 89 women who chose not to attend (non-intervention). RESULTS: Mean (SD) weight gain in the intervention group [4.5 (4.6) kg] was less than in the non-intervention group [10.3 (4.4) kg] between antenatal booking and 36 weeks of gestation (< 0.001). This was associated with a 95% reduction in the risk of gestational hypertension during pregnancy and a general reduction in pregnancy complications. There was no effect of the intervention upon gestational diabetes or complications in labour other than post-partum haemorrhage (reduced by 55%). The impact of the intervention on gestational weight gain was greater in women with BMI >40 kg m(-2) at booking. There were no adverse effects of the intervention, even though 21% of the intervention group lost weight during their pregnancy. CONCLUSIONS: Intensive, personalised weight management intervention may be an effective strategy for the prevention of hypertensive disorders during pregnancy.

Assessing communication skills in dietetic consultations: the development of the reliable and valid DIET-COMMS tool.

BACKGROUND: There is an increasing emphasis on the development of communication skills for dietitians but few evidence-based assessment tools available. The present study aimed to develop a dietetic-specific, short, reliable and valid assessment tool for measuring communication skills in patient consultations: DIET-COMMS. METHODS: A literature review and feedback from 15 qualified dietitians were used to establish face and content validity during the development of DIET-COMMS. In total, 113 dietetic students and qualified dietitians were video-recorded undertaking mock consultations, assessed using DIET-COMMS by the lead author, and used to establish intra-rater reliability, as well as construct and predictive validity. Twenty recorded consultations were reassessed by nine qualified dietitians to assess inter-rater reliability: eight of these assessors were interviewed to determine user evaluation. RESULTS: Significant improvements in DIET-COMMS scores were achieved as students and qualified staff progressed through their training and gained experience, demonstrating construct validity, and also by qualified staff attending a training course, indicating predictive validity (P < 0.05). An acceptable level of intra-rater reliability (rs  = 0.90) and a moderate level of inter-rater reliability (r = 0.49) were demonstrated. Interviews identified many positive features and possible uses for DIET-COMMS in both pre- and post-registration settings. The need for assessor training was emphasised and how readily qualified dietitians would accept assessment of skills in practice was questioned. DISCUSSION: DIET-COMMS is a short, user-friendly, reliable and valid tool for measuring communication skills in patient consultations with both pre- and post-registration dietitians. Additional work is required to develop a training package for assessors and to identify how DIET-COMMS assessment can acceptably be incorporated into practice.

Timing of the introduction of complementary feeding and risk of childhood obesity: a systematic review.

The World Health Organisation recommends exclusive breastfeeding until 6 months of age and continued breastfeeding until 2 years of age or beyond. Appropriate complementary foods should be introduced in a timely fashion, beginning when the infant is 6 months old. In developing countries, early or inappropriate complementary feeding may lead to malnutrition and poor growth, but in countries such as the United Kingdom and United States of America, where obesity is a greater public health concern than malnutrition, the relationship to growth is unclear. We conducted a systematic review of the literature that investigated the relationship between the timing of the introduction of complementary feeding and overweight or obesity during childhood. Electronic databases were searched from inception until 30 September 2012 using specified keywords. Following the application of strict inclusion/exclusion criteria, 23 studies were identified and reviewed by two independent reviewers. Data were extracted and aspects of quality were assessed using an adapted Newcastle-Ottawa scale. Twenty-one of the studies considered the relationship between the time at which complementary foods were introduced and childhood body mass index (BMI), of which five found that introducing complementary foods at <3 months (two studies), 4 months (2 studies) or 20 weeks (one study) was associated with a higher BMI in childhood. Seven of the studies considered the association between complementary feeding and body composition but only one study reported an increase in the percentage of body fat among children given complementary foods before 15 weeks of age. We conclude that there is no clear association between the timing of the introduction of complementary foods and childhood overweight or obesity, but some evidence suggests that very early introduction (at or before 4 months), rather than at 4-6 months or >6 months, may increase the risk of childhood overweight.