Infrared Spectroscopic Analysis in the Differentiation of Epithelial Misplacement From Adenocarcinoma in Sigmoid Colonic Adenomatous Polyps.

Purpose: The differential diagnosis of epithelial misplacement from invasive cancer in the colon is a challenging endeavour, augmented by the introduction of bowel cancer population screening. The main aim of the work is to test, as a proof-of concept study, the ability of the infrared spectroscopic imaging approach to differentiate epithelial misplacement from adenocarcinoma in sigmoid colonic adenomatous polyps. Methods: Ten samples from each of the four diagnostic groups, normal colonic mucosa, adenomatous polyps with low grade dysplasia, epithelial misplacement in adenomatous polyps and adenocarcinoma, were analysed using IR spectroscopic imaging and data processing methods. IR spectral images were subjected to data pre-processing and cluster analysis based segmentation to identify epithelial, connective tissue and stromal regions. Statistical analysis was carried out using principal component analysis and linear discriminant analysis based cross validation, to classify spectral features according to the pathology, and the diagnostic attributes were compared. Results: The combined 4-group classification model on an average showed a sensitivity of 64%, a specificity of 88% and an accuracy of 76% for prediction based on a 'single spectrum', whilst a 'majority-vote' prediction on an average showed a sensitivity of 73%, a specificity of 90% and an accuracy of 82%. The 2-group model, for the differential diagnosis of epithelial misplacement versus adenocarcinoma, showed an average sensitivity and specificity of 82.5% for prediction based on a 'single spectrum' whilst a 'majority-vote' classification showed an average sensitivity and specificity of 90%. A 92% area under the curve (AUC) value was obtained when evaluating the classifier using the Receiver Operating Characteristics (ROC) curves. Conclusions: IR spectroscopy shows promise in its ability to differentiate epithelial misplacement from adenocarcinoma in tissue sections, considered as one of the most challenging endeavours in population-wide diagnostic histopathology. Further studies with larger series, including cases with challenging diagnostic features are required to ascertain the capability of this modern digital pathology approach. In the long-term, IR spectroscopy based pathology which is relatively low-cost and rapid, could be a promising endeavour to consider for integration into the existing histopathology pathway, in particular for population based screening programmes where large number of samples are scrutinised.

Associations between number of siblings, birth order, eating rate and adiposity in children and adults.

Eating quickly is associated with eating larger amounts at mealtimes and faster eaters tend to have a higher BMI. Evidence suggests that sibling structure influences the development of childhood eating behaviours. We hypothesized that number of siblings and birth order might play a role in the development of eating rate. In two UK studies, children in Bristol (n = 132; Study 1) and adults and children in London (adults n = 552, children n = 256; Study 2) reported their eating rate, number of siblings, and birth order. A BMI measurement was obtained and in Study 2 waist circumference was recorded. Ordered logistic regression was used to examine effects of sibling structure on eating rate and linear regression assessed effects of eating rate on BMI. Faster eating was associated with higher BMI and a larger waist, in children and adults (ps < .01). In Study 1, first-born children were twice as likely to eat faster compared to children who were not first-born (P < .04). In Study 2, only-child adults reported eating slower than adults who were not first-born (P < .003). Additionally, higher number of siblings was associated with faster eating rate in children from Bristol (P < .05), but not in children from London. London adults without siblings ate slower than those with two or more (P = .01), but having one sibling was associated with eating faster than having two or more (P = .01). These findings reveal how birth order and number of siblings might influence eating rate. Exploring these relationships through direct observation would be beneficial in future studies.

Food portion size influences accompanying beverage selection in adults.

When trying to reduce food portion size, it is important that meal satisfaction is, as far as possible, preserved. Otherwise, individuals may select accompaniments to the meal (e.g., snacks, beverages) to achieve satisfaction and, in doing so, negate any benefit of the original portion size reduction. This study investigated whether varying portion sizes of food would influence choice of accompanying beverages. That is, when presented with a food portion size that is smaller or larger than their ideal, an individual may compensate by choosing a beverage based on its satiating and/or orosensory properties to balance the expected satiation and satisfaction of a meal. Data from an online interactive study (n = 93) was analysed using multilevel ordinal logistic regression models. Food portion size (100, 300, 500, 700, or 900 kcal) predicted beverage choice (water, low-energy sweetened beverage, high-energy sweetened beverage). For example, the sweetened beverages were more likely to be selected with small food portion sizes (p < .001). Participant ideal food portion size did not interact with this relationship. Participants appear to have recognised that sweetened beverages provide flavour and/or energy, and used them to compensate for a smaller meal. While switching to a low-energy beverage with an increased food portion size is advantageous for energy balance, choosing a high-energy beverage with a decreased food portion size is likely to be detrimental for those attempting to reduce energy intake and body weight.

Role Reversal: The Influence of Slot Machine Gambling on Subsequent Alcohol Consumption.

Experimental studies examining the relationship between alcohol use and gambling have focused predominantly on alcohol's influence on gambling behavior. There has been little consideration of the reverse pathway: whether gambling influences subsequent alcohol use. Two experiments examined whether gambling and gambling outcomes (i.e. profits during a gambling session) influenced subsequent alcohol consumption. Experiment 1 (n = 53) used an ad libitum consumption test, in which participants could request beverages during a 30 min window. Experiment 2 (n = 29) used a beer taste test procedure, in which participants were asked to rate a series of beers. In both studies, male regular gamblers were assigned to watch a television show or play a modern slot machine for 30 min, before being provided with access to alcohol. On the ad libitum procedure, gambling significantly increased the number of alcoholic drinks ordered, the volume of alcohol consumed, the participants' speed of drinking, and their intention to drink alcohol. These effects were not corroborated using the taste test procedure. Across both studies, gambling outcomes were not associated with alcohol consumption. In conjunction with prior findings, the observation that gambling can promote alcohol consumption under certain conditions highlights a possible feedback loop whereby gambling and alcohol reinforce one another. However, the divergent results between the ad libitum and taste test experiments point to boundary conditions for the effect and raise methodological considerations for future work measuring alcohol consumption in gambling environments.

Breaking the fast: Meal patterns and beliefs about healthy eating style are associated with adherence to intermittent fasting diets.

Many believe that eating three meals each day is healthy and that skipping meals can be detrimental. What remains unclear is whether this belief undermines attempts to restrict energy intake by skipping meals. In an online survey, participants (N = 312) with experience of intermittent fasting (IF) reported their beliefs about healthy meal and snack frequency, as well as their non-fasting-dasy and fasting-day eating patterns. They also reported their level of concern with fasting-day meal patterns and their concern to generate fullness when selecting foods. Individuals currently following an IF diet (Current-IF dieters) and those who had previously attempted an IF diet but were non-adherent (Former-IF dieters) took part. Former-IF dieters were more likely to believe that it is healthy to eat three meals a day, punctuated by several snacks. On fasting-days, Former-IF dieters were also more likely to eat breakfast, a mid-morning snack, lunch, and a mid-afternoon snack whereas Current-IF dieters tended to save their eating for dinner and a late evening snack. Former-IF dieters were also more likely to be concerned about the negative consequences of missing a meal, to eat in anticipation of future hunger, and to prioritise fullness over taste when selecting foods. These findings reveal how beliefs about a healthy eating style can play an important role in shaping dietary patterns. Interventions aimed at modifying beliefs about healthy meal patterns may promote IF diet adherence.

Improvement in staff compliance with a safety standard checklist in endoscopy in a tertiary centre.

National Health Service England published the National Safety Standards for Invasive Procedures (NatSSIP) in 2015. They mandated that individual trusts produce Local Safety Standards for Invasive Procedures (LocSSIPs), a set of safety standards drawn from the NatSSIP that apply to a particular clinical situation in a given department, for all invasive procedures. The project goal was to design and implement the LocSSIP within the endoscopy department. A draft LocSSIP was produced, and a pilot study conducted to gain initial feedback on its use. Version 1 of the checklist was produced and after approval, rolled out for use within the endoscopy department at 'time out' and 'sign out'. A scoring system was developed that allowed the quality of the performance of LocSSIPs to be assessed and recorded as a 'compliance score'. After 2 months, an independent observer spent a week assessing use of the checklist, recording completion and a compliance score. Analysis of this data led to a number of changes in performing the checklist, wider multidisciplinary team education and integration of the checklist into existing documentation, before reassessing at 12 months. In 2016, 'time out' checks were completed in 100% of cases, but full completion was only observed in 68%. 'Sign out' checks were completed in 91% of cases, with full completion in 71%. In 2017, 'time out' checks were completed in 100% of cases, with full completion in 85%. 'Sign out' checks were completed in 100% of cases, with full completion in 91%. The composite score for compliance in 2016 was 57% increasing to 90% in 2017. In conclusion, stronger departmental leadership, broadening education and integration of the checklist into routine documentation to reduce duplication led to significant improvements in compliance with use of the checklist. Ongoing education and assessment is imperative to ensure that compliance is maintained to ensure patient safety.

Better governance, better access: practising responsible data sharing in the METADAC governance infrastructure.

BACKGROUND: Genomic and biosocial research data about individuals is rapidly proliferating, bringing the potential for novel opportunities for data integration and use. The scale, pace and novelty of these applications raise a number of urgent sociotechnical, ethical and legal questions, including optimal methods of data storage, management and access. Although the open science movement advocates unfettered access to research data, many of the UK's longitudinal cohort studies operate systems of managed data access, in which access is governed by legal and ethical agreements between stewards of research datasets and researchers wishing to make use of them. Amongst other things, these agreements aim to respect the reasonable expectations of the research participants who provided data and samples, as expressed in the consent process. Arguably, responsible data management and governance of data and sample use are foundational to the consent process in longitudinal studies and are an important source of trustworthiness in the eyes of those who contribute data to genomic and biosocial research. METHODS: This paper presents an ethnographic case study exploring the foundational principles of a governance infrastructure for Managing Ethico-social, Technical and Administrative issues in Data ACcess (METADAC), which are operationalised through a committee known as the METADAC Access Committee. METADAC governs access to phenotype, genotype and 'omic' data and samples from five UK longitudinal studies. FINDINGS: Using the example of METADAC, we argue that three key structural features are foundational for practising responsible data sharing: independence and transparency; interdisciplinarity; and participant-centric decision-making. We observe that the international research community is proactively working towards optimising the use of research data, integrating/linking these data with routine data generated by health and social care services and other administrative data services to improve the analysis, interpretation and utility of these data. The governance of these new complex data assemblages will require a range of expertise from across a number of domains and disciplines, including that of study participants. Human-mediated decision-making bodies will be central to ensuring achievable, reasoned and responsible decisions about the use of these data; the METADAC model described in this paper provides an example of how this could be realised.

An Overview of the Current Management of Bilobar Colorectal Liver Metastases.

Bilobar colorectal liver metastases (BCRLM) present a challenging scenario for liver surgeons globally. The following article aims to provide an overview of the different strategies which may be utilised in order to successfully manage advanced BCRLM.

Individual variability in preference for energy-dense foods fails to predict child BMI percentile.

Many studies show that higher dietary energy density is associated with greater body weight. Here we explored two propositions: i) that child BMI percentile is associated with individual differences in children's relative preference for energy-dense foods, ii) that child BMI percentile is associated with the same individual differences between their parents. Child-parent dyads were recruited from a local interactive science center in Bristol (UK). Using computerized tasks, participants ranked their preference and rated their liking for a range of snack foods that varied in energy density. Children (aged 3-14years, N=110) and parents completed the tasks for themselves. Parents also completed two further tasks in which they ranked the foods in the order that they would prioritize for their child, and again, in the order that they thought their child would choose. Children preferred (t(109)=3.91, p<0.001) and better liked the taste of (t(109)=3.28, p=0.001) higher energy-dense foods, and parents correctly estimated this outcome (t(109)=7.18, p<0.001). Conversely, lower energy-dense foods were preferred (t(109)=-4.63, p<0.001), better liked (t(109)=-2.75, p=0.007) and served (t(109)=-15.06, p<0.001) by parents. However, we found no evidence that child BMI percentile was associated with child or parent preference for, or liking of, energy-dense foods. Therefore, we suggest that the observed relationship between dietary energy density and body weight is not explained by individual differences in preference for energy density.

Challenging diagnostic issues in adenomatous polyps with epithelial misplacement in bowel cancer screening: 5 years' experience of the Bowel Cancer Screening Programme Expert Board.

The diagnostic difficulties of differentiating epithelial misplacement from invasive cancer in colorectal adenomatous polyps have been recognised for many years. Nevertheless, the introduction of population screening in the UK has resulted in extraordinary diagnostic problems. Larger sigmoid colonic adenomatous polyps, which are those most likely to show epithelial misplacement, are specifically selected into such screening programmes, because these polyps are likely to bleed and screening is based on the detection of occult blood. The diagnostic challenges associated with this particular phenomenon have necessitated the institution of an 'Expert Board': this is a review of the first five years of its practice, during which time 256 polyps from 249 patients have been assessed. Indeed, the Expert Board contains three pathologists, because those pathologists do not necessarily agree, and a consensus diagnosis is required to drive appropriate patient management. However, this study has shown substantial levels of agreement between the three Expert Board pathologists, whereby the ultimate diagnosis has been changed, from that of the original referral diagnosis, by the Expert Board for half of all the polyps, in the substantial majority from malignant to benign. In 3% of polyp cases, the Expert Board consensus has been the dual diagnosis of both epithelial misplacement and adenocarcinoma, further illustrating the diagnostic difficulties. The Expert Board of the Bowel Cancer Screening Programme in the UK represents a unique and successful development in response to an extraordinary diagnostic conundrum created by the particular characteristics of bowel cancer screening.

Large Portions Encourage the Selection of Palatable Rather Than Filling Foods.

BACKGROUND: Portion size is an important driver of larger meals. However, effects on food choice remain unclear. OBJECTIVE: Our aim was to identify how portion size influences the effect of palatability and expected satiety on choice. METHODS: In Study 1, adult participants (n = 24, 87.5% women) evaluated the palatability and expected satiety of 5 lunchtime meals and ranked them in order of preference. Separate ranks were elicited for equicaloric portions from 100 to 800 kcal (100-kcal steps). In Study 2, adult participants (n = 24, 75% women) evaluated 9 meals and ranked 100-600 kcal portions in 3 contexts (scenarios), believing that 1) the next meal would be at 1900, 2) they would receive only a bite of one food, and 3) a favorite dish would be offered immediately afterwards. Regression analysis was used to quantify predictors of choice. RESULTS: In Study 1, the extent to which expected satiety and palatability predicted choice was highly dependent on portion size (P < 0.001). With smaller portions, expected satiety was a positive predictor, playing a role equal to palatability (100-kcal portions: expected satiety, ß: 0.42; palatability, ß: 0.46). With larger portions, palatability was a strong predictor (600-kcal portions: ß: 0.53), and expected satiety was a poor or negative predictor (600-kcal portions: ß: -0.42). In Study 2, this pattern was moderated by context (P = 0.024). Results from scenario 1 replicated Study 1. However, expected satiety was a poor predictor in both scenario 2 (expected satiety was irrelevant) and scenario 3 (satiety was guaranteed), and palatability was the primary driver of choice across all portions. CONCLUSIONS: In adults, expected satiety influences food choice, but only when small equicaloric portions are compared. Larger portions not only promote the consumption of larger meals, but they encourage the adoption of food choice strategies motivated solely by palatability.

Bowel cancer screening-generated diagnostic conundrum of the century: pseudoinvasion in sigmoid colonic polyps.

The introduction of bowel cancer screening, in the United Kingdom, United States of America, and many other Western countries, has provided considerable interest and no little diagnostic consternation for pathologists. In the United Kingdom, the universal introduction of bowel cancer screening, initially by fecal occult blood testing and more recently by the introduction of flexible sigmoidoscopy, has provided four main areas of pathological diagnostic difficulty. This is the biopsy diagnosis of adenocarcinoma, serrated pathology, the diagnosis and management of polyp cancer, and, finally, the phenomenon of pseudoinvasion/epithelial misplacement (PEM), particularly in sigmoid colonic adenomatous polyps. The diagnostic difficulties associated with the latter phenomenon have provided particular problems that have led to the institution of a UK national 'Expert Board', comprising three pathologists, who adjudicate on difficult cases. The pathological features favoring PEM are well recognized but there is no doubt that there can be profound mimicry of adenocarcinoma, and, as yet, no adjunctive diagnostic tools have been developed to allow the differentiation in difficult cases. Research in this area is proceeding and some methodologies do show promise in this difficult diagnostic area.

GPIb potentiates GPVI-induced responses in human platelets.

Platelet adhesion to vascular subendothelial proteins at the site of blood vessel injury is critical for initiating haemostasis. Collagen is a major matrix protein that binds plasma von Willebrand factor (vWF) when the endothelium becomes damaged and therefore in vivo platelets are likely to encounter both of these agonists simultaneously, through glycoprotein VI (GPVI) and alpha2beta1 receptors for collagen and GPIb-V-IX and alphaIIbbeta3 receptors for vWF. We hypothesised a potentiatory role for vWF that would synergise with collagen leading to functional activation and show this to be the case for platelet aggregation, 5-HT secretion and calcium responses. Synergy between these two agonists is likely to involve receptors GPVI and GPIb-V-IX, for collagen and vWF, respectively, since 5-HT secretion in response to collagen is potentiated by vWF in the presence of either EGTA or EDTA, which prevent binding to integrins alphaIIbbeta3 (EGTA) or both alphaIIbbeta3 and alpha2beta1 (EDTA). In addition, vWF is also able to potentiate 5-HT secretion responses to collagen-related peptide, confirming that GPVI is able to support synergy with vWF. These findings are important in that they reveal a novel role for vWF in platelet activation as a potentiator of platelet activation by collagen.