Functional bowel disease : a challenging frontier in gastroenterology

The last 30 years have seen incredible advances in the science and practice of gastroenterology and hepatology. In the 1970s, the fiberoptic endoscopic revolution facilitated the visualization of the mucosa of a large segment of the gastrointestinal tract and afforded the opportunity for specialized studies using histological and biochemical analyses. The impact of fiberoptic endoscopy on surveillance or screening for cancer of the colon will be more apparent in the next millennium. Novel pharmacological approaches have had a dramatic impact on gastroenterology.peer-reviewe

Broad-spectrum antibiotic use in Europe : more evidence of cultural influences on prescribing behaviour

Objectives: Sociocultural factors have been hypothesized as important drivers of inappropriate antibiotic prescribing in European ambulatory care. This study sought to assess whether they can also explain the reported variation in broad-spectrum antibiotic (Br-Ab) use among EU/European Economic Area (EEA) countries. Methods: Correlation and regression analysis were performed, using the bootstrap method, between Br-Ab ratios reported from 28 EU countries by the ECDC, and national Hofstede cultural dimensions and control of corruption (CoC) scores. Results: Significant bootstrapping correlation coefficients were identified between Br-Ab ratios and the dimension of uncertainty avoidance (UAI) as well as CoC. However, following both bootstrapping multiple regression and generalized linear modelling, only UAI was retained as the sole predictor. A logarithmic model explained 58.6% of the variation in European Br-Ab variability solely using national UAI scores (P,0.001). Conclusions: Br-Ab prescribing appears to be driven by the level of UAI within the country. Any interventions aimed at reducing Br-Ab in high-consuming EU/EEA countries need to address this cultural perception to maxi-mize their chances of success.peer-reviewe

What’s new in functional and motility disorders in the lower GI tract?

This review addresses what is new in functional and motility disorders in the lower gastrointestinal tract: biomarkers and actionable biomarkers in irritable bowel syndrome (IBS), dietary and pharmacological treatment of abdominal pain in IBS, how to screen for rectal evacuation disorders in chronic constipation, hypotheses on the etiology of infantile colic, and lessons learned from the appraisal of an esoteric colonic motor disorder, that is, megacolon in association with multiple endocrine neoplasia type 2B. Understanding the mechanisms has moved these from idiopathic or cryptogenic disorders to organic diseases and has changed the attitude of health care providers to empathize with the suffering and legitimate pleas of millions of patients for effective therapies.peer-reviewe

Understanding the epidemiology of MRSA in Europe : do we need to think outside the box?

Background: The epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) infections, using bacteraemia as a marker, shows a striking geographical pattern in Europe. The prevalence of MRSA is low in Northern European countries, increases into central Europe and reaches its highest levels in the Mediterranean region. This has been attributed to varying levels of implementation of infection control and antibiotic stewardship (ICAS) programmes, but reasons for this variation have not been clearly established. Aim: To investigate the possible impact of national cultural dimensions on the epidemi- ology of MRSA in Europe. Methods: Median proportions of MRSA bacteraemia were sourced for countries partici- pating in the EARS-Net surveillance network in 2010, and correlated with the national cultural dimension scores of Hofstede et al. Findings: Significant associations were identified between MRSA proportions and the cultural constructs of uncertainty avoidance (UAI), masculinity (MAS) and power distance. Multiple regression models found significant associations for UAI, MAS and short-term orientation (R2 adjusted 1⁄4 0.475; P < 0.001). The model was found to be predictive of MRSA trends identified in several European countries between 2006 and 2010. Conclusion: Implementation of ICAS programmes often requires behavioural change. Cultural dimensions appear to be key factors affecting perceptions and values among healthcare workers, which in turn are critical for compliance and uptake. Customizing ICAS initiatives to reflect the local cultural background may improve their chances of success.peer-reviewe

Role of prucalopride, a serotonin (5-HT4) receptor agonist, for the treatment of chronic constipation

Constipation affects up to a quarter of the population in developed countries and is associated with poor quality of life and significant economic burden. Many patients with chronic constipation are dissatisfied with current therapy due to lack of long-term efficacy or side effects. Previous nonselective 5-hydroxytryptamine receptor 4 (5-HT4) agonists have been associated with significant interactions with other receptors (5-HT1B, 5-HT1D, and 5-HT2B for tegaserod; hERG for cisapride), leading to adverse cardiovascular events resulting in withdrawal of these drugs from the market. Prucalopride is a novel gastrointestinal prokinetic agent. It acts as a high affinity, highly-selective 5-HT4 agonist. Its efficacy in patients with chronic constipation has been demonstrated in several phase II and phase III clinical trials showing significant improvements in bowel transit, bowel function, gastrointestinal symptoms, and quality of life, with benefit maintained for up to 24 months in open label, multicenter, follow-up studies. Prucalopride’s high selectivity for the 5-HT4 receptor may explain its favorable safety and tolerability profiles, even in elderly subjects with stable cardiovascular disease. Prucalopride is a well tolerated and efficacious prokinetic medication that should enhance the treatment of chronic constipation unresponsive to first-line treatments

Automated identification and behaviour classification for modelling social dynamics in group-housed mice

Mice are often used in biology as exploratory models of human conditions, due to their similar genetics and physiology. Unfortunately, research on behaviour has traditionally been limited to studying individuals in isolated environments and over short periods of time. This can miss critical time-effects, and, since mice are social creatures, bias results. This work addresses this gap in research by developing tools to analyse the individual behaviour of group-housed mice in the home-cage over several days and with minimal disruption. Using data provided by the Mary Lyon Centre at MRC Harwell we designed an end-to-end system that (a) tracks and identifies mice in a cage, (b) infers their behaviour, and subsequently (c) models the group dynamics as functions of individual activities. In support of the above, we also curated and made available a large dataset of mouse localisation and behaviour classifications (IMADGE), as well as two smaller annotated datasets for training/evaluating the identification (TIDe) and behaviour inference (ABODe) systems. This research constitutes the first of its kind in terms of the scale and challenges addressed. The data source (side-view single-channel video with clutter and no identification markers for mice) presents challenging conditions for analysis, but has the potential to give richer information while using industry standard housing. A Tracking and Identification module was developed to automatically detect, track and identify the (visually similar) mice in the cluttered home-cage using only single-channel IR video and coarse position from RFID readings. Existing detectors and trackers were combined with a novel Integer Linear Programming formulation to assign anonymous tracks to mouse identities. This utilised a probabilistic weight model of affinity between detections and RFID pickups. The next task necessitated the implementation of the Activity Labelling module that classifies the behaviour of each mouse, handling occlusion to avoid giving unreliable classifications when the mice cannot be observed. Two key aspects of this were (a) careful feature-selection, and (b) judicious balancing of the errors of the system in line with the repercussions for our setup. Given these sequences of individual behaviours, we analysed the interaction dynamics between mice in the same cage by collapsing the group behaviour into a sequence of interpretable latent regimes using both static and temporal (Markov) models. Using a permutation matrix, we were able to automatically assign mice to roles in the HMM, fit a global model to a group of cages and analyse abnormalities in data from a different demographic

Playing nomic using a controlled natural language

Controlled natural languages have been used in a variety of domains, to enable information extraction and formal reasoning. One major challenge is that although the syntax is restricted to enable processing, without a similar restricted domain of application, it is typically difficult to extract useful results. In this paper we look at the development of a controlled natural language to reason about contractual clauses. The language is used to enable human players to play a variant of Nomic — a game of changing contracts, whose very nature makes it extremely challenging to mechanise. We present the controlled natural language with its implementation in the Grammatical Framework, and an underlying deontic logic used to reason about the contracts proposed by the players.peer-reviewe

A novel method of personnel cooling in an operating theatre environment

Funding obtained from University of Malta.An optimized theatre environment, including personal temperature regulation, can help maintain concentration, extend work times and may improve surgical outcomes. However, devices, such as cooling vests, are bulky and may impair the surgeon's mobility. We describe the use of a low-cost, low-energy 'bladeless fan' as a personal cooling device. The safety profile of this device was investigated by testing air quality using 0.5- and 5-µm particle counts as well as airborne bacterial counts on an operating table simulating a wound in a thoracic operation in a busy theatre environment. Particle and bacterial counts were obtained with both an empty and full theatre, with and without the 'bladeless fan'. The use of the 'bladeless fan' within the operating theatre during the simulated operation led to a minor, not statistically significant, lowering of both the particle and bacterial counts. In conclusion, the 'bladeless fan' is a safe, effective, low-cost and low-energy consumption solution for personnel cooling in a theatre environment that maintains the clean room conditions of the operating theatre.peer-reviewe

A generative traversability model for monocular robot self-guidance

The research work disclosed in this publication is partially funded by the Strategic Educational Pathways Scholarship (Malta). The scholarship is part-financed by the European Union - European Social Fund (ESF) under the Operational Programme II - Cohesion Policy 2007-2013, Empowering People for More Jobs and a Better Quality of Life.In order for robots to be integrated into human active spaces and perform useful tasks, they must be capable of discriminating between traversable surfaces and obstacle regions in their surrounding environment. In this work, a principled semi-supervised (EM) framework is presented for the detection of traversable image regions for use on a low-cost monocular mobile robot. We propose a novel generative model for the occurrence of traversability cues, which are a measure of dissimilarity between safe-window and image superpixel features. Our classification results on both indoor and outdoor images sequences demonstrate its generality and adaptability to multiple environments through the online learning of an exponential mixture model. We show that this appearance-based vision framework is robust and can quickly and accurately estimate the probabilistic traversability of an image using no temporal information. Moreover, the reduction in safe-window size as compared to the state-of-the-art enables a self-guided monocular robot to roam in closer proximity of obstacles.peer-reviewe

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis

Objective To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. Data sources We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. Study selection Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. Data extraction and synthesis Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. Outcomes Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week. Results Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week. Conclusions Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC