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Protocols for the Use of Gut Models to Study the Potential Contribution of the Gut Microbiota to Human Nutrition Through the Production of Short-Chain Fatty Acids
No full textThe colonic microbiota influences human energy status through the metabolic activity of the taxonomically diverse prokaryotic residents that number up to 1012 cells per gram. The principal means by which this happens is probably via short-chain fatty acids (SCFAs) (mainly acetate, propionate and butyrate), which are continually produced by fermentation of dietary fibre, absorbed through the colonic epithelium, transported via the hepatic portal vein to the liver and then converted to glucose and other lipids. SCFAs may also regulate appetite via G protein-coupled receptor (GPR43) activation and signalling. Since the colonic microbiota is inaccessible for routine investigation, microbiologists have used human faeces as a surrogate for intestinal contents, animal models and various in vitro systems. These range in complexity from batch cultures of isolated gut bacteria through defined consortia grown in batch and continuous culture to multistage continuous culture models that reproduce features of the proximal and distal colons. Such systems have been used to investigate the metabolism of gut bacteria for several decades and can be adopted for studies specifically focussing on SCFA production in the context of nutrition/obesity. SCFAs generated by bacterial fermentation can be analysed using gas chromatography, or more inclusive data can be obtained via metabonomics/metabolomics. Whilst culture and FISH provide a useful means of bacteriological analysis, next-generation sequencing (NGS) has facilitated major advances in our understanding of this complex ecosystem. The following protocol details the establishment of a three-stage continuous culture microcosm of the human colon and outlines options for bacteriological and metabolite analyses
The development of Neolithic house societies in Orkney
No full textThis volume examines the Neolithic period in Orkney through a substantial fieldwork project running from 1994 - 2013. Employing the evidence from this fieldwork, the investigation focuses on social and material strategies running through the 4th and 3rd millennium BC within a modified framework of House Societies as identiified by Levi Strauss
Factors associated with improvement in disease activity following initiation of etanercept in children and young people with Juvenile Idiopathic Arthritis: results from the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study
No full textObjectives. The objectives of this study were to investigate change in disease activity, and explore factors associated with response, in children with JIA over the initial year of etanercept treatment.Methods. This analysis included children with JIA starting etanercept in the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study. Response was assessed using change in juvenile arthritis disease activity score-71 (JADAS-71), an excellent response (ACR Pedi 90), and achieving minimal disease activity (MDA) at 1 year. Change in JADAS-71 was evaluated over time. Multivariable backward stepwise logistic regression was performed to identify factors associated with ACR Pedi 90 and MDA.Results. A total of 496 children were included. Over the first year, 17 stopped due to inefficacy, 9 due to adverse events and 7 for other reasons. One child stopped for remission. At 1 year, 74, 69 and 38% reached ACR Pedi 30, 50 and 90, respectively, and 48% had achieved MDA. Independent predictors of achieving ACR Pedi 90 at 1 year included shorter disease duration [odds ratio (OR) 0.91; 95% CI: 0.85, 0.97)], no concurrent oral corticosteroid use (OR 0.48; 95% CI: 0.29, 0.80) and history of uveitis (OR 2.26; 95% CI: 1.08, 4.71). Independent predictors of achieving MDA at 1 year included younger patients (OR 0.60; 95% CI: 0.38, 0.95), and disease not treated with concurrent oral corticosteroids (OR 0.57; 95% CI: 0.35, 0.93).Conclusion. Among this real-world cohort of children with severe JIA, a significant proportion of children achieved an excellent ACR Pedi response and MDA within 1 year of starting etanercept, although few clinical factors could predict this outcome
Re-refinement of 4g4a: room-temperature X-ray diffraction study of cisplatin and its binding to His15 of HEWL after 14 months chemical exposure in the presence of DMSO
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Prospective cohort feasibility study of a transdiagnostic group intervention for common mental health problems: The Take Control Course
No full textObjectives: While transdiagnostic psychological treatments appear to be promising, they require greater empirical support. This study is a preliminary examination of the effectiveness, feasibility and acceptability of a new transdiagnostic 6-session group-based intervention (Take Control Course; TCC) predominantly aimed at clients within primary care. Briefer interventions are gaining an increasing evidence base and this study seeks to compare the TCC to an established brief intervention within primary care. Design: Prospective cohort study comparing two active psychological treatments. Methods: TCC group (n = 66) was compared to a non-randomised control group of clients accessing low-intensity interventions (n = 43) using random-effect regression models. Primary outcomes were depression and anxiety scores; additional outcomes included social and other functioning. Results: For the TCC group, changes on all pre-post outcomes were significant with moderate effect sizes. The between group differences were not significant. Conclusions: Results show potential for TCC to be an effective intervention, but further work is required to validate these findings in a more rigorous, randomised study
Matching Exponential-Based and Resolvent-Based Centrality Measures
No full textThe relative importance of nodes in a network can be quantified via functions of the adjacency matrix. Two popular choices of function are the exponential, which is parameter-free, and the resolvent function, which yields the Katz centrality measure. Katz centrality can be the more computationally efficient, especially for large directed networks, and has the benefit of generalizing naturally to time-dependent network sequences, but it depends on a parameter. We give a prescription for selecting the Katz parameter based on the objective of matching the centralities of the exponential counterpart. For our new choice of parameter the resolvent can be very ill conditioned, but we argue that the centralities computed in floating point arithmetic can nevertheless reliably be used for ranking. Experiments on six real networks show that the new choice of Katz parameter leads to rankings of nodes that generally match those from the exponential centralities well in practice
Natural Language Search Interfaces: Health Data Needs Single-Field Variable Search
No full textBackground: Data discovery, particularly the discovery of key variables and their inter-relationships, is key to secondary data analysis, and in-turn, the evolving field of data science. Interface designers have presumed that their users are domain experts, and so they have provided complex interfaces to support these “experts.” Such interfaces hark back to a time when searches needed to be accurate first time as there was a high computational cost associated with each search. Our work is part of a governmental research initiative between the medical and social research funding bodies to improve the use of social data in medical research. Objective: The cross-disciplinary nature of data science can make no assumptions regarding the domain expertise of a particular scientist, whose interests may intersect multiple domains. Here we consider the common requirement for scientists to seek archived data for secondary analysis. This has more in common with search needs of the “Google generation” than with their single-domain, single-tool forebears. Our study compares a Google-like interface with traditional ways of searching for noncomplex health data in a data archive. Methods: Two user interfaces are evaluated for the same set of tasks in extracting data from surveys stored in the UK Data Archive (UKDA). One interface, Web search, is “Google-like,” enabling users to browse, search for, and view metadata about study variables, whereas the other, traditional search, has standard multioption user interface. Results: Using a comprehensive set of tasks with 20 volunteers, we found that the Web search interface met data discovery needs and expectations better than the traditional search. A task × interface repeated measures analysis showed a main effect indicating that answers found through the Web search interface were more likely to be correct (F1,19=37.3, P<.001), with a main effect of task (F3,57=6.3, P<.001). Further, participants completed the task significantly faster using the Web search interface (F1,19=18.0, P<.001). There was also a main effect of task (F2,38=4.1, P=.025, Greenhouse-Geisser correction applied). Overall, participants were asked to rate learnability, ease of use, and satisfaction. Paired mean comparisons showed that the Web search interface received significantly higher ratings than the traditional search interface for learnability (P=.002, 95% CI [0.6-2.4]), ease of us
Observation of viscosity transition in α-pinene secondary organic aerosol
No full textUnder certain conditions, secondary organic aerosol (SOA) particles can exist in the atmosphere in an amorphous solid or semi-solid state. To determine their relevance to processes such as ice nucleation or chemistry occurring within particles requires knowledge of the temperature and relative humidity (RH) range for SOA to exist in these states. In the Cosmics Leaving Outdoor Droplets (CLOUD) experiment at The European Organisation for Nuclear Research (CERN), we deployed a new in situ optical method to detect the viscous state of α-pinene SOA particles and measured their transition from the amorphous highly viscous state to states of lower viscosity. The method is based on the depolarising properties of laboratory-produced non-spherical SOA particles and their transformation to non-depolarising spherical particles at relative humidities near the deliquescence point. We found that particles formed and grown in the chamber developed an asymmetric shape through coagulation. A transition to a spherical shape was observed as the RH was increased to between 35 % at −10 °C and 80 % at −38 °C, confirming previous calculations of the viscosity-transition conditions. Consequently, α-pinene SOA particles exist in a viscous state over a wide range of ambient conditions, including the cirrus region of the free troposphere. This has implications for the physical, chemical, and ice-nucleation properties of SOA and SOA-coated particles in the atmosphere