330 research outputs found
Defamation, A Camouflage of Psychic Interests: The Beginning of a Behavioral Analysis
No full textDoes the law of defamation need to be reformed? The author thinks so. Professor Probert rejects the doctrine of libel per se and questions the courts\u27 understanding and use of the term reputation. It is his belief that plaintiffs on an individual basis should have increased benefit of the knowledge accumulated by the various social sciences in proving the harm done by the alleged defamation, with more liberalization in the requirements of pleading and proof than is now generally countenanced by the courts
Microscopic Colitis
No full textThe book Recent Advances in Gastroenterology 12 covers key topics in gastroenterology and hepatology. It includes conditions such as ulcerative colitis and Crohn’s disease, which have seen significant developments. Topics which were not reviewed earlier like IgG4 syndrome and small intestinal imaging have been covered. Common diseases like microscopic colitis and coeliac disease are better understood in this book. Other disorders such as Helicobacter infection, alcoholic liver disease and viral hepatitis have gathered world attention. The book also discusses on exciting advances in the management of upper gastrointestinal bleeding, luminal imaging and endoscopy
The use of randomisation-based efficacy estimators in non-inferiority trials
No full textBackground: In a non-inferiority (NI) trial, analysis based on the intention-to-treat (ITT) principle is anti-conservative, so current guidelines recommend analysing on a per-protocol (PP) population in addition. However, PP analysis relies on the often implausible assumption of no confounders. Randomisation-based efficacy estimators (RBEEs) allow for treatment non-adherence while maintaining a comparison of randomised groups. Fischer et al. have developed an approach for estimating RBEEs in randomised trials with two active treatments, a common feature of NI trials. The aim of this paper was to demonstrate the use of RBEEs in NI trials using this approach, and to appraise the feasibility of these estimators as the primary analysis in NI trials. Methods: Two NI trials were used. One comparing two different dosing regimens for the maintenance of remission in people with ulcerative colitis (CODA), and the other comparing an orally administered treatment to an intravenously administered treatment in preventing skeletal-related events in patients with bone metastases from breast cancer (ZICE). Variables that predicted adherence in each of the trial arms, and were also independent of outcome, were sought in each of the studies. Structural mean models (SMMs) were fitted that conditioned on these variables, and the point estimates and confidence intervals compared to that found in the corresponding ITT and PP analyses. Results: In the CODA study, no variables were found that differentially predicted treatment adherence while remaining independent of outcome. The SMM, using standard methodology, moved the point estimate closer to 0 (no difference between arms) compared to the ITT and PP analyses, but the confidence interval was still within the NI margin, indicating that the conclusions drawn would remain the same. In the ZICE study, cognitive functioning as measured by the corresponding domain of the QLQ-C30, and use of chemotherapy at baseline were both differentially associated with adherence while remaining independent of outcome. However, while the SMM again moved the point estimate closer to 0, the confidence interval was wide, overlapping with any NI margin that could be justified. Conclusion: Deriving RBEEs in NI trials with two active treatments can provide a randomisation-respecting estimate of treatment efficacy that accounts for treatment adherence, is straightforward to implement, but requires thorough planning during the design stage of the study to ensure that strong baseline predictors of treatment are captured. Extension of the approach to handle nonlinear outcome variables is also required. Trial registration: The CODA study: ClinicalTrials.gov, identifier: NCT00708656. Registered on 8 April 2008. The ZICE study trial: ClinicalTrials.gov, identifier: NCT00326820. Registered on 16 May 2006
Studies of the hindgut and faecal volatile organic compound metabolome and microbiome of the horse
No full textThe horse is a hindgut fermenter which relies on microbial digestion to provide more than half of its energy requirements. Disturbances to the microbiota can lead to colic (abdominal pain), diarrhoea and other disorders in horses. Advances in techniques to characterise the equine gut microbiome have revealed that this is a complex population and many factors are thought to contribute towards the composition of species present. Epidemiological studies have identified various horse and management risk factors for colic including season (and associated management changes), foaling and tapeworm infections. The contribution of the intestinal microbiota to the development of colic in relation to these risk factors is unknown. The aim of this thesis is to investigate the association of these factors with the intestinal (or faeces as a proxy) microbiome and metabolome. Few studies to date have attempted to understand the equine gut mycobiome and functional equine microbiome (metabolome). The faecal metabolome may provide simple, cost effective markers for microbial shifts that may be associated with equine disease including increased likelihood of colic. A method to extract volatile organic compounds (VOCs) from equine ... (continues
Food additives : Assessing the impact of exposure to permitted emulsifiers on bowel and metabolic health – introducing the FADiets study
No full textAcknowledgements Additional members of the academic team including Dr Carrie Duckworth, Professor John Wilding, Professor Mark Pritchard and Professor Chris Probert (University of Liverpool, UK), Professor Harry Flint (Rowett Institute, UK), Dr Graham Horgan (Biomathematics and Statistics Scotland), Professor Johan Söderholm and Dr Åsa Keita (University Hospital Linköping, Sweden). Funding This study is funded by the Medical Research Council (MR/P023606/1).Peer reviewe
DL_MG: a parallel multigrid Poisson and Poisson−Boltzmann solver for electronic structure calculations in vacuum and solution
No full textThe solution of the Poisson equation is a crucial step in electronic structure calculations, yielding the electrostatic potential—a key component of the quantum mechanical Hamiltonian. In recent decades, theoretical advances and increases in computer performance have made it possible to simulate the electronic structure of extended systems in complex environments. This requires the solution of more complicated variants of the Poisson equation, featuring nonhomogeneous dielectric permittivities, ionic concentrations with nonlinear dependencies, and diverse boundary conditions. The analytic solutions generally used to solve the Poisson equation in vacuum (or with homogeneous permittivity) are not applicable in these circumstances, and numerical methods must be used. In this work, we present DL_MG, a flexible, scalable, and accurate solver library, developed specifically to tackle the challenges of solving the Poisson equation in modern large-scale electronic structure calculations on parallel computers. Our solver is based on the multigrid approach and uses an iterative high-order defect correction method to improve the accuracy of solutions. Using two chemically relevant model systems, we tested the accuracy and computational performance of DL_MG when solving the generalized Poisson and Poisson–Boltzmann equations, demonstrating excellent agreement with analytic solutions and efficient scaling to ∼109 unknowns and 100s of CPU cores. We also applied DL_MG in actual large-scale electronic structure calculations, using the ONETEP linear-scaling electronic structure package to study a 2615 atom protein–ligand complex with routinely available computational resources. In these calculations, the overall execution time with DL_MG was not significantly greater than the time required for calculations using a conventional FFT-based solver
The role of volatile organic compounds in the diagnosis and treatment of irritable bowel syndrome.
No full textIrritable bowel syndrome (IBS) is a prevalent and burdensome disorder of gut–brain interaction,
defined by intrusive abdominal pain and disordered bowel habits. It affects a significant proportion of
the global population and contributes substantially to healthcare expenditure in the United Kingdom.
Despite its impact, the pathophysiology of IBS remains poorly understood, and treatment remains
largely symptom-based, lacking alignment with clearly defined biological mechanisms. This unmet
need has made understanding the drivers of IBS symptoms a top research priority.
The gut microbiota has long been implicated in IBS, yet consistent microbial signatures remain elusive.
Whilst advances in sequencing have enabled detailed analysis of microbial composition, these
methods are expensive, technically complex, and often fail to infer functionality. Crucially, large shifts
in community composition do not necessarily reflect functional change, and the most metabolically
active organisms may paradoxically be those present in the lowest abundance. In this context,
metabolomic approaches - particularly volatile organic compound (VOC) analysis - offer a promising,
rapid, scalable, and cost-effective means to gain functional insight into the gut microenvironment,
capturing end-products of microbial (and host) metabolism. Indeed, early evidence suggests that VOC
profiles can not only distinguish IBS from other gastrointestinal disorders but may also help predict
responsiveness to dietary interventions.
Solid-phase microextraction gas chromatography–mass spectrometry (SPME-GC-MS) was employed
to profile VOCs emitted into the faecal headspace of well-phenotyped individuals with IBS. The
application of both unsupervised and supervised clustering methods enabled the stratification of
patients based on metabolic profiles. This revealed two robust and reproducible metabotypes,
including a metabolically agile group characterised by a relative abundance of short-chain fatty acids
(SCFAs), associating with a specific microbial signature, more severe clinical features and enhanced
clinical response to the restriction of FODMAPs (fermentable oligosaccharides, disachharides,
monosachharides and polyols). A statistical model can be built around these metabotypes, enabling
the prediction of microbial signature at baseline using just five VOCs.
Complementary analysis of urine via derivatized GC-MS further enriched insights into the relationship
between faecal metabolites and more complex downstream mediators, demonstrating strong
correlations between faecal SCFAs and urinary markers of tryptophan metabolism, suggesting a
possible SCFA-serotonin axis in IBS. Compellingly, stark differences in the baseline urinary
metabotypes of responders and non-responders to FODMAP restriction suggest, for the first time, a
feasible and acceptable non-invasive tool for pre-treatment stratification.
Collectively, these findings enhance our understanding of IBS pathophysiology and support the
integration of metabolomic stratification into clinical care - bringing precision, biologically grounded
IBS care closer to clinical reality
"Why Should They Cite Us?": Lessons from an "Uncommon" Family Lawyer's Influence on the Common Law
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