Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial

Background: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond

An Assessment of Contaminants in UK Road-Verge Biomass and the Implications for Use as Anaerobic Digestion Feedstock

Biomass from harvested road-verge herbage has potential value as a feedstock for anaerobic digestion (AD) energy plants. However, the proximity to road traffic related pollution sources introduces the possibility of contamination by potentially toxic elements and polycyclic aromatic hydrocarbons. Potential sources of pollution from road traffic emissions are identified and the consequent likelihood of certain contaminants being present at elevated levels is assessed. Samples of road verge biomass harvested from selected locations in Lincolnshire UK for use in AD plants were analysed to produce a set of measurements for the presence of the contaminants of interest. The measured levels of these contaminants are compared to reported background levels in UK herbage and soils to assess if there is significant increased concentration in road-verge biomass. Samples of digestate from an AD plant using the road-verge biomass as feedstock were also analysed to determine if there is notable risk of transfer and concentration of contaminants into agricultural land where the digestate may be used for fertilisation. While elevated levels of contaminants were detected, they were not found in concentrations on road verge biomass at high enough levels to cause adverse effects or concerns for its safe use as an AD feedstock

First measurement of coherent ρ0 photoproduction in ultra-peripheral Xe–Xe collisions at √sNN = 5.44 TeV

The first measurement of the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Xe–Xe collisions at sNN=5.44 TeV is presented. This result, together with previous HERA γp data and γ–Pb measurements from ALICE, describes the atomic number (A) dependence of this process, which is particularly sensitive to nuclear shadowing effects and to the approach to the black-disc limit of QCD at a semi-hard scale. The cross section of the Xe+Xe→ρ0+Xe+Xe process, measured at midrapidity through the decay channel ρ0→π+π−, is found to be dσ/dy=131.5±5.6(stat.)−16.9+17.5(syst.) mb. The ratio of the continuum to resonant contributions for the production of pion pairs is also measured. In addition, the fraction of events accompanied by electromagnetic dissociation of either one or both colliding nuclei is reported. The dependence on A of cross section for the coherent ρ0 photoproduction at a centre-of-mass energy per nucleon of the γA system of WγA,n=65 GeV is found to be consistent with a power-law behaviour σ(γA→ρ0A)∝Aα with a slope α=0.96±0.02(syst.). This slope signals important shadowing effects, but it is still far from the behaviour expected in the black-disc limit.publishedVersio

A(c)(+) Production and Baryon-to-Meson Ratios in pp and p-Pb Collisions at root S-NN=5.02 TeV at the LHC

The prompt production of the charm baryon \u39bc+ and the \u39bc+/D0 production ratios were measured at midrapidity with the ALICE detector in pp and p-Pb collisions at sNN=5.02 TeV. These new measurements show a clear decrease of the \u39bc+/D0 ratio with increasing transverse momentum (pT) in both collision systems in the range 2<12 GeV/c, exhibiting similarities with the light-flavor baryon-to-meson ratios p/\u3c0 and \u39b/KS0. At low pT, predictions that include additional color-reconnection mechanisms beyond the leading-color approximation, assume the existence of additional higher-mass charm-baryon states, or include hadronization via coalescence can describe the data, while predictions driven by charm-quark fragmentation processes measured in e+e- and e-p collisions significantly underestimate the data. The results presented in this Letter provide significant evidence that the established assumption of universality (colliding-system independence) of parton-to-hadron fragmentation is not sufficient to describe charm-baryon production in hadronic collisions at LHC energies

A(c)(+) Production and Baryon-to-Meson Ratios in pp and p-Pb Collisions at root S-NN=5.02 TeV at the LHC

The prompt production of the charm baryon Λ_{c}^{+} and the Λ_{c}^{+}/D^{0} production ratios were measured at midrapidity with the ALICE detector in pp and p-Pb collisions at sqrt[s_{NN}]=5.02  TeV. These new measurements show a clear decrease of the Λ_{c}^{+}/D^{0} ratio with increasing transverse momentum (p_{T}) in both collision systems in the range 2<p_{T}<12  GeV/c, exhibiting similarities with the light-flavor baryon-to-meson ratios p/π and Λ/K_{S}^{0}. At low p_{T}, predictions that include additional color-reconnection mechanisms beyond the leading-color approximation, assume the existence of additional higher-mass charm-baryon states, or include hadronization via coalescence can describe the data, while predictions driven by charm-quark fragmentation processes measured in e^{+}e^{-} and e^{-}p collisions significantly underestimate the data. The results presented in this Letter provide significant evidence that the established assumption of universality (colliding-system independence) of parton-to-hadron fragmentation is not sufficient to describe charm-baryon production in hadronic collisions at LHC energies