Faecal microbiota transplantation for Clostridium difficile infection in the United Kingdom

AbstractFaecal microbiota transplantation (FMT) has been shown to be highly effective in treating recurrent Clostridium difficile infection, but to date there have been no data from the United Kingdom. An electronic survey was developed at Portsmouth Hospitals' National Health Service (NHS) Trust and sent out to UK hospital specialists utilizing the contact databases of the British Infection Association and the Royal College of Gastroenterologists. A total of 162 responses were received, representing nearly one in every seven of the United Kingdom's infection specialists and a response from one in every two UK NHS acute trusts or boards. Ninety-six per cent believe that the evidence base supports the use of FMT, and 94% reported consulting on at least one patient a year in whom they would recommend FMT. However, only 22% reported FMT use in their institution in the last 10 years, and 6% reported performing more than ten FMTs in the last 10 years. Concerns with patient acceptance, donor selection, availability of screened faecal solution, feasibility of procedure and availability of local expertise were reported as inhibiting the use of FMT. More than 90% of respondents would like access to regional guidelines, prescreened faecal solution and expert advice to facilitate implementation, and more than two thirds of respondents would support a regional FMT referral centre. A large gap exists in the United Kingdom between physicians desire to use FMT and the ability and facilities to provide it as a therapy at the bedside

Immediate-release granule formulation of hydrocortisone, Alkindi®, for treatment of paediatric adrenal insufficiency (Infacort development programme)

INTRODUCTION: Treatment of paediatric patients with adrenal insufficiency is challenging due to the lack of appropriate glucocorticoid preparations for children, and the use of either pharmacy- or parent-compounded hydrocortisone tablets. Alkindi (hydrocortisone granules in capsules for opening) is a new therapeutic option for paediatric adrenal insufficiency. Areas Covered: Drawbacks of current therapy and formulation and clinical trial programme for Alkindi. Expert Commentary: Compounding hydrocortisone has multiple issues including inconsistent dosing with under and over treatment and practical problems for parents who compound the drug themselves or travel long distances to a compounding pharmacy and the cost of compounding by the pharmacy. Alkindi® is a novel paediatric formulation of immediate release hydrocortisone licensed for use in paediatric adrenal insufficiency. Alkindi® is formulated to address the needs of neonates, infants and young children, being available at appropriate paediatric doses of 0.5, 1.0, 2.0 and 5.0 mg, is multiparticulate, allowing either direct oral dosing or dosing mixed with food, is taste masked to obscure the bitter taste of hydrocortisone and is bioequivalent to current hydrocortisone preparations. Clinical trials in young children with adrenal insufficiency demonstrated cortisol levels after dosing similar to those seen in healthy children and the drug was well tolerated and favoured over current therapy by parents. Alkindi® will provide a licenced treatment option for accurate dosing in children with adrenal insufficiency where compounded adult tablets of hydrocortisone are unsuitable

A novel method to characterize the elastic/plastic deformation response of thin films

A novel experimental/numerical test method has been developed which allows accurate characterization of the elastic and large-strain plastic mechanical response of thin films. Silicon micromachining techniques have been used to fabricate isolated film features which are mechanically tested using our ultralow-load indentation test system. Macro-scale laboratory testing and finite element analysis were employed to optimize the design of the geometric feature used and to benchmark our analysis capabilities. A simple rigid-plastic geometric analysis of our test structure is developed and applied to the observed force-displacement response, allowing us to extract the uniaxial inelastic stress-strain response of micrometer-scale thin film structures. To our knowledge, this is the first time that the inelastic deformation behavior of metal alloy features of this size scale has been quantitatively determined

Cut-offs and pile-ups in shock acceleration spectra

We have examined cutoffs and pile-ups due to various processes in the spectra of particles produced by shock acceleration, and found that, even in the absence of energy losses, the shape of the spectrum of accelerated particles at energies well below the nominal maximum energy depends strongly on the energy dependence of the diffusion coefficient. This has implications in many areas, for example, in fitting the observed cosmic ray spectrum with models based on power-law source spectra and rigidity dependent diffusive escape from the galaxy. With continuous energy losses, prominent pile-ups may arise, and these should be included when modelling synchrotron X-ray and inverse Compton gamma-ray spectra from a shock-accelerated electron population. We have developed a Monte Carlo/numerical technique to model the shape of the spectrum for the case of non-continuous energy losses such as inverse Compton scattering in the Klein-Nishina regime. We find that the shapes of the resulting cut-offs differ substantially from those arising from continuous processes, and we suggest that such differences could be observable through their effect on the spectrum of radiation emitted by a population of recently accelerated electrons as, for example, may exist in young supernova remnants.Comment: 23 pages, 8 figures, submitted to Astroparticle Physic

Aspects of meson properties in dense nuclear matter

We investigate the modification of meson spectral densities in dense nuclear matter at zero temperature. These effects are studied in a fully relativistic mean field model which goes beyond the linear density approximation and also includes baryon resonances. In particular, the role of N*(1520) and N*(1720) on the rho meson spectral density is highlighted. Even though the nucleon-nucleon loop and the nucleon-resonance loop contribute with the opposite sign, an overall reduction of rho meson mass is still observed at high density. Importantly, it is shown that the resonances cause substantial broadening of the rho meson spectral density in matter and also induces non-trivial momentum dependence. The spectral density of the a0 meson is also shown. We study the dispersion relations and collective oscillations induced by the rho meson propagation in nuclear matter together with the influence of the mixing of rho with the a0 meson. The relevant expression for the plasma frequency is also recovered analytically in the appropriate limit.Comment: 19 pages, 17 figure

The effects of a 12-Month weight loss intervention on cognitive outcomes in adults with overweight and obesity

Obesity is associated with poorer executive functioning and reward sensitivity. Yet, we know very little about whether weight loss through diet and/or increased exercise engagement improves cognitive function. This study evaluated whether weight loss following a dietary and exercise intervention was associated with improved cognitive performance. We enrolled 125 middle-aged adults with overweight and obesity (98 female) into a 12-month behavioral weight loss intervention. Participants were assigned to one of three groups: energy-restricted diet alone, an energy-restricted diet plus 150 min of moderate intensity exercise per week or an energy restricted diet plus 250 min of exercise per week. All participants completed tests measuring executive functioning and/or reward sensitivity, including the Iowa Gambling Task (IGT). Following the intervention, weight significantly decreased in all groups. A MANCOVA controlling for age, sex and race revealed a significant multivariate effect of group on cognitive changes. Post-hoc ANCOVAs revealed a Group x Time interaction only on IGT reward sensitivity, such that the high exercise group improved their performance relative to the other two intervention groups. Post-hoc ANCOVAs also revealed a main effect of Time, independent of intervention group, on IGT net payoff score. Changes in weight were not associated with other changes in cognitive performance. Engaging in a high amount of exercise improved reward sensitivity above and beyond weight loss alone. This suggests that there is additional benefit to adding exercise into behavioral weight loss regimens on executive functioning, even without additional benefit to weight loss

Development and verification of an endogenous PBPK model to inform hydrocortisone replacement dosing in children and adults with cortisol deficiency

The goal of hormone replacement is to mirror physiology. Hydrocortisone granules and modified release formulations are being developed to optimise cortisol replacement in the rare disease of adrenal insufficiency. To facilitate clinical development, we built and verified a physiologically based pharmacokinetic (PBPK) model for the endogenous hormone cortisol (hydrocortisone) in healthy adults, and children and adults with adrenal insufficiency. The model predicted immediate-release hydrocortisone pharmacokinetics in adults across the dose range 0.5 to 20 mg, with predicted/observed AUCs within 0.8 to 1.25-fold. The model also tightly predicted pharmacokinetic parameters for modified-release formulations, with AUCs within 0.8 to 1.25-fold after single and multiple dosing. Predicted modified-release formulation pharmacokinetics (PK) in 12 to 18-year olds showed PK to be similar to adults. This hydrocortisone PBPK model is a useful tool to predict adult and paediatric pharmacokinetics of both immediate- and modified-release hydrocortisone formulations, and develop clinical dosing regimens

The effects of meson mixing on dilepton spectra

The effect of scalar and vector meson mixing on the dilepton radiation from hot and dense hadronic matter is estimated in different isospin channels. In particular, we study the effect of $\sigma$-$\omega$ and $\rho-a_0$ mixing and calculate the corresponding rates. Effects are found to be significant compared to standard $\pi$-$\pi$ and $K$-${\bar K}$ annihilations. While the mixing in the isoscalar channel mostly gives a contribution in the invariant mass range between the two-pion threshold and the $\omega$ peak, the isovector channel mixing induces an additional peak just below that of the $\phi$. Experimentally, the dilepton signals from $\rho$-$a_0$ mixing seem to be more tractable than those from $\sigma$-$\omega$ mixing.Comment: 10 pages, 9 figure

The TeraGyroid Experiment

The TeraGyroid experiment at SC 03 addressed a large-scale problem of genuine scientific interest at the same time as showing how intercontinental grids enable new paradigms for collaborative computational science that can dramatically reduce the time to insight. TeraGyroid used computational steering to accelerate the exploration of parameter space in condensed matter simulations. The scientific objective was to study the self-assembly, defect pathways and dynamics of liquid crystalline cubic gyroid mesophases using the largest set of lattice-Boltzmann (LB) simulations ever performed, involving in some cases lattices of over one billion sites and for highly extended simulation times. We describe the application in sufficient detail to reveal how it uses the grid to support interactions between its distributed parts, where the interfaces exist between the application and the middleware infrastructure, what grid services and capabilities are used, and why important design decisions were made. We also describe how the resources of highend computing services were federated with the UK e-Science Grid and the US TeraGrid to form the TeraGyroid testbed, and summarise the lessons learned during the experiment