Differing commissioning arrangements may contribute to geographic variation in clinical management of digital ulcers in systemic sclerosis

Phosphodiesterase inhibitors (such as sildenafil) and endothelin receptor antagonist, bosentan, are effective for digital ulcer disease in systemic sclerosis (SSc-DU) and are endorsed in international treatment recommendations. Commissioning of high-cost drugs, such as bosentan, however, differs across devolved nations of the UK. We report a multicentre service evaluation project to examine ‘real world’ management of SSc-DU before and following the 2015 UK Scleroderma Study Group (UKSSG) guidance, across southwest (SW) England and Wales. Results showed that iloprost and sildenafil use for SSc-DU was higher in patients in Wales prior to 2015. Between 2015–2017, sildenafil use for SSc-DU increased in SW England while remaining stable in Wales. Bosentan use for SSc-DU after 2015 in SW England increased, while remaining stable and proportionately lower in Wales. These findings demonstrate that differing commissioning guidance across devolved nations of the UK seems to contribute to geographic variation in patient care.</p

Elasticity of Gaussian and nearly-Gaussian phantom networks

We study the elastic properties of phantom networks of Gaussian and nearly-Gaussian springs. We show that the stress tensor of a Gaussian network coincides with the conductivity tensor of an equivalent resistor network, while its elastic constants vanish. We use a perturbation theory to analyze the elastic behavior of networks of slightly non-Gaussian springs. We show that the elastic constants of phantom percolation networks of nearly-Gaussian springs have a power low dependence on the distance of the system from the percolation threshold, and derive bounds on the exponents.Comment: submitted to Phys. Rev. E, 10 pages, 1 figur

Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Dynamics of weakly aggregated colloidal particles - discussion

We discuss the behaviour of the dynamics of colloidal particles with a weak attractive interparticle interaction that is induced through the addition of polymer to the solvent. We briefly review the description of their behaviour in terms of the jamming phase diagram, which parametrized the fluid–to–solid transition due to changes in volume fraction, attractive energy or applied stress. We focus on a discussion of ageing of the solid gels formed by these colloid–polymer mixtures. They exhibit a delayed collapse induced by gravity. The time evolution of the height of the sediment exhibits an unexpected scaling behaviour, suggesting a universal nature to this delayed collapse. We complement these measurements of the scaling of the collapse with microscopic investigations of the evolution of the structure of the network using confocal microscopy. These results provide new insight into the origin of this ageing behaviour