Richmond Royal Hospital

Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF). In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7mL/m2 and was lower with cimlanod (29 ± 9mL/m2 ; P=0.03) and NTG (28 ± 8mL/m2 ; P=0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e' (P=0.006) and E/A ratio (P=0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo. In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure.

108Background: In a phase 1/2 study, the combination of E, a selective oral inhibitor of the IDO1 enzyme, plus P, a PD-1 inhibitor, suggested promising antitumor activity with minimal additive toxicity. ECHO-301/KEYNOTE-252 (NCT02752074) is a phase 3, randomized, double-blind study evaluating the efficacy and safety of E + P vs placebo + P in pts with untreated unresectable or metastatic melanoma. Methods: Pts had histologically confirmed unresectable stage III or IV melanoma and were treatment naive for advanced or metastatic disease, except for pts with the BRAF V600 mutation who could have received prior BRAF/MEK therapy. Pts were stratified by PD-L1 expression and BRAF mutation status (BRAF mutant with prior BRAF-directed therapy, BRAF mutant without prior BRAF-directed therapy, and BRAF wild type) and randomized 1:1 to E 100 mg BID + P 200 mg Q3W or matched E placebo + P 200 mg Q3W. Response was assessed per RECIST v1.1 and irRECIST (both by central review). The primary endpoints were PFS per RECIST ...

Competition for fish oil from human nutritional supplements (nutraceuticals) is starting to threaten its supply for aquaculture feeds. World supply of fish oil is not increasing but is the main source of healthy omega-3 fats (n-3 LC-PUFA). Fish oil demand by nutraceuticals is a derived demand for such fats. Demand growth and insecure supply are causing price inflation of fish oil, helping to drive its substitution in aquaculture feeds by vegetable oils. This is reducing the content of n-3 LC-PUFA in aquaculture products, especially salmon, with potentially negative health implications. Given the scope for further substitution of fish oil, it is unlikely that future growth of global aquaculture will be constrained by reducing omega-3 content, although it will complicate consumer marketing of salmon. Nutraceuticals is paying more than aquaculture for fish oil based on omega-3 content, but novel sources of n-3 LC-PUFA will become available in the medium term.

Journal Article Orphée et les chrétiens: La réception du mythe d’Orphée dans la littérature chrétienne grecque des cinq premiers siècles. Volume 1: Orphée, du repoussoir au préfigurateur du Christ: Réécriture d’un mythe à des fins protreptiques chez Clément d’Alexandrie. By Fabienne Jourdan. Get access Orphée et les chrétiens: La réception du mythe d’Orphée dans la littérature chrétienne grecque des cinq premiers siècles. Volume 1: Orphée, du repoussoir au préfigurateur du Christ: Réécriture d’un mythe à des fins protreptiques chez Clément d’Alexandrie. By Fabienne Jourdan. Pp. 486. (Anagôgê, 4.) Paris: Les Belles Lettres, 2009. isbn978 2 251 181103. Paper €45. Piotr Ashwin-Siejkowski Piotr Ashwin-Siejkowski Richmond, Surrey P.Ashwin-Siejkowski@chi.ac.uk Search for other works by this author on: Oxford Academic Google Scholar The Journal of Theological Studies, Volume 62, Issue 1, April 2011, Pages 352–355, https://doi.org/10.1093/jts/flq154 Published: 02 December 2010

This paper describes Aerogility - an intelligent decision support system for managing service-based aftermarkets. Aerogility uses multi-agent software technology to implement a dynamic model of an aerospace aftermarket. The model is realistic and includes all the assets, people and processes in a dynamic and interactive representation of the business. An initial model can be implemented quickly then enhanced and extended in stages. Individual stakeholders can contribute their understanding of the business to their part of the model. The operational parameters and business rules that drive the behaviour of the model can be easily changed. A management team can work through a variety of what-if scenarios and comparative simulations to evaluate options and policy innovations. Each scenario can be bench-marked with various analytical information that facilitates detailed analysis and powerful insight.

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Professionals working in child and adolescent mental health services are increasingly encouraged to examine the evidence underlying their clinical practice. Embracing evidence-based practice can present difficulties, as barriers to changing practice exist. These difficulties are examined, along with the meaning of evidence-based practice in a multidisciplinary speciality, and the potential benefits that develop from it.