IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis.

BACKGROUND: Alcohol consumption causes a spectrum of liver abnormalities and leads to over 3 million deaths per year. Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The aim of this study is to explore the potential benefits of the IL-1ß antibody, canakinumab, in the treatment of AH. METHODS: This is a multicentre, double-blind, randomised placebo-controlled trial. Participants will be diagnosed with AH using clinical criteria. Liver biopsy will then confirm that all histological features of AH are present. Up to 58 participants will be recruited into two groups from 15 centres in the UK. Patients will receive an infusion of Canakinumab or matched placebo by random 1:1 allocation. The primary outcome is the difference between groups in the proportion of patients demonstrating histological improvement and will compare histological appearances at baseline with appearances at 28 days to assign a category of "improved" or "not improved". Patients with evidence of ongoing disease activity will receive a second infusion of canakinumab or placebo. Participants will be followed up for 90 days. Secondary outcomes include mortality and change in MELD score at 90 days. DISCUSSION: This phase II study will explore the benefits of the IL-1ß antibody, canakinumab, in the treatment of AH to provide proof of concept that inhibition of IL-1ß signalling may improve histology and survival for patients with AH. TRIAL REGISTRATION: EudraCT 2017-003724-79 . Prospectively registered on 13 April 2018.

Role of surface microgeometries on electron escape probability and secondary electron yield of metal surfaces.

The influence of microgeometries on the Secondary Electron Yield (SEY) of surfaces is investigated. Laser written structures of different aspect ratio (height to width) on a copper surface tuned the SEY of the surface and reduced its value to less than unity. The aspect ratio of microstructures was methodically controlled by varying the laser parameters. The results obtained corroborate a recent theoretical model of SEY reduction as a function of the aspect ratio of microstructures. Nanostructures - which are formed inside the microstructures during the interaction with the laser beam - provided further reduction in SEY comparable to that obtained in the simulation of structures which were coated with an absorptive layer suppressing secondary electron emission.