An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): Protocol for a randomized controlled trial

Background

Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients.

This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μg.kg^-1.min^-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom.

This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action.

Rapid design of discrete orthonormal wavelet transforms using silicon IP components

A rapid design methodology for orthonormal wavelet transform cores has been developed. This methodology is based on a generic, scaleable architecture utilising time-interleaved coefficients for the wavelet transform filters. The architecture has been captured in VHDL and parameterised in terms of wavelet family, wavelet type, data word length and coefficient word length. The control circuit is embedded within the cores and allows them to be cascaded without any interface glue logic for any desired level of decomposition. Case studies for stand alone and cascaded silicon cores for single and multi-stage wavelet analysis respectively are reported. The design time to produce silicon layout of a wavelet based system has been reduced to typically less than a day. The cores are comparable in area and performance to handcrafted designs. The designs are portable across a range of foundries and are also applicable to FPGA and PLD implementations.

Out of the Shadows: A one day investigation of the politics of architecture explored through the lens of post-conflict, Belfast

This booklet covers the itinerary and some of the findings of a day-long visit to Belfast on the 7th November 2014 by Peter Oborn; Vice President International of the Royal Institute of British Architects. His visit was in response to a motion submitted to the RIBA council (19.05.2014) calling for the suspension of the Israeli Association of United Architects from the International Union of Architects. Despite members of council speaking against the motion it was carried; 23 members voting for, 16 against, and 10 abstentions. Subsequently the RIBA came under considerable pressure to consider its position in such critical contexts. This visit to Belfast was part of a wider fact-finding mission and evidence taking. At its heart was the question: 'Is it appropriate for the institute (RIBA) to engage with communities facing civil conflict and/or natural disaster and, if so, how it can do so most effectively.' The visit was facilitated by Ruth Morrow, Professor of Architecture, School of Planning, Architecture & Civil Engineering, Queen's University Belfast, and Martin Hare, Royal Society of Ulster Architects (RSUA) president.