As above, the expected cost surface associated with a given set of parameter values (as obtained by MCMC, described below), can be explored using standard Monte Carlo methods. At each time step, MCMC is used to produce 10,000 samples from the current posterior distribution on model parameters. These samples are thinned to 100 samples, and for each of these 100 samples the optimal variable stop time vaccination strategy is calculated as described above. The adaptive strategy to be implemented at that Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target? Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and – despite many unanswered questions – therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial. We clearly need to understand better the mechanisms that underlie MODS. The endothelium certainly plays an active role in MODS. It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration. An important regulator of these systems is the angiopoietin/Tie2 signalling system. In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy. Critical illness is a life-threatening disease by definition. Patients treated for critical illness in the intensive care unit have underlying causes such as infection, trauma, major surgery, hemorrhagic shock, pancreatitis and other major insults. Despite maximal supportive care, severely ill patients treated in intensive care units are still likely to die, usually after an episode of increasing failure of multiple organs [1] .