Known Unknowns in Exocytosis

Sepsis-related stress response: known knowns, known unknowns, and unknown unknowns

The hypothalamic-pituitary-adrenal (HPA) axis response in sepsis remains to be elucidated. Apart from corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol, many other neuroendocrine factors participate in the regulation of HPA stress response. The HPA response to acute and chronic illness exerts a biphasic profile. Tissue corticosteroid resistance may also play an importan...

Known Unknowns: Novelty Detection in Condition Monitoring

In time-series analysis it is often assumed that observed data can be modelled as being derived from a number of regimes of dynamics, as e.g. in a Switching Kalman Filter (SKF) [8, 2]. However, it may not be possible to model all of the regimes, and in this case it can be useful to represent explicitly a ‘novel’ regime. We apply this idea to the Factorial Switching Kalman Filter (FSKF) by intro...

Known Unknowns in Large-Scale System Monitoring

This paper addresses a central challenge in PRISM, a large-scale distributed monitoring system: coping with the uncertainties and ambiguities introduced by network and node failures. In particular, in a large scale monitoring system, such failures interact badly with techniques needed for scalability like hierarchy, arithmetic filtering, and temporal batching. For example, if a monitoring subtr...

Known knowns, known unknowns, and unknown unknowns: can systems medicine provide a new approach to sepsis?

Known knowns, known unknowns, unknown unknowns and the propagation of scientific enquiry.

In February 2002, Donald Rumsfeld, the then US Secretary of State for Defence, stated at a Defence Department briefing: ‘There are known knowns. There are things we know that we know. There are known unknowns. That is to say, there are things that we now know we don’t know. But there are also unknown unknowns. There are things we do not know we don’t know.’ As a result, he was almost universall...