CKDu: the known unknowns

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...

The known unknowns of HPV natural history.

The discovery that certain high-risk strains of human papillomavirus (HR-HPV) cause nearly 100% of invasive cervical cancer has spurred a revolution in cervical cancer prevention by promoting the development of viral vaccines. Although the efficacy of these vaccines has already been demonstrated, a complete understanding of viral latency and natural immunity is lacking, and solving these myster...

T cell vaccinology: exploring the known unknowns.

The objective of modern vaccine development is the safe generation of protective long-term immune memory, both prophylactic and therapeutic. Live attenuated vaccines generate potent cellular and humoral immunity [1-3], but numerous problems exist with these vaccines, ranging from production and storage issues to adverse reactions and reversion to virulence. Subunit vaccines are safer, more stab...

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