reflected research showing diminished in vitro activity of natural killer cells isolated from patients. Neurasthenia had been proposed as an historical diagnosis that occupied a similar medical and cultural space to CFS. Royal Free disease was named after the historically significant outbreak in 1955 at the Royal Free Hospital used as an informal synonym for "benign myalgic encephalomyelitis". Tapanui flu was a term commonly used in New Zealand, deriving from the name of a town, Tapanui, where numerous people had the syndrome. Society and culture Naming Many names have been proposed for the illness. Currently, the most commonly used are "chronic fatigue syndrome", "myalgic encephalomyelitis", and the umbrella term "ME/CFS". Reaching consensus on a name is challenging because the cause and pathology remain unknown. The term "chronic fatigue syndrome" has been criticized by some patients as being both stigmatizing and trivializing, and which in turn prevents the illness from being seen as a serious health problem that deserves appropriate research. While many patients prefer "myalgic encephalomyelitis", which they believe better reflects the medical nature of the illness, there is resistance amongst some clinicians toward the use of myalgic encephalomyelitis on the grounds that the inflammation of the central nervous system (myelitis) implied by the term has not been demonstrated. A 2015 report from the Institute of Medicine recommended the illness be renamed "systemic exertion intolerance disease", (SEID), and suggested new diagnostic criteria, proposing post-exertional malaise, (PEM), impaired function, and sleep problems are core symptoms of ME/CFS. Additionally, they described cognitive impairment and orthostatic intolerance as distinguishing symptoms from other fatiguing illnesses. Economic impact Economic costs due to CFS are "significant." A 2021 paper by Leonard Jason and Arthur Mirin estimated the impact in the US to be $36-51 billion per year, or $31,592 to $41,630 per person, considering both lost wages and healthcare costs. The CDC estimated direct healthcare costs alone at $9-14 billion annually. A 2017 estimate for the annual economic burden in the United Kingdom was £3.3 billion. Awareness day 12 May is designated as ME/CFS International Awareness Day. The day is observed so that stakeholders have an occasion to improve the knowledge of "the public, policymakers, and health-care professionals about the symptoms, diagnosis, and treatment of ME/CFS, as well as the need for a better understanding of this complex illness." It was chosen because it is the birthday of Florence Nightingale, who had an illness appearing similar