For a feedback loop, therefore, we need to assume that oral ulceration and/or fatigue preceded urinary IL-6 concentration changes by up to 12 h; ii) as to the relation between IL-6 and oral ulcers, the non-significant negative correlation at +lag 4 is in fact a meaningful finding when we keep in mind that both significant coefficients and temporal patterns of [non-significant] coefficients are important in the interpretation of integrative single-case studies (15). The gene discussed is IL6; the disease is Oral ulcer.