Construction of rhythm-specified reference intervals and regions, with emphasis on 'hybrid' data, illustrated for plasma cortisol.

Time-specified reference intervals, so-called chronodesms for the interpretation of single samples, have heretofore been proposed for longitudinal data, consisting of repeated samples from a single individual, and for transverse data: single time-specified samples from many individuals. Herein the problem of dealing with hybrid data, namely time series of data collected on a group of subjects, is considered for a derivation of reference intervals that take into account both inter- and intra-individual variability. The formulae are applied to cortisol data (72 samples from each of 10 healthy young adult North American women) with interpretation from both Bayesian and frequentist viewpoints. The provision of reference limits for both single samples and paired rhythm characteristics offers the opportunity of introducing an overdue time-specification and time-structure evaluation into microscopic chronobiology and through it into medical, veterinarian and other practice.