Annual rhythm in filgrastim use in southeast Florida.

e20697 Background: Circadian, seasonal and annual temporal organization characterizes earth-evolved life forms. Cellular proliferation in human bone marrow shares this temporal organization. Careful clinical trials have documented that bone marrow damage from a range of cytotoxic anti-cancer drugs is predictably greater and lesser when these drugs are given at specific times of day and seasons of the year to human beings with cancer. Filgrastim is a human growth factor, which is given to stimulate the production of neutrophils that have been depressed to low levels by cancer chemotherapy, in order to prevent infectious complications. We hypothesized that administration of filgrastim, stimulated by dangerously low neutrophil counts, would be initiated non-randomly with reproducible seasonality and annual rhythmicity. Methods: All claims from contracted healthplans submitted by oncologists in southeast Florida were tabulated by month of service date, during the calendar years of 2010, 2011, and 2012 (n=2,506). These numbers were de-trended, tested by linear regression, ANOVA and multi-component least squares cosine curve fitting for annual rhythmicity. Results: Similar stable annual time structures characterize filgrastim use in this population for each of these three years. An overall increasing trend (p 0.004) was present in its use during this three year span. Time of year effects were present (ANOVA p<0.058), demonstrating a prominent annual rhythm (p 0.006). The annual use pattern peaks during late winter and early spring and is lower in summer and fall. Conclusions: A large literature documents expected annual rhythmicity of cytotoxic drug bone marrow damage as reflected in circulating neutrophil count. Substantial annual rhythms characterize the clinical use of filgrastim in southeast Florida for this indication. The relative contributions of “snowbird” migration and the temporal organization of hematopoiesis remain to be fully elucidated. [Table: see text]

Annual rhythm of germination of seeds of Mesembryanthemum nodiflorum 32 years after collection

Dry plants of Mesembryanthemum nodiflorum L. (Aizoaceae), with mature seeds enclosed in their dry capsules, were collected in the Judean Desert near Jericho, Israel, in the summer of 1972, and have been stored dry under room conditions [15–30°C, 15–25% relative humidity (RH)] since then. More than 31 years after maturation, these unimbibed seeds retained an annual rhythm of germination. A significantly higher percentage of seeds originating from the terminal, central and basal parts of the capsules germinated in February or March compared to other months of the year. This phenomenon was repeated in all three groups of seeds in 2001, 2002 and 2003 for germination in darkness at 15°C, and in terminal seeds germinated at 25°C in darkness for 4 years from 2001 to 2004. The annual rhythm of M. nodiflorum germination may regulate the season and percentage of seeds that germinate at the proper time of the year, even after many years. But the open question still remains: how do dry seeds measure time, and what are the mechanisms involved?