Chronobiology (n., from Gk chronos = time, Gk bios = life and Gk logos = science) is a computer-aided tool for objectively quantifying, mapping and investigating mechanisms of biological time structures, including those in the otherwise neglected normal range. It is here defined by the criteria of the authors who do not claim to be representative of the views of others who accept the fiction of a relative constancy or homeostasis and hence do single-sample spotchecks used as imaginary "baselines". Chronobiology describes everyday physiology under ordinary conditions as well as after the standardization or constancy, as far as possible, of environmental temperature, lighting, the availability of food and other manipulable local conditions, while consulting records of as yet mostly unalterable variability in space weather and other conditions. The transdisciplinary effects of weather near and far are the topic of chronomics, which focuses on interactions among chronomes -- time structures -- in us and chronomes around us, from which the former developed in the first place. Chronobiology and chronomics, figurative microscopies and telescopies in time, isolate rhythms from chaotic changes and from trends (with age and/or with other varying internal chronobiology and external chronomics conditions). For example, chronobiology detects conditions such as a change beyond gender- and age-matched limits for blood pressure amplitude, \(A\) (a circadian blood pressure overswing that if consistent in certain populations can represent a risk of ischemic stroke within 6 years greater than that of hypertension).
History and applications
Chronobiology is a tool of a new biology, or rather of a new unified science. Indeed, studies of rhythms in and around us are steps toward a broader transdisciplinary science including all branches of biology, chemistry, physics, medicine, sociology, and in particular cosmology. Figure 1 sketches Minnesotan developments starting with counts of circulating blood eosinophils by light-microscopy and figuratively by microscopy in time, by repeating the counts around the clock, concomitantly with electroencephalograms in the early 1950s. Whatever the variable examined, it had an ~24-hour cycle. If the data were dense enough, cycles were shorter than 24 hours; if the time series was long enough, cycles were longer than 24 hours. After neighboring circadian, ultradian and infradian spectral regions were delineated, objective endpoints of time structure were formulated and assessed from a combination of time-varying and global analytical methods, i.e., by proceedings glocal in time and in space. The spatial slogan "think globally, act locally" was extended to analyses of the longest available time series at a given time and of its sections, varied systematically in length to obtain information in both the frequency and time domains, in the longer and shorter intervals analyzed.
Focus in the clinic and in the laboratory was directed upon adrenocortical/brain interactions, studied by a remove-and-replace approach, complemented by mitotic counts and cellular biochemistry, leading to the discovery by 1958 of circadian rhythms in RNA and DNA formation in this sequence within a mitotic cycle. Separate independent cellular peripheral as well as central oscillating mechanisms were eventually documented at the molecular level. Clock genes have been identified, among others, in the mammalian heart, where they are of particular interest since the circadian characteristics of heart rate were demonstrated to be inherited by studies on twins reared apart, revealing a high degree of emergenic heritability by a statistically significant intraclass correlation coefficient for monozygotes but not for dizygotes. A nucleated unicell, estimated to have existed on earth for millions of years, has highly statistically significant circadian rhythms with less prominent about 7-day rhythms. As a population, Acetabularia also mimics a circadecadal solar cycle. In continuous light, the circadian amplitude of electrical activity in Acetabularia is smaller than the circaseptan, and the latter is desynchronized from the societal week. Circadian rhythmicity in a prokaryote like E. coli, where it was first described, and in many other bacteria and in an archaeon demonstrates the importance of biological time structure from an evolutionary perspective. Cycles at the origin of life may have been a condition for their development, are ubiquitous in individuals and habitats, and of critical importance as a challenge in human affairs.
A few examples of chronobiologic applications include timing the intake of calories ( Figure 2), checking on responses to sodium intake ( Figure 3), timing drug treatment ( Figure 4), and radiotherapy ( Figure 5). The discovery of alterations in circadian blood pressure rhythm parameters constituting a risk greater than hypertension for stroke or nephropathy, see Figure 6 and Figure 7 (even in the absence of a high blood pressure, cf. Figure 8) is a critically important, underutilized chronobiologic finding. Sometimes as simple a decision as altering the timing of medication (cf. Figure 9), eliminates that risk.
Some subdivisions of chronobiology are:
- Chronoanalysis provides, i.a.,
- checks of the validity of a cycle by the fit of a model such as a (set of) cosine curve(s) for a test of the zero amplitude∆, A, assumption and if A=0 is rejected,
- dynamic parameters such as the amplitude, \(A\ ,\) and the acrophase, \(\varphi\ ,\) and the \((A,\varphi)\) pairs of harmonics (the latter to assess the waveform), in addition to a MESOR, M, short for Midline-Estimating Statistic Of Rhythm, as compared to the arithmetic mean. The M is usually more accurate in unequidistant data and more precise in equidistant data; and
- non-parametric endpoints derived from stacking over a known or newly found time scale such as a period in whatever body function is being analyzed.
- Chronophysiology replaces the fiction of "baselines" in an imaginary homeostasis by dynamic parameters and eventually with complement feedbacks and feedforwards in organisms by feedsidewards in a collateral hierarchy of living things and of external-internal interactions. The same stimulus, if its timing is analyzed, has very different effects at certain predictable stages of a rhythm's time scale. Responses can then be quantified in light of reference values, as for instance by a parametric and nonparametric summary (sphygmochron) of blood pressure and heart rate variability over time, qualified by gender, age and ethnicity in health, Figure 10, eventually to be extended to each (clinically or otherwise) relevant periodicity, chaotic endpoint, such as a correlation dimension, and linear or other trend involved.
- Chronohygiene for prehabilitation detects risk elevation by an alteration of rhythm characteristics before as well as after deviations in the overall mean occur, thus recognizing an elevation of disease risk and covert pathology before pathology becomes overt and symptomatic by a conventional approach relying on a normal range. For instance, the monitoring of blood pressure and heart rate in time, combined with chronobiologic data analysis (chronobiometry), detects unfavorable constellations of certain temporal parameters early, e.g., before hypertension occurs. Prehabilitation is concerned with the improvement of health by the implementation of prophylactic intervention aimed at disease risk-lowering, relying on procedures such as the scheduling of food intake (timing, Figure 2). Exercise must not be scheduled so that it inadvertently induces a circadian blood pressure overswing. Meditation, prayer, self-hypnosis and other activities could explore any influence by the time structures of both the organism and its environment. Societal and broad environmental-organismic interactions such as those in association with the about 10-year solar activity cycle and/or magnetic storms have effects that may eventually lead to a space weather report and to corresponding preventive research (see Chronomics). The study of genes associated with disease in the current genome research may well be complemented by the genome mapping in the light of characteristics such as the circadian periods, amplitudes and phases both in the more readily assessed 24-hour synchronized state and under conditions of desynchronization or multiple synchronization.
- Chronotherapy involves timing treatment to maximize the desired effects while minimizing the undesired effects. Whenever possible, treatment is timed to marker rhythms for each desired effect and for each undesired effect, Figure 4 (bottom half) and Figure 5. Chronotherapy requires a set of different variables in the case of cancer, including a physical marker, such as tumor temperature, Figure 5, or a chemical tumor marker such as CA125 and/or hematological gauges of the bone marrow's integrity, and vascular variables, to gauge cardiotoxicity, among others. When blood pressure and/or heart rate reveal a vascular variability disorder, VVD, Figure 11, the same chronobiologically interpreted ambulatory BP monitoring (C-ABPM) may provide information concerning the need for treatment and for its timing and for the validation of both its desired and some of its undesired effects, Figure 11, in order to avoid the status quo with misdiagnosed VVDs, Figure 12, described in Figure 11 and Figure 13.
The very active field of chronomolecular biology is a chapter unto itself, far beyond the details of mechanisms approached as biological clocks. Pertinent to a broader chronobiology are the findings that infradians -- such as half-weekly, weekly, circaparasemiannual, half-yearly, para-annual, transyearly, yearly and even transtridecadal modulations of the circadian rhythm characteristics -- are now demonstrated to have important associations in health and disease. Infradians and some ultradians (such as the courtship song of a fruit fly) may be tied to the circadian system, as may be the development of a roundworm in the laboratory. More important questions awaiting answers based on models from humans for whom womb-to-tomb monitoring of at least some vital functions is indicated.
In Biological Rhythms in Clinical and Laboratory Medicine, Touitou and Haus wrote:
Together with the recent advances in chronopharmacology, [the] application of [chronobiologic concepts and methods to clinical medicine] appears now timely and in some areas urgent. ... The human time structure is a basic fact of our existence, no matter if one wants to study it or not. … [Thus,] Chronobiology and its subspecialties, like chronopharmacology, will certainly play an important role in the clinical medicine of the future. 
Whether this prediction of the 1950s becomes reality may depend on the recognition of the roles played by weather in space as well as on earth and on the recognition that just as heating and air conditioning have become important for human existence, so will be heretofore not generally recognized aspects of space weather, the topic of chronomes, complementing chronobiology, just as telescopes complement microscopes, to enable us to comprehend what our human senses have not yet identified [2, 3].
- a. Halberg F. Chronobiology. Annu Rev Physiol 1969; 31: 675-725, for introducing term;
- b. Cambrosio A, Keating P. The disciplinary stake: the case of chronobiology. Social Studies of Science 1983; 13: 323-353, history;
- c. Halberg F et al. Transdisciplinary unifying implications of circadian findings in the 1950s. J Circadian Rhythms 2003; 1: 2. 61 pp. www.JCircadianRhythms.com/content/pdf/1740-3391-2-3.pdf, history
- a. Halberg F. Chronobiology: methodological problems. Acta med rom 1980; 18: 399-440, method
- b. Refinetti R, Cornélissen G, Halberg F. Procedures for numerical analysis of circadian rhythms. Biological Rhythm Research 2007; 38 (4): 275-325. http://dx.doi.org/10.1080/09291010600903692, method
- c. Halberg F. Quo vadis basic and clinical chronobiology: promise for health maintenance. Am J Anat 1983; 168: 543-594, maps
- d. Cornélissen G, Halberg F. Introduction to Chronobiology. Medtronic Chronobiology Seminar #7, April 1994, 52 pp. (Library of Congress Catalog Card #94-060580; URL http://www.msi.umn.edu/~halberg/), maps
Books: Available on the Internet
- Cornélissen G, Halberg F. Introduction to Chronobiology. Medtronic Chronobiology Seminar #7, April 1994, 52 pp. (Library of Congress Catalog Card #94-060580; URL http://www.msi.umn.edu/~halberg/)
- Halberg F, Cornélissen G, International Womb-to-Tomb Chronome Initiative Group: Resolution from a meeting of the International Society for Research on Civilization Diseases and the Environment (New SIRMCE Confederation), Brussels, Belgium, March 17-18, 1995: Fairy tale or reality ? Medtronic Chronobiology Seminar #8, April 1995, 12 pp. text, 18 figures. URL http://www.msi.umn.edu/~halberg/
- Ahlgren A, Halberg F. Cycles of Nature: An Introduction to Biological Rhythms. Washington DC: National Science Teachers Association; 1990. 87 pp.
- Ajuriaguerra I de (ed). Symposium Bel-Air III. Cycles biologiques et psychiatrie / publie sous la direction du professeur I. de Ajuriaguerra. Geneva: Georg / Paris: Masson et Cie; 1968. 423 pp.
- Aschoff J, Ceresa F, Halberg F, editors. Chronobiological aspects of endocrinology. 8th Capri Conference, 1974. Chronobiologia 1, Suppl. 1. Milan: Il Ponte; 1974. 509 pp.
- Aschoff J, Ceresa F, Halberg F, editors. Chronobiological aspects of endocrinology. 8th Capri Conference, 1974. Stuttgart/New York: Schattauer; 1974. 463 pp.
- Birkenhäger WH, Halberg F, Prikryl P, editors. Proc. Int. Symp. on Hypertension, Brno, Czechoslovakia, April 9-10, 1990. Brno: Masaryk University, 1990. 182 pp.
- Carandente F, Halberg F, editors. Chronobiology of blood pressure in 1985. Chronobiologia 1984; 11: #3. p. 189-341.
- Cornélissen G (editor), Schwartzkopff O, Niemeyer-Hellbrügge P, Halberg F (co-editors). Time structures -- chronomes -- in child development. International Interdisciplinary Conference, Nov. 29-30, 2002, Munich, Germany. Neuroendocrinol Lett 2003; 24 (Suppl 1). 256 pp.
- Cornélissen G, Halberg E, Bakken E, Delmore P, Halberg F, eds. Toward phase zero preclinical and clinical trials: chronobiologic designs and illustrative applications. University of Minnesota Medtronic Chronobiology Seminar Series, #6, September 1992. Minneapolis: Medtronic Inc.; 1992. 411 pp. Second extended edition, February 1993.
- Cornélissen G, Halberg E, Haus E, O'Brien T, Berg H, Sackett-Lundeen L, Fujii S, Twiggs L, Halberg F, International Womb-to-Tomb Chronome Initiative Group: Chronobiology pertinent to gynecologic oncology. University of Minnesota/Medtronic Chronobiology Seminar Series, #5, Iuly 1992. Minneapolis: Medtronic Inc.; 1992. 25 pp. text, 7 tables, 30 figures.
- Dunlap JC, Loros JJ, DeCoursey PJ, eds. Chronobiology: Biological Timekeeping. Sunderland, MA: Sinauer Associates; 2004. 406 pp.
- Ferin M, Halberg F, Richart RM, Vande Wiele R, eds. Biorhythms and Human Reproduction. New York: John Wiley & Sons; 1974. 665 pp.
- Foster R, Kreitzman L. Rhythms of Life: The Biological Clocks That Control the Daily Lives of Every Living Thing. London: Profile; 2004. 320 pp.
- Fraisse P, Halberg F, Lejeune H, Michon JA, Montangero J, Nuttin J, Richelle M, eds. Du Temps Biologique au Temps Psychologique. Paris: Presses Universitaires de France; 1979.
- Graeber RC, Gatty R, Halberg F, Levine H. Human eating behavior: preferences, consumption patterns and biorhythms. NATICK/TR-78/022 Technical Reports. Natick, Mass.: U.S. Army; 1978. 287 pp.
- Halberg F, editor. Proc. XII Int. Conf. International Society for Chronobiology, Washington, DC, August 10-15, 1975. Milan: II Ponte; 1977. 782 pp.
- Halberg F, Breus TK, Cornélissen G, Bingham C, Hillman DC, Rigatuso J, Delmore P, Bakken E, International Womb-to-Tomb Chronome Initiative Group: Chronobiology in space. Keynote, 37th Ann. Mtg. Japan Soc. for Aerospace and Environmental Medicine, Nagoya, Japan, November 8-9, 1991. University of Minnesota/Medtronic Chronobiology Seminar Series, #1, December 1991, 21 pp. of text, 70 figures.
- Halberg F, Carandente F, Cornélissen G, Katinas GS. Glossary of chronobiology. Chronobiologia 1977; 4 (Suppl. 1), 189 pp.
- Halberg F, Cornelissen G, Halberg E, Halberg I, Delmore P, Shinoda M, Bakken E. Chronobiology of human blood pressure. Medtronic Continuing Medical Education Seminars, 4th ed. Minneapolis: Medtronic Inc.; 1988. 242 pp.
- Halberg F, Kenner T, Fiser B, editors. Proceedings, Symposium: The Importance of Chronobiology in Diagnosing and Therapy of Internal Diseases. Faculty of Medicine, Masaryk University, Brno, Czech Republic, January 10-13, 2002. Brno: Masaryk University, 2002. 206 pp.
- Halberg F, Kenner T, Fiser B, Siegelova J, editors. Proceedings, Cardiovascular Coordination in Health and Blood Pressure Disorders. Brno, Czech Republic: Medical Faculty, Masaryk University; May 24, 1996. 65 pp.
- Halberg F, Kenner T, Fiser B, Siegelova J, eds. Proceedings, Symposium, Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006.
- Halberg F, Kenner T, Fiser B, Siegelova J, eds. Proceedings, Noninvasive Methods in Cardiology, Brno, Czech Republic, October 4-7, 2008. 304 pp. http://web.fnusa.cz/files/kfdr2008 /sbornik_2008.pdf
- Halberg F, Kenner T, Fiser B, Siegelova J, eds. Proceedings, Noninvasive Methods in Cardiology, Brno, Czech Republic, July 7-10, 2009. (Dedicated to the 90th Anniversary of Prof. Franz Halberg.) 402 pp. http://web.fnusa.cz/files/kfdr2009/sbornik_2009.pdf
- Halberg F, Kenner T, Siegelova J, editors. Proceedings, Symposium, Chronobiological Analysis in Pathophysiology of Cardiovascular System. Brno: Masaryk University; 2003. 186 pp.
- Halberg F, Reale L, Tarquini B. (eds.). Proc. 2nd Int. Conf. Medico-Social Aspects of Chronobiology, Florence, Oct. 2, 1984. Rome: Istituto Italiano di Medicina Sociale, 1986. 791 pp.
- Halberg F, Scheving LE, Powell EW, Hayes DK, eds. Chronobiology, Proc. XIII Int. Conf. Int. Soc. Chronobiol., Pavia, Italy, September 4-7, 1977. Milan: Il Ponte; 1981. 394 pp.
- Halberg F, Watanabe H. (eds.). Workshop on Computer Methods on Chronobiology and Chronomedicine. 20th Int. Cong. Neurovegetative Research, Tokyo, Sept. 10-14, 1990. Tokyo: Medical Review; 1992. 297 pp.
- Hillman DC, Cornélissen G, Scarpelli PT, Otsuka K, Tamura K, Delmore P, Bakken E, Shinoda M, Halberg F, International Womb-to-Tomb Chronome Initiative Group. Chronome maps of blood pressure and heart rate. University of Minnesota/Medtronic Chronobiology Seminar Series, #2, December 1991, 3 pp. of text, 38 figures.
- Koukkari WL, Sothern RB. Introducing Biological Rhythms: A primer on the temporal organization of life, with implications for health, society, reproduction and the natural environment. New York: Springer; 2006. 655 pp.
- Otsuka K, Cornélissen G, Halberg F (eds). Chronocardiology and Chronomedicine: Humans in Time and Cosmos. Tokyo: Life Science Publishing; 1993. 147 pp.
- Prikryl P, Siegelova J, Cornélissen G, Dusek J, Dankova E, Fiser B, Vacha J, Ferrazzani S, Tocci A, Caruso A, Rao G, Fink H, Halberg F, International Womb-to-Tomb Chronome Initiative Group: Chronotherapeutic pilot on 6 persons may guide tests on thousands: Toward a circadian optimization of prophylactic treatment with daily low-dose aspirin. University of Minnesota/Medtronic Chronobiology Seminar Series, #3, December 1991, 4 pp. text, 4 figures.
- Refinetti R. Circadian Physiology. 2nd ed. Boca Raton, FL: CRC Press; 2006. 700 pp.
- Reinberg A, Halberg F, editors. Chronopharmacology. Oxford/New York: Pergamon Press, 1979, 429 pp.
- Reinberg A, Smolensky MH. Biological rhythms and medicine. Cellular, metabolic, physiopathologic, and pharmacologic aspects. New York: Springer; 1983. 305 pp.
- Schaefer KE, editor. Man's Dependence on the Earthly Atmosphere. New York: Macmillan; 1962. 416 pp.
- Scheving LE, Halberg F, editors. Chronobiology: Principles and Applications to Shifts in Schedules. Alphen aan den Rijn, Netherlands: Sijthoff & Noordhoff; 1980. 572 pp.
- Scheving LE, Halberg F, Ehret CF, editors. Chronobiotechnology and Chronobiological Engineering. Dordrecht, The Netherlands: Martinus Nijhoff; 1987. 453 pp.
- Scheving LE, Halberg F, Pauly JE, editors. Chronobiology, Proc. Int. Soc. for the Study of Biological Rhythms, Little Rock, Ark. Stuttgart: Georg Thieme Publishers/Tokyo: Igaku Shoin Ltd.; 1974. 784 pp.
- Suda M, Hayaishi O, Nakagawa H, editors. Biological Rhythms and Their Central Mechanisms. Naito Foundation. Amsterdam: Elsevier North-Holland Biomedical Press; 1979. 453 pp.
- Takahashi R, Halberg F, Walker C, editors. Toward Chronopharmacology, Proc. 8th IUPHAR Cong. and Sat. Symposia, Nagasaki, July 27-28, 1981. Oxford: Pergamon Press, 1982, 444 pp.
- Touitou Y, Haus E, editors. Biological Rhythms in Clinical and Laboratory Medicine. Berlin: Springer-Verlag; 1992. 730 pp.
- Valleron AJ, Macdonald PDM, eds. Biomathematics and Cell Kinetics. Amsterdam: Elsevier/North-Holland Biomedical Press; 1978. 431 pp.
- Youan BC, ed. Chronopharmaceutics: Science and Technology for Biological Rhythm-Guided Therapy and Prevention of Diseases. Hoboken, NJ: Wiley; 2009.
(modified or amplified from Chronobiology glossary cf. Halberg F, Carandente F, Cornélissen G, Katinas GS. Glossary of chronobiology. Chronobiologia 1977; 4 [Suppl. 1], 189 pp) where more information (∆) can be found.
Large ongoing international cooperative projects such as those revolving around chronobiologic self-help in health care often pose semantic problems that jeopardize the implementation of the work and lead to waste. This glossary should reduce, if not eliminate, semantic misunderstandings and thus contribute to the success of ongoing projects such as that on The BIOsphere and the COSmos, BIOCOS. Steps being implemented toward international cooperation require a selection of comparable if not unified reference standards. Only thus can the definition of certain rhythm (cycle) characteristics become meaningful. By the same token, there is the need for using comparable analytical procedures that are generally applicable to systematically collected and stored data on blood pressure, heart rate and on other time series. Broad international agreements can be reached toward the factual as well as semantic standardization of information capture, transfer, storage, analysis and updating from appropriate (data) bases: the characteristics of rhythms, estimated at different times and in different localities, will become amenable to a more facile and meaningful, direct comparison and integration. These are challenges and opportunities for the development of a serially updated individualized health form, card, booklet or equivalent, such as a cellphone, containing the information necessary for the precise early recognition of risk and thus for endeavors toward the prevention of diseases of individuals and (when data are pooled from many individuals) for learning about solar effects upon societal ills, for the development of countermeasures. In this glossary, the as yet uninitiated reader may also find a stimulus toward gaining an interest in the time dimension necessary to reach a more dynamic understanding of the entire field of biology and broader science as it relates, beyond personal health, to society's ills and to our environment, in the atmosphere of the sun as a whole in which we happen to live.
ACROPHASE θ, φ, Φ measure of timing; the lag from a defined timepoint (acrophase∆ reference) of the crest time in the function ∆ appropriately approximating a rhythm∆ ; the phase∆ angle of the crest, in relation to the specified reference timepoint, of a single best fitting cosine (unless another approximating function is specified.)
Units: angular measures: degrees, radians; time units: seconds, minutes, hours, days, months, years, decades, centuries etc.; or physiological episodic units: number of heart beats, respirations etc. Angular measures are directly applicable to any cycle∆ length and hence are proposed for general use because of greater familiarity; degrees (with 360 degrees equated to period of rhythm) are preferred over radians.
AMPLITUDE, A measure of one half the extent of rhythmic change in a cycle∆ estimated by the sinusoidal (or other) function used to approximate the rhythm∆, e.g., difference between maximum ∆ and MESOR ∆ of a best fitting cosine.
Units: original physiological units, e.g., number of heart beats, mmHg in blood pressure, etc.
ANGULAR FREQUENCY, ω special case of frequency∆ of a periodic process expressed in degrees or radians per unit of time obtained by equating one cycle∆ to 2π, e.g., ω in equation y(t) = M + A cos(ωt + φ) used to approximate a rhythm. Observe relation between angular frequency and frequency: ω = 2π/ τ = 2πf since frequency is the reciprocal of the period∆: f = 1/ τ Note: equivalent to angular velocity, usually visualized on polar coordinates.
CHAT Circadian hyper-amplitude-tension or circadian overswing, with circadian double amplitude exceeding the upper limit(s) of reference value(s) derived from peers matched by gender and age.
CHRONODESM time-qualified reference interval, e.g., time-qualified prediction or tolerance interval.
CHRONOBIOLOGY Computer-aided study in the biosphere of time structures, chronomes consisting of cycles, trends (that can be parts of cycles longer than a time series) and deterministic (and other) chaos (that can generate cycles).
CHRONOMICS Computer-aided study of interacting time structures in the biosphere and in its environment.
CIRCADIAN Relating to biologic variations or rhythms∆ with a frequency∆ of 1 cycle∆ in 24 ± 4 h; circa (about, approximately) and dies (day or 24 h).
CIRCASEMISEPTAN half-weekly variation. Circasemiseptans characterize widely differing phenomena, such as the behavior on different lighting regimens of an enucleated giant green alga, or an aspect of the biochemistry of (anucleate) platelets and even sudden human death. Thus, in the last few decades in Canada, most sudden human cardiac deaths peak on Mondays, with a second peak on Thursdays. A 3.5-day cosine curve fits such data better than a 7-day cosine curve.
CIRCASEPTAN about-weekly variation. Some human hormonal bioperiodicities, including rhythms, follow a roughly weekly pattern, such as those in circulating cortisol. Circaseptans are also found to characterize death from a mouse malaria or the rejection of allografts of heart, pancreas or kidney in untreated rats. Human kidney transplant rejection episodes are also more likely to occur around the 7th, 14th, 21st and 28th days after operation, or near other multiples of 7 post-operative days.
CIRCATRIGINTAN variation, such as the human menstrual cycle, that approximates a month in duration; such bioperiodicities, including rhythms, are also found before menarche and after menopause, and in men.
CONGRUENCE overlying or overlapping uncertainties (e.g., 95% confidence intervals) of 2 or more periods estimated in a time series
COSINOR statistical summary preferably with display of a biologic rhythm's amplitude∆ and acrophase∆ relations, on rectangular or polar coordinates; along the latter, by means of the length and the angle of a directed line, shown with a bivariate 95% or other statistical confidence∆ region computed (at chosen trial period∆) 1) to detect a rhythm∆ (by a confidence∆ region not overlapping zero, along rectangular coordinates, or the center of the plot, the pole, along polar coordinates) and 2) to estimate confidence∆ intervals for the rhythm parameters.
Notes: among procedures for the analysis, mostly, of short time∆ series, three kinds of cosinor have been designed in an integrated routine, each appropriate to a different situation: 1) Single cosinor, cosinor-S procedure applicable to a single biologic time series (from an individual or group); 2) Group mean-cosinor, cosinor-G: a cosinor procedure applicable to data from 2 or more individuals for characterizing a rhythm in that particular group only; 3) Population mean-cosinor, cosinor-P: the original cosinor procedure applicable to parameter ∆ estimates from 3 or more biologic series for assessing the rhythm characteristics of a population. All three cosinors use a cosine function: g(t) = M + A cos(ωt + Φ)
DEFICIENT HEART RATE VARIABILITY (DRV) a standard deviation of heart rate (determined around the clock for 7-days at 1-hour or shorter intervals) below the threshold of 7 beats/minute, a criterion to be further qualified for gender and age.
DESYNCHRONIZATION state of two or more previously synchronized rhythmic variables that have ceased to exhibit the same frequency∆ and/ or the same acrophase∆ relationships and show changing time relations.
ECPHASIA odd acrophase outside reference values of gender and age- matched peers
ECFREQUENTIA odd frequency outside reference values of gender and age- matched peers
ENTRAINMENT interaction between two or more organismic rhythms∆ or the effect upon rhythm(s) of an (external) synchronizer∆ resulting in identical frequencies among interactions or in frequencies constituting integral multiples of one another (frequency∆ -- multiplication or demultiplication).
EXCESSIVE PULSE PRESSURE above the threshold of 60 mmHg (determined in a record of 7 days at 1-hour or shorter intervals), a criterion to be further qualified for gender and age.
FREE-RUNNING pertaining to continuance of bioperiodicity with a natural frequency∆ usually at least slightly different from any known environmental schedule.
FREQUENCY, f the number of occurrences of a given type of event or the number of members in a population falling into a specified class.
Note: in the study of periodicity it is the number of cycles occurring per time unit, i.e., f is the reciprocal of the period (τ) f = 1/τ
GLOCAL and GLOCALITY adjective and noun, respectively, beginning with the first syllable of GLObal and ending with the last syllable of loCAL, as "smog" is formed from SMoke and fOG. "Glocal" is proposed to designate, in principle and as method, an approach that is global and local both in time and in space. This is 1) global, both a) in time, insofar as it relates to the structure (or chronome) of a time series as a whole (in the longest available data series) and b) in space, insofar as it wishes to do so from the earth and other locations, such as the solar system, as a whole, as possible and reasonable and 2) local, again a) in time, insofar as it wishes to examine separately a set of intervals of different lengths and b) in space, namely separately from each of several terrestrial and other locations. As an example the incidence pattern of natality, morbidity or mortality can be studied in global and local statistics by spectra of entire time series and in intervals of each of the series of different length. In combination with spectral windows of an entire series, aligned gliding spectral windows, focusing on a given frequency region, and chronobiologic serial sections, focusing upon a single or few frequencies and their time course, are glocal procedures. The slogan "think globally, act locally" can thus be extended spatiotemporally.
INFRADIAN relating to certain biologic variations or rhythms ∆ with a frequency ∆ lower-than-circadian∆
LEAST-SQUARES METHOD estimation technique for determining quantities by minimizing the error (or residual) sum of squares. In a linear model, this method produces the best linear unbiased estimate (b.l.u.e.) in terms of variance. Note: two types of least-squares methods are considered: linear or nonlinear.
MARKER RHYTHM rhythm∆ of use in practical monitoring and, where appropriate, decision-making -- in applied or basic physiologic or pharmacologic work, in preventive health maintenance (prophylactic marker rhythm), risk monitoring (risk marker rhythm), for diagnostic purposes (diagnostic or screening marker rhythm), for timing therapy (chronotherapeutic marker rhythm) or for assessing therapeutic response (response marker rhythm) without any implication of necessarily causal relations between the process and its rhythmic marker.
MESOR, M rhythm-determined average of Midline Estimating Statistic of Rhythm, e.g., in the case of a single cosine approximation, the value midway between the highest and lowest values of function ∆ used to represent a rhythm∆
MESOR-HYPERTENSION, MH for systolic and/or diastolic blood pressure, a transient∆ or lasting elevation of the circadian∆ (about-24-h) rhythm-adjusted mean (MESOR, M∆) as validated statistically against the person's (patient's) own MESOR at another time and/or against a peer reference standard.
PERIOD (Greek τ) duration of one complete cycle∆ in a rhythmic variation.
Note: biologic rhythms can be analyzed in terms of a spectrum∆ with statistically significant components in several spectral∆ domains. Period notation is customary within a given region or (e.g., circadian∆) domain of the spectrum. Frequency∆ (defined as the inverse of the period f= 1/τ) notation facilitates discussions of phenomena involving several broad spectral domains.
PREDICTION INTERVAL a range of values expected to contain, on the average, a specified proportion of a population or of a distribution (of values) from an individual.
RESONANCE property of a system oscillating (or capable of oscillating) with some natural frequency∆ (or rhythm∆) to exhibit an increased amplitude (or to begin oscillating) when subjected to an external periodic influence or force with a frequency similar to that of the system, the amplitude of the resonant frequency increasing as the outside periodic influence approaches the natural frequency of the system.
RHYTHM a periodic component of (biologic) time∆ series, demonstrated by inferential statistical means, preferably with objectively quantified characteristics (i.e., frequency∆ f, acrophase∆ [phi], amplitude∆ A, MESOR∆ M, and/ or waveform∆ W).
SYNCHRONIZER, Sy environmental periodicity determining the temporal placement of a given biologic rhythm∆ along an appropriate time scale, by impelling the rhythm to assume synchronization, i.e., its frequency∆ or an integer multiple or submultiple of its frequency and a specifiable acrophase∆ Note: also called zeitgeber, a time-giver, entraining agent (ever though the environmental cycle does not give time), clue or cue. Adjectives primary, dominant and secondary describe relative roles played by different environmental synchronizers. In several strains of inbred mice fed ad libitum, the lighting regimen is the primary synchronizer of the blood eosinophil rhythm. Adjectives dominant and modifying also can be used to describe the effect of a given environmental factor in relation to a given rhythm. Under unusual circumstances a secondary synchronizer may become dominant. Thus in C3H (Minnesota) mice subjected to a 50 percent restriction in dietary calories, the feeding time (of a diet restricted in calories) may be dominant over the lighting regimen. Moreover, under conditions of time-restricted access to food, synchronization by the lighting regiment may be largely though not fully overridden by meal timing. Thus, limited access time to food can be largely but not entirely dominant over lighting regimen with respect to the synchronization of the rhythm in telemetered intraperitoneal temperature. A secondary effect of the lighting regimen remains apparent as the result of interference between synchronizers. Finally, a rhythm can be influenced by secondary synchronizers and modifying factors, modulators, or, more generally, influencers.
ULTRADIAN a variation with a frequency higher than 1 cycle in 20 hours, i.e., with a period of less than 20 hours. An example of an ultradian is the sleep-wake cycle of patients with narcolepsy, a sleep disorder in which patients fall asleep several times daily, e.g., with average periods of 1.7 hours.
VASCULAR VARIABILITY ANOMALY (VVA): an alteration of variability as compared to that of healthy peers, found in a 7-day record of hourly or denser measurements analyzed as a whole, of blood pressure or heart rate. Examples are MESOR-hypertension; CHAT (circadian hyper-amplitude-tension); odd timing, or ecphasia; odd frequency, or ecfrequentia; excessive pulse pressure and deficient heart rate variability.
VASCULAR VARIABILITY DISORDER (VVD) a VVA replicated in at least three 7-day profiles at hourly or shorter intervals, each analyzed as a whole.
VASCULAR VARIABILITY SYNDROME (VVS) two or more VVDs present simultaneously in the same patients replicated in three 7-day/24-hour records.