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Поддержка: США. Национальный Институт Здоровья(GM-13981)(FH), Миннесотский Технологический Институт(GC, FH) На протяжении нескольких десятилетий было проведено хронобиологическое мониторирование сердечно-сосудистых, психофизиологических, эндокринных и других показателей, включая температуру ядра. Полученные показатели обладают широким спектром периодов, некоторые из которых имеют аналогичные показатели с земными, межпланетарными и солнечными ритмами. Было проведено картирование циркасептальных, цирканнуальных ритмов изучаемых параметров. Установлено, что имеется определенная степень синхронизации ритмов, которая затухает при отсутствии или уменьшении активности окружающей среды и возрастает с активацией этой среды. Аналогичная направленность показателей была выявлена для периодичности ритмов террористических атак и крупных землетрясений. Синхронизация(копериодизм) циклов биосферы с циклами гидросферы, атмосферы, ионосферы и т.д. обосновывает создание междисциплинарного термина хроносфера («хронос» - время, «сфера» - земной шар). Изучение хроносферы позволяет избежать последствий природных катаклизмов, а хронобиологическое мониторирование сердечно-сосудистой системы является значительно более эффективным способом предупреждения заболеваний по сравнению с обычной системой медицинского наблюдения.

Dynamics of blood pressure (BP) and heart rate (HR) was traced by automatic monitoring every 30 min uninterruptedly along several months in a patient suffering from combined atrial fibrillation and heart failure during the development of disease and its therapeutic and surgical treatment (pacemaker implanting and atrioventricular ablation). Analyses of spectral components as well as signal's shape revealed instabilities in circadian and semicircadian parameters. A new approach for signal's form description without using cosine approximation is suggested. The meaning that referring a patient as dipper, night peaker, or nondipper might be useful at choosing tactics of his treatment is impugned, because all these "types" can transform themselves in the same person in few days. Optimization timing of treatment provides better results if not the "types" of daily profile would be taken to account but the real form of the BP-signal and timing its first and second derivatives.

The mapping of time structures, chronomes, constitutes an endeavor spawned by chronobiology: chronomics. This cartography in time shows signatures on the surface of the earth, cycles, also accumulating in life on the earth's surface. We append a glossary of these and other cycles, the names being coined in the light of approximate cycle length. These findings are transdisciplinary, in view of their broad representation and critical importance in the biosphere. Suggestions of mechanisms are derived from an analytical statistical documentation of characteristics with superposed epochs and superposed cycles and other "remove-and-replace" approaches. These approaches use the spontaneously changing presence or absence of an environmental, cyclic or other factor for the study of any corresponding changes in the biosphere. We illustrate the indispensability of the mapping of rhythm characteristics in broader structures, chronomes, along several or all available different time scales. We present results from a cooperative cartography of about 10, about 20, and about 50-year rhythms in the context of a broad endeavor concerned with the Biosphere and the Cosmos, the BIOCOS project. The participants in this project are our co-authors worldwide, beyond Brno and Minneapolis; the studies of human blood pressure and heart rate around the clock and along the week may provide the evidence for those influences that Mendel sought in meteorology and climatology.

An impeccable time series, published in 1930, consisting of hourly observations on colony advance in a fluid culture of E. coli, was analyzed by a periodogram and power spectrum in 1961. While the original senior author had emphasized specifically periodicity with no estimate of period length, he welcomed further analyses. After consulting his technician, he knew of no environmental periodicity related to human schedules other than an hourly photography. A periodogram analysis in 1961 showed a 20.75-h period. It was emphasized that "... the circadian period disclosed is not of exactly 24-h length." Confirmations notwithstanding, a committee ruled out microbial circadian rhythms based on grounds that could have led to a different conclusion, namely first, the inability of some committee members to see (presumably by eyeballing) the rhythms in their own data, and second, what hardly follows, that there were "too many analyses" in the published papers. Our point in dealing with microbes and humans is that analyses are indispensable for quantification and for discovering a biologically novel spectrum of cyclicities, matching physical ones. The scope of circadian organization estimated in 1961 has become broader, including about 7-day, about half-yearly, about-yearly and ex-yearly and decadal periodisms, among others. Microbial circadians have become a field of their own with eyeballing, yet time-microscopy can quantify characteristics with their uncertainties and can assess broad chronomes (time structures) with features beyond circadians. As yet only suggestive differences between eukaryotes and prokaryotes further broaden the perspective and may lead to life's sites of origin and to new temporal aspects of life's development as a chronomic tree by eventual rhythm dating in ontogeny and phylogeny.

As an extension of the chronobiological serial section, gliding spectra illustrate the changing time structure (chronome) of physiological, physical and/or other variables in a given frequency range. For this purpose, least squares spectra are computed over a specified interval (much shorter than the observation span) that is progressively displaced by a given increment throughout the entire record. Results can be displayed either as 3D charts or as surface charts, displaying the estimated amplitudes, percentage rhythms or ordering P-values at each trial period for each interval. The procedure is illustrated for the record of Wolf numbers as a gauge of solar activity and for the number of marriages and divorces in Japan during the past century. Major components in these time series show deviations in period length and relative prominence over time. Particularly in the case of non-stationary time series, gliding spectra offer themselves as useful tools to examine changes in time structure beyond a specific spectral component.

Putative circadecadal modulations of a circannual variation in diastolic blood pressure are explored in a still accumulating 35 year record of self-measurements by a clinically healthy man. Analyses of monthly means by gliding spectra, one-way analysis of variance (ANOVA), and cosinor were carried out after removing data collected during travel across time zones or during illness. An about yearly change in diastolic blood pressure may or may not be detected with statistical significance by cosinor or ANOVA, apparently as a function of solar cycle number and/or stage. It appears to be, however, 1 year synchronized in the entire span analysed as a whole. A given variable such as diastolic blood pressure may be characterized by multifrequency rhythms that may intermodulate, so that findings in different stages of cycles with the lowest (e.g., circadecadal) frequency mapped may determine different outcomes in cycles with higher frequencies, such as circannuals.

In order to investigate infradian aspects of sudden death, the daily incidence of 70,531 cases recorded in response to a call for an ambulance during 3 years (1979-1981) in Moscow, Russia, were re-analysed, focusing on multiseptans (components with periods of 7 days and/or multiples thereof). Apart from a prominent yearly and half-yearly variation in the daily incidence of sudden death, least squares spectra revealed the presence of about-weekly and two-weekly components. The about 15.2-day variation was validated by nonlinear least squares and shown to differ in period length from that found in the local index of geomagnetic activity, K. This result suggests that apart from any geomagnetic influence on sudden death, changes in lifestyle (such as alcohol consumption) associated with the twice-a-month salary schedule may affect the occurrence of sudden death. Such a component is not prominently seen for the incidence of other cardiovascular conditions recorded in the same database. The weekly pattern of sudden death, peaking on Saturdays, also differs from those of other cardiovascular conditions, characterized by a higher daily incidence on Mondays. The possibility to now record events in cardioverter-defibrillators offers an opportunity to explore broad chronomes of potentially lethal arrhythmia that may lead to a better understanding of underlying triggers, so that novel countermeasures may be designed and implemented.

We honor Theo Hellbrugge's acclaimed endeavors in the rehabilitation, or rather the prehabilitation of handicapped children. So far, he has focused on obvious handicaps, and we trust that he will include concern for everybody's silent handicaps in the future by screening for abnormal variability inside the physiological range. Therein, we introduce cis- and trans-years, components of transdisciplinary spectra that are novel for biology and also in part for physics. These components have periods, respectively, shorter and longer than the calendar year, with a counterpart in magnetoperiodism. Transyears characterize indices of geomagnetic activity and the solar wind's speed and proton density. They are detected, alone or together with circannuals, in physiology as well as in pathology, as illustrated for sudden cardiac death and myocardial infarction, a finding calling for similar studies in sudden infant death syndrome (SIDS). As transyears can beat with circannuals, and depend on local factors, their systematic mapping in space and time by transdisciplinary chronomics may serve a better understanding of their putative influence upon the circadian system. Longitudinal monitoring of blood pressure and heart rate detects chronome alterations underlying cardiovascular disease risk, such as that of myocardial infarction and sudden cardiac death. The challenge is to intervene in a timely fashion, preferably at birth, an opportunity for pediatricians in Theo Hellbrugge's footsteps.

The need for systematic around-the-clock self-measurements of blood pressure (BP) and heart rate (HR), or preferably for automatic monitoring as the need arises and can be met by inexpensive tools, is illustrated in two case reports. Miniaturized unobtrusive, as yet unavailable instrumentation for the automatic measurement of BP and HR should be a high priority for both government and industry. Automatic ambulatorily functioning monitors already represent great progress, enabling us to introduce the concept of eventually continuous or, as yet, intermittent home ABPM. On BP and HR records, gliding spectra aligned with global spectra visualize the changing dynamics involved in health and disease, and can be part of an eventually automated system of therapy adjusted to the ever-present variability of BP. In the interim, with tools already available, chronomics on self- or automatic measurements can be considered, with analyses provided by the Halberg Chronobiology Center, as an alternative to "flying blind", as an editor put it. Chronomics assessing variability has to be considered.

The case report presented herein aims at promoting the awareness in medical, notably cardiological, practice of the importance of, first, collecting at least a week-long record of around-the-clock measurements of blood pressure (BP) and heart rate (HR) (and a much longer record if the 7 day record so indicates) and, second, of analysing the data chronobiologically in the light of reference values specified as a function of time, gender and age as a minimum. In addition to diagnosing deviations in a chronome (time structure)-adjusted mean value, a chronobiological approach identifies abnormalities in the variability of BP and/or HR, gauged by the circadian characteristics (double amplitude and acrophase, measures of the extent and timing of predictable change within a cycle) and by the standard deviation. A woman in presumably good health was 60 years of age at the start of intermittent monitoring over a 7 year span. The case report illustrates the extent to which a decision based on single BP readings and even on 24 hour averages may be misleading. Treatment based on an initial week-long monitoring may benefit from continued long-term monitoring.

A scientific optimization may become possible in ethics to the extent to which any reproducible since cyclic features of spirituality and of criminality become measurable. Should either or both the 'good' or the 'bad' be found to be at least passively influenced by cyclic physical environmental factors, as is putatively the case, these aspects of behavior may eventually become actively manipulable, perhaps utilizable for human survival. Toward this goal, chronomics has already mapped time structures in religious behavior that can lead to a study of underlying geographic/geomagnetic latitude-associated mechanisms. This paper, with further but clearly insufficient data, revealing the hurdle of relative brevity of the available time series constitutes a plea for much longer and denser worldwide time series, for further endeavors in various methods of analyses, some of which are promisingly available.

Half-hourly systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) monitoring with gaps demonstrates transient elevations of unknown origin of the chronome (time structure)-adjusted mean, the MESOR, M, of BP, and of the circadian double amplitude of BP of TS, a clinically healthy-appearing engineering student who was 27 years of age at the start of the study. An assessment of large and small arterial vessel elasticity was in keeping with no detection of functional or structural alteration in her vasculature. The recovery of normality in BP endpoints at the time of this report is speculatively associated with a weight loss of 40 pounds and the formation of a friendship by correspondence. Whatever the underlying mechanisms of a long series of abnormal records may be, a 'baseline' can include weeklong spans of abnormality and is best replaced by comparisons with chronomic reference values.

Afew puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-one-goes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individual's needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal.

Self-experimentation concerns not only scientists, but also each individual for the sake of his/her chronobiologic health and science literacy, eventually to be acquired in primary and secondary education. Public education ensures that everybody who knows how to read or write can dispense with the service of a costly scribe. At all ages, public education can teach equally well how to find out whether one's blood pressure (BP) and heart rate (HR) responds to an increase in sodium intake with a rise, with no change or with a decrease in BP. This task and many others could become a matter of informed self-surveillance. Whenever there are inter-individual, sometimes opposite differences in response, government-sponsored trials on groups that do not consider such differences cannot solve what only the individual can do, at first by help from schools. Eventually special institutions may be designed for chronomics, the monitoring, interpretation and archivization of chronomes (time structures; from chronos = time and nomos = rule) of biological variables, also charged with a demographic analyzing and reporting system. Each individual's properly coded record, to guard confidentiality, becomes part of a promptly accessible database for one's own needs and for society's requirements. What individuals and small groups started as chronobiology, what is immediately available on back burners, as a service by an international project on the biosphere and the cosmos (BIOCOS) (corne001@umn.edu) could become a public system of planned surveillance archivization of one's rhythms from womb to tomb. Alterations of a rhythm's amplitude or acrophase or of a deterministic or other chaotic endpoint, such as a correlation dimension and approximate entropy, or of a standard deviation, among a multitude of other endpoints, can signal (in the otherwise neglected normal range) reversible risk elevations. If these elevated risks are detected and prompt the institution of countermeasures, such prehabilitation can save the cost of rehabilitation or of long-term care after morbid events; suffering also can be prevented such as that by those who are unlucky enough to helplessly survive a massive brain, heart or societal "stroke". As an equally important dividend, science gains in basic and applied terms, as illustrated herein by the demonstration of a trans-year, an approximately 1.3 to 1.6-year, heretofore unknown component of the human BP and HR spectrum, beating with the circannual component and characterizing the same data. Chronomically interpreted self-monitoring is a civic duty for both one's health and everybody's science.

In order to re-examine the extent to which secular circulatory variation can be resolved into possibly accountable, if not yet predictable behavior, the 15-year record of blood pressure and heart rate of an adult male cardiologist (Y.W.) is reanalyzed. Gliding spectral windows with an interval of 4 years progressively displaced throughout the data series examine monthly means from August 1987 to August 2002. A circannual variation is only intermittent and appears to drift for years. A circasemiannual variation is consistent and prominent, yet only for a fraction of the record examined. By contrast to the circadian rhythm in blood pressure and heart rate, which is reliably detectable in most subjects in clinical health, the circannual variation in the human circulation is inconsistent and hence should be monitored, as in this case for its assessment as one goes, a conclusion that also applies to the circasemiannual variation, prominent for years but not detected thereafter. The results prompt the search for interactions between the photic, thermic and societal effects of the seasons that, if solely pertinent, should yield a consistent 1-year spectral component. That non-photic effects may also play an important role may point to modulation by solar cycle stage and solar cycle number, perhaps mediated by the solar wind. This conclusion is extended in proof to the role played by the most recently discovered transannual component in human blood pressure and heart rate, which is a probable further signature of the solar wind. The beating of the transannual and circannual components documented on another data series may contribute to the lack of a consistent 1-year synchronized circannual variation in this case and many others.

Gliding spectral windows illustrate the changes as a function of time in the relative prominence of signals in a given frequency range, viewed in 3D or as surface charts. As an example, the method is applied to a 2,189-year series of averages of ring measurements on 11 sequoia trees published by Douglass. Analyses of the original data and after filtering reveal, among others, components with periods of about 10.5 and 21 years similar to the Schwabe and Hale solar activity cycles. An alignment of gliding spectra with a global spectrum serves to define, by minima, the ranges of variability around the anticipated Schwabe and Hale cycles. This procedure may have more general applicability when dealing with ranges of only transiently synchronized, wobbly, and perhaps sometimes free-running periodicities. Solar activity is known to affect climate and changes in climate are reflected to some extent in tree growth. The spectral structure in tree rings could serve not only to check any relations of climate with sunspots, auroras and more modern measures of solar activity, but also to check any purely mathematical extrapolations from the much shorter available actual data on solar activity. With such extrapolated series and the data analyzed herein, the task remains to align physical and physiological variables to further study the influence of natural environmental factors near and far on biota, including international battles, which cover an even longer span of 2,556 years.

Taking the heart rate (HR) for one cycle, whether to examine behavior in the region of periods of 1 s, 1 day, 1 week, 1.3 or 10.5 years, etc., is hazardous. Replications, when possible are mandatory for examining altered variability, whatever the period(s) involved may be. This replication in the individual, and across individuals when the periods are long, measured in decades, may serve for diagnosis and treatment. This rule applies in particular to a seemingly transient circadian hyper-amplitude-tension (CHAT), an over peer-threshold variability in blood pressure (BP), based on the fit of a 24-h cosine curve to time series of appropriate length, rather than to a mere snapshot covering just a single day or week. Transient CHAT may turn into intermittent CHAT, as determined in two cases presented herein. One case of transient CHAT could be so named after a successful treatment (Rx) change eliminated CHAT as an effect validated by monitoring at 30-min intervals for a 7-day span on a new treatment. CHAT disappeared for over 300 consecutive half-hourly measurements, but thereafter it reappeared. During the ensuing nearly continuously monitored 5 years, CHAT continued to appear and disappear sometimes without a treatment change. In another case, which was responsive to a change in the timing of medication, CHAT also disappeared and thereafter reappeared. In a short-term perspective of weeks or months of monitoring, CHAT seemed to be transient, but further monitoring again revealed it to be intermittent. Cases of intermittent CHAT require follow-up for outcomes by comparison with the population at large. Miniaturized instrumentation for their detection should be a high priority, but it must be realized that the automatic ambulatorily functioning monitors, available at 10% of the regular price through a BIOCOS project (corne001@umn.edu), already signify great progress, as compared to previously used manual measurements made around the clock by hypertensive opinion leaders in medicine from diagnosis to death. On automatically collected time series of BP and HR, gliding pergressive spectral windows as such, or such pergressive windows aligned further with global spectral windows, visualize the changing dynamics involved in health and disease, in the steps of Werner Menzel and Paolo Scarpelli.

We suggest a putative benefit from timing nutriceuticals (substances that are both nutrients and pharmaceuticals) such as antioxidants for preventive or curative health care, based on the proven merits of timing nutrients, drugs, and other treatments, as documented, i.a., in India. The necessity of timing melatonin, a major antioxidant, is noted. A protocol to extend the scope of chronoradiotherapy awaits testing. Imaging in time by mapping rhythms and broader time structures, chronomes, for earliest diagnoses, for example detection of vascular disease risk, is recommended. The study of rhythms and broader chronomes leads to a dynamic functional genomics, guided by imaging in time of free radicals and antioxidants, amongst many other variables.

Objectives: To review mechanisms of circadian variations in heart rate variability (HRV) and blood pressure variability (BPV) and mortality and morbidity due to cardiovascular diseases (CVD)., Methods: Results from 7-day/24-h HRV and BPV are interpreted by gender and age-specified reference values in the context of a Medline search., Results: Abnormal HRV and BPV measured around the clock for 7 days provides information on the risk of subsequent morbid events in subjects without obvious heart disease and without abnormality outside the conventional (in the sense of chronobiologically unquantified) physiological range. Meditation, beta-blockers, ACE inhibitors, n-3 fatty acids and estrogens may have a beneficial influence on HRV, but there is no definitive outcome-validated therapy. Low HRV has been associated with a risk of arrhythmias and arrhythmic death, unstable angina, myocardial infarction, progression of heart failure and atherosclerosis. BPV may be characterized by treatable circadian-hyper-amplitude-tension (CHAT), which can be transient '24-h CHAT' or '7-day-CHAT', MESOR-hypertension and/or an unusually-timed (odd) circadian acrophase (ecphasia), all associated with an increased risk of stroke, stroke death, myocardial infarction, and kidney disease., Conclusions: Precise insight into the patho-physiology in time of HRV and BPV is needed with development of a consensus on best measures of HRV for clinical purposes and to determine when a 7-day record interpreted chronobiologically suffices and when it does not, for detection within as well as outside the conventional normal range, for diagnostic clinical practice and to direct therapy of risk greater than that associated with hypertension, smoking or any other risk factor.

This study aimed to describe quantitatively some changes in sleep behavior. During 70 consecutive nights, 28 women and 3 men, 30 to 40 years of age and presumably clinically healthy, recorded the time of each awakening. Time of falling asleep were estimated from markings at 10-min. intervals from the times of lying down to sleep as an indication that the subject had not yet fallen asleep. Sleep duration and an index of effective sleep derived therefrom were analyzed by rhythmometric methods. On a group basis, anticipated components with periods of 1 and 0.5 wk., synchronized with the social schedule, were detected with statistical significance. Until long-term polysomnographic monitoring can readily cover the week automatically rather than only one or a few daily sleep spans, the self-monitoring of sleep behavior, yielding the circaseptan endpoints derived herein, may serve as a cost-effective tool in sleep research. By virtue of their relative simplicity, they could be part of a protocol designed to assess pharmacologic or nonpharmacologic interventions of sleep disturbance aimed at restoring undisturbed sleep.

System time is defined as the duration (T) and sampling density (deltat) of a given study. A time horizon is obtained by combining analytical results on endpoints of time structures (chronomes), usually on control groups, from accumulating diverse studies carried out with drastically different values of T and deltat. These two design considerations depend upon and are limited by resources. The desideratum of a small At e.g., for studies of chaotic endpoints, limits T, e.g., has thus far precluded a continuous mapping of decadal cycles in endpoints such as the approximate entropy or the correlation dimension. Time horizons are being documented for an increasing number of variables that undergo cycles with infra-annual frequencies - with one cycle in about one, two and/or five decades - in the biosphere as in the environment. These infra-annuals, in and around us, modulate ultra-annuals, including circadians, as well as about 7-day (circaseptan) and about half-yearly (circasemiannual) cycles, all prominent, e.g., in geophysical and biospheric specta. Neglect of infra-annual chronomics can lead to blunders. A statistically highly significant decrease in the excretion of steroidal metabolites (or in heart rate variability) may be misinterpreted as premature aging if it lasts for several years, and may be unnecessarily acted upon, e.g., by drugs. The decrease, however, may only be transient, occurring only during a given stage of a circadecadal cycle, and it may be followed for the next several years by an also spurious "rejuvenation", possibly misinterpreted as a drug effect. When recognized as the alternating stages of decadal cycles and assessed with an affordable deltat, infra-annuals of variables involved in major problems of our day, including homicides and wars, may lead us to manipulable internal or external mechanisms, and thus, eventually, possibly to countermeasures to crime and terror as well as to the optimization of aims such as spirituality.

During the past half-century, the differences found in the spectral element of marriages vs. divorces in Tokyo reveal a half-year aspect which increasingly dominates in marriages, probably as a result of a mix of socio-economic, climatic and/or geomagnetic, as well as human affection-related factors, On the other hand, a decadal component is prominent in divorces, possibly in association with non-photic solar activity. Sparser (yearly, not monthly) records, obtained over a century at different latitudes in Japan, demonstrate that the decadal components are not consistent in moving spectra of original (as yet not detrended) data. Longer and denser series over much greater differences in latitudes and longitudes will have to be subjected to a much more thorough scrutiny, in conjunction with a series of possibly pertinent variables, to assess the contributions of different sources of variation in different areas of Japan and world wide, preferably in democratic, non-combatant areas, where the socio-economical, political and other war-associated conditions are mostly in the background.

We chronobiologically estimate the time relations of physiological and morphological changes in breast tissue during the luteal phase of the menstrual cycle, as a cascade led by the progesterone peak. The timing and uncertainties of maxima in epithelial mitotic frequency, breast and epithelial volume, breast surface temperature, water content, blood flow and apoptosis are given as parts of a rhythmic element in a broader time structure or chronome.

The spectrum of biological rhythms is extended far beyond circadians, circannuals, and ultradians, such as 1.5-hourly melatonin and 8-hourly endothelin-1 (ET-1) rhythms by statistics of natality, growth, morbidity, and mortality, some covering decades or centuries on millions of individuals. These reveal infradian cycles to be aligned with half-weekly rhythms in ET-1, weekly and half-yearly ones in melatonin, and even longer--about 50-, about 20-, and about 10-year cycles found in birth statistics. About daily, weekly, yearly, and ten-yearly patterns are also found in mortality from myocardial infarctions; the 10-yearly ones are also in heart rate and its variability; in steroid excretion, an aspect of resistance, for example, to bacteria; and in the genetic changes of the bacteria themselves. Automatic physiological measurements cover years and, in one case, cover a decade; the latter reveal an about 10-year (circadecennial) cycle. ECGs, covering months beat-to-beat, reveal circaseptans, gaining prominence in response to magnetic storms or after coronary artery bypass grafting. A spectrum including cycles from fractions of 1 Hz to circasemicentennians is just one element in biological time structures, chronomes. Chaos, trends, and any unresolved variability are the second to fourth elements of chronomes. Intermodulations, feedsidewards, account for rhythmically and thus predictably recurring quantitive differences and even for opposite treatment effects of the same total dose(s) of (1) immunomodulators inhibiting or stimulating DNA labeling of bone in health or speeding up versus slowing down a malignant growth and thus shortening or lengthening survival time, or (2) raising or lowering blood pressure or heart rate in the vascular aspect of the body's defense. Latitude-dependent competing photic and nonphotic solar effects upon the pineal are gauged by alternating yearly (by daylight) and half-yearly (by night) signatures of circulating melatonin at middle latitudes and by half-yearly signatures at noon near the pole. These many (including novel near 10-yearly) changes, for example, in 17-ketosteroid excretion, heart rate, heart rate variability, and myocardial infarction in us and those galactic, solar, and geophysical ones around us have their own special signatures and contribute to a cosmo-vasculo-immunity and, if that fails, to a cosmo(immuno?) pathology.

Week-long or longer monitoring of blood pressure and heart rate, coupled to time-structure analyses, can help detect disease-risk elevations, as a warning of the need for a preventive prehabilitation. Within the normal range of physiologic variation, computer methods quantify time structures, or chronomes, that can serve as reference values. The major applied purpose for mapping chronomes is the detection of disease-risk syndromes such as blood pressure "overswinging" and heart rate "underswinging." Too much blood pressure variability (circadian hyperamplitude tension; CHAT), is a risk factor for vascular disease. Other risk syndromes are chronome alterations of heart rate variability (CAHRVs), consisting of a loss of "jitter", i.e., a reduced standard deviation of heart rate or of alterations in the spectral element of the heart-rate-variability chronome, such as in the correlation dimension, an endpoint of deterministic chaos. These alterations can again serve for prehabilitation. On the basic side, the spectral element of the heart-rate-variability chronomes extends from focus on the heartbeat's period of about 1 second to periods in heart rate and its standard deviation that are numerical equivalents of about 10.5- and about 21-year cycles of solar activity. A seemingly unnatural physiologic rhythm or pattern (such as one of 81.6 hours) may correspond numerically to a purely physical environmental rhythm. For example, interplanetary magnetic storms, with their cycles as external chronome components, trigger myocardial infarctions, strokes, and traffic accidents. The systematic monitoring of external rhythms along with physiologic ones for the concurrent analysis of rhythms with longer and longer periods could detect alterations anywhere in and between the 1 cycle/sec and the 1 cycle/10.5- or 21-years regions of the spectrum. Chronobiomimetic engineering for discovering both instantaneous and long-term chronorisk alterations can provide warnings of increased risk. If risk-lowering therapy is then instituted automatically, instrumented health care will be extended beyond the pacemaker-cardioverter-defibrillator, which focuses on the frequency of 1 cycle/sec. Instrumentation that automatically detects blood pressure that varies too much and heart rate that varies too little is needed for prompting prophylactic CHAT and CAHRV treatment. A database of reference values that can be used for chronodiagnosis is now accumulating.