A chronomic tree of life: ontogenetic and phylogenetic 'memories' of primordial cycles--keys to ethics.

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.

100 or 30 years after Janeway or Bartter, Healthwatch helps avoid 'flying blind'.

Longitudinal records of blood pressure (BP) and heart rate (HR) around the clock for days, weeks, months, years, and even decades obtained by manual self-measurements (during waking) and/or automatically by ambulatory monitoring reveal, in addition to well-known large within-day variation, also considerable day-to-day variability in most people, whether normotensive or hypertensive. As a first step, the circadian rhythm is considered along with gender differences and changes as a function of age to derive time-specified reference values (chronodesms), while reference values accumulate to also account for the circaseptan variation. Chronodesms serve for the interpretation of single measurements and of circadian and other rhythm parameters. Refined diagnoses can thus be obtained, namely MESOR-hypertension when the chronome-adjusted mean value (MESOR) of BP is above the upper limit of acceptability, excessive pulse pressure (EPP) when the difference in MESOR between the systolic (S) and diastolic (D) BP is too large, CHAT (circadian hyper-amplitude tension) when the circadian BP amplitude is excessive, DHRV (decreased heart rate variability) when the standard deviation (SD) of HR is below the acceptable range, and/or ecphasia when the overall high values recurring each day occur at an odd time (a condition also contributing to the risk associated with 'non-dipping'). A non-parametric approach consisting of a computer comparison of the subject's profile with the time-varying limits of acceptability further serves as a guide to optimize the efficacy of any needed treatment by timing its administration (chronotherapy) and selecting a treatment schedule best suited to normalize abnormal patterns in BP and/or HR. The merit of the proposed chronobiological approach to BP screening, diagnosis and therapy (chronotheranostics) is assessed in the light of outcome studies. Elevated risk associated with abnormal patterns of BP and/or HR variability, even when most if not all measurements lie within the range of acceptable values, becomes amenable to treatment as a critical step toward prevention (prehabilitation) to reduce the need for rehabilitation (the latter often after costly surgical intervention).

Melatonin, refractory hypertension, myocardial ischemia and other challenges in nightly blood pressure lowering.

A test of the relative merits of timed melatonin for the treatment of cardiac ischemia as well as hypertension refractory to other drugs is documented against the background of earlier chronobiological studies on blood pressure (BP), disease risks, circadian hyper-amplitude-tension and melatonin effects broadly.

Chronoastrobiology: proposal, nine conferences, heliogeomagnetics, transyears, near-weeks, near-decades, phylogenetic and ontogenetic memories.

"Chronoastrobiology: are we at the threshold of a new science? Is there a critical mass for scientific research?" A simple photograph of the planet earth from outer space was one of the greatest contributions of space exploration. It drove home in a glance that human survival depends upon the wobbly dynamics in a thin and fragile skin of water and gas that covers a small globe in a mostly cold and vast universe. This image raised the stakes in understanding our place in that universe, in finding out where we came from and in choosing a path for survival. Since that landmark photograph was taken, new astronomical and biomedical information and growing computer power have been revealing that organic life, including human life, is and has been connected to invisible (non-photic) forces, in that vast universe in some surprising ways. Every cell in our body is bathed in an external and internal environment of fluctuating magnetism. It is becoming clear that the fluctuations are primarily caused by an intimate and systematic interplay between forces within the bowels of the earth--which the great physician and father of magnetism William Gilbert called a 'small magnet'--and the thermonuclear turbulence within the sun, an enormously larger magnet than the earth, acting upon organisms, which are minuscule magnets. It follows and is also increasingly apparent that these external fluctuations in magnetic fields can affect virtually every circuit in the biological machinery to a lesser or greater degree, depending both on the particular biological system and on the particular properties of the magnetic fluctuations. The development of high technology instruments and computer power, already used to visualize the human heart and brain, is furthermore making it obvious that there is a statistically predictable time structure to the fluctuations in the sun's thermonuclear turbulence and thus to its magnetic interactions with the earth's own magnetic field and hence a time structure to the magnetic fields in organisms. Likewise in humans, and in at least those other species that have been studied, computer power has enabled us to discover statistically defined endogenous physiological rhythms and further direct effects that are associated with these invisible geo- and heliomagnetic cycles. Thus, what once might have been dismissed as noise in both magnetic and physiological data does in fact have structure. And we may be at the threshold of understanding the biological and medical meaning and consequences of these patterns and biological-astronomical linkages as well. Structures in time are called chronomes; their mapping in us and around us is called chronomics. The scientific study of chronomes is chronobiology. And the scientific study of all aspects of biology related to the cosmos has been called astrobiology. Hence we may dub the new study of time structures in biology with regard to influences from cosmo- helio- and geomagnetic rhythms chronoastrobiology. It has, of course, been understood for centuries that the movements of the earth in relation to the sun produce seasonal and daily cycles in light energy and that these have had profound effects on the evolution of life. It is now emerging that rhythmic events generated from within the sun itself, as a large turbulent magnet in its own right, can have direct effects upon life on earth. Moreover, comparative studies of diverse species indicate that there have also been ancient evolutionary effects shaping the endogenous chronomic physiological characteristics of life. Thus the rhythms of the sun can affect us not only directly, but also indirectly through the chronomic patterns that solar magnetic rhythms have created within our physiology in the remote past. For example, we can document the direct exogenous effects of given specific solar wind events upon human blood pressure and heart rate. We also have evidence of endogenous internal rhythms in blood pressure and heart rate that are close to but not identical to the period length of rhythms in the solar wind. These were installed genetically by natural selection at some time in the distant geological past. This interpretive model of the data makes the prediction that the internal and external influences on heart rate and blood pressure can reinforce or cancel each other out at different times. A study of extensive clinical and physiological data shows that the interpretive model is robust and that internal and external effects are indeed augmentative at a statistically significant level. Chronoastrobiological studies are contributing to basic science--that is, our understanding is being expanded as we recognize heretofore unelaborated linkages of life to the complex dynamics of the sun, and even to heretofore unelaborated evolutionary phenomena. Once, one might have thought of solar storms as mere transient 'perturbations' to biology, with no lasting importance. Now we are on the brink of understanding that solar turbulences have played a role in shaping endogenous physiological chronomes. There is even documentation for correlations between solar magnetic cycles and psychological swings, eras of belligerence and of certain expressions of sacred or religious feelings. Chronoastrobiology can surely contribute to practical applications as well as to basic science. It can help develop refinements in our ability to live safely in outer space, where for example at the distance of the moon the magnetic influences of the sun will have an effect upon humans unshielded by the earth's native magnetic field. We should be better able to understand these influences as physiological and mechanical challenges, and to improve our estimations of the effects of exposure. Chronoastrobiology moreover holds great promise in broadening our perspectives and powers in medicine and public health right here upon the surface of the earth. Even the potential relevance of chronoastrobiology for practical environmental and agricultural challenges cannot be ruled out at this early stage in our understanding of the apparently ubiquitous effects of magnetism and hence perhaps of solar magnetism on life. The evidence already mentioned that fluctuations in solar magnetism can influence gross clinical phenomena such as rates of strokes and heart attacks, and related cardiovascular variables such as blood pressure and heart rate, should illustrate the point that the door is open to broad studies of clinical implications. The medical value of better understanding magnetic fluctuations as sources of variability in human physiology falls into several categories: 1) The design of improved analytical and experimental controls in medical research. Epidemiological analyses require that the multiple sources causing variability in physiological functions and clinical phenomena be identified and understood as thoroughly as possible, in order to estimate systematic alterations of any one variable. 2) Preventive medicine and the individual patients'care. There are no flat 'baselines', only reference chronomes. Magnetic fluctuations can be shown statistically to exacerbate health problems in some cases. The next step should be to determine whether vulnerable individuals can be identified by individual monitoring. Such vulnerable patients may then discover that they have the option to avoid circumstances associated with anxiety during solar storms, and/or pay special attention to their medication or other treatments. Prehabilitation by self-help can hopefully complement and eventually replace much costly rehabilitation. 3) Basic understanding of human physiological mechanisms. The chronomic organization of physiology implies a much more subtle dynamic integration of functions than is generally appreciated. All three categories of medical value in turn pertain to the challenges for space science of exploring and colonizing the solar system. The earth's native magnetic field acts like an enormous umbrella that offers considerable protection on the surface from harsh solar winds of charged particles and magnetic fluxes. The umbrella becomes weaker with distance from the earth and will offer little protection for humans, other animals, and plants in colonies on the surface of the moon or beyond. Thus it is important before more distant colonization is planned or implemented to better understand those magnetism-related biological- solar interactions that now can be studied conveniently on earth. (ABSTRACT TRUNCATED)

Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond.

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.

Chronomics of tree rings for chronoastrobiology and beyond.

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.

Circasemiannual chronomics: half-yearly biospheric changes in their own right and as a circannual waveform.

Geomagnetic activity has a strong half-yearly but no precise yearly component in its spectrum, as Armin Grafe suggested nearly half a century ago. We have postulated elsewhere that non-photic cycles such as those in geomagnetics may have signatures in the biosphere and vice versa that biological rhythms have likely counterparts in the physical environment. Accordingly, we document phenomena characterized by a prominent about half-yearly variation, re-analyzed to constitute the start of a transdisciplinary chronomic (time structural) map, aligning these conditions with a half-yearly cycle in the geomagnetic index Kp. At least some biospheric phenomena fitted concomitantly with 1- and 0.5-year cosine curves exhibit an amplitude (A) ratio of A(0.5-year)/A(1-year) larger than unity. Methodologically, it is pertinent that even if data were read off published graphs, the resulting analyses were practically the same as those in the original data received subsequently. The main point is a circasemiannual pattern in status epilepticus, in several morbid oral conditions, in the cell density of vasopressin-containing neurons in the human suprachiasmatic nuclei (SCN), in circulating melatonin at middle latitudes at night during years of minimal solar activity or around noon at high latitudes, and in an unusual circasemiannual aspect of a birth-month-dependence of human longevity. Others have asked whether annual rhythms in human reproduction are biological, sociological or both. We show some other possibilities herein, involving the physical environment, hardly to be neglected in the case of open systems. As to almost certainly multifactorial circasemiannual rhythms, geomagnetics may also be a signal, a proxy or a putative, at least partial mechanism. Geomagnetic activity is related in its turn to solar and galactic activity, and may be a marker for other cyclic events that affect the biosphere. The similarity of cycle lengths in itself can only be a hint prompting the search for causal relations.

Blood pressure self-surveillance for health also reflects 1.3-year Richardson solar wind variation: spin-off from chronomics.

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.

Transient circadian hyper-amplitude-tension (CHAT) may be intermittent: case reports illustrating gliding spectral windows.

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.

Stress/strain/life revisited. Quantification by blood pressure chronomics: benetensive, transtensive or maletensive chrono-vasculo-neuro-immuno-modulation.

We propose to initiate the automatic self-assessment of wear and tear as "stress and strain" by the time structures of blood pressure (BP) and heart rate (HR), in order to arrive eventually at an individualized timely and timed routine of life and to early preventive intervention as soon as needed. The routine may involve physiological scheduling of physical and mental activities and meals, and if need be of non-drug or drug treatment for stress amplification, e.g., by exercise, and/or strain (not stress) relief by relaxation. In so doing, we recognize the circulation as a pillar and marker of preventive and active neuroimmunomodulation (NIM), suggesting that some concerns of a vasculo- and broader NIM can be quantified by transdisciplinary chronobiology using its cartography--chronomics--of time structures, i.e., chronomes, from chronos = time and nomos = rule. Thus, we are introducing the chronomics of BP, HR and of other variables in the historical context of pioneers who were indispensable to experimental medicine. We build upon their contributions, but we must point out when, in the past, by necessity rather than choice, the giants provided rationalizing truisms that are no substitute for systematic serial data collection and appropriate computer analysis. A time-unspecified spotcheck as a baseline is much better than no measurement, but very often it is not enough, and it is always insufficient when an estimate of variability constitutes the information needed. For dynamic cycles, there are only reference cycles as a routine, although when maps are available, single timed spotchecks can be invaluable. With reference to their historical context, here we rely only upon data which necessity, rather than philosophy, compels us to collect.