Научная статья на тему 'Monitoring of factors of space weather and parameters of blood pressure'

Monitoring of factors of space weather and parameters of blood pressure Текст научной статьи по специальности «Клиническая медицина»

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Похожие темы научных работ по клинической медицине , автор научной работы — Halberg Franz, Cornélissen Germaine, Sothern Robert B., Dewayne Hillman, Katinas George S.

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Текст научной работы на тему «Monitoring of factors of space weather and parameters of blood pressure»

MONITORING OF FACTORS OF SPACE WEATHER AND PARAMETERS OF BLOOD PRESSURE.

Franz Halberg1, Germaine Cornelissen1, Robert B. Sothern1, Dewayne Hillman1, George S. Katinas1, Sergei M.

Chibisov2, Kuniaki Otsuka3, Victor A. Frolov2, Jarmila Siegelova4, Frank Greenway5, Alok Gupta5, Miguel Revilla6,

Anatoly Masalov7, Elena V. Syutkina8, Inna Malkova8, Ellis S. Nolley9, Larry A. Beaty9, Agraval R2, Dabhi R.K2, Othild

Schwartzkopff and Earl E. Bakken10

University of Minnesota, Minneapolis, MN, USA

2People's Friendship University of Russia, Moscow, Russia

3Tokyo Women's Medical University, Medical Center East, Tokyo, Japan

4Masaryk University, Brno, Czech Republic

5Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA

6University of Valladolid, Spain

7Lebedev Physical Institute, Moscow, Russia

8Scientific Center for Children's Health, Academy of Medical Sciences, Moscow, Russia

9Phoenix Group, Institute of Electrical and Electronics Engineers, Minneapolis, MN, USA (http://www.phoenix.tc-

ieee.org; cf. http://www.sphygmochron.org)

10North Hawaii Community Hospital Inc., Kamuela, HI, USA

Objective. In keeping with Walter Kofler's extended view of health and ecology (1), focus on time structures, i.e., chronomes extends into (and assesses) the everyday variability of the biosphere and into its complementary cosmos by,

1. the current provision of computer-aided analyses (in exchange for the data), initially mainly of blood pressures (BP) and heart rates (HR), not only for clinics and care providers, but above all for the public, for self-helpers in individualized vascular health care;

2. by a service of transdisciplinary comparative analyses of a vast array of physiological and archival time series, and by

3. using the accumulating information base for a cartography leading to an atlas with reference standards as a requisite for diagnoses already being delivered of otherwise silent vascular variability disorders (VVD) that may coexist as a vascular variability syndrome (VVS);

4. seeking further improvements of individuals' as well as populations' health and well-being, by

a. obtaining improved gender, age and ethnicity-qualified reference values for BP and HR now in the light of decades-long (2, 3) and eventually for lifelong outcomes, and

b. obtaining refined harbingers of hard events;

c. mapping social time structures including religious proselytism (4), crime (5), terrorism (6) and other aggression (7), all possibly related to unseen, not consciously felt magnetic and other nonphotic as well as photic influences,

d. analyzing any triggering (as Chizhevsky put it), and/or any more consistent roles played by the cosmos, such as pulling, driving or amplifying built-in frequencies (8) in important events among human affairs related to the ills of society;

5. and eventually for developing countermeasures for the undesirable consequences of unseen magnetics and other nonphotics, just as we heat and air condition against seen and felt photic and thermal effects.

Incidence of Vascular Variability Disorders (VVD) in an Adult Japanese Study Population (N=297)

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36.7%

38.7%

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VVD (N irrespective of kind)

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VVDs considered are MESOR-Hypertension, Excessive Pulse Pressure (>60 mmHg), CHAT (24h BP amplitude above upper 95% prediction limit of healthy peers matched by gender and age), and Deficient Heart Rate Variability (around-the-clock standard deviation of HR <7.5 beats/min) obtained from 48-hour records.

Figure 1.

hyper-amplitude-tension. Both MHT and CHAT are diagnosed on the basis of a from gender- and age-matched peers;

c. an excessive above-threshold (of 60 mm Hg) pulse pressure (EPP);

d. a deficient heart rate variability, DHRV, and

Status quo. An international BIOCOS project (on The BIOsphere and the COSmos) currently provides a multilingual, transdisciplinarily educative and analytical worldwide service. Thereby, BIOCOS renders a diagnosis relating to high BP more reliable (a below) and/or detects other different forms of vascular variability disorders (VVD), including

a. MESOR-hypertension (MHT), as a diagnosis of consistently high BP based on an account of variability (vs. "hypertension" that may lack such a safeguard) and

b. CHAT, short for circadian comparison with reference standards

0

e. ecphasia, an odd timing of the arcadian rhythm of BP but not of that of HR. Irrespective of kind of VVD, Figures 1

and 2 show how often the first

Incidence of Vascular Variability Disorders (VVD) in an Adult Study Population (N=1177) of both Genders (30-91 years of age)

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— 500 -

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58.1%

28.4%

9.1%

3.6%

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VVD (N irrespective of kind)

VVDs considered are MESOR-Hypertension, Excessive Pulse Pressure (>60 mmHg), CHAT (24h BP amplitude above upper 95% prediction limit of healthy peers matched by gender and age), ecphasia (odd timing of circadian blood pressure but not heart rate rhythm), and Deficient Heart Rate Variability (around-the-clock standard deviation of HR <7.5 beats/min) obtained from 24-hour records.

Figure 2.

Vascular Variability Disorders in a Study Population

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DHRV CHAT EPP MH

Vascular variability disorders consdered are MESOR-Hypertension, Excessve Pulse Pressure (>60 mmHg), CHAT (24h BP amplitude above upper 95% prediction limit of healthy peers matched by gender and age), and Deficient Heart Rate Variability (around-the-clock standard deviation of HR <7.5 beats/min)

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Vascular Variability Disorders in a Study Population

Vascular variability disorders considered are MESOR-Hypertension, Excessive Pulse Pressure (>60 mmHg), CHAT (24h BP amplitude above upper 95% prediction limit of healthy peers matched by gender and age), ecphasia (odd timing of 24h BP but not HR rhythm) and Deficient Heart Rate Variability (around-the-clock standard deviation of HR <7.5 beats/min).

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Figure 3.

the built-in nature insofar as part of it persists, albeit with some damping, when

4 (a-d) VVDs coexist, and that as yet all 5 conditions have not been found to coexist in the same person in a population of 1171 people.

Figure 3 illustrates, for two populations, the N of cases in each category and Figure 4 shows a high risk of severe vascular disease, notably when these VVDs, other than a high BP (MHT), coexist. Coexistence then constitutes a vascular variability syndrome (VVS) with 2 or more (up to 4) components without or usually with end organ damage. A VVD or a VVS is silent to the conventional care provider as well as the care receiver. In the absence of MHT, VVDs can characterize prehypertension, Figure 5 (9), and prediabetes, i.e., individuals with a fasting hyperglycemia and an impaired morning oral glucose tolerance test (10), Figure 6a-d (11). VVDs can further constitute complications for patients with MHT who are being treated for it. It is important for "hypertensives" and validated patients with MHT alike to ascertain that the treatment, albeit reducing or eliminating, e.g., a high BP does not do so at the cost of inducing another VVD in BP and/or HR with a still higher risk of hard events.

If these services, offered by BIOCOS in exchange for the data analyzed, can be extended on an appropriate scale, the accumulating transverse data could also help track biological effects of solar variability analyzed by time-structural chronomics and may complement the lessons learned thus far longitudinally. The discovery of transyears is a case in point, prompting a "remove and replace" approach in physiology, Figure 7, where surgery is replaced by solar variability. We document a. the driving by the solar wind of a spectral component (transyear with a period of ~13 years) in BP (by finding its partial loss when the same component is no longer detected in the solar wind), and b.

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Decreased Heart Rate Variability (DHRV), Circadian Hyp er-Amplitude-Tension (CHAT) and Elevated Pulse Pressure (EPP) are Separate Cardiovascular Disease Risks'

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■Results from 6-year prospective study on 237 (adding ail Ns) patients cJassified by 3 nsks (8 circles}, supported by findings on tote I of 2,807 subjects for total of over 160,769 sets of blood pressure and heart rate measurements. Data from KOtsuka.

Figure 4. Decreased heart rate variability (DHRV), circadian hyper-amplitude-tension (CHAT) and elevated pulse pressure (EPP) are separate cardiovascular disease risks*. CHAT is one of several conditions related to the variability in blood pressure (BP) and/or heart rate (HR) that is associated with an increase in vascular disease risk. The circadian (or preferably circaseptan profile) with too large a pulse pressure (the difference between systolic [S] BP and diastolic [D] BP, i.e., between the heart's contraction or relaxation, or the extent of change in pressure during a cardiac cycle) and a decreased HR variability (gauged by the standard deviation of HR) in relation to a threshold, preferably eventually all in gender- and age-matched peers are two other risk conditions (as is an abnormal circadian timing of BP but not of HR, not shown). Vascular disease risk is elevated in the presence of any one of these risk factors, and is elevated further when more than a single risk factor is present, suggesting that these abnormalities in variability of BP and HR are mostly independent and additive. Abnormalities in the variability of blood pressure and heart rate, impossible to find in a conventional office visit (the latter aiming at the fiction of a "true" blood pressure), can raise cardiovascular disease risk (gauged by the occurrence of a morbid event like a stroke in the next six years) from 4% to 100%. By comparison to subjects with acceptable blood pressure and heart rate variability, the relative cardiovascular disease risk associated with a decreased heart rate variability (DHRV), an elevated pulse pressure (EPP) and/or circadian hyper-amplitude-tension (CHAT) is greatly and statistically significantly increased. These risks, silent to the person involved and to the care provider, notably the risk of CHAT, can usually be reversed by chronobiologic self-help, also with a non-pharmacologic approach in the absence of MESORhypertension.

Day-Night Ratio (DNR) of Systolic Blood Pressure (SBP) Found ABNORMAL in HEALTH but ACCEPTABLE in "PRE-HYPERTEXSION" *

Systolic Blood Pressure

* Comparison of 'Truly Normotensive Subjects" (TNS) and "Putatively Normotensive Subjects" (PNS) with Incipient Signs of Hypertensive Retinopathy. Data from P Cugini et al (International Ophthalmology 1999; 22: 145-149). Minimal retinal alterations, presumably reflecting an increased vascular disease risk, are NOT associated with abnormal DNR, but rather with the chranobiologically predicted elevation in circadian BP amplitude (middle, right). Figure 5: Subjects with minimal change retinopathy have daytime mean values of systolic blood pressure (SBP) higher than those without retinopathy by day (top left); a dipping classification not only fails to resolve prehypertension, but misleads, being normal in the presence of a minimal-change retinopathy, yet abnormal in the absence of minimal change retinopathy (bottom). Chronobiology shows an increase in circadian amplitude as well as MESOR, in the presence (PNS) versus the absence (TNS) of minimal retinopathy, top right. © Halberg. the solar wind loses that component. Transyears gain in applied importance, when in some geographic locations they replace a calendar-year component in the spectrum of sudden cardiac death (12) and suicides (13), yet overall in all available data as a whole, the photic, thermic and social calendar dominates worldwide. Transyears again gain even more in importance when, in the biggest MIPT Terrorism Knowledge Base (1968-2005), they dominate the spectrum in the absence

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Altered Blood Pressure and Heart Rate Variability in "Prediabetes" but not in Normoglycemia

KS Diastolic CHAT P < Q.QQ1

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MESOR-Hypertension {66.7%)

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Figure 6a. Several vascular variability disorders

characterizing prediabetes (right half) may be part of a premetabolic syndrome. Note that they are missing in the (small sample of) six control subjects, with normoglycemia and an acceptable glucose

tolerance test (left half) (11). See also Figures 6c and d. Data of A. Gupta. © Halberg.

Incidence of Altered Blood Pressure Dipping* Similar in "Prediabetes" and in Normoglycemia

* Irrespective of systolic or diastolic blood pressure

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Prediabetes (N=6)

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Figure 6b. A dipping classification fails to separate prediabetes from normoglycemia (when a chronobiologic approach does so, Figure 6a) (11). Dipping also fails in other situations (and misled in the case of Cugini's prehypertension [Fig. 5]). Data of A. Gupta. © Halberg.

of a calendar-year component (6), as they do in mental function of a human adult (14). This figurative telescopy and microscopy in time now rests mainly on longitudinal (decades-long) data from a few test pilots and decades-, and in a few cases centuries-long archived data from the biosphere and its cosmos, but a stream of hybrid (linked cross-sectional) worldwide data could constitute a major service of monitoring solar variability. The physiological data could be aligned and analyzed for associations and interrelations with the cosmos, with which they likely resonate at built-in frequencies. Results thus far already pertain to individual (12, 13) and societal, biological and economic health. The accumulating information base on time-varying behavior of cycles with congruent transdisciplinary periods constitutes indispensable information for health and ecology (1-3) to be collected systematically by a website, Figure 8 (14).

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Daily Incidence of Vascular Variability Disorders* in Prediabetes (7-12) versus Normoglycemics (1-6)

* MESOR-Hypertension, Excessive Pulse Pressure, Circadian Hyper-Amplitude-Tension, and/or Deficient Heart Rate Variability (irrespective of kind of VVS)

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Figure 6c. variability irrespective separate 2

Vascular disorders, of kind, groups of

subjects in 7-day records but not in 24-hour records. Large diamonds indicate that a vascular variability disorder also characterized the record as a whole when a two-component model consisting of cosine curves with periods of 24 and 12 hours was fitted by least squares to all data, thereby washing out any occasional transient abnormality.

Subject Number (N)

Ordinate indicates the percentage of days when at least one parameter deviated from 90% prediction limits describing clinically healthy peers matched by gender and age (100% is the total number of days in each individual record, varying from 3 (N=1), 4 (N=1) and 6 (N=2) to otherwise 7 days) (11). Data of A. Gupta. © Halberg.

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This international multilingual website managed with pertinent educative endeavors) sooner or later will require permanent national and international governmental centers in their own right to serve for:

1) education of the public in self-help for health care, preferably in late primary and earliest secondary education (15), including adult individuals interested in learning about preventive health care and wishing to be informed about the status of their BP and HR at any given time (not flying blind) (16) notably when being treated by care providers;

2) education of the care provider upstream in medical and other health related schools and downstream in postgraduate courses in interpreting sphygmochrons, the extended cosinor and broader chronomic analyses;

3) thus replacing the homeostatic misconception of a "true" BP value (even though it was historically most useful by leading many millions of people to effective treatment) by the dynamics in the form of generally understandable parametric and nonparametric indices of BP and HR (a true BP has been untenable since 1880 [17] and 1904 [18; cf. 19]). Guidelines based on reference values for physiological variability and available background literature with minimal standards for data collection and analysis are to be offered (2, 3, 19-22);

Incidence (% days/subject) of Certain Vascular Variability Disorders Investigated

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Figure 6d. Separate breakdown by four different variability disorders documenting the merits of an initial 7-day record vs. one based on fewer days (11). Data of A. Gupta. © Halberg.

4) providing information about and standards for commercially available tools for manual or automatic measurement, some ambulatorily usable monitors being available through BIOCOS in exchange for the data to be collected, with an 80% reduction in cost by contacting corne001@umn.edu;

5) lead up to international agreement on minimal sampling and, given appropriate time series, minimal analysis requirements, as standards, recommended by institutions such as the IEEE and the International Union of Physiological Sciences consulting and reporting to professional societies of care givers;

6) making chronobiologic procedures for diagnosis (as a sphygmochron [19, 20]) and therapeutics (as a sequential test [23] and parameter comparison [24]) (preferably automatically) available on an appropriate scale for the worldwide public, with some computer-savvy individuals, saving care providers' time, as long as no abnormality is found and informing and educating the care provider as need be (see 2 above). BIOCOS services have already documented the ubiquity of a VVD (25). Although the incidence of VVDs is relatively low, the associated risk is high. Their assessment concerns all of those now diagnosed and treated for high BP worldwide (since VVDs can silently complicate this condition), i.e., hundreds of millions of people worldwide; incapacitation after a

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Figure 7. Time courses of the frequency structures of the speed of the solar wind (SWS) (top) and of an elderly man's (FH) systolic and diastolic blood pressure and heart rate, SBP, DBP and HR (rows 2-4, respectively), examined by

100

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gliding spectral windows. Human systolic (S) blood pressure (BP) selectively resonates with solar wind speed (SWS) (top 2 sections). No obvious resonance, only minor coincident change in diastolic BP (DBP) or heart rate (HR) is seen (bottom 2 sections). Aeolian Rhythms* in gliding spectra of SWS and SBP change in frequency (smoothly [A] or abruptly [B,C,D], bifurcating [D,F] and rejoining [G], they also change in amplitude (B) (up to disappearing [C,E] and reappearing). During a nearly 16- year span there are no consistent components with a period averaging precisely 1 year in the 3 physiologic variables, probably an effect of advancing age. While post hoc ergo propter hoc reasoning can never be ruled out, an abrupt change on top in SWS is followed in the second row in SBP by the disappearance of some components, suggesting that as a first demonstration, some of FH's cis- and transyear components were driven by the SW [since they disappeared with a lag of about a transyear following the disappearance (subtraction) of the same components from the SWS spectrum]. The persistence of other spectral features in turn suggests endogenicity, i.e., an evolutionary acquisition of solar transyear oscillations that may reflect solar dynamics for the past billions of years. Blood pressure and heart rate data are from a man 70 years of age at start of around-the-clock monitoring, mostly at 30-min intervals, with interruptions for nearly 16 years.

*FH, man, 70 years (y) of age at start of automatic half-hourly around the clock measurements for ~ 16 y (N=2418 daily averages, total ~ 55000). Gliding spectra computed with interval = 8 y, resolution low in time but high in frequency, increment = 1 month, trial periods from 2.5 to 0.4 y, with harmonic increment = 0.05. Darker shading corresponds to larger amplitude. When several of these broad bands disappear in the SWS, at E, parts of the bands in SBP also disappear, with a lag (delay) at E', while other parts persist. These components are presumably built into organisms over billions of years, as persistence without corresponding components in SWS shows, but can be driven in part by the solar wind, as their disappearence after loss of corresponding components in SWS suggests. "Aeolian", derived from Aeolus, Greek god of winds, who packed the winds up, then let them loose and had them change, conceivably a proper choice for the solar wind's pervasive role in human affairs. © Halberg.

Preventive (left) and curative (lower right) health care can yield the dividend of biomedical monitoring of space weather [top right) by time-structural analyses of ambulatory blood pressure and heart rate series'

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Figure 8. The Phoenix Project of volunteering members of the Twin Cities chapter of the Institute of Electrical and Electronics Engineers (http://www.phoenix.tc-ieee.org) is planning on developing an inexpensive, cuffless automatic monitor of blood pressure and on implementing the concept of a website (www.sphygmochron.org) for a service in exchange for the data that in turn are to be used for refining methods and for monitoring psychophysiological effects of their variability in space weather. © Halberg. massive stroke can also match any other insult. The costs are great. There is an urgent need for prehabilitation by education, Figure 9. The same vascular and broader transdisciplinary surveillance resolves new spectra of magnetic signatures, Figure 10, and may help clarify the effect of solar variability upon human affairs as an endeavor complementing the monitoring in physics introduced by Humboldt, Gauss and Sabine. Tangible current challenges and

future applications lead to the roots of social disease, to crime (5) and violence (6, 7), as well as to sudden cardiac death (12) and suicide (13), to even broader global health and ecology.

Figure 9. Pre-habilitation, preferably before as well as with or after rehabilitation (for further vascular disease prevention and more generally). By the early detection of disease risk syndromes in the individual subject, countermeasures for primary prevention can be instituted. Such pre-habilitation in health can also complement rehabilitation in disease and can be a major goal of health care. Pre-habilitation would complement an across-the-board reduction of risk factors, the latter implemented by changes in lifestyle. The three entangled structures under Chronomics stand for trends (left), chaos (right) and transdisciplinary cycles (above) that constitute the reproducible element of the many matching time structures resolved in both the biosphere and its cosmos in the last decade, extending the view of health and ecology (1). © Halberg.

1. Kofler WW. The need on a "critical extended evolution related view" of reality as a basis for an "extended view" of health. Science without Borders, Transactions of the International Academy of Science H&E, 2003/2004; 1: 27-54.

2. Müller-Bohn T, Cornelissen G, Halhuber M, Schwartzkopff O, Halberg F. CHAT und Schlaganfall. Deutsche Apotheker Zeitung 2002; 142: 366-370 (January 24).

3. Halberg F, Schwartzkopff O, Cornelissen G, Hardeland R, Müller-Bohn T, Katinas G, Revilla MA, Beaty L, Otsuka K, Jozsa R, Zeman M, Csernus V, Hoogerwerf WA, Nagy G, Stebelova K, Olah A, Singh RB, Singh RK, Siegelova J, Dusek J, Fiser B, Czaplicki J, Kumagai Y, Chibisov SM, Frolov VA. Vaskuläres Variabilitäts-Syndrom (VVS) und andere Chronomik 2005-2007. Sitzungsberichte der Leibniz-Sozietät, in press.

4. Starbuck S, Cornelissen G, Halberg F. Is motivation influenced by geomagnetic activity? Biomedicine & Pharmacotherapy 2002; 56 (Suppl 2): 289s-297s.

5. Halberg F, Otsuka K, Katinas G, Sonkowsky R, Regal P, Schwartzkopff O, Jozsa R, Olah A, Zeman M, Bakken EE, Cornelissen G. A chronomic tree of life: ontogenetic and phylogenetic 'memories' of primordial cycles - keys to ethics. Biomedicine & Pharmacotherapy 2004; 58 (Suppl 1): S1-S11.

6. Grigoryev PYe, Vladimirskii BM. The cosmic weather affects the terrorist activity. Reports of Taurida University, in press.

7. Halberg F, Cornelissen G, Schack B, Wendt HW, Minne H, Sothern RB, Watanabe Y, Katinas G, Otsuka K, Bakken EE. Blood pressure self-surveillance for health also reflects 1.3-year Richardson solar wind variation: spin-off from chronomics. Biomedicine & Pharmacotherapy 2003; 57 (Suppl 1): 58s-76s.

8. Halberg F, Cornelissen G, Sothern RB, Hillman D, Schwartzkopff O, Beaty LA, Nolley ES, Otsuka K, Watanabe Y, Siegelova J, Fiser B, Homolka P, Singh RB. Re: Global Health and Ecology: Individualized inferential statistical blood pressure assessment for health care and large-scale space weather monitoring. Invited presentation for Natural cataclysms and global problems of modern civilization, Baku, Azerbaijan, September 24-28, 2007, in press.

9. Cugini P, Cruciani F, Turri M, Regine F, Gherardi F, Petrangeli CM, Gabrieli CB. 'Minimal-change hypertensive retinopathy' and 'arterial pre-hypertension', illustrated via ambulatory blood-pressure monitoring in putatively normotensive subjects. International Ophthalmology 1999; 22(3): 145-149.

10. Sanchez de la Pena S, Gonzalez C, Cornelissen G, Halberg F. Blood pressure (BP), heart rate (HR) and non-insulin-dependent diabetes mellitus (NIDDM) chronobiology. S8-06, 3rd Int Congress on Cardiovascular Disease, Taipei, Taiwan, 26-28 Nov 2004. Int J Cardiol 2004; 97 (Suppl 2): S14.

11. Gupta AK, Greenway FL, Cornelissen G, Halberg F. Vascular variability disorders in Louisiana, in prediabetes and in healthy women taking sex hormones. In preparation.

12. Halberg F, Cornelissen G, Katinas G, Tvildiani L, Gigolashvili M, Janashia K, Toba T, Revilla M, Regal P, Sothern RB, Wendt HW, Wang ZR, Zeman M, Jozsa R, Singh RB, Mitsutake G, Chibisov SM, Lee J, Holley D, Holte JE, Sonkowsky RP, Schwartzkopff O, Delmore P, Otsuka K, Bakken EE, Czaplicki J, International BIOCOS Group. Chronobiology's progress: season's appreciations 2004-2005. Time-, frequency-, phase-, variable-, individual-, age- and site-specific chronomics. J Applied Biomedicine 2006; 4: 1-38. http://www.zsf.jcu.cz/vyzkum/jab/4_1/halberg.pdf.

13. Cornelissen G, Halberg F. Chronomics of suicides and the solar wind. Br J Psychiatry 2006; 189: 567-568.

14. Sothern RB, Katinas GS, Cornelissen G, Czaplicki J, Halberg F. Differential congruence of periods in helio- and/or geomagnetics and in human psychophysiology. 2nd World Congress of Chronobiology, Tokyo, November 4-6, 2007, in press.

15. Halberg F. Challenges from "60 years of [not yet] translational chronobiology". (Lecture opening a symposium at Experimental Biology 2007, Washington DC, April 29, 2007, on "Circadian rhythms: from animals to humans".) Reports of Taurida University, in press.

16. Halberg F, Smith HN, Cornelissen G, Delmore P, Schwartzkopff O, International BIOCOS Group. Hurdles to asepsis, universal literacy, and chronobiology—all to be overcome. Neuroendocrinol Lett 2000; 21: 145-160.

17. Fossel M. Editor's Note [to Halberg F, Cornelissen G, Halberg J, Fink H, Chen C-H, Otsuka K, Watanabe Y, Kumagai Y, Syutkina EV, Kawasaki T, Uezono K, Zhao ZY, Schwartzkopff O. Circadian Hyper-Amplitude-Tension, CHAT: a disease risk syndrome of anti-aging medicine. J Anti-Aging Med 1998; 1: 239-259]. J Anti-Aging Med 1998; 1: 239.

18. Zadek I. Die Messung des Blutdrucks am Menschen mittelst des Basch'chen Apparates. Berlin, med. F., Diss., 25. Nov 1880. Berlin: Schumacher; 1880. 48 p.

19. Janeway TC. The clinical study of blood pressure. New York: D. Appleton & Co.; 1904. 300 pp.

20. Cornelissen G, Halberg F, Bakken EE, Singh RB, Otsuka K, Tomlinson B, Delcourt A, Toussaint G, Bathina S, Schwartzkopff O, Wang ZR, Tarquini R, Perfetto F, Pantaleoni GC, Jozsa R, Delmore PA, Nolley E. 100 or 30 years after Janeway or Bartter, Healthwatch helps avoid "flying blind". Biomedicine & Pharmacotherapy 2004; 58 (Suppl 1): S69-S86.

21. Halberg F, Cornélissen G, Wall D, Otsuka K, Halberg J, Katinas G, Watanabe Y, Halhuber M, Müller-Bohn T, Delmore P, Siegelova J, Homolka P, Fiser B, Dusek J, Sanchez de la Peña S, Maggioni C, Delyukov A, Gorgo Y, Gubin D, Carandente F, Schaffer E, Rhodus N, Borer K, Sonkowsky RP, Schwartzkopff O. Engineering and governmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate screening. Biomedical Instrumentation & Technology 2002: Part I, 36: 89-122; Part II, 36: 183-197.

22. Halberg F, Cornélissen G, Halberg J, Schwartzkopff O. Pre-hypertensive and other variabilities also await treatment. Am J Medicine 2007; 120: e19-e20. doi:10.1016/j.amjmed.2006.02.045.

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23. Cornélissen G, Halberg F, Otsuka K, Singh RB, Chen CH. Chronobiology predicts actual and proxy outcomes when dipping fails. Hypertension 2007; 49: 237-239. doi:10.1161/01.HYP.0000250392.51418.64.

24. Cornélissen G, Halberg F, Hawkins D, Otsuka K, Henke W. Individual assessment of antihypertensive response by self-starting cumulative sums. J Medical Engineering & Technology 1997; 21: 111-120.

25. Bingham C, Arbogast B, Cornélissen Guillaume G, Lee JK, Halberg F. Inferential statistical methods for estimating and comparing cosinor parameters. Chronobiologia 1982; 9: 397-439.

26. Cornélissen G, Delcourt A, Toussaint G, Otsuka K, Watanabe Y, Siegelova J, Fiser B, Dusek J, Homolka P, Singh RB, Kumar A, Singh RK, Sanchez S, Gonzalez C, Holley D, Sundaram B, Zhao Z, Tomlinson B, Fok B, Zeman M, Dulkova K, Halberg F. Opportunity of detecting pre-hypertension: worldwide data on blood pressure overswinging. Biomedicine & Pharmacotherapy 2005; 59 (Suppl 1): S152-S157.

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