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1.  The Chronobra identifies prevailing mammary vascularity as a candidate variable in breast cancer post-operative outcome prediction 
SpringerPlus  2013;2:241.
We previously described a menstrual heat cycle of the breast in four groups of women (healthy, family history of breast cancer, benign breast disease, ‘cancer-associated’) who wore a thermometric brassiere (Chronobra). We now ask if ‘breast minus oral temperature’, indicating ‘breast-associated vascularity’, could be associated with breast cancer cell vascular access around different aspects of the menstrual cycle rhythm and survival. Thirty-six pre-menopausal breast cancer patients (average age: 38.97 y) were enrolled consecutively over 15 y and followed for more than 22 y after surgery in order to compare survival and peri-operative vascularity. Each subject wore the Chronobra, which provides an internal bioassay of the vascularity of both breasts, including the operated breast, during 1 h each evening at home for one menstrual cycle, and collected saliva for “free” progesterone to confirm pre-menopausal status and ovulation. Sixty-five healthy age-matched pre-menopausal women served as controls. Both oral and breast temperatures revealed menstrual cycle oscillations, rising just before ovulation until menses onset. Breast-adjusted vascularity also showed menstrual cycle oscillations, with levels differing significantly between the 3 groups during the luteal phase only. At the end of the follow-up span, 18 post-operative breast cancer patients had died from “disseminated” breast cancer and 18 were alive and well. Median follow-up time was 22.6 y for survivors, 6.2 y for non-survivors, and 21.0 y for controls (3 died from diseases unrelated to breast cancer). Based on ‘during luteal-phase breast-adjusted vascularity’, breast cancer survivors (mean ± SD: -1.65 ± 0.23°C) were significantly hypo-vascular (i.e., -0.23°C cooler) compared with controls (-1.42 ± 0.09°C), while non-survivors (-1.25 ± 0.12°C) were highly significantly hyper-vascular compared with survivors (+0.41°C warmer) and controls (+0.23°C warmer). This suggests that in pre-menopausal breast cancer patients, peri-operative mammary vascularity could offer an outcome test of survival and biologically may be on the “final common pathway” of any tumor to metastatic risk and recurrence.
doi:10.1186/2193-1801-2-241
PMCID: PMC3668130  PMID: 23741657
Breast cancer; Breast temperature; Chronobra; Luteal phase; Menstrual cycle; Vascularity; Breast cancer survival
2.  Sunspot Dynamics Are Reflected in Human Physiology and Pathophysiology 
Astrobiology  2011;11(2):93-103.
Abstract
Periodic episodes of increased sunspot activity (solar electromagnetic storms) occur with 10–11 and 5–6 year periodicities and may be associated with measurable biological events. We investigated whether this sunspot periodicity characterized the incidence of Pap smear-determined cervical epithelial histopathologies and human physiologic functions. From January 1983 through December 2003, monthly averages were obtained for solar flux and sunspot numbers; six infectious, premalignant and malignant changes in the cervical epithelium from 1,182,421 consecutive, serially independent, screening Pap smears (59°9″N, 4°29″E); and six human physiologic functions of a healthy man (oral temperature, pulse, systolic and diastolic blood pressure, respiration, and peak expiratory flow), which were measured ∼5 times daily during ∼34,500 self-measurement sessions (44°56″N, 93°8″W). After determining that sunspot numbers and solar flux, which were not annually rhythmic, occurred with a prominent 10-year and a less-prominent 5.75-year periodicity during this 21-year study span, each biological data set was analyzed with the same curve-fitting procedures. All six annually rhythmic Pap smear-detected infectious, premalignant and malignant cervical epithelial pathologies showed strong 10-year and weaker 5.75-year cycles, as did all six self-measured, annually rhythmic, physiologic functions. The phases (maxima) for the six histopathologic findings and five of six physiologic measurements were very near, or within, the first two quarters following the 10-year solar maxima. These findings add to the growing evidence that solar magnetic storm periodicities are mirrored by cyclic phase-locked rhythms of similar period length or lengths in human physiology and pathophysiology. Key Words: Cervical infections—Cervical premalignancy—Geo-solar magnetic interactions—Pap smear—Schwabe cycle—10-year rhythm. Astrobiology 11, 93–103.
doi:10.1089/ast.2010.0574
PMCID: PMC3063695  PMID: 21391821
3.  Circadian aspects of hyperthermia in mice induced by Aconitum napellus 
Pharmacognosy Magazine  2011;7(27):234-242.
Background:
Aconitum napellus (Acn) is used topically to relieve pain, itching and inflammation, and internally to reduce febrile states, among others. Any circadian time-related consequences of Acn administration are unknown. The objective of this study was to explore the effects of two doses of Acn on body temperature (BT) of mice treated at six different times over 24 hours.
Materials and Methods:
BALB/c female mice were housed in six chambers (six mice each) with air temperature 24 ± 3°C, humidity 60 ± 4%, and a 12-hours light (L)/12-hours dark cycle, but with L-onset staggered by 4 hours between chambers so that study at one external test time resulted in six test times (02, 06, 10, 14, 18 and 22 hours [h] after light onset). Rectal temperature (RT; in °C) was measured at baseline (B) and 1 hour after oral treatment with placebo (P) or two doses of Acn (6C and 30C, two studies each) in six studies over an 8 day span. The difference in RT for each mouse from the respective B + P timepoint mean RT was computed following each Acn treatment, and data from each of the six studies (original RT and difference from B + P) were analyzed for time-effect by analysis of variance (ANOVA) and for circadian rhythm by 24-hour cosine fitting.
Results:
A circadian rhythm in RT was found at B and after P (mean: 35.58°C vs. 35.69°C; peak: 15:31 h vs. 15:40 h) and after each Acn dose (30C or 6C). Acn induced hyperthermia and the overall change in BT was rhythmically significant for each dose (mean = +1.95°C vs. +1.70°C), with greatest hyperthermia observed during the L-span for each dose (peak = 08:56 h vs. 05:17 h).
Conclusion:
Acn administered around the clock induced hyperthermia overall and in a time-dependent manner, with greatest effects during the resting (L) span. Thus, time of day may significantly impact the outcome of Acn and other homeopathic treatments and should be considered in determining optimal dosing and treatment time(s) in order to increase the desired outcome and decrease undesired effects.
doi:10.4103/0973-1296.84238
PMCID: PMC3173899  PMID: 21969795
Aconite; Aconitum napellus; chronotherapy; circadian; homeopathy; hyperthermia; pharmacognosy
4.  Chronomics, human time estimation, and aging 
Clinical interventions in aging  2008;3(4):749-760.
Background
Circadian rhythm stage affects many outcomes, including those of mental aging.
Methods
Estimations of 1 minute ~5 times/day for a year, 25 years apart, by a healthy male biomedical scientist (RBS), are analyzed by the extended cosinor.
Results
Cycles of a half-week, a week, ~30 days, a half-year and a year, in self-assessed 1-minute estimation by RBS between 25 and 60 years of age in health, are mapped for the first time, compared and opposite effects are found. For RBS at 60 vs at 25 years of age, it takes less time in the morning around 10:30 (P < 0.001), but not in the evening around 19:30 (P = 0.956), to estimate 1 minute.
Discussion
During the intervening decades, the time of estimating 1 minute differed greatly, dependent on circadian stage, being a linear decrease in the morning and increase in the evening, the latter modulated by a ~33.6-year cycle.
Conclusion
Circadian and infradian rhythm mapping is essential for a scrutiny of effects of aging. A ~30-day and a circannual component apparent at 25 years of age are not found later; cycles longer than a year are detected. Rhythm stages await tests as markers for timing therapy in disease.
PMCID: PMC2662403  PMID: 19281067
circadian rhythm; mental function; time estimation
5.  Chronomics, human time estimation, and aging 
Clinical Interventions in Aging  2008;3(4):749-760.
Background
Circadian rhythm stage affects many outcomes, including those of mental aging.
Methods
Estimations of 1 minute ~5 times/day for a year, 25 years apart, by a healthy male biomedical scientist (RBS), are analyzed by the extended cosinor.
Results
Cycles of a half-week, a week, ~30 days, a half-year and a year, in self-assessed 1-minute estimation by RBS between 25 and 60 years of age in health, are mapped for the first time, compared and opposite effects are found. For RBS at 60 vs at 25 years of age, it takes less time in the morning around 10:30 (P < 0.001), but not in the evening around 19:30 (P = 0.956), to estimate 1 minute.
Discussion
During the intervening decades, the time of estimating 1 minute differed greatly, dependent on circadian stage, being a linear decrease in the morning and increase in the evening, the latter modulated by a ~33.6-year cycle.
Conclusion
Circadian and infradian rhythm mapping is essential for a scrutiny of effects of aging. A ~30-day and a circannual component apparent at 25 years of age are not found later; cycles longer than a year are detected. Rhythm stages await tests as markers for timing therapy in disease.
PMCID: PMC2662403  PMID: 19281067
circadian rhythm; mental function; time estimation
6.  Transdisciplinary unifying implications of circadian findings in the 1950s 
A few 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.
doi:10.1186/1740-3391-1-2
PMCID: PMC317388  PMID: 14728726

Results 1-6 (6)