Cosinor Regression Research Articles

Pituitary-hormone secretion by thyrotropinomas

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.

Circa-and ultradians in the occurrence of simple extrasystoles in healthy men at lowland in the light of inferential statistics

An exact description of circadian and ultradian rhythms of simple extrasystoles in healthy subjects is lacking. Thirty-seven healthy male subjects, aged 50-76, were randomly taken. Simple extrasystoles from 24-hour Holter ECG were registered and calculated per each hour and processed by cosinor regression. Their occurrence is formulated by 95% confidence and tolerance corridors for supraventricular and ventricular extrasystoles. The number of extrasystoles is relatively low, dispersion of ventricular extrasystoles is significantly higher than supraventricular ones. A significant increase of their frequency versus the general zero trend straight line was found only around 9 a.m. In supraventricular ones a significant increase around 6-7 a.m., 9 a.m., noon, and 4-5 p.m. and a significant depression around 1-2 a.m. and 10 p.m. was present. Only the 24-hour rhythm is significantly present (alpha=0.05) in ventricular beats while in supraventricular ones also the period lengths of 12, 6, 4, 3.4 and 2.4 hours are significant. The significant difference between supraventricular and ventricular extrasystoles exists in the 24-hour amplitudes and 6-hour acrophases. One circadian and several ultradian rhythms of simple extrasystoles are present in healthy male subjects over 50 years of age. The 95% tolerance chronograms can be exploited in clinical practice.

Seasonality of births and childhood inflammatory bowel disease

In some geographical areas, including Slovakia, children with diabetes mellitus type 1 are born more often in summer than in late autumn and winter. Does this also apply to another autoimmune disorder - inflammatory bowel disease - in Slovakia? The month of birth was recorded for 30 boys and 36 girls with Crohn disease and 23 boys and 40 girls with ulcerative colitis. The monthly numbers of births were adapted to the length of the given month, divided by the number of boys or girls born in the whole Slovak children population in the same calendar month in comparable years, transformed to moving averages from three successive values each, and expressed as the fraction of the yearly total, which was equal to 1. According to the null hypothesis, there should be equal probability (1/12) of being born in any month. The significance of departures from this value was evaluated with cosinor regression using two sinusoidal functions with period lengths of 12 and 6 months. The most illustrative measure is the relation of the corridor of 95% confidence for the total approximating function to the midline estimating statistic of rhythm (the mesor) (1/12). Significant departures up or down are recognized as nonoverlapping of the mesor straight line by the confidence corridor. These were similar to those reported for childhood diabetes mellitus type 1. In our sample of Crohn disease, the number of births was markedly higher between June and October and lower between December and March. In ulcerative colitis, there was a slight increase between June and August and a decrease between December and February. The seasonal effect on births of children with later childhood-onset Crohn disease is similar to that described for diabetes mellitus type 1, i.e., maximal frequency of births in summer.

Temporal pattern in swimming activity of two fish species ( Danio rerio and Leucaspius delineatus ) under chemical stress conditions

Circadian periodicity of swimming activity was investigated in two fish species, the zebrafish (Danio rerio) and the sunbleak (Leucaspius delineatus) under sublethal long-term exposure to the cyanobacteria toxin microcystin-LR (nominal concentrations of 0.5 μg l − 1, 5 μg l − 1, 15 μg l − 1, 50 μg l − 1) in 15-litre tanks. Swimming activity of fish was monitored continuously by using an automated video-monitoring and object-tracing system over a period of 17 days. Influenced by long-term exposure to microcystin-LR, Leucaspius delineatus reversed their significant diurnal swimming activity and the fish became statistically significant nocturnal. Danio rerio remained diurnal active, but a significant phase shift was registered. In both Danio rerio and Leucaspius delineatus analysis of time series by cosinor regression revealed microcystin-LR induced dose-dependent alterations of the mean of oscillation, amplitude, acrophase and period length in a different extent. For Danio rerio the periodogram analysis revealed a significant circadian component of swimming activity for control as well as exposure groups, whereby the spectral amplitude clearly decreased at microcystin-LR concentrations of 15 and 50 μg l − 1. For Leucaspius delineatus the amplitude of circadian rhythm was decreased at all exposure concentrations of MC-LR. Furthermore the dominance of circadian rhythm was clearly reduced, whereas the rate of ultradian rhythms increased at elevated MC-LR concentrations of 5 μg l − 1, 15 μg l − 1 and 50 μg l − 1. The studied temporal aspects of behaviour clearly indicated stress symptoms in both fish species, therefore it proved to be a relevant method to characterise the impact of toxic substances in the environment and for biomonitoring.

Chronobiological aspects of adult-onset Crohn disease

To study the time course of Crohn disease and its signs. To compare the results with the world literature and draw conclusions for practice. Fifty-six patients were studied retrospectively: 31 males aged 19-48 years with disease duration 1-8 years, and 25 females aged 21-65 with disease duration 1-13 years. The disease was active (Crohn disease activity index > 150) in 25 patients and inactive in 31. Plasma levels of interleukin-6 (normal upper value 8 pg/ml) were investigated with radioimmunoassay. Bone mineral density was measured as the T-score (normal range between -1 and 0 standard deviations) in the forearm using dual-energy X-ray absorptiometry. The seasonality of births of the patients in relation to the total Slovak population and seasonality of severity of three important disease signs were examined with Halberg cosinor regression. The dependence of the signs on age and duration of disease was evaluated using quadratic regression. Results are presented as 95% confidence intervals (for means) and 95% tolerance intervals (for individuals). The level of statistical significance was set at alpha = 0.05. Significant seasonality in births was found: decreased frequency in May-June and increased frequency in September-January. Significant spring elevation of interleukin-6 levels, accompanied by significant spring rise of the disease activity index and by decrease of bone density, is described. Among patients with active disease, interleukin-6 levels significantly increased up to the age of 41 years, whereas linear increase of disease activity during aging was on the borderline level of significance in the same subgroup. No significant age trend was encountered in T-score for either subgroup. The same was true for interleukin-6 and disease activity versus duration. Significant decrease in T-score paralleled disease duration up to seven years in the subgroup with active disease. The course of Crohn disease is influenced by time, including the seasons of the year. However, this does not find full agreement in the world literature, probably because of geographic, socioeconomic and epidemiologic differences, as well as varying approaches in method. In practice, regular monitoring of the time course is necessary in provision of appropriately timed treatment.

Seasonal Variations in Admissions for Acute Myocardial Infarction. The PRIMVAC Study

Some authors have described seasonal variations in the incidence of acute myocardial infarction. The aim of this study was to determine the existence of seasonal rhythms in admissions for acute myocardial infarction to coronary care units, and in mortality, and to analyze the influence of age on environmental factors. The study included a total of 8400 consecutive patients with acute myocardial infarction admitted to 12 coronary care units in the PRIMVAC registry from January 1995 to December 1999. Seasonal rhythms were analyzed with the time series method and the Cosinor regression equation. The influence of age was analyzed with the chi 2 test. The total number of admissions increased in winter and decreased in summer. The highest peak (acrophase) occurred in winter, with 2183 cases (r2=0.91), specifically in February, with 742 cases (r2=0.66). The age of the patients conditioned seasonal variations (P=.006), and the influence was statistically significant for patients over 65 years of age. Changes in mortality with time did not reach statistical significance. A seasonal rhythm in admissions for acute myocardial infarction was found, with an increase in winter and a decrease in summer. Age conditioned the effect of environmental factors on acute myocardial infarction, and patients aged 65 years or older were more sensitive to mechanisms that led to increases in admissions in winter.

Daily birth numbers in Passo Fundo, South Brazil, 1997-1999: trends and periodicities.

Between October 6, 1997 and April 30, 1999, 5011 births (mean: 8.76 per day) were registered in the city of Passo Fundo, South Brazil. The sequence of 572 daily birth numbers was not random (iteration test). Neyman distribution (m = yen ) showed the best fit. Clusters of days with higher birth numbers alternated with days with low numbers of births. Periodogram analysis revealed a significant periodicity of 6.98 days. The cosinor regression, testing 10 a priori supposed period lengths, found significant seasonality peaking in August-September and significantly highest birth numbers on Thursdays. Among the lunar and solar rotation cycles, the tropic lunar cycle and its 4th harmonic were most pronounced, in agreement with results concerning natality in Germany obtained by Svante Arrhenius in the 19th century. These findings confirm Derer-Halberg's concept of multiseptans. In addition to cycling, a significantly increasing linear trend with a daily increase of 0.0045 births was encountered. This documents a growth of the population in agreement with national statistical data.

Gout attacks and lunar cycle

The aim was to search for periodical fluctuations in daily occurrence of gout attacks during the synodic lunar cycle. 126 gout attacks were recorded between 1972 and 1994 at known calendar dates. The synodic plexogram, displaying the number of attacks for each day of the cycle, was processed by cosinor regression. A pronounced cycling was found, with highest peaks under the new and full moon (syzygigies). Thus, the maximal occurrence of attacks coincides with the peaking lunisolar tidal effect. Similar relation of attacks to synodic moon was seen in bronchial asthma of children, and a reciprocal one in paroxysmal tachyarrhythmia. Differing pathogenetic backgrounds of these diseases substantiate the observed differences in their putative reactions on the changing cosmogeophysical environment.

Seasonal and circadian rhythms in suicide in Cagliari, Italy

Background. In previous studies of the seasonality of suicide, peaks have often been found in the number of suicides in the spring and early summer in both northern and southern hemispheres. The purpose of the present study was to investigate the distribution of suicide as to month, seasons, day of the week, and time of the day. Method. Data on suicides in Cagliari (Italy) in the period 1990–1994 were analyzed by means of spectral analysis, cosinor and multiple regression analysis. Results. Two seasonal rhythms, i.e. an annual and a semiannual rhythm, accounted for 25% of the variation in the total number of suicides. The peak number of suicides occurred in February with a second less significant peak in June and July. Lows were found in November and December. There were no significant differences in number of suicides in relation to days of the week. Three rhythms, i.e. 24 hours (circadian), 8 hours and 1 hour, explained 63.9% of the variance in the number of suicides by time of the day. Peak numbers in number of suicides were found between 08:31 and 12:30h, while the number of suicides was also significantly higher between 12:31h and 20:30h than between 20.31h and 8.30h. Age and gender did not significantly affect the seasonal and circadian rhythms in suicide. Conclusions. The results show that there is a significantly seasonal variation and a highly significant variation by time of the day in suicide in Cagliari, Italy.

Circadian Variation in the Rupture of Abdominal Aortic Aneurysms

Circadian variations in the incidence of myocardial infarction, sudden death, and stroke have been attributed to diurnal fluctuations in catecholamine release, blood pressure, heart rate, fibrinolytic activity, and platelet aggregation. As similar factors could precipitate the rupture of an abdominal aortic aneurysm, a retrospective chart review was undertaken in an effort to define the timing of aneurysm rupture and any associated circadian variation. One hundred forty-three patients with a ruptured abdominal aortic aneurysm (rAAA) and a documented time of presentation were evaluated. Eighty-one patients (56.7%) presented within 2 hours of the onset of symptoms and were examined for diurnal variability in their presentation. The hourly rate of rAAA presentation between 8 AM and 10 PM (4.3 per hour) was more than twice that observed during the night (2.1 per hour, p<0.001). The distribution of presentation times among this group was significantly different from uniform (p=0.05), implying circadian variability to aneurysm rupture. The time-dependent rate of rAAA presentation could be predicted (R2=0.77) with cosinor regression methods, although this model was not statistically significant (F= 4.9, p >0.10). Abdominal aortic aneurysm rupture occurs with a diurnal variation having a peak during waking hours. The relationship of aneurysm rupture to known physiological circadian rhythms may give further insight into the underlying pathophysiology and has implications for patient management.

A seasonal variation in the incidence of ruptured abdominal aortic aneurysms

To discover whether there is a seasonal variation in the incidence of rupture of abdominal aortic aneurysms. Deaths per month due to rupture of abdominal aortic aneurysm were analysed retrospectively using a cosinor regression model. England and Wales. 19,599 patients who died from rupture of abdominal aortic aneurysm between January 1991 and December 1995 according to death certification data. None. A seasonal variation in the incidence of rupture of abdominal aortic aneurysm occurs, with a peak in winter (p = 0.003). The ratio of rupture of abdominal aortic aneurysm in males and females decreased from more than 12 to 1 below age 60 years to less than 5 to 1 over age 80 years. There is a seasonal variation in the incidence of recorded deaths from abdominal aortic aneurysm in England and Wales, with a peak of deaths in the cold winter months. The underlying cause is unknown, but hypertension and tobacco smoking are predisposing factors to aortic aneurysm rupture. Exposure to tobacco smoke is known to be greater indoors in cold weather and there is a winter peak of blood pressure in hypertensive patients.

Women's patterns of activity over 6 months after coronary artery bypass surgery

To examine the relationships between objectively measured activity patterns over 6 months after coronary artery bypass surgery (CABS) and their relationship to self-reported functional recovery at 6 weeks and 6 months after CABS. Time series, descriptive-correlational, convenience sample. Hospital and home environment. Thirteen women who had undergone CABS. The mean age was 62 years (SD 10.76, range, 43 to 78). The mean preoperative New York Heart Association Functional Classification was 2.08 (SD 1.26, range, 1 to 4). Wrist-worn accelerometers and the Sickness Impact Profile (SIP). Women wore the accelerometers for 4 week-long intervals: the first postoperative week (T1), the first week after hospitalization (T2), the sixth postoperative week (T3), and the first week of the sixth postoperative month (T4). The SIP was administered at the end of each week of data collection. Circadian rhythms and linear trends in activity were examined with spectral, cosinor, and least squares regression analyses. Repeated measures ANOVA over T1 through T4 demonstrated statistically significant increases in the strength of the circadian rhythms and means levels of activity over T1 to T4. There were no statistically significant relationships between activity parameters at T1, T3, or T4 and SIP scores at T3 or T4. This study is the first to report changes in circadian rhythms and levels of objectively measured activity over 6 months after CABS. The findings suggest that women's levels of activity and the strength of the circadian rhythm of activity increase between the early postoperative period and the sixth postoperative month. More research is needed to further explore the trajectory of activity patterns after CABS, their relationships to recovery and to determine the need for and effectiveness of interventions designed to promote recovery through activity patterning.

Age-related alterations in the circadian rhythms of pulsatile luteinizing hormone and testosterone secretion in healthy men.

The effect of advancing age on the chronobiology of testosterone (T) and luteinizing hormone (LH) secretion in healthy men was investigated. Twenty young (average age 30.4 yrs) and 14 elderly (average age 70.4 yrs) men underwent 10 min blood sampling for 25 hrs to evaluate the circadian periodicity of LH, LH pulse frequency, and T. Using cosinor regression analysis, young men were found to have a significant (p less than .05) circadian variation in LH pulse frequency, with slowing of LH pulses during the night (maximum slowing at 2230 hr). There was also a tendency for LH pulse amplitude to increase at night (p = .06) in young men. However, no significant circadian pattern in LH pulse frequency or amplitude was detected in the elderly men. Mean LH by radioimmunoassay (RIA) and bioassay did not vary over the 24-hr period in either age group. Both young and elderly men had significant circadian rhythms in serum T, although the rhythm in elderly men was considerably blunted and was shifted in time compared to the young. These data provide evidence for age-related changes in the circadian rhythms of LH pulse frequency and T secretion and suggest that the LHRH pulse generator loses its circadian rhythmicity with normal aging in men.

Three views of the annual phase map of the domestic cat,Felis catusL.

Abstract Longitudinal studies for a period of a year were conducted on five variables with eight normal adult male cats. The variables were adrenaline, noradrenaline, glucocorticoid hormones, body weight, and food intake. Body weight and food intake were determined once every two weeks for the period of a year, and the urinary content of adrenaline, noradrenaline and glucocorticoid hormones were determined once a month for the same period. The annual trend was viewed in three ways, by plotting the means, by a “cosinor‐like coordinate plot, and by a periodic regression technique. The results indicate that the periodic regression technique provided a good representation of the data in all cases, but the cosinor plot had limited applicability. In the special case when the annual sine curve accounted for all the trend, the cosinor and periodic regression technique are equivalent. Limitations of the cosinor representation involve the non‐sinusoidal shape of the data and the ubiquity of bimodal patterns, a ubi...

The effect of age on the circadian rhythms of 23 liver or brain enzymes from C57BL/6J mice.

Mice were standardized to 12 h of light exposure alternating with 12 h of darkness and were fed ad libitum. The mice in the first group were 8 weeks old and in the other 104-116 weeks old. Subgroups of 7 animals from each age group were killed at 6 circadian stages. Enzyme activities of 23 enzymes from liver or brain were measured by an analysis of variance for each age group. All but 1 enzyme from young mice, and all but 9 from older mice showed significant changes over time (p less than 0.01). The data from the 22 enzymes from young mice and the 14 enzymes from old mice were fit to the cosinor regression model to further characterize the rhythm. 15 enzymes from the young and 8 from the aged mice showed a significant regression to a 24-hour cosine curve (p less than 0.01); of the 8, 7 were the same enzymes in both groups. Amplitude changes, where they could be compared from the cosinor data (7 enzymes), were not statistically different. When total variance was compared, 12 enzymes showed unequal variance. Of these, old mice had the larger variance in 9 enzymes. Another difference between the young and the old was changes in mean enzyme activities. 12 enzymes from aged mice had decreased mesors, 2 had increased mesors, and 9 were unchanged. In general, our data suggest that some enzyme activity rhythms were lost, others were altered and a few were not affected by aging. In the case of many enzymes, older mice have a diminished ability to synchronize to the light signals.

The effects of continuous illumination (LL) and continuous darkness (DD) on the daily rhythms of membrane‐bound and microsomal enzymes in the adrenal gland and kidney of the rat

AbstractA daily rhythm was demonstrated in levels of specific activity for the Na, K‐ATPase and glucose‐6‐phosphatase enzymes in adrenal and renal subcellular fractions in the rat. A bimodal daily rhythm was observed for 5′‐nucleotidase in a renal subcellular fraction. The rats were maintained on a 12:12 light‐dark (LD) regimen. Animals were killed at approximately 4‐hour intervals.The daily rhythm in Na, K‐ATPase and glucose‐6‐phosphatase activities persisted in animals maintained under continuous illumination (LL) and continuous darkness (DD). The 5′nucleotidase activity persisted under LL, and under DD.The data from the enzyme assays were analyzed by fitting to a cosinor regression model designed to assess the rhythmic nature of the findings. A linear transformation method was applied to assess the closeness of fit to the cosinor regression model.The Na, K‐ATPase and glucose‐6‐phosphatase activities appeared to be endogenous circadian rhythms. Glucose‐6‐phosphatase activity in renal fractions appeared to be influenced by the feeding cycle. The 5′‐nucleotidase enzyme appeared to have an ultradian rhythm. The ultimate derivation and significance of these observed rhythms remains to be determined; however, they appear to be independent of the light‐dark cycle.