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The capacity to learn abstract concepts such as 'sameness' and 'difference' is considered a higher-order cognitive function, typically thought to be dependent on top-down neocortical processing. It is therefore surprising that honey bees apparantly have this capacity. Here we report a model of the structures of the honey bee brain that can learn sameness and difference, as well as a range of complex and simple associative learning tasks. Our model is constrained by the known connections and properties of the mushroom body, including the protocerebral tract, and provides a good fit to the learning rates and performances of real bees in all tasks, including learning sameness and difference. The model proposes a novel mechanism for learning the abstract concepts of 'sameness' and 'difference' that is compatible with the insect brain, and is not dependent on top-down or executive control processing., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients with chronic fatigue syndrome (CFS) show evidence of circadian rhythm disturbances. We aimed to determine whether CFS symptoms were alleviated by melatonin and bright-light phototherapy, which have been shown to improve circadian rhythm disorders and fatigue in jet-lag and shift workers., Design: Thirty patients with unexplained fatigue for > 6 months were initially assessed using placebo and then received melatonin (5 mg in the evening) and phototherapy (2500 Lux for 1 h in the morning), each for 12 weeks in random order separated by a washout period. Principal symptoms of CFS were measured by visual analogue scales, the Shortform (SF-36) Health Survey, Mental Fatigue Inventory and Hospital Anxiety and Depression Scale. We also determined the circadian rhythm of body temperature, timing of the onset of melatonin secretion, and the relationship between these., Results: Neither intervention showed any significant effect on any of the principal symptoms or on general measures of physical or mental health. Compared with placebo, neither body temperature rhythm nor onset of melatonin secretion was significantly altered by either treatment, except for a slight advance of temperature phase (0.8 h; P = 0.04) with phototherapy., Conclusion: Melatonin and bright-light phototherapy appear ineffective in CFS. Both treatments are being prescribed for CFS sufferers by medical and alternative practitioners. Their unregulated use should be prohibited unless, or until, clear benefits are convincingly demonstrated.

There were 15 healthy female subjects, differing in their position on the "morningness-eveningness" scale, studied for 7 consecutive days, first while living a sedentary lifestyle and sleeping between midnight and 08:00 and then while undergoing a "constant routine." Rectal temperature was measured at regular intervals throughout this time, and the results were subjected to cosinor analysis both before and after "purification" for the effects of physical activity. Results showed that there was a phase difference in the circadian rhythm of core temperature that was associated with the morningness score, with calculations that "morning types" would be phased earlier than "evening types" by up to about 3 h. This difference in phase (which was also statistically significant when the group was divided by a median split into a "morning group" and an "evening group") could not be attributed to effects of waking activity and existed in spite of the subjects keeping the same sleep-wake schedule. Moreover, it persisted when the subjects' data had been purified and when the data were obtained from the constant routine. That is, there was an endogenous component to this difference in phase of the core temperature. The morning group also showed a greater fall of core temperature during sleep; this was assessed in two ways, the main one being a comparison of constant routine and nychthemeral data sets after correction for any effects of activity. Even though the morning group was sleeping at a later phase of their circadian temperature rhythm than was the evening group, neither group showed a fall of temperature due to sleep that varied with time elapsed since the temperature acrophase. It is concluded that another factor that differs between morning and evening types is responsible for this difference.

Nine healthy females were studied about the time of the spring equinox while living in student accommodations and aware of the passage of solar time. After 7 control days, during which a conventional lifestyle was lived under a 24h "constant routine," the subjects lived 17 x 27h "days" (9h sleep in the dark and 18h wake using domestic lighting, if required). Throughout the experiment, recordings of wrist activity and rectal (core) temperature were taken. The raw temperature data were assessed for phase and amplitude by cosinor analysis and another method, "crossover times," which does not assume that the data set is sinusoidal. Two different purification methods were used in attempts to remove the masking effects of sleep and activity from the core temperature record and so to measure more closely the endogenous component of this rhythm; these two methods were "purification by categories" and "purification by intercepts." The former method assumes that the endogenous component is a sinusoid, and that the masking effects can be estimated by putting activity into a number of bands or categories. The latter method assumes that a temperature that would correspond to complete inactivity can be estimated from measured temperatures by linear regression of these on activity and extrapolation to a temperature at zero activity. Three indices were calculated to assess the extent to which exogenous effects had been removed from the temperature data by these purification methods. These indices were the daily variation of phase about its median value; the ratio of this variation to the daily deviation of phase about midactivity; and the relationship between amplitude and the square of the deviation of phase from midactivity. In all cases, the index would decrease in size as the contribution of the exogenous component to a data set fell. The purification by categories approach was successful in proportion to the number of activity categories that was used, and as few as four categories produced a data set with significantly less masking than raw data. The method purification by intercepts was less successful unless the raw data had been "corrected" to reflect the direct effects of sleep that were independent of activity (a method to achieve this being produced). Use of this purification method with the corrected data then gave results that showed least exogenous influences. Both this method and the purification by categories method with 16 categories of activity gave evidence that the exogenous component no longer made a significant contribution to the purified data set. The results were not significantly influenced by assessing amplitude and phase of the circadian rhythm from crossover times rather than cosinor analysis. The relative merits of the different methods, as well as of other published methods, are compared briefly; it is concluded that several purification methods, of differing degrees of sophistication and ease of application to raw data, are of value in field studies and other circumstances in which constant routines are not possible or are ethically undesirable. It is also concluded that such methods are often somewhat limited insofar as they are based on pragmatic or biological, rather than mathematical, considerations, and so it is desirable to attempt to develop models based equally on mathematics and biology.

Fifteen healthy female subjects were studied for eight days while living conventionally. Subjects were free to choose the ways they spent their time within a framework of regular times of retiring and rising; in practice, much of the waking time was spent in sedentary activities. Nine of the subjects were aware of the natural light-dark cycle, this approximating to a 12:12 L:D schedule at the time of year when the study took place. Before the study, subjects were assessed for their degree of "morningness" by questionnaire; throughout the study, they wore a rectal probe, and an activity meter on their non-dominant wrist. The timing (phase) and amplitude of the circadian rectal temperature rhythm were assessed on each day by cosinor analysis as well as by a method based on visual inspection of the data. These two parameters were also assessed after the temperature data for each day had been "purified" by a number of methods. From these results it was possible to investigate the effect of purification upon the amplitude of the circadian rhythm of temperature. Also, the day-by-day variability of phase, and the relationship between morningness and phase, were compared using these methods of phase estimation, and using cross-correlation between data sets from adjacent days; in all cases, raw and purified temperature data were used. There was a significantly greater amount of daily variation in phase using purified rather than raw data sets, and this difference was present with all methods of purification as well as with all methods for estimating phase. Purification decreased the amplitude of the circadian temperature rhythm by about 30%. Finally, there was a significant correlation between the morningness score of the subjects and the phase of the circadian temperature rhythm, the phase becoming earlier with increasing morningness; when this relationship was re-examined using purified data, it became more marked. These results reflect the masking effects exerted upon raw temperature data by lifestyle. The extent to which the purification methods enable the endogenous component of a circadian rhythm - and, by implication, the output of the endogenous circadian oscillator - to be estimated in subjects living normally is addressed.

The diurnal variation in a range of psychological functions and core body temperature were investigated in a series of studies involving a total of 24 highly practised young women who lived in a controlled environment and on a strictly regimented 24-hour routine for 6 or 7 days. Ten participants were exposed to the natural light/dark cycle (L/Dc) through windows, whereas the 14 remaining participants saw no daylight, but all had access to normal clock time. A battery of mood and performance tests was completed every 2 hours whilst awake (08:00-00:00), resulting in nine equally spaced measures per waking day. Average time of day (ToD) functions were calculated from the last 5 or 6 days spent in the controlled environment. Significant ToD effects were found for many of the variables taken although the nature of these effects differed across measures, with a 'post-lunch dip' being observed at 16:00 in some variables. Analysis of the standardized data established that all variables presented reliably different ToD functions to core body temperature, whilst factor analyses indicated possible relationships between the variables. It was concluded that those variables that exhibited diurnal variation showed trends that did not parallel those in core body temperature.

Fourteen ambulatory subjects, varying in their amount of habitual physical activity, were studied for 24 h during a total of 25 "typical" days. Rectal temperature was recorded every 6 minutes, an activity diary was filled in every half hour, and wrist activity and heart rate were monitored every minute. Actimetry and heart rate data generally showed close parallelism with each other and with the masking effects on body temperature. Psychological stressors such as public speaking produced a greater effect on heart rate and body temperature than on wrist movement, while typing produced high values for wrist movement, but affected heart rate and temperature much less. When data for the circadian rhythm of body temperature were purified, the diary, actimetry, and measurement of heart rate were all useful in reducing masking effects, but the present evidence indicates that heart rate can be more successful than actimetry--as judged by the closeness of the purified data to a sinusoid. This superiority of heart rate monitoring over wrist activity as a method of purification might be because core temperature can be increased by stressor-induced thermogenesis, as well as by physical activity, and because wrist movement can, with some activities, give an inaccurate estimate of the factors that contribute to whole-body thermogenesis.

Nine healthy female subjects were studied when exposed to the natural light-dark cycle, but living for 17 "days" on a 27h day (9h sleep, 18h wake). Since the circadian endogenous oscillator cannot entrain to this imposed period, forced desynchronization between the sleep/activity cycle and the endogenous circadian temperature rhythm took place. This enabled the effects of activity on core temperature to be assessed at different endogenous circadian phases and at different stages of the sleep/activity cycle. Rectal temperature was measured at 6-minute intervals, and the activity of the nondominant wrist was summed at 1-minute intervals. Each waking span was divided into overlapping 3h sections, and each section was submitted to linear regression analysis between the rectal temperatures and the total activity in the previous 30 minutes. From this analysis were obtained the gradient (of the change in rectal temperature produced by a unit change in activity) and the intercept (the rectal temperature predicted when activity was zero). The gradients were subjected to a two-factor analysis of variance (ANOVA) (circadian phase/ time awake). There was no significant effect of time awake, but circadian phase was highly significant statistically. Post hoc tests (Newman-Keuls) indicated that gradients around the temperature peak were significantly less than those around its trough. The intercepts formed a sinusoid that, for the group, showed a mesor (+/-SE) of 36.97 (+/-0.12) and amplitude (95% confidence interval) of 0.22 degrees C (0.12 degrees C, 0.32 degrees C). We conclude that this is a further method for removing masking effects from circadian temperature rhythm data in order to assess its endogenous component, a method that can be used when subjects are able to live normally. We suggest also that the decreased effect of activity on temperature when the endogenous circadian rhythm and activity are at their peak will reduce the possibility of hyperthermia.

Nine subjects were studied for 16 days in an isolation unit where they lived on normal time, working at a decision-making, computer-driven task during the daytime. Interspersed among these control days were three occasions when sleep was curtailed. Rectal temperature and activity (non-dominant wrist) were measured throughout. Any effects of sleep loss on core temperature and activity were assessed by comparing these variables on control days with values during the daytime immediately following sleep loss, and during the next (recovery) day. During the daytime following sleep loss, activity showed no significant changes. By contrast, core temperature was significantly lower, particularly after the night of complete sleep loss. On recovery days also, activity was not significantly changed from control days but core temperatures during work were significantly lower than on control days if there had been no sleep the previous night. These results indicate that the effects of sleep loss on core temperature can persist for at least 24 h, and that they occur in the absence of parallel changes in activity.

Two groups of healthy subjects were studied indoors, first while living normally for 8 days (control section) and then for 18 x 27 h "days" (experimental section). This schedule forces the endogenous (body clock-driven) and exogenous (lifestyle-driven) components of circadian rhythms to run independently. Rectal temperature and wrist movement were measured throughout and used as markers of the amplitude of the circadian rhythm, with the rectal temperature also "purified" by means of the activity record to give information about the endogenous oscillator. Results showed that, during the experimental days, there were changes in the amplitude of the overt temperature rhythm and in the relative amounts of out-of-bed and in-bed activity, both of which indicated an interaction between endogenous and exogenous components of the rhythm. However, the amplitude and the amount of overlap were not significantly different on the control days (when endogenous and exogenous components remained synchronized) and those experimental days when endogenous and exogenous components were only transiently synchronized; also, the amplitudes of purified temperature rhythms did not change significantly during the experimental days in spite of changes in the relationship between the endogenous and exogenous components. Neither result offers support for the view that the exogenous rhythm alters the amplitude of oscillation of the endogenous circadian oscillator in humans.

Twelve subjects have been studied in a chamber that isolated them from external noise and lighting. After several control days, one group (n = 6) was subjected to 18 x 27-h 'days' and the other to 11 x 30-h 'days'. Sleep was in the dark, and awake times were spent in normal domestic lighting (150-500 lux). Rectal temperature and wrist actimetry were measured throughout, and the phase of the circadian oscillator was inferred from that of the temperature data, purified to remove direct effects of activity. During the experimental 'days' the rhythms showed a mean period of 24.4 h. A detailed examination of the phase shifts from one day to the next showed that small advances and delays were superimposed upon this drift. Moreover, the mean size and direction of these shifts depended upon the time of exposure to lighting relative to the temperature minimum, as would be predicted from a phase-response curve.

The purpose of the present study was to evaluate the simultaneous effects on sleep of prior time awake (PRW) and time of day (TOD). Eight male subjects spent 13 days in an isolated sleep lab and had three 8-h baseline sleeps and then 18 4-h sleeps, distributed to provide three sleeps starting at 2400, 0400, 0800, 1200, 1600, and 2000. The three sleeps were preceded by 4, 8, and 12 h of PRW, respectively. ANOVA showed that TST and subjective sleepiness increased with PRW and with closeness to the trough of the circadian rhythm of rectal temperature, whereas sleep latency showed the opposite pattern, and rapid eye movement sleep (REM) latency strongly decreased with PRW and with closeness to the trough. Slow-wave sleep (SWS) increased with PRW, whereas SWS latency and final time awake decreased. REM sleep increased with closeness to the circadian trough, and time awake decreased. Multiple-regression analysis showed that REM latency was closely related to increased SWS in the first sleep cycle, reduced SWS latency, and increased PRW [a short PRW before sleep at noon yielded an extremely short (14 min) REM latency]. Sleep latency and final time awake showed almost exactly the same relationship to TOD and PRW. It is concluded that both homeostatic and circadian influences simultaneously affect sleep, that REM latency is very sensitive to the need for SWS, and that the circadian acrophase strongly interferes with sleep. It should be emphasized that the conclusions should not be extrapolated to longer (> 12 h) wake spans.

Objectives: This study examined the hypothesis that alertness can be used to predict time-of-day effects on performance., Methods: For 6 or 7 days the volunteers (24, highly practiced young women) were required to retire to bed at 0000 and were awakened at 0800. A battery of mood and performance tests was completed every 2 hours while the women were awake; the result was 9 equally spaced measures per day. Measures of mood, serial reaction time, and memory scanning were recorded. Rectal temperature was recorded continuously., Results: After omitting the data from the first day to avoid any carry-over from the "first-night" effect on sleep, average time-of-day functions were calculated for each subject, for each variable, and were then z-transformed. Cross-correlations between the pooled time-of-day trends indicated that, while alertness was a reasonably good "predictor" of the simple perceptual-motor speed measures, it fared less well for some of the other measures. Two-way analyses of variance indicated that the time-of-day trend for all measures differed from that for alertness, although the magnitude of this difference varied substantially and, for some measures, was very largely due to the last reading of the day (0000)., Conclusion: It is clear from these results that, while alertness may successfully "predict" variations in some measures of performance capability, and especially those of simple perceptual motor speed, care should be exercised in extrapolating to other performance measures.

Background: Most studies on lifestyle changes in old age have been transverse. We have conducted a longitudinal study., Subjects: 112 non-institutionalized subjects were studied in 1984 and again 10 years later (ages in 1984 ranged from 53-82 years)., Protocol: On each occasion subjects recorded in a diary their times of retiring and rising and of taking meals, during a 'typical week'. They also recorded whether they lived alone or with somebody., Analysis: The diaries were scored to establish any effects of age or living alone on the timing and variability of their lifestyle., Results: Age was associated with changes in the sleep/wake schedule and mealtimes and a decrease of daily variation in these variables. When these changes were compared in subjects living alone and with somebody, the increase in time spent in bed and the decreases in variability of times of rising and meals were more marked in subjects living with somebody., Conclusions: A deteriorating body clock contributes to some of these changes, but an increasingly inflexible lifestyle will offset some of the effects of this decline in circadian rhythmicity.

The present study used short sleep episodes to explore the relation between subjective sleep quality, timing and physiological content of sleep. Eight subjects participated in 18 4-h sleep episodes to provide 4, 8, and 12 h of prior time awake before bedtimes at six different times of day in a sleep laboratory insulated from environmental disturbances. The results were analysed by ANOVAs and multiple regression techniques. Subjective sleep quality, calmness of sleep, ease of falling asleep, ability to 'sleep through', number of awakenings, and sleep latency showed a significant pattern of 'better' sleep with increasing prior time awake and with closeness to the circadian minimum (nadir) of rectal temperature (morning hours). 'Ease of awakening' in contrast, 'decreased' with increasing time awake and with closeness to the nadir/ morning hours. Multiple regression analysis showed that subjective sleep quality was predicted by subjective calmness of sleep and ease of falling asleep, among the subjective measures, and by total sleep time (TST) and slow-wave sleep (SWS - stages 3+4) among the physiological sleep measures. The subjective ease of awakening was predicted by slow-wave sleep (negatively) and the circadian maximum of rectal temperature. The results indicate that the duration of wakefulness prior to sleep and the timing of sleep determine its physiological expression, which in turn determines its subjective impression.

Although homeostatic mechanisms remain of utmost importance, rhythmic changes are present also. The main ones have a period of 24 h (circadian) or about 2-3 h (ultradian). Circadian rhythms are derived from a body clock, found in the base of the brain, and from the pattern of our sleep-wake cycle, including activity and meal times. These rhythms promote the regular changes between an active wake period and a recuperative sleep period. Ultradian rhythms are also widespread and reflect external (lifestyle) and internal factors. The internal factors include biochemical need and some sort of oscillator; but details of how many oscillators, and exactly where they are, remain to be established. Food intake, appetite, digestion and metabolism have been shown to illustrate these principles. Moreover, these principles become important when special circumstances exist as far as meal times are concerned; the particular difficulties of night workers is a good example.

Adjustment of circadian rhythms to changed sleep/wake schedules, as after time-zone transitions and during night work, is not immediate. Different variables appear to adjust at different rates, and such external and internal dissociation is linked with a general malaise ("jet lag") after a time-zone transition. Work using "constant routines" and "purification" methods indicates that the internal dissociation results from differences between variables in the relative contribution of exogenous ("masking") effects to the measured rhythm. These results indicate, therefore, there is no need to postulate the presence of more than one body clock which is responsible for the endogenous component of a circadian rhythm, and that heavily masked circadian rhythms will be poor indicators of the rate of adjustment of this clock. Nevertheless, it will be the measured rhythm that describes most directly the disruption to circadian rhythmicity caused by changed sleep/wake schedules.

This paper reports the results of a study designed to explore the validity of a shiftwork model of affective disorders. Fifty-five student nurses doing nightwork for the first time were recruited to a study designed both to replicate an earlier study of the effects of nightwork on cognitive, emotional and neurovegetative measures and to assess the effects of nightwork on personality measures and the role of personality factors and nightwork induced disturbances in predicting accommodation to nightwork. As in the earlier study, concentration, interest, energy, sleep and appetite were significantly disturbed by nightwork and there was an increased perception of recent criticism from other. The findings from both studies were, therefore, aggregated to explore further possible relations between outcomes and the pre-nightwork level of affective symptoms and sensitivity to interpersonal criticism. These predicted poor response. In contrast, measures of cognitive style and symptom interpretation did not predict outcome. The findings are not inconsistent with proposals that disturbance of circadian rhythms consequent on psychosocial disruptions may play a part in the genesis of or maintenance of depression. They also support a proposal that nightwork induced changes may be a suitable human model for investigation of aspects of the affective disorders.

Eight nurses have been studied during rest days and three successive night shifts. Measurements of wrist activity have been made and used to assess the extent to which the pattern of daily activity changes between control (rest) days and days involving night work. One analysis considered wrist activity during time spent in bed; this appears to decrease in parallel with the amount of time in bed that is lost during night work but, when this effect is corrected for, there is greater activity during time spent in bed in the daytime compared with control days (when time in bed is during the night). The dichotomy of activity (between lower values during time spent in bed and higher values when out of bed) also decreases if time in bed is during the daytime while on night shifts. These changes in the amount of wrist activity and the dichotomy between activity in and out of bed are related to the changed quality and quantity of sleep that has been measured by self-report questionnaires and the sleep EEG. It is concluded that results from wrist actimetry can provide valuable information regarding the process of adjustment to night work, and that its convenience (to subject and experimenter), coupled with the new analytical approaches described here, make it a viable method for field studies.

Nine healthy subjects have been studied while exposed to the normal alternation of light and dark, but with their sleep and activity pattern adjusted to a 27-h "day" for 17 imposed "days." Rectal temperature showed clearly the competing influences of 27-h and 24-h components, and these were separated by the method of "purification." The method indicated that the endogenous component had a constant amplitude throughout the experiment and remained entrained to solar (24-h) time; by contrast, the exogenous component followed the imposed 27-h "day" and increased rectal temperature in proportion to the amount of subjects' activity. Wrist movement was used to assess activity while in bed (attempting sleep) and out of bed (when naps were forbidden). While these results confirmed adherence of the subjects to the imposed 27-h "days," they also showed that the dichotomy between "out of bed" activity and "in bed" inactivity depended on the phase relationship between endogenous (24h) and exogenous (27h) components. Thus, the dichotomy was highest and was equal to that during control days (with a conventional 24-h life-style) when the two components were in phase and lowest when the solar and imposed day were in antiphase. This was due to changes in activity, both during time spent in bed and out of bed. We confirm that this protocol can produce valuable information about the properties of the circadian system in humans and the value of the process of purification of temperature data. We have established also that the very simple and noninvasive measurement of wrist movement, coupled with its use to calculate dichotomy indices, provides valuable information that both confirms and extends the results obtained from the more conventional (but also more invasive) measurement of rectal temperature.

Many patients with chronic fatigue syndrome (CFS) display features of hypothalamic dysfunction. We have investigated aspects of circadian rhythmicity, an important hypothalamic function, in 20 CFS patients and in 17 age- and sex-matched healthy control subjects. There were no differences between the two groups in the amplitude, mesor (mean value) or timing of the peak (acrophase) of the circadian rhythm of core temperature, or in the timing of the onset of melatonin secretion. However, the CFS patients showed no significant correlation between the timing of the temperature acrophase and the melatonin onset (P < 0.5), whereas the normal significant correlation was observed in the controls (P < 0.05). Dissociation of circadian rhythms could be due to the sleep deprivation and social disruption, and/or the reduction in physical activity which typically accompany CFS. By analogy with jet-lag and shift-working, circadian dysrhythmia could be an important factor in initiating and perpetuating the cardinal symptoms of CFS, notably tiredness, impaired concentration and intellectual impairment.

The activity records of five groups of healthy or ill subjects have been measured for 4-26 days by an accelerometer placed on the nondominant wrist. These data, together with a record of times retiring to/rising from bed, have been used to produce a series of dichotomy indices for comparing the amounts of activity when in bed and out of bed. Reliable differences between individuals were found, with healthy subjects showing a greater degree of dichotomy than one subject with delayed sleep phase syndrome or three subjects with colorectal cancer. The method is convenient for extended data collection and offers the possibility of describing an individual's activity profile in a variety of circumstances.

Measured circadian rhythms consist of endogenous (clock-driven) and exogenous (lifestyle-driven) components. The exogenous components cause difficulties of interpretation of phase and amplitude information. Such effects can be removed by "constant routines", but these protocols are restricted to the laboratory. By contrast, the process of "purification" of circadian rhythms uses the knowledge of an individual's normal lifestyle to separate a measured rhythm into its two components. This method has been shown to be practicable in a variety of circumstances and to provide a feasible alternative to constant routines.

The mean arterial blood pressure (MABP), heart rate, and skin temperature were monitored every 15 minutes in the first 10 days after birth in 34 preterm infants, gestational age 24 to 33 weeks. Ultrasound brain scans carried out daily showed that a periventricular haemorrhage (PVH) occurred in a subgroup of infants (n = 15) of lower birthweight and gestational age. In infants without PVH the daily median of MABP increased with birthweight and postnatal age; that of heart rate was not affected by postnatal age, body weight, or gestational age; and that of skin temperature showed a slight fall with postnatal age. In infants with PVH, on or before the day of PVH, daily medians of MABP and skin temperature were not significantly different from those of infants without PVH, but the daily median of heart rate tended to be slightly higher. The percentage of positive correlations between the 96 15 minute values per day for heart rate and MABP increased with postnatal age and with birthweight, but did not differ in infants who developed a PVH. The coefficient of variation (CV) of the 96 15 minute values for MABP tended to be higher in infants on the day of PVH, and a similar trend was apparent on the day before. The processes of development of blood pressure, heart rate, and skin temperature are similar in infants with or without PVH but at lower gestational ages altered blood pressure control may cause brain haemorrhage.

The present study sought to investigate the meaning of subjectively good sleep, using a longitudinal and intraindividual design. Eight subjects slept in an isolation unit according to an irregular schedule of 6 h sleeps and 1 h naps, designed to give normal amounts of time in bed (1/3 of total), but variable sleep quality. Eight sleeps and eight naps were used for longitudinal simple and multiple regression analyses with standard polysomnographical sleep variables as predictors and subjective sleep quality as dependent variables. The results showed that subjective sleep quality (and related variables) was closely related to sleep efficiency, but not sleep stages. At least 87% efficiency was required for ratings of 'rather good' sleep. In addition, sleep quality ratings improved with closeness (of the awakening) to the circadian acrophase (17.00-21.00 hours) of the rectal temperature rhythm. The subjective ease of awakening differed from most other other variables in that it was related to low sleep efficiency. Objective and subjective homologues of sleep length and sleep latency showed high mean intraindividual correlations (r = 0.55 and 0.64, respectively). It was concluded that objective measures of sleep continuity were closely reflected in perceived sleep quality and that sleep quality essentially means sleep continuity.

This overview considers the origins of jet lag in terms of altered circadian rhythmicity. The properties required of a chronobiotic--an agent to cause phase adjustment of the body clock--are discussed, and an account is given of the major candidates at the present time: light, melatonin, activity, and benzodiazepines. It is concluded that current knowledge indicates that a combination of factors is likely to be most effective.

The present experiment used an intraindividual design to investigate the meaning and measurement of "good sleep". Each of 16 subjects slept in an isolation unit according to a schedule (15 sleeps) designed to give variable quality of sleep. Self-rated sleep measures (from the Karolinska Sleep Diary) were obtained after each sleep and subjected to intraindividual regression analyses across time. Most subjective sleep measures showed a strong covariation across conditions. Subjective quality of sleep mainly involved variables of sleep continuity, in particular, perceived calmness of sleep and sleep efficiency. "Sleep quality," "calm sleep," "ease of falling asleep," and ability to "sleep throughout" the time allotted strongly covaried and formed an index of sleep quality. Self-rated ease of awakening deviated from the general pattern and was associated with poor sleep quality. So was reported dreaming (related to awakenings). It was concluded that most subjective sleep measures tend to covary across conditions and that "good sleep" is mainly a question of sleep continuity.

Objectives: The aim of the present study was to define the effect of masking on the estimation of circadian adjustment of and interindividual differences between nurses on a rapidly rotating shift schedule., Methods: The phase shift of the circadian rhythm of rectal temperature was studied in 17 subjects. The following three different methods for estimating the circadian phase shift were compared: (i) cosinor analysis, (ii) a method using normative endogenous data in which the masking effects are removed ("purification"), and (iii) a method using normative endogenous data in which the masking effects are not removed., Results: The mean phase delay during the second night shift (compared with the morning shift) was 6.3 h according to the cosinor analyses of the raw data and 6.2 h according to the cross-correlation method of the raw data. When the masking effects were removed ("purification"), the phase shift was only 1.7 h. Diurnal type did not significantly explain the differences between individuals in the amount of phase shift of the raw data but was the only significant factor, explaining 32% of the variation between individuals in the phase shift of the purified data., Conclusions: Masking effects on body temperature should be taken into account before any definite conclusions can be drawn about the relation between individual factors and the adjustment of the circadian rhythm of body temperature.

Fifteen female nurses, aged between 21 and 29 years and employed in an intensive care unit, were examined with the aim of evaluating their psychophysical adaptation to one of the most commonly used, rapidly rotating shift systems, the "metropolitan rota" (2-2-2-2), with the length of the shifts modified according to the work load (including night shifts of 10h) and with the start of the morning shift delayed (to 7 a.m.). Subjective evaluations of work load and psycho-physical conditions as well as performance measures (reaction time, search and memory test), blood pressure and heart rate were recorded at the start, middle and end of the work shifts on the last 4 days of the shift cycle, comprising one morning, one afternoon and two consecutive nights. During the shifts, plasma cortisol and urinary excretion rate of 6-sulphatoxymelatonin, adrenaline and noradrenaline were also recorded, as well as oral temperature and activity-sleep logs. The results showed that this rapidly rotating shift system including two consecutive night shifts does not significantly alter the normal circadian rhythms of the body, particularly as concerns performance levels, body temperature and hormone excretion. Moreover, the lengthening of the night shift to 10h can be considered acceptable in terms of work efficiency, provided that work load is reduced and there are sufficient rest pauses available to compensate for tiredness and sleepiness. On the other hand, the shortening of the day shifts to 7h and the delayed start of the morning shift to 7 a.m. appeared convenient in relation to both work load and sleep duration.

For many occupational groups there is an implicit requirement that sleep be taken according to very irregular schedules. The purpose of this study was to investigate the effects of an irregular sleep schedule on sleep and to determine if such effects could be attributed to the timing of sleep. Eight subjects slept in an isolation unit according to an irregular schedule comprising four 8-hour sleep periods, 12 6-hour sleep periods and 12 1-hour naps. The schedule was designed to give normal amounts of time (1/3 of total) in bed. Large variations in mean sleep efficiency (100-46%) were observed, which in individual cases frequently involved a complete absence of sleep. In 6-hour sleep periods the loss was due to an inability to maintain sleep, whereas in naps the loss was due to an inability to initiate sleep. The major causes of reduced sleep were short prior time awake and bedtime close to the circadian acrophase of rectal temperature (i.e. late afternoon). These two components accounted for 46% of the intraindividual variance of total sleep time (TST). TST increased by 9.2 minutes for each hour of prior time awake and by 10 minutes for each hour of deviation from the circadian acrophase of rectal temperature. Prior time awake also exerted a strong influence on slow-wave sleep (SWS), and circadian phase exerted a similar influence on rapid eye movement sleep. We concluded that irregular sleep patterns strongly affect sleep and that circadian and homeostatic influences are clearly discernible despite the irregularity.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety on shift systems will depend, at least in part, on the adjustment of shiftworkers' circadian (c.24h) rhythms in performance capabilities which will in turn depend on their underlying control. In the present study three volunteers lived on a 30h 'day' and performed a range of tasks every 2h (while awake) to allow estimates of the relative magnitude of the endogenous (body clock) and exogenous (masking) components of their rhythms to be made. Performance rhythms were found to differ considerably in this respect with, for example, speed on a 4-choice serial reaction time task appearing to be largely endogenously determined while that on a 5-target Sternberg task was more dependent on exogenous (i.e., 30h) factors. This implies that performance measures may adjust at very different rates to one another to night work, and hence that the optimal form of shift system may vary according to the precise demands of the shiftworker's task.

Twenty very premature babies, born at 24-29 weeks gestation, have been studied while they were maintained in intensive care with continuous intravenous feeding and constant ambient lighting and temperature. Hourly records of insulated skin temperature and heart rate were made for a continuous period of 6-17 weeks, always starting the recording within 24 h of birth. The development of rhythms within the ultradian, circadian and infradian domains was sought by methods including maximum entropy spectral analysis and autocorrelation. Circadian and ultradian rhythms were present, but not regularly so; rather they appeared and disappeared erratically in successive weeks. As a consequence, the group as a whole did not show an increasing rhythmicity with chronological age. In some cases, babies were later placed in a ward in which the lighting was dimmed at night, and feeding by mouth at regular intervals was instituted. There was some evidence for increases in circadian and ultradian rhythmicity after these changes. These results enable inferences to be drawn as to the origin of fetal rhythms in the third trimester of pregnancy, as well as speculation to be made on the ontogeny of ultradian and circadian rhythms in the neonate.

Whether or not the pineal gland has a significant physiological role in humans is not known. There has nevertheless been speculation about the potential therapeutic use of melatonin (in view of its hypnotic and possible zeitgeber properties) in conditions such as insomnia and jet lag, and in shift-workers. Our work concerns the effects of melatonin administration in humans and the interactions between melatonin and other circadian variables. Chronic (one month), timed (1700 h), low-dose (2 mg daily) melatonin administration to normal subjects without environmental control consistently increased evening fatigue and slightly modified the 24 h prolactin rhythm without effect on cortisol, growth hormone, luteinizing hormone, thyroxine, testosterone or self-rated mood. In five out of 11 subjects the endogenous melatonin rhythm was advanced by one to three hours. During fractional desynchronization of circadian rhythms by increasing imposed 'day' length (26-29 h, 24 days, 500 lux), 5 mg melatonin per os at lights-out in two subjects resulted in better entrainment of the fatigue rhythm to the zeitgeber than in five out of six control subjects, without major consistent effects on other measured circadian variables. Using a new radioimmunoassay for 6-hydroxymelatonin sulphate (aMT6s), the major melatonin metabolite, we have shown that the urinary aMT6s rhythm is closely correlated to that of melatonin in plasma and is completely suppressed by an acute dose of atenolol (100 mg per os), a peripheral beta-adrenergic antagonist. During fractional desynchronization by increasing imposed 'day' length in one subject and decreasing imposed 'day' length in two subjects, the urinary aMT6s rhythm behaved similarly to that of core temperature. The results suggest that fatigue (or alertness) may be entrained by melatonin, but whether critical performance rhythms can be suitably manipulated remains to be clarified. It is likely that melatonin production is linked to the so-called 'strong' circadian oscillator.

Two groups of subjects (total N = 6) were studied in an isolation chamber for a period of 3 weeks whilst living on a 22.8 hr "day". Regular samples of urine were taken when the subjects were awake, deep body temperature was recorded continuously and polygraphic EEG recordings were made of alternate sleeps. The excretion in the urine of potassium, sodium, phosphate, calcium and a metabolite of melatonin were estimated. Measurements of the quantity and quality of sleep were made together with assessments of the temperature profiles associated with sleep. In addition, cosinor analysis of circadian rhythmicity in urinary variables and temperature was performed. The 22.8 hr "days" affected variables and subjects differently. These differences were interpreted as indicating that the endogenous component of half the subjects adjusted to the 22.8 hr "days" but that, for the other three, adjustment did not occur. When the behaviour of different variables was considered then some (including urinary potassium and melatonin, sleep length and REM sleep) appeared to possess a larger endogenous component than others (for example, urinary sodium, phosphate and calcium), with rectal temperature behaving in an intermediate manner. In addition, a comparison between different rhythms in any subject enabled inferences to be drawn regarding any links (or lack of them) that might exist between the rhythms. In this respect also, there was a considerable range in the results and no links between any of the rhythms appeared to exist in the group of subjects as a whole. Two further groups (total N = 8) were treated similarly except that the chamber clock ran at the correct rate. In these subjects, circadian rhythms of urinary excretion and deep body temperature (sleep stages and urinary melatonin were not measured) gave no evidence for deterioration. We conclude, therefore, that the results on the 22.8 hr "day" were directly due to the abnormal "day" length rather than to a prolonged stay in the isolation chamber.

Relations among circadian rhythms in serum iron, glucagon and insulin and urinary cyclic AMP excretion differ drastically when diurnally active, nocturnally resting human adults consume all daily food for one week as breakfast only and for another week as dinner only - a finding of interest to diverse fields, e.g., for optimizing certain kinds of therapy or for a better utilization of calories.