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Biomedical subjects

J Waterhouse

Publications and source records attributed to J Waterhouse.

At least 19 recordsLinked to original sources

Identifying some determinants of "jet lag" and its symptoms: a study of athletes and other travellers.

BACKGROUND: Travelling across multiple time zones disrupts normal circadian rhythms and induces "jet lag". Possible effects of this on training and performance in athletes were concerns before the Sydney Olympic Games. OBJECTIVE: To identify some determinants of jet lag and its symptoms. METHODS: A mixture of athletes, their coaches, and academics attending a conference (n = 85) was studied during their flights from the United Kingdom to Australia (two flights with a one hour stopover in Singapore), and for the first six days in Australia. Subjects differed in age, sex, chronotype, flexibility of sleeping habits, feelings of languor, fitness, time of arrival in Australia, and whether or not they had previous experience of travel to Australia. These variables and whether the body clock adjusted to new local time by phase advance or delay were tested as predictors for jet lag and some of its symptoms by stepwise multiple regression analyses. RESULTS: The amount of sleep in the first flight was significantly greater in those who had left the United Kingdom in the evening than the morning (medians of 5.5 hours and 1.5 hours respectively; p = 0.0002, Mann-Whitney), whereas there was no significant difference on the second flight (2.5 hours v 2.8 hours; p = 0.72). Only the severity of jet lag and assessments of sleep and fatigue were commonly predicted significantly (p<0.05) by regression analysis, and then by only some of the variables. Thus increasing age and a later time of arrival in Australia were associated with less jet lag and fatigue, and previous experience of travel to Australia was associated with an earlier time of getting to sleep. Subjects who had adjusted by phase advance suffered worse jet lag during the 5th and 6th days in Australia. CONCLUSIONS: These results indicate the importance of an appropriate choice of itinerary and lifestyle for reducing the negative effects of jet lag in athletes and others who wish to perform optimally in the new time zone.

Adult↗

Influence of environmental parameters on the accuracy of nitrogen dioxide passive diffusion tubes for ambient measurement.

Two studies at three sites in the UK provided confirmation that systematic positive bias in NO2 diffusion tube measurement occurred because of changes to "within-tube" chemistry, rather than eddy diffusion at the mouth of the tube. In the first study in Cambridge, UK, sampler overestimation for 1 and 2 week exposures was compared to corresponding time-averaged monitor measurements (NO-NO2-NOx, O3) and weather variables. Noninearity between sampler and monitor NO2 measurements was interpreted in terms of spatial and temporal variations in relative and absolute availability of NO, NO2 and O3 at the site. A maximum overestimation occurred for an exposure mean NO2/NOx approximately 0.5. The separate contributions of reduced NO2 photolysis and eddy diffusion were compared in Study II using samplers of two materials, acrylic and quartz, and of different lengths (40, 55, 71 and 120 mm) at three sites: Norwich background, Cambridge intermediate, London kerbside. For compared sites, NO2 measured by acrylic samplers was significantly higher than for equivalent quartz samplers. For quartz samplers [NO2]mean was only just above the monitor at Norwich and London; sampler/monitor NO2 = 1.04 (P = 0.59) and 1.01(P = 0.76), respectively. For acrylic samplers the order of [NO2]mean was 40 mm > 120 mm > 71 mm > or = 55 mm. Excepting 40 mm samplers, this accords with a chemical bias where co-diffusing NO and 03 molecules in longer tubes have more time to react to form excess NO2. Bias in 40 mm samplers is discussed. Eddy diffusion is negligible for standard samplers because [NO2]mean was equivalent for 55 mm and 71 mm acrylic samplers and close to monitor NO2 for 71 mm quartz tubes. Both studies showed that sampler accuracy was dependent on location. Significantly, overestimation was greatest (approximately 3-4 ppb) where the NO2 annual mean was approximately 20 ppb, close to the UK and EU air quality standard of 21 ppb.

Air Pollutants↗

Are there hangover-effects on physical performance when melatonin is ingested by athletes before nocturnal sleep?

Athletes ingest melatonin in an attempt to improve sleep quality or alleviate symptoms of jet lag after transmeridian travel. It is not known whether there are residual effects of this hormone on physical performance in fit subjects. After a sample size estimation involving a meaningful effect on performance of 5%, five milligrams of melatonin or placebo were ingested by twelve physically-active subjects before sleep in a double-blind experiment. The following morning, subjective sleep quality (latency and maintenance) were measured together with intra-aural temperature, grip strength of the left and right hands, and time to complete a 4 km time trial on a cycle ergometer. The subjects also rated perceived exertion during the latter test. The null hypothesis of no effect of melatonin on either subjective sleep quality or physical performance measured the morning after administration could not be rejected on the basis of our observations (P > 0.30). The mean differences between treatments were less than 1% for the strength tests and time trial performance. The confidence intervals for these differences for left and right grip strength and the cycling test were - 2.1 to 2.8 kg, - 3.1 to 2.7 kg and -3.0 to 4.5 s, respectively. In conclusion, it is unlikely that 5 mg of melatonin would have any meaningful effects on physical performance in the morning after fit subjects ingest the hormone. There was also little evidence that it improves sleep quality in this population. Further research is needed concerning the effects of daytime and nighttime admistration of melatonin on performance, in both situations of normal and disturbed sleep.

Adult↗

Temperature profiles, and the effect of sleep on them, in relation to morningness-eveningness in healthy female subjects.

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.

Behavior↗

How to show that unicorn milk is a chronobiotic: the regression-to-the-mean statistical artifact.

Few chronobiologists may be aware of the regression-to-the-mean (RTM) statistical artifact, even though it may have far-reaching influences on chronobiological data. With the aid of simulated measurements of the circadian rhythm phase of body temperature and a completely bogus stimulus (unicorn milk), we explain what RTM is and provide examples relevant to chronobiology. We show how RTM may lead to erroneous conclusions regarding individual differences in phase responses to rhythm disturbances and how it may appear as though unicorn milk has phase-shifting effects and can successfully treat some circadian rhythm disorders. Guidelines are provided to ensure RTM effects are minimized in chronobiological investigations.

Biometry↗

Community and connectivity: summary of a community based monitoring program set up to assess the movement of nutrients and sediments into the Great Barrier Reef during high flow events.

The Great Barrier Reef (GBR) system encompasses the largest system of corals and related life forms anywhere in the world. The health of this extensive system, particularly the inshore area, is dependent on the relationship between the GBR and adjacent coastal catchments. The major impact of agricultural practices on the GBR is the degradation of water quality in receiving (rivers) waters, caused by increased inputs of nutrients, suspended sediments and other pollutants. For the past three years, the Great Barrier Reef Marine Park Authority (GBRMPA) has been involved with the co-ordination of a river-monitoring program, specifically targeting the sampling of rivers during flood events. Representative sites were set up along two North Queensland rivers, the Russell-Mulgrave and Barron Rivers. This monitoring program is run in conjunction with the Queensland Department of Natural Resources' Waterwatch program. The program involves intensive sampling of first flush, extreme flow and post flood conditions over the two rivers. Extreme flow conditions are sampled over a limited time span (48 hours) with trained volunteers at 4-hour intervals. Concentrations measured in the flood events are dependent on land use characteristic, and extent of flow. Concentrations of dissolved and particulate nutrients are higher if the extreme flow event is part of the first flush cycle. Concentrations of DIN and DIP measured before, during and after a major flood event suggest that there is a large storage of inorganic material within the Barron and Russell-Mulgrave agricultural subcatchments that move over a period of days, and perhaps weeks. This program created a forum in which GBRMPA liased with the Barron and Russell-Mulgrave community about the connectivity existing between the river and the Great Barrier Reef lagoon.

Agriculture↗

Catchment management and the Great Barrier Reef.

Pollution of coastal regions of the Great Barrier Reef is dominated by runoff from the adjacent catchment. Catchment land-use is dominated by beef grazing and cropping, largely sugarcane cultivation, with relatively minor urban development. Runoff of sediment, nutrients and pesticides is increasing and for nitrogen is now four times the natural amount discharged 150 years ago. Significant effects and potential threats are now evident on inshore reefs, seagrasses and marine animals. There is no effective legislation or processes in place to manage agricultural pollution. The Great Barrier Reef Marine Park Act does not provide effective jurisdiction on the catchment. Queensland legislation relies on voluntary codes and there is no assessment of the effectiveness of the codes. Integrated catchment management strategies, also voluntary, provide some positive outcomes but are of limited success. Pollutant loads are predicted to continue to increase and it is unlikely that current management regimes will prevent this. New mechanisms to prevent continued degradation of inshore ecosystems of the Great Barrier Reef World Heritage Area are urgently needed.

Agriculture↗

Reliability of nitrogen dioxide passive diffusion tubes for ambient measurement: in situ properties of the triethanolamine absorbent.

Factors concerning NO2 uptake by the absorbent triethanolamine (TEA) in NO2 diffusion tubes are examined. Although the nominal freezing point of TEA is 17.9-21.2 degrees C, we show that, for a range of aqueous TEA solutions (0-20%, H2O), no freezing occurs even at -10 degrees C. Therefore NO2 collection efficiency is unlikely to be impaired by low temperature exposure. The recovery of TEA from the meshes of exposed samplers is determined as approximately 98%, even after 42 days, showing that the stability in situ of TEA is unaffected by long-term exposure. A model of a diffusion tube sampling array for simultaneous exposures, with a 0.1 m sampler spacing, shows that NO2 uptake by individual samplers is not affected by the presence of neighbouring tubes in the array. This is confirmed by sampler precision at two Cambridge sites. Four sampler preparation methods are compared for differences in NO2 uptake of exposed samplers. All methods employ TEA as absorbent, transferred by either dipping meshes in a TEA-acetone solution or pipetting aliquots of a TEA-H2O solution onto the meshes. For samplers prepared by three of the methods, no difference in NO2 uptake is found, but for samplers prepared using a 50% v/v TEA-H2O solution, a mean reduction of 18% is found. Student's t-tests show that the difference is highly significant (P < or = 0.001). Reasons for the difference are discussed.

Absorption↗

Estimates of the daily phase and amplitude of the endogenous component of the circadian rhythm of core temperature in sedentary humans living nychthemerally.

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.

Activities of Daily Living↗

Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones.

Subjective, physiological and physical performance variables are affected following travel across multiple time-zones (jet-lag). The objective of the study was to examine the effects of oral melatonin in alleviating jet-lag by investigating its effects on subjects who had flown from London to Eastern Australia, 10 time-zones to the east. Melatonin (5 mg day(-1)) or placebo capsules were administered to 14 experimental (13 males and 1 female) and 17 control subjects (15 males and 2 females), respectively, in a double-blind study; the time of administration was in accord with the current consensus for maximizing its hypnotic effect. Grip strength and intra-aural temperature were measured on alternate days after arrival at the destination, at four different times of day (between the times 07:00 - 08:00 h, 12:00 - 13:00 h, 16:00 - 17:00 h and 19:00 - 20:00 h local time). In addition, for the first 6 - 7 days after arrival in Australia, subjective ratings of jet-lag on a 0 - 10 visual analogue scale and responses to a Jet-lag Questionnaire (incorporating items for tiredness. sleep, meal satisfaction and ability to concentrate) were recorded at the above times and also on retiring (at about midnight). Subjects continued normally with their work schedules between the data collection times. Subjects with complete data (13 melatonin and 13 placebo subjects), in comparison with published data, showed partial adjustment of the diurnal rhythm in intra-aural temperature after 6 days. A time-of-day effect was evident in both right and left grip strength during adjustment to Australian time; there was no difference between the group taking melatonin and that using the placebo. Right and left grip strength profiles on day 6 were adjusted either by advancing or delaying the profiles, independent of whether subjects were taking melatonin or placebo tablets. Subjects reported disturbances with most measures in the Jet-lag Questionnaire but, whereas poorer concentration and some negative effects upon sleep had disappeared after 3 - 5 days, ratings of jet-lag and tiredness had not returned to 'zero' (or normal values), respectively, by the sixth day of the study. Subjects taking melatonin showed no significant differences from the placebo group in perceived irritability, concentration, meal satisfaction, ease in getting to sleep and staying asleep, frequency of bowel motion and consistency of the faeces. These results suggest that, in subjects who, after arrival, followed a busy schedule which resulted in frequent and erratic exposure to daylight, melatonin had no benefit in alleviating jet-lag or the components of jet-lag, and it did not influence the process of phase adjustment.

Adult↗

Do subjective symptoms predict our perception of jet-lag?

A total of 39 subjects were studied after a flight from the UK to either Sydney or Brisbane (10 time-zones to the east). Subjects varied widely in their age, their athletic ability, whether or not they were taking melatonin, and in their objectives when in Australia. For the first 6 days after arrival, subjects scored their jet-lag five times per day and other subjective variables up to five times per day, using visual analogue scales. For jet-lag, the scale was labelled 0 = no jet-lag to 10 = very bad jet-lag; the extremes of the other scales were labelled - 5 and + 5, indicating marked changes compared with normal, and the centrepoint was labelled 0 indicating 'normal'. Mean daily values for jet-lag and fatigue were initially high (+ 3.65 +/- 0.35 and + 1.55 +/- 0.22 on day 1, respectively) and fell progressively on subsequent days, but were still raised significantly (p < 0.05) on day 5 (fatigue) or day 6 (jet-lag). In addition, times of waking were earlier on all days. By contrast, falls in concentration and motivation, and rises in irritability and nocturnal wakings, had recovered by day 4 or earlier, and bowel activity was less frequent, with harder stools, on days 1 and 2 only. Also, on day 1, there was a decrease in the ease of getting to sleep (- 1.33 +/- 0.55), but this changed to an increase from day 2 onwards (for example, + 0.75 +/- 0.25 on day 6). Stepwise regression analysis was used to investigate predictors of jet-lag. The severity of jet-lag at all the times that were measured was strongly predicted by fatigue ratings made at the same time. Its severity at 08:00 h was predicted by an earlier time of waking, by feeling less alert 30 min after waking and, marginally, by the number of waking episodes. Jet-lag at 12:00 and 16:00 h was strongly predicted by a fall of concentration at these times; jet-lag at mealtimes (12:00, 16:00 and 20:00 h) was predicted by the amount of feeling bloated. Such results complicate an exact interpretation that can be placed on an assessment of a global term such as jet-lag, particularly if the assessment is made only once per day.

Adult↗

Circadian rhythm of heart rate, urinary cortisol excretion, and sleep in civil air traffic controllers.

The examination of Air Traffic Controllers (ATCs) from the Warsaw Airport (Poland) included 24-hr ECG monitoring. The participants were 10 civil ATCs, 9 males and 1 woman. The study was carried out on a group of 19 ATCs during their duty periods, 14 of them working 12-hr shifts and 5 performing 24-hr duties. The participants collected urine every 4 hrs, and cortisol concentration was determined. Further, the survey included the quality and duration of sleep, and subjective fatigue in the 62 participants. In ATCs, shift work modifies natural rhythms of the circulatory system and decreases the ability for intensified mental work at night. In consequence ATCs experience frequent sleep disorders.

Adult↗

A comparison of the immediate effects of moderate exercise in the late morning and late afternoon on core temperature and cutaneous thermoregulatory mechanisms.

Twelve healthy male subjects each undertook two bouts of moderate exercise (70% VO2max for 30 minutes) in the morning (08:00) and late afternoon (18:00) at least 4 days apart. Measurements were made of heart rate, core (rectal) temperature, sternum skin temperature, and forearm skin blood flow during baseline conditions, during the bout of exercise, and throughout a 30-minute recovery period. Comparisons were made of the changes of heart rate, temperature, and skin blood flow produced by the exercise at the two times of day. Student t tests indicated that baseline values for core temperature (37.15 degrees C +/- 0.06 degrees C vs. 36.77 degrees C +/- 0.06 degrees C) and sternum temperature (33.60 degrees C +/- 0.29 degrees C vs. 32.70 degrees C + 0.38 degrees C) were significantly (p < .05) higher in the late afternoon than the early morning. Two-way analysis of variance (ANOVA) indicated that the increases in core and sternum temperatures during exercise were significantly less (p = .0039 and .0421, respectively) during the afternoon bout of exercise compared with the morning, even though the work loads, as determined by changes in heart rate, were not significantly different (p = .798) at the two times of testing. There were also tendencies for resting forearm skin blood flow to be higher in the afternoon than in the morning and for exercise to produce a more rapid rise in this variable in the afternoon. The possible mechanisms producing these responses to exercise are discussed in terms of those that are responsible for the normal circadian rhythm of core temperature. It is concluded that the body's ability to remove a heat load is less in the early morning, when the circadian system is in a "heat gain" mode, than in the late afternoon, when heat gain and "heat loss" modes are balanced more evenly.

Adult↗

A comparison of some different methods for purifying core temperature data from humans.

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.

Body Temperature↗

Some factors influencing the sensitivity of body temperature to activity in neonates.

In adult humans, core temperature is influenced by activity; the sensitivity of core temperature to such effects shows a phase dependence and is also influenced by the environment and whether the individual is asleep or awake. We have investigated if similar effects are evident in neonates, in whom thermoregulation and the circadian rhythm of core temperature are not fully developed. Eleven full-term, healthy babies were studied singly (light 07:00-19:00) at 2 days of age and again 4 weeks after birth; between these times, they were tended routinely on a communal ward. On study days, 10-minute recordings were made of rectal and skin (abdominal) temperature, heart rate (HR), and behavioral state. Sensitivities of the temperatures to activity ("arousal") were assessed throughout the 24h by measuring the gradient of (temperature/HR). Sensitivities measured at 01:00, 05:00, 09:00, 13:00, 17:00, and 21:00 were used as dependent variables in stepwise regression and linear regression analyses, with "subjects," "light versus dark," "behavioral state," and "difference between time of measurement and the acrophase of the endogenous component of the temperature rhythm" (ignoring sign) as possible predictors. (Acrophases of the temperature rhythms had been estimated from 24h data purified using the behavioral state record.) Light versus dark acted as a significant predictor of the sensitivity of rectal temperature to arousal on day 2 and week 4, the sensitivity increasing in the light, and there was limited evidence for behavioral state acting as a predictor on day 2. Neither factor was a significant predictor when the sensitivity of the babies' skin temperatures to arousal was investigated. There was also some evidence that the difference between the time of measurement and the temperature acrophase acted as a predictor of sensitivity to arousal in both rectal (day 2) and skin (week 4) temperature, with larger differences decreasing the sensitivity. These results indicate that there are masking effects on body temperature due to arousal in neonates, the size of which depends on both internal and external factors. However, this sensitivity of temperature to arousal shows differences from the sensitivity of temperature to physical activity in both adult humans and adult mice. One possible explanation of this result is that temperature regulation and the circadian system are not fully developed in humans at this age.

Adult↗

Diurnal variations in the mood and performance of highly practised young women living under strictly controlled conditions.

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.

Adult↗

Marked 24-h rest/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status.

The rest/activity circadian cycle has been used as a reference for chemotherapy administration at specific times to improve tolerability and efficacy. Because cancer processes may be associated with alterations of circadian rhythms, the rest/activity cycle was monitored noninvasively to assess its relationship with tumor response, survival, and quality of life in 200 patients with metastatic colorectal cancer. Patients wore an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days before receiving chronomodulated chemotherapy. The circadian rhythms in activity were estimated by two robust parameters: the autocorrelation coefficient at 24 h (r24), and the dichotomy index (I<O) for comparing amounts of activity when in bed and out of bed. Accurate data for inclusion, quality of life, response, and survival were available for 192 patients. Survival at 2 years was 5-fold higher (P = 10(-4)) in patients with marked activity rhythm (I<O in upper quartile) than in those with rhythm alteration (I<O in lower quartile). These results were supported by the multivariate Cox analysis. Multivariate regression analysis showed that circadian rhythms in activity (I<O; P = 3 x 10(-4)) and in WBCs (P = 0.03) as well as performance status (P = 0.02) were jointly prognostic of response. Patients with marked rest/activity rhythms also had better quality of life and reported significantly less fatigue. The individual rest/activity cycle provides a novel independent prognostic factor for cancer patients' survival and tumor response as well as a quantitative indicator for quality of life.

Adult↗

Daily activity and body temperature rhythms do not change simultaneously with age in laboratory mice.

Daily rhythms of locomotor activity (AR) and body temperature (TR) were investigated in juvenile, adult, and senile female laboratory mice (5, 16, or 65 weeks old). All daily patterns were bimodal, with a main maximum in the dark and a secondary one immediately following lights on. The juvenile mice showed the highest magnitude of oscillation of the AR but the lowest magnitude of the TR; the magnitudes of the TR of adult and senile animals were not different, whereas those of AR in senile mice approached zero. For the AR, but not the TR, a phase advance with age was observed. The effect of locomotor activity on the body temperature was higher during the light time (minimum of motor activity) than during the dark time (maximum activity), and was least in juvenile mice. The calculated daily temperatures corresponding to zero activity gave rhythms that showed no age-dependent differences in daily mean or magnitude. This implies that the age-dependent changes of the TR were due mainly to masking effects.

Aging↗