Joint NASA-ESA-DARA Study. Part three: circadian rhythms and activity-rest cycle under different CO2 concentrations.

BACKGROUND: During manned space missions, the actual concentration of carbon dioxide (CO2) is frequently elevated to a degree that may affect human functioning and productivity. Therefore, a ground-based international study was performed that tested various psychological and physiological functions under the condition of two different levels of CO2. Thus, a specific experiment aimed at the influence of enhanced CO2-concentrations on the sleep-wake cycle and the circadian system. METHODS: Four volunteers were subjected to a CO2 concentration of 0.7% and 1.2%, respectively, for 24 consecutive days under each condition. Before they were exposed to these elevated levels, baseline measurements were conducted during 5 d under ambient CO2 concentrations (<0.1%). Circadian parameters were assessed by continuous recording of body temperature and by the determination of excretion rates of cortisol, 6-hydroximelatoninsulfate and catecholamines at 3-h intervals during wake. These measurements were conducted on 3 consecutive days 4 times during the two campaigns. Nondominant wrist activity and subjective fatigue was monitored throughout both study phases. RESULTS: Daily means of activity showed significant differences between the two study conditions (with lower values during the 1.2% condition), but these differences only occurred during day-time, whereas during sleep activity levels remained the same. Diurnal mean and circadian amplitude of the temperature rhythm was also significantly lower during the 1.2% condition. CONCLUSIONS: The lower daily mean and circadian amplitudes of temperature during the higher CO2 level can be explained by lower physical activity that was monitored under this level, i.e., a masking effect. We hesitate to explain the lower activity (and hence temperature) as a response to the changed CO2 concentration. More probably, subjects became so acquainted with the procedures of the study protocol during the second study phase (1.2% CO2) that they did not need similar effort to conduct the tasks as during the first phase. The activity level during sleep which was the same during the two phases may support this conclusions. Thus, we conclude that CO2 levels up to 1.2% do not impair the circadian rhythm of healthy men.

Two-crew operations: stress and fatigue during long-haul night flights.

BACKGROUND: As part of a research program concerning legal aspects of two-pilot operations on long-haul routes, the purpose of the study was to investigate two-crew extended range operations during a flight roster with two consecutive night flights and a short layover. HYPOTHESIS: Present flight time regulations may not be adequate for two-crew minimum operations. METHODS: The study was conducted in cooperation with a German airline company on the route Frankfurt (FRA)-Mahe (SEZ). There were 11 rotations (22 flights) that were investigated by pre-, in- and post-flight data collection each time from the two pilots. Recordings included sleep, taskload, fatigue and stress by measurement of EEG, ECG, motor activity, and subjective ratings. The average actual flight times were 9:15 h (FRA-SEZ) and 9:53 h (SEZ-FRA). All flights took place at night. The layover duration in Mahe was 13:30 h during day-time. RESULTS: During layover, sleep was shortened by 2 h on average compared with 8-h baseline sleep. The two consecutive night duties resulted in a sleep loss of 9.3 h upon return to home base. Inflight ratings of taskload showed moderate grades, but for fatigue ratings an increasing level was observed. Fatigue was more pronounced during the return flight and several pilots scored their fatigue at a critical level. Motor activity, brainwave activity (occurrences of micro-events) and heart rate indicated drowsiness and a low state of vigilance and alertness during both night flights, but these effects were more pronounced during the second flight. CONCLUSIONS: From the findings it is concluded that a duty roster, as conducted in this study, may impose excessive demands on mental and physiological capacity.

Aircrew fatigue in long-haul operations.

The studies were conducted on the transmeridian routes Düsseldorf (DUS)-Atlanta (ATL) and Hamburg (HAM)-Los Angeles (LAX), and on the north-south route Frankfurt (FRA)-Mahe (SEZ). Scheduled flight duration was between 8:50 hours (ATL-DUS) and 11:50 hours (HAM-LAX). In total, 25 rotations (50 flights) have been investigated by pre-, in- and post-flight data collection of sleep, taskload, fatigue and stress by electroencephalogram and electrocardiogram measurements and subjective ratings. Inflight ratings of taskload showed low perceived exertion during the Atlantic flights, and were moderate during the north-south transitions. Fatigue ratings increased with progressing flight duration. Towards the end of long U.S.-westcoast flights performed at day-time, and in all night flights, fatigue was elevated compared to the 'baseline' ratings collected during the day-time DUS-ATL flights. Fatigue was rated as being 'critical' by several pilots, particularly during the return flight SEZ-FRA when fatigue was severely pronounced. From the findings it is concluded that duty schedules, as performed on the route HAM-LAX (because of long duty hours), and particularly on the route FRA-SEZ (because of consecutive night work), may place excessive demands on mental and physiological capacity. With respect to legal aspects, the results are significant and should promote further deliberations for advanced schemes of flight duty time limitations and rest requirements.

Eradication of penicillin-resistant pneumococci in the nasopharynx with antibiotic combinations including rifampicin: experiences from the South Swedish Pneumococcal Intervention Project.

39 children with prolonged nasopharyngeal carriage (48-328 days) of intermediately to highly penicillin-resistant pneumococci (PRP) were treated for 7 days with rifampicin in combination with amoxicillin (n = 18) erythromycin (n = 17) or clindamycin (n = 4), according to resistance pattern. In all children, except for 1 carrying a rifampicin-resistant strain, control cultures from the nasopharynx 1-2 weeks after the last antibiotic dosage, yielded no growth of PRP. In 2 brothers, PRP with the same serogroup and resistance pattern were found in nasopharynx 10 weeks after the antibiotic treatment. These preliminary findings indicate that antibiotic regimens including rifampicin are effective in eradicating nasopharyngeal carriage, but reappearance of the same strain may occur after several weeks. Such treatments should be given with caution due to the risk of selecting rifampicin-resistant strains. Further controlled studies are needed to determine the optimal combination of antibiotics and appropriate duration of therapy.

[Stress and fatigue in long distance 2-man cockpit crew]. / Stress und Ermüdung im Zwei-Mann-Cockpit auf Langstrecken.

Common rules on flight-duty times and rest requirements within the European Union are under intense discussion. In the deliberations, results from scientific investigations should be considered. As part of a research programme concerning legal aspects of two-pilot operations on long-haul routes, the purpose of the studies was to investigate two-crew extended range operations during transmeridian and transequatorial flight schedules. The studies were conducted with two German charter airlines on the transmeridian routes Düsseldorf (DUS)-Atlanta (ATL) and Hamburg (HAM)-Los Angeles (LAX), and on the north-south route Frankfurt (FRA)-Mahe (SEZ) including two consecutive night flights with a short layover. In total, 25 rotations (50 flights) have been investigated by pre-, in-, and post-flight data collection from the two pilots being the minimum required crew. Recordings included sleep, taskload, fatigue and stress by measurements of EEG, ECG, motor activity and subjective ratings. During the transmeridian schedules, pilots lost one night of sleep because of the return flights which were conducted at night. The resulting sleep deficit was 8.2 h. During the layover of the SEZ-rotation with a duration of 14 h on average, sleep was shortened by 2 h compared with baseline sleep. The two consecutive night flights resulted in a sleep loss of 9.3 h upon return to home base. Inflight ratings of taskload showed low levels during the atlantic flights, and moderate grades during the north-south transitions. Fatigue ratings exhibited an increasing level with progressing flight duration. Towards the end of long US-westcoast flights performed at day-time, and in all night flights, fatigue was enhanced compared to the "baseline" ratings collected during the DUS-ATL flights. Fatigue was scored at a critical level by several pilots, particularly during the return flight SEZ-FRA when fatigue was severely pronounced. The subjective fatigue ratings were confirmed by the objective measurements of motor activity, brain-wave activity (occurrences of micro-sleep) and heart rate which indicated drowsiness and a low state of vigilance and alertness during all night flights under study. From the findings it is concluded that duty schedules, as conducted on the route HAM-LAX (because of long duty hours), and particularly on the route FRA-SEZ, (because of consecutive night duties) are coming close to the limits of mental and physiological capacity. With respect to legal aspects, the results have significance and should promote further deliberations for advanced schemes of flight duty time limitations and rest requirements.

Jet lag and sleepiness in aircrew.

Jet-lag and day-time sleepiness cannot be avoided in transmeridian operations, because work hours of aircrews interfere with the circadian system through irregular work-rest schedules and rapid time-zone transitions. Although the primary cause of accidents is usually the human factor, jet lag and sleepiness have seldom been officially identified as causes of inadequate functioning in the cockpit. However, research clearly indicates that flights at night and/or across time zones will impair performance and reduce safety. Research on countermeasures have focused on on-board napping, crew augmentation, behavioural strategies against jet-lag, light treatment and melatonin administration. Regrettably, scientific knowledge has been successfully transmitted to only a very few national authorities responsible for work hours of aircrews.

Sleepiness of civil airline pilots during two consecutive night flights of extended duration.

Sleepiness of civil airline pilots was studied in a two-crew cockpit during two consecutive night flights of about 10 h duration each. Sleepiness was assessed by EEG recordings and subjective ratings during hourly recurrent short experimental phases. On the second night flight, the alertness component that is related to the preceding sleep showed a modification due to reduced quality and quantity of sleep between flights. The daytime sleep during layover was not sufficient to maintain the same alertness level as observed during the initial flight. This result is in coincidence with investigations in shift workers starting a period of night shifts. It is concluded that improvements such as the introduction of a nap schedule should be considered to alleviate spontaneous sleepiness in the cockpit.

Sleep and circadian rhythm during a short space mission.

An experiment was conducted to assess sleep and circadian regulation in an orbiting spacecraft. In orbit the weakened influence of 24-h zeitgebers could result in delayed circadian phases with the possibility of a transition to free-running circadian rhythms. This and the specific stressors of a space mission may lead to changes in ultradian sleep regulation and in reduced sleep quantity and quality. During the mission sleep was recorded polygraphically on tape, as was body temperature. Daytime alertness was rated subjectively by a mood questionnaire. For comparison the same parameters were measured during a baseline period preceding the space mission. The circadian rhythms of body temperature and alertness were found to be delayed in space compared to baseline. This may mark a phase shift or the transition to a circadian state of free-run. Sleep was shorter and more disturbed. The structure of sleep was significantly altered. In space REM latency was shorter, there was less REM sleep in the second non-REM/REM cycle, and slow-wave sleep was redistributed from the first to the second cycle. The self-assessed mood resembled sleep disturbances and adaptation to the space environment. Reduced sleep quality and quantity are likely to result in fatigue and lower daytime performance. Countermeasures should be adopted to improve sleep of astronauts.

Pre-adaptation to shiftwork in space.

Astronauts are often required to work in shift schedules. To test pre-mission adaptation strategies and effects on the circadian system, a study was performed using microgravity simulation by head-down bedrest. Eight male subjects were studied over 4 control days, and 7 days each for pre-mission adaptation, bedrest, and readjustment. The circadian system was assessed by monitoring ECG and temperature, and by collecting urine for determination of hormones and electrolytes. Rhythms did not achieve complete adjustment within the adaptation period when the sleep-wake cycle was shortened by 1 h/day, but resynchronization continued during bedrest. After the bedrest period when the time shift was reversed by a 7-h delay within 2 days, resynchronization was achieved satisfactorily only within 7 days. From the results it is concluded that a sleep-wake cycle advance as used in this study is insufficient to keep the circadian system in pace. Under operational conditions the circadian system of astronauts may become longer and more destabilized than under controlled laboratory conditions.

Response of the circadian system to 6 degrees head-down tilt bed rest.

The influence of simulated microgravity and reduced zeitgebers on the circadian system was examined in eight subjects. The 12-d study included a 3-d period for baseline measurements, 7 d of 6 degrees head-down bed rest, and 2 d for recovery. The sleep-wake cycle was kept constant during the study. The state of the circadian system was assessed from continuous measurements of temperature and ECG, and collections of urine at 3-h intervals for the determination of hormone and electrolyte excretions. Results indicate that only minor changes occurred in rhythm acrophases, whereas daily means for several physiological functions and their circadian amplitudes were significantly altered during the bed-rest phase. These studies using head-down tilt confirm previous findings with horizontal bed rest and indicate that rhythm disturbances can occur without change in the sleep-wake cycle. To the degree that bed-rest studies simulate manned spaceflights, results indicate that variations in circadian cycles can occur even during short-term missions and must be taken into account when interpreting subsequently obtained physiological data.

Influence of melatonin treatment on human circadian rhythmicity before and after a simulated 9-hr time shift.

The hormone melatonin is currently proposed by some investigators to be an efficient means for decreasing the impairing effects of jet lag. Eight healthy male subjects, aged 20 to 32, underwent a 9-hr advance shift in the isolation facility of our institute during two periods each of 15 days' duration. In a double-blind, crossover design, subjects took either melatonin or placebo at 1800 hr local time for 3 days before the time shift and at 1400 hr for 4 days afterwards. The time shift was simulated on days 7 and 8 by shortening the sleep period by 6 hr and the following wake period by 3 hr. Body temperature was recorded every 90 min, and urine was collected at 3-hr intervals all day and night. Melatonin treatment enhanced the resynchronization speed of some, but not all, hormone and electrolyte excretion rates for several days after the time shift. The adaptation speed of the temperature rhythm significantly increased during one postshift day. In addition, the circadian temperature rhythm had a significantly higher amplitude under melatonin treatment than under placebo after the time displacement. For the placebo group, the rhythm of 6-hydroxymelatoninsulfate excretion exhibited an advance shift in five subjects, whereas the other three showed a delay shift, and adjustment did not achieve more than one-half of the expected value within 8 days. A significantly different adjustment could be observed in the melatonin-treated group: Seven subjects underwent an advance shift of the expected 9 hr within an average of 8 days. The results suggest that melatonin treatment can accelerate resynchronization of the melatonin excretion rhythm after eastward time zone transitions. The improvement is not, however, sufficiently great that we can recommend melatonin for the alleviation of jet lag.

Sleep, sleepiness, and circadian rhythmicity in aircrews operating on transatlantic routes.

This study was performed on B-747 aircrews operating on regular passenger flights between Frankfurt and the U.S. west coast (9 h time difference). In an initial phase, sleep behavior was surveyed by daily logs in 38 crewmembers. The results for the layover period indicate congruent sleep patterns with shifts in sleep onset distinctly less than 9 h. In comparison with preflight control data, sleep duration was significantly prolonged and, on average, no sleep deficits were experienced before commencing the return flight. The main part of the study consisted of polygraphic sleep recordings and multiple sleep latency tests (MSLT) applied to four complete cockpit crews (12 members total) in a baseline period, during layover, and after return to homebase. In addition, body temperature and ECG were continuously recorded. During layover, mean bed times were shifted by 4.5 h at maximum. Sleep was disturbed by early and prolonged awakenings which led to a reduction of sleep efficiency. In contrast, no sleep deficits nor increases in daytime sleepiness occurred. Night duty associated with the return flight caused sleep deprivation which conversely resulted in good sleep during the first night back in Germany. However, during the second night after return, impaired sleep was observed, at least in part caused by the rhythm disturbances. As predicted by our resynchronization model, ECG and rectal temperature recordings gave evidence for a desynchronization of the circadian system and an internal dissociation of different body functions.

Discordant bone maturation of the hand in children with precocious puberty and congenital adrenal hyperplasia.

Difference between the bone maturation scores for the tubal and carpal bones of the hand and wrist were assessed by the method of Tanner et al. on X-rays from 10 children with precocious puberty and 10 children with late-diagnosed congenital adrenal hyperplasia, and compared with results in 20 normal children. Scores for the tubular bones were significantly more advanced than those for the carpal bones in both groups of patients, emphasizing the need for caution when using standards derived from normal children to assess bone age in children with markedly accelerated bone maturation.