Modulation of rapid eye movement sleep in humans by drugs that modify monoaminergic and purinergic transmission.

Modulation of rapid eye movement (REM) sleep is a well-established effect of many centrally acting drugs. However, there is uncertainty concerning the nature of the changes and their significance, and it is in this context that we have analyzed the effects of several groups of drugs that alter monoaminergic or purinergic transmission on sleep in humans. The analysis shows that drugs that modulate noradrenergic and serotonergic transmission lead to marked suppression of REM sleep, irrespective of any increase or decrease in sleep duration. There is no evidence that the timing of the ultradian cycle of REM sleep relative to sleep onset is altered by these drugs. On the other hand, reduced REM sleep with dopamimetic drugs is due solely to increased wakefulness. However, there can be more subtle effects of some drugs on REM sleep. Benzodiazepine receptor agonists and drugs that modify purinergic transmission modulate the appearance of early REM activity. There may, therefore, be two discrete systems that control entry into REM sleep, and that are responsive to drugs. The exact appearance and timing of REM periods may be modulated by a feedback mechanism involving GABAergic, or possibly purinergic, transmission, while monoaminergic and cholinergic influences exert a reciprocal and overriding control of REM sleep.

Rapid eye movement sleep in man: modulation by benzodiazepines.

The modulation of rapid eye movement REM sleep in man by benzodiazepines has been analysed using 366 sleep recordings with at least 3 REM periods, obtained in 25 individuals, over 9 years. Sleep-dependent and sleep-independent mechanisms are believed to control REM activity, and the effect of benzodiazepines can be explained if the sleep-dependent influence is modified. It is suggested that a negative feedback mechanism, which usually encourages the appearance of REM periods, is depressed, while a threshold and oscillator which determine the cyclical appearance of the activity, and its relation with the onset of sleep, are unaffected.

Modulation of delta activity by hypnotics in middle-aged subjects: studies with a benzodiazepine (flurazepam) and a cyclopyrrolone (zopiclone).

Period crossing analysis was used to study the effects of flurazepam (30 mg) and zopiclone (5, 7.5, and 10 mg) on delta wave activity (0.5-2.0 Hz) during the first 4 h of sleep in middle-aged subjects. The drugs do not affect the visual scoring of slow wave sleep in middle age, but modification of delta activity does occur. Mean amplitude of delta wave activity over the 4-h period was reduced by both drugs, while the total number of delta waves and their mean period increased. The number of high-amplitude delta waves (greater than 60 microV) was decreased by the drugs, and those of low amplitude (10-60 microV) increased. Power in the frequency band 1.2-2.0 Hz was reduced.

Sub-cutaneous fat thickness measured by magnetic resonance imaging, ultrasound, and calipers.

Sub-cutaneous fat thickness was measured at 12 sites on the body surface of 24 males and 26 females using magnetic resonance imaging (MRI), skinfold calipers, and A-mode ultrasound. The mean of the 12 fat thickness measurements and individual site thicknesses were compared between individuals using analysis of variance. In males, the mean thicknesses for ultrasound and calipers were similar (P greater than 0.05) but both were less than the MRI (P less than 0.001). MRI and ultrasound were similar in females but less than calipers (P less than 0.001). A good between-subject correlation was found between all three methods in the males but only the calipers and MRI were well correlated in females. Within-subject correlations are poor for all measures and in both sexes. Factor loadings for a varimax rotation of two principal components indicate that the fat is distributed in 1 of 2 patterns: either principally on the trunk or on the limbs. The principal component analysis and the result of canonical correlations obtained from the factor loadings confirm the findings of the analysis of variance, in that a general level of fatness is measurable by all three methods over a range of subjects. However, the pattern of fat thicknesses measured over a number of specific sites by one method of measurement is unlikely to be duplicated by either of the other two methods on the same individual.

HUMEX, a study on the survivability and adaptation of humans to long-duration exploratory missions, part I: lunar missions.

The European Space Agency has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis has been laid on human health and performance care as well as advanced life support developments including bioregenerative life support systems and environmental monitoring. The overall study goals were as follows: (i) to define reference scenarios for a European participation in human exploration and to estimate their influence on the life sciences and life support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of advanced life support developments and to propose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as testbeds in preparation for human exploratory missions and to develop a test plan for ground and space campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. This paper covers the part of the HUMEX study dealing with lunar missions. A lunar base at the south pole where long-time sunlight and potential water ice deposits could be assumed was selected as the Moon reference scenario. The impact on human health, performance and well being has been investigated from the view point of the effects of microgravity (during space travel), reduced gravity (on the Moon) and abrupt gravity changes (during launch and landing), of the effects of cosmic radiation including solar particle events, of psychological issues as well as general health care. Countermeasures as well as necessary research using ground-based test beds and/or the International Space Station have been defined. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnostic systems become essential. Finally, a European strategy leading to a potential European participation in future human exploratory missions has been recommended.

Determining aircrew helmet size design requirements using statistical analysis of anthropometric data.

Traditionally, the number of aircrew helmet size rolls has been determined using head length and breadth for specified percentile ranges of a target population. Helmet mounted display technology will require taking the third dimension (pupil-vertex height) into account. Using data from "An Anthropometric Survey of 2000 Royal Air Force Aircrew, 1970/1971," the three head dimensions of length, breadth, and pupil-vertex height were plotted for each subject. A minimum number of helmet sizes was calculated to achieve a reasonable quality of fit. The 93.5% of subjects grouped around the population mean was the largest fraction which had a reasonable quality of fit while using nine sizes. Attempts to fit a larger percentage would require either a large increase in the number of sizes or a relaxing of fitting quality.

Operational characteristics of liquid-conditioned suits.

The data from several studies of liquid-conditioned suits carried out over the last 12 years at the RAF Institute of Aviation Medicine have been collated, collectively reanalysed, and used to describe the characteristics of personal liquid-conditioning systems in terms of interactions between the conditioning and the conditioned system. Heat exchange across a liquid-conditioned suit (LCS) is shown to be proportional to the inlet temperature (Tin) of the conditioning liquid. Choice of Tin is determined, for resting subjects, primarily by the environmental temperature, by the length of the heat exchange tubing, and by the insulation value of the clothing worn over the LCS. Mean skin temperature (Tsk), but not core temperature (Tc) is directly related to Tin. However, certainly in exercising subjects, steady-state values for Tc can be increased by selecting very low values for Tin, which reduce Tsk below 29 degrees C. It is suggested that mean Tsk should not fall below 30 degrees C when the LCS is used for personal cooling. When the LCS is used for personal heating, sweating should be minimised, or prevented, by not allowing Tsk to rise to levels sufficient to cause an increase in Tc.

Core temperature measurement in man.

Transient changes in core temperature were induced in 12 subjects--passively by immersion in a hot bath, and actively by light intermittent exercise. Measurements of core temperature were made at four sites--the auditory canal, mouth, rectum, and oesophagus--and, by using the measurements from the first three of these sites, a mathematical model was derived which permits the calculation of a predicted value for oesophageal temperature (Toe). This model--which takes the general form Toe = ATx + BdTx/dt + C where Tx = amplitude of the temperature change at a specific site, dTx/dt = rate of change of temperature at that site, and A, B, and C = site constants (different for passive and active heating)--provides an accurate prediction of Toe (to within 0.1 degrees C) from both auditory canal and mouth temperature. For prediction of Toe from rectal temperature, however, two models appear to be necessary--one to predict Toe when core temperature is rising, and another to predict Toe during the return to equilibrium when core temperature is declining.

Prediction of body temperatures during exercise in flying clothing.

A mathematical model has been used to describe experimental results for core and skin temperatures in subjects undergoing a rest/activity cycle in two aircrew clothing assemblies at two environmental temperatures (wet bulb, globe temperature (WBGT) indices of 25.9 and 28.9 degrees C). The model presented compares well with published data for subjects in standard aircrew equipment assemblies. Aircrew flying at a WBGT of 28.9 degrees C in chemical defence clothing may reach an unacceptable level of mean body temperature within 40 min and deep body temperature will rise at 1 degree C.hr-1. To prevent deterioration in flying performance during repeated sorties, an alteration in the work/rest activity pattern or the introduction of effective cabin or personal conditioning systems may be required,

Effect of cockpit temperature gradients on the validity of single-point measurements.

Dry bulb temperature was measured at six sites throughout seven sorties in F4E aircraft in a study of vertical and lateral cockpit temperature gradients designed to determine the validity of single-point measurements. The results show that both vertical and lateral gradients exist in F4E aircraft and that single-point measurements of Tdb close to the right shoulder show a bias of up to 4 degrees C in relation to mean cockpit dry bulb temperature derived from measurements at five sites. This bias may be removed by using the predictive relationships developed in this study. The relationship between black globe and dry bulb temperatures is also given for F4E aircraft flown in warm, sunny conditions.

Duration of activity and mode of action of modafinil: Studies on sleep and wakefulness in humans.

The duration of activity of modafinil was investigated in healthy male volunteers in two double-blind crossover studies. Mode of action was explored using a statistical model concerned with the relationship between total sleep duration and that of rapid eye movement (REM) sleep. Nocturnal sleep (23:00-07:00) followed by next-day performance (09:00-17:00) was studied in 12 subjects administered 100, 200, 300 mg modafinil and placebo, 0.5 h before bedtime. Performance overnight (19:00-08:45) followed by sleep (09:15-15:15) was studied in nine subjects administered 100, 200, 300, 400 mg modafinil, 300 mg caffeine and placebo at 22:15. Modafinil dose-dependently reduced sleep duration (nocturnal: 200 mg, p<0.05; 300 mg, p<0.001; morning: 300 and 400 mg, p<0.05) and REM sleep (nocturnal: 300 mg; morning: 400 mg; p<0.05). The statistical model revealed that reduced REM sleep was due to alerting activity, with no evidence of direct suppression of REM sleep, suggesting dopaminergic activity. Enhanced performance with modafinil during overnight work varied with dose (200 mg>100 mg; 300, 400 mg>200, 100 mg, caffeine). However, in the study of next-day performance, the enhancement was attenuated at the highest dose (300 mg) by the greater disturbance of prior sleep. These findings indicate that modafinil has a long duration of action, with alerting properties arising predominantly from dopaminergic activity.

Development of physical selection procedures for the British Army. Phase 2: relationship between physical performance tests and criterion tasks.

This paper is the second in a series of three to describe the development of physical selection standards for the British Army. The first paper defined criterion tasks (single lift, carry, repetitive lift and carry, and loaded march tasks) and set standards on the criterion tasks for all British Army trades. The principal objective was to determine which combination of physical performance tests could be best used to predict criterion task performance. Secondary objectives included developing so-called 'gender-free' and 'gender-unbiased' models. The objectives were met by analysing performance data on the criterion tasks and a large battery of physical performance tests collected from 379 trained soldiers (mean age 23.5 (SD 4.45) years, stature 1734 (SD 79.5) mm, body mass 71.4 (SD 10.58) kg). Objective 1 was met: the most predictive physical performance tests were identified for all criterion tasks. Both single lift tasks were successfully modelled using muscle strength and fat free mass scores. The carry model incorporated muscle endurance and body size data, but the errors of prediction were large. The repetitive lift models included measures of muscle strength and endurance, and body size, but errors of prediction were also large. The loaded march tasks were successfully modelled incorporating indices of aerobic fitness, supplemented by measures of strength, endurance or body size and composition. The secondary objectives were partially fulfilled, though limitations in the data hampered the process. Although only one model (a loaded march) was gender-free, three models were gender-related (i.e. contained 'gender' explicitly in the model). The remaining six were gender-specific (i.e. were appropriate for men or for women). Owing to both a lower accuracy of prediction in women's scores and a greater tendency for the women's scores to be distributed around the pass standards, a greater percentage of women than men were misclassified as passing or failing, resulting in indirect discrimination. A validation of the models in a separate sample of the user population of recruits is reported in the third paper in this series.

Changes in electrical activity of the brain with vigilance.

The relationship between EEG and vigilance was studied in subjects performing tasks of differing complexity over a 15 h period by examining the structural changes of the EEG as vigilance deteriorates. Calculation of canonical variates indicated that two directions explained the changes in vigilance, though one direction was dominant across subjects and tasks, and likely to reflect decreased arousal. The second direction indicated some evidence for a second underlying change in the EEG related to vigilance in some subjects particularly in the more complex task, and this would reflect mechanisms other than drowsiness. The relationship between EEG and vigilance was modelled by fitting a linear function of EEG variables to the proportion of missed responses. The coefficient of multiple correlation was significant for most subjects, and the relationship is likely to represent changes in arousal. The most useful discriminator of worsening vigilance common to both tasks was beta activity (14-21 Hz).

Prediction of oesophageal temperatures from core temperatures measured at other sites in man.

Transient changes in core temperature were induced in seven subjects by immersion in a hot, then a cold, bath and by light intermittent exercise. Measurements of core temperature were made at four sites: the external auditory canal, the oesophagus, the rectum and the gastrointestinal tract. A mathematical model was derived to enable prediction of oesophageal temperature from measurements made at any one of the other sites. The equations for auditory canal and rectal temperatures were very similar to those previously derived in the Institute of Aviation Medicine; use of an equation to predict oesophageal temperatures from gastrointestinal tract temperatures measured in the field using a radio-pill would therefore appear to be reasonable.

Large color differences and the geometry of Munsell color space.

Multidimensional scaling of subjective similarity estimates for colors varying extensively in Munsell hue, value, and chroma produced a configuration that concurred with the postulated organization of Munsell color space, and indicated step-size relationship between attributes. Implications for the determination of color difference are discussed.

Effects of pemoline on spontaneous and event-related electrical activity of the brain.

The effect of pemoline on the electrical activity of the brain (electroencephalogram, EEG) was studied in relation to time since sleep and time of day in 6 healthy subjects carrying out periods of work lasting 18 h. Power of the spontaneous EEG increased with time since sleep and amplitude of the P3 event-related response decreased. The changes may be interpreted as the reduction in alertness with time awake. In contrast, pemoline decreased power of the spontaneous EEG and increased the amplitude the P3 response, effects that are consistent with improved alertness. The changes in brain activity were paralleled by effects on performance, in terms of percentage of correct responses and reaction time. Performance decreased with time awake, and was improved by pemoline compared with placebo. The drug counteracted the adverse effects of time since sleep, with the beneficial effect of the drug persisting over the 18-hour period of work. The findings emphasise that spontaneous and event-related activity of the EEG may be used both to complement measures of performance in the laboratory and to assess behaviour in occupational situations where performance testing is impractical.