Investigating the relative effects of sleep deprivation and time of day on fatigue and performance

Time of day and the time since last sleep are acknowledged causes of fatigue, but comparatively little is known about how they interact. This study examines the relative effects of time of day and sleep deprivation on fatigue and performance. Two independent groups were exposed to 28 h of sleep deprivation beginning at 06:00 h for one group (n = 39) and at 00:00 h for the other (n = 22). By varying the start time for the two groups, but keeping constant the duration of sleep deprivation, the effects of variations in the time of day of testing could be examined. For the 06:00 h start group the longest period without sleep occurred close to the low point of the circadian rhythm. For the 00:00 h start group the circadian low point coincided with only two to six hours of sleep deprivation. Performance was evaluated two-hourly using eight computer-based tests and subjective fatigue ratings. The results showed a clear interaction effect. Both time of day and sleep deprivation affected performance but only in combination; neither had independent effects. These findings have implications for fatigue management.     

Natural polysaccharides platforms for oral controlled release of ketoprofen lysine salt

Context: Ketoprofen lysinate (KL) is one of the most widely used non-steroidal anti-inflammatory drugs in the symptomatic treatment of some chronic inflammatory diseases. Compared to ketoprofen, KL shows better pharmacokinetics and tolerability. However, due to its short half-life of 1–2?h, a multiple dose regimen is required for oral administration. Thus, the present work deals with its encapsulation in a hydrogel-based system by prilling in order to prolong its activity.

Objective: In this paper, we propose alginate and pectin as carriers and release tailoring agent for the development of hydrogel-based beads for KL retarded and sustained release.

Materials and methods: Beads were produced by a Nisco Encapsulator® using alginate or pectin. Operative variables were optimized to produce beads with desired morphology and size. Solid state properties were analyzed by SEM and DSC. Drug release performance was studied by Pharmacopeia pH-change assay to simulate gastrointestinal environment.

Results and discussion: Prilling technique was successfully used to encapsulate high soluble drugs as KL in polysaccharides-based hydrogels. Pectin proved to be a proper polymer able to encapsulate ketoprofen lysine salt. Formulation (F8) showed good morphological properties and size, high drug content (15.6%) and encapsulation efficiency (93.5%) and promising drug release profiles. Hosting F8 in an acid-resistant capsule (DR^®caps) a delivery platform has been developed to control KL release in a delayed (90?min lag time) and prolonged way (270?min complete release).

Conclusion: The platform may be proposed as potentially useful in the oral administration of NSAIDs in chronic inflammatory diseases affected by circadian rhythm.     

慢波和异相睡眠生理功能与人类工效的探讨

文章通过回顾近年来对睡眠成份ＳＷＳ和ＲＥＭＳ的研究资料，认为ＳＷＳ和ＲＥＭＳ节律在人的一生睡眠中的不同时期除了本身的生理需要外，还可通过现在已知的外界人控因素加以改变，这些因素对ＳＷＳ和ＲＥＭＳ节律的调节具有预防、治疗疾病和提高人类工效的作用。文章着重讨论和介绍了身心健康和不健康的个体如何增加或减少ＳＷＳ和ＲＥＭＳ的多种简单、实用的方法。     

睡眠剥夺对警觉能力的影响

为探讨不同睡眠剥夺（sleep deprivation，SD）时间对于警觉性的影响，将24名正常青年男性分为SD21h组、SD45h组、SD69h组，每组8名，主要应用三个字母（C、G、N）的划销测验来测查不同SD条件下的警觉能力。测试时间分别为每天的7：00、10：00、13：00、16：00、19：00、22：00、l：00、4：00，采用组间比较和自身前后比较。结果：sD后，完成时间、总击中数、假阳性数和倒数第二分钟击中数表现出成绩显著下降，并同SD时间有关；完成时间和总击中数表现出生物节律的作用；倒数第二分钟击中数同SD相关系数最高，为非常好地评定警觉性的指标。结论：SD后警觉水平下降，并且同SD时间长短有关；SD时，字母划销测验是非常好的测查警觉性的测验。     

The distribution of sleepiness,sleep and work hours during a long distance morning trip: A comparison between night- and non-night workers

Few studies have examined the extent of driver sleepiness during a long distance morning trip. Sleepiness at this time may be high because of night work, waking early to commence work or travel, sleep disorders and the monotony of driving long distances. The objective of this study was to estimate the prevalence of chronic sleepiness (Epworth sleepiness score ≥ 10) and sleep restriction (≤5 h) in a sample of 649 drivers. Participants driving between 08:00 and 10:00 on three highways in regional Australia participated in a telephone interview. Approximately 18% of drivers reported chronic sleepiness. The proportions of night workers (NW) and non-night workers (NNW) with chronic sleepiness were not significantly different but males reported a significantly greater proportion of chronic sleepiness than females. The NW group had a significantly greater proportion of drivers with ≤5 h of sleep in the previous 24 and 48 h, fewer nights of full sleep (≤4), acute sleepiness and longer weekly work hours. The NW group reported driving a significantly longer distance at Time 1 (Mean = 140.29 ± 72.17 km, versus 117.55 ± 89.74 km) and an additional longer distance to complete the journey (Mean = 89.33 ± 95.23 km, versus 64.77 ± 94.07 km). The high proportions of sleep restriction and acute sleepiness among the NW group, and the amount of chronic sleepiness in the NW and NNW groups reported during a long distance morning trip may be of concern for driver safety.     

Diurnal variation in subsidiary reaction time in a long-term driving task

Traffic accidents show a marked diurnal rhythm, which is a seldom investigated phenomenon. One possible background factor examined in the present study is the biological circadian rhythm. Eight subjects drove for 3 hr, beginning at 0300, 0900, 1500 and 2100. During each session a subsidiary reaction time task was used as an indirect measure of driving performance. Critical confounding factors, such as lighting conditions, traffic intensity, amount of sleep preceding the session and temperature in the car were considered. The results showed that there were small differences in the level of performance among the four sessions. However, differences in the rate of performance deterioration were not observed. From these results it was concluded that biological rhythm as a single variable has only a minor influence on this type of performance. Consequently the diurnal rhythm of traffic accidents must be attributed to other factors such as long hours of driving and/or sleep deprivation which culminate during the morning hours.     

An exploration of the utility of mathematical modeling predicting fatigue from sleep/wake history and circadian phase applied in accident analysis and prevention: the crash of Comair Flight 5191

On 27 August 2006 at 0606 eastern daylight time (EDT) at Bluegrass Airport in Lexington, KY (LEX), the flight crew of Comair Flight 5191 inadvertently attempted to take off from a general aviation runway too short for their aircraft. The aircraft crashed killing 49 of the 50 people on board. To better understand this accident and to aid in preventing similar accidents, we applied mathematical modeling predicting fatigue-related degradation in performance for the Air Traffic Controller on-duty at the time of the crash. To provide the necessary input to the model, we attempted to estimate circadian phase and sleep/wake histories for the Captain, First Officer, and Air Traffic Controller. We were able to estimate with confidence the circadian phase for each. We were able to estimate with confidence the sleep/wake history for the Air Traffic Controller, but unable to do this for the Captain and First Officer. Using the sleep/wake history estimates for the Air Traffic Controller as input, the mathematical modeling predicted moderate fatigue-related performance degradation at the time of the crash. This prediction was supported by the presence of what appeared to be fatigue-related behaviors in the Air Traffic Controller during the 30 min prior to and in the minutes after the crash. Our modeling results do not definitively establish fatigue in the Air Traffic Controller as a cause of the accident, rather they suggest that had he been less fatigued he might have detected Comair Flight 5191's lining up on the wrong runway. We were not able to perform a similar analysis for the Captain and First Officer because we were not able to estimate with confidence their sleep/wake histories. Our estimates of sleep/wake history and circadian rhythm phase for the Air Traffic Controller might generalize to other air traffic controllers and to flight crew operating in the early morning hours at LEX. Relative to other times of day, the modeling results suggest an elevated risk of fatigue-related error, incident, or accident in the early morning due to truncated sleep from the early start and adverse circadian phase from the time of day. This in turn suggests that fatigue mitigation targeted to early morning starts might reduce fatigue risk. In summary, this study suggests that mathematical models predicting performance from sleep/wake history and circadian phase are (1) useful in retrospective accident analysis provided reliable sleep/wake histories are available for the accident personnel and, (2) useful in prospective fatigue-risk identification, mitigation, and accident prevention.     

An in vitro and in vivo investigation into the suitability of compression coated tablets of indomethacin for the treatment of rheumatoid arthritis which follow circadian rhythms

Objective: The aim of this study was to develop chronotherapeutic drug delivery system of indomethacin using polyethylene oxide (PEO) with a predetermined lag time of 6 h by compression coating technique.

Materials and methods: Solid dispersions (SD) of indomethacin were prepared using novel carrier sucrose fatty acid ester (SFE 1815) to increase the in vitro dissolution. The optimized SD was formulated as immediate release core tablet which were further coated with PEO (WSR Coagulant or WSR N12 K) using compression coating technique. Compression coated tablets formulated with PEO WSR Coagulant in 1:1.7 ratio of core tablet weight and coating polymer was considered as optimized formulation, which was further characterized by differential scanning calorimetry, X-ray diffractometry, Fourier transformed infrared spectroscopy, and scanning electron microscopy.

Results: The results indicated that there was no chemical incompatibility and slight change in surface properties. C_max, area under the curve (AUC_0-t), and T_max following oral ingestion of commercial capsule (Indocap) and optimized formulation (CT 4) were found to be 1973.18 ± 36.89 ng/mL, 11090.09 ± 131.21 ng/mL/h, 0.99 ± 0.02 h and 2115.46 ±6 2.61, 10413.14 ± 299.66 ng/mL/h, 7.00±0.02 h, respectively.

Conclusion: Unaltered AUC_0-t and C_max, but delayed T_max indicated clear lag time before immediate release of drug which is suitable for treating rheumatoid arthritis following circadian rhythm.     

Developing measures of fatigue using an alcohol comparison to validate the effects of fatigue on performance

The effects of 28 h of sleep deprivation were compared with varying doses of alcohol up to 0.1% blood alcohol concentration (BAC) in the same subjects. The study was conducted in the laboratory. Twenty long-haul truck drivers and 19 people not employed as professional drivers acted as subjects. Tests were selected that were likely to be affected by fatigue, including simple reaction time, unstable tracking, dual task, Mackworth clock vigilance test, symbol digit coding, visual search, sequential spatial memory and logical reasoning. While performance effects were seen due to alcohol for all tests, sleep deprivation affected performance on most tests, but had no effect on performance on the visual search and logical reasoning tests. Some tests showed evidence of a circadian rhythm effect on performance, in particular, simple reaction time, dual task, Mackworth clock vigilance, and symbol digit coding, but only for response speed and not response accuracy. Drivers were slower but more accurate than controls on the symbol digit test, suggesting that they took a more conservative approach to performance of this test. This study demonstrated which tests are most sensitive to sleep deprivation and fatigue. The study therefore has established a set of tests that can be used in evaluations of fatigue and fatigue countermeasures.     

Preparation of polymer-blended quinine nanocomposite particles by spray drying and assessment of their instrumental bitterness-masking effect using a taste sensor

Abstract

Context: The development of taste-masking technologies for foods and drugs is essential because it would enable people to consume and receive healthy and therapeutic effect without distress.

Objective: In the current study, in order to develop a novel method to prepare nanocomposite particles (microparticles containing bitter nanoparticles) in only one step, by using spray drying, a two-solution mixing nozzle-equipped spray dryer that we previously reported was used. The nanocomposite particles with or without poorly water-soluble polymers prepared using our spray-drying technique were characterized.

Methods: (1) The organic solution containing quinine, a model of bitter compound and poorly water-soluble polymers and (2) sugar alcohol (mannitol) aqueous solution were separately flown in tubes and two solutions were spray dried through two-solution type spray nozzle to prepare polymer-blended quinine nanocomposite particles. Mean diameters of nanoparticles, taste-masking effect and dissolution rate of quinine were evaluated.

Results: The results of taste masking by taste sensor suggested that the polymer (Eudragit EPO, Eudragit S100 or Ethyl cellulose)-blended quinine nanocomposite particles exhibited marked masking of instrumental quinine bitterness compared with the quinine nanocomposite particles alone. Quinine nanocomposite formulations altered the quinine dissolution rate, indicating that they can control intestinal absorption of quinine.

Conclusion: These results suggest that polymer-blended quinine composite particles prepared using our spray-drying technique are useful for masking bitter tastes in the field of food and pharmaceutical industry.     

Cognitive components of simulated driving performance: Sleep loss effects and predictors

Driving is a complex task, which can be broken down into specific cognitive processes. In order to determine which components contribute to drowsy driving impairments, the current study examined simulated driving and neurocognitive performance after one night of sleep deprivation. Nineteen professional drivers (age 45.3 ± 9.1) underwent two experimental sessions in randomised order: one after normal sleep and one after 27 h total sleep deprivation. A simulated driving task (AusEd), the psychomotor vigilance test (PVT), and neurocognitive tasks selected from the Cognitive Drug Research computerised neurocognitive assessment battery (simple and choice RT, Stroop Task, Digit Symbol Substitution Task, and Digit Vigilance Task) were administered at 10:00 h in both sessions. Mixed-effects ANOVAs were performed to examine the effect of sleep deprivation versus normal sleep on performance measures. To determine if any neurocognitive tests predicted driving performance (lane position variability, speed variability, braking RT), neurocognitive measures that were significantly affected by sleep deprivation were then added as a covariate to the ANOVAs for driving performance. Simulated driving performance and neurocognitive measures of vigilance and reaction time were impaired after sleep deprivation (p < 0.05), whereas tasks examining processing speed and executive functioning were not significantly affected by sleep loss. PVT performance significantly predicted specific aspects of simulated driving performance. Thus, psychomotor vigilance impairment may be a key cognitive component of driving impairment when sleep deprived. The generalisability of this finding to real-world driving remains to be investigated.     

An assessment of the relevance of laboratory and motorcycling tests for investigating time of day and sleep deprivation influences on motorcycling performance

The aim of this study was to assess time of day and sleep deprivation impacts on motorcycling performance taking into consideration key variables, such as reaction time, motor coordination and vigilance that are principally involved in a riding task. Eight subjects participated in different tests sessions planned at 06:00 and 18:00h after a normal night's sleep and after a night of total sleep deprivation. During each session all subjects completed "laboratory" and "motorcycling" tests that were designed to assess each of the variables tested. As classically observed in sport performance, motorcycling performance demonstrates a time of day fluctuation by increasing from 06:00 to 18:00h during the day after a normal night's sleep. For each variable tested, the effects of sleep deprivation depend on the design of the test conditions. Thus, the data collected in laboratory specific conditions are more affected than those noted in arranged motorcycling situations. Taking into account that the sample size used in this study was limited, which may limit the results interpretations, these discrepancies suggest that during complex tasks, compensation mechanisms may be set up between different resources so as to maintain a good level of performance.     

The transfer of TEM00 and TEM01 beams through a hard-aperture

Abstract

We determine the far-field divergence angle θ ₀₀ (θ ₀₁) resulting from the diffraction of a TEM₀₀ (TEM₀₁) beam incident on a circular aperture. It is demonstrated that, with a suitable choice of the aperture radius, the ratio θ ₀₁/θ ₀₀ is enhanced to about 2, while its value is 1.64 without the aperturing effect. It is shown that this effect allows high discrimination between TEM₀₀ and TEM₀₁ modes either in the case of a spatial filter or in the case of an apertured resonator.     

Effects of an afternoon nap on nighttime alertness and performance in long-haul drivers

The effects of an afternoon nap on alertness and psychomotor performance were assessed during a simulated night shift. After a night of partial sleep restriction, eight professional long-haul drivers either slept (nap condition) or engaged in sedentary activities (no-nap condition) from 14:00 to 17:00 h. Alertness and performance testing sessions were conducted at 12:00 (pre-nap baseline), 24:00, 02:30, 05:00 and 07:30 h, and followed 2-h runs in a driving simulator. In the nap condition, the subjects showed lower subjective sleepiness and fatigue, as measured by visual analog scales, and faster reaction times and less variability on psychomotor performance tasks. Electrophysiological indices of arousal during the driving runs also reflected the beneficial effects of the afternoon nap, with lower spectral activity in the theta (4–7.75 Hz), alpha (8–11.75 Hz) and fast theta-slow alpha (6–9.75 Hz) frequency bands of the electroencephalogram, indicating higher arousal levels. Thus, a 3-h napping opportunity ending at 17:00 h improved significantly several indices of alertness and performance measured 7–14 h later.     

Synchronisation mechanisms of circadian rhythms in the suprachiasmatic nucleus

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is considered as the master circadian pacemaker. Each cell in the SCN contains an autonomous molecular clock, and the SCN is composed of multiple single-cell circadian oscillators. The fundamental question is how the individual cellular oscillators, expressing a wide range of periods, interact and assemble to create an integrated pacemaker that can govern behavioural and physiological rhythmicity and be reset by environmental light. The key is that the heterogeneous network formed by the cellular clocks within the SCN must synchronise to maintain timekeeping activity. To study the synchronisation mechanisms and the circadian rhythm generation, we propose a model based on the structural and functional heterogeneity of the SCN. The model is a heterogeneous network of circadian oscillators in which individual oscillators are self-sustained. The authors show that the dorsomedial region can smooth the periodic light?dark (LD) signal curve and affect its wave form. The authors also study the rhythmic process of the circadian oscillators under the effect of the daily LD cycle, including three courses: information afferent inputs, oscillation and information efferent outputs. The numerical simulations are also given to demonstrate the theoretical results.     

Nanoethosomal formulation of gammaoryzanol for skin-aging protection and wrinkle improvement: a histopathological study

Background: Free radical scavengers and antioxidants, with the main focus on enhanced targeting to the skin layers, can provide protection against skin ageing.

Objective: The aim of the present study was to prepare nanoethosomal formulation of gammaoryzanol (GO), a water insoluble antioxidant, for its dermal delivery to prevent skin aging.

Methods: Nanoethosomal formulation was prepared by a modified ethanol injection method and characterized by using laser light scattering, scanning electronic microscope (SEM) and X-ray diffraction (XRD) techniques. The effects of formulation parameters on nanoparticle size, encapsulation efficiency percent (EE%) and loading capacity percent (LC%) were investigated. Antioxidant activity of GO-loaded formulation was investigated in vitro using normal African green monkey kidney fibroblast cells (Vero). The effect of control and GO-loaded nanoethosomal formulation on superoxide dismutase (SOD) and malondialdehyde (MDA) content of rat skin was also probed. Furthermore, the effect of GO-loaded nanoethosomes on skin wrinkle improvement was studied by dermoscopic and histological examination on healthy humans and UV-irradiated rats, respectively.

Results: The optimized nanoethosomal formulation showed promising characteristics including narrow size distribution 0.17?±?0.02, mean diameter of 98.9?±?0.05?nm, EE% of 97.12?±?3.62%, LC% of 13.87?±?1.36% and zeta potential value of –15.1?±?0.9?mV. The XRD results confirmed uniform drug dispersion in the nanoethosomes structure. In vitro and in vivo antioxidant studies confirmed the superior antioxidant effect of GO-loaded nanoethosomal formulation compared with control groups (blank nanoethosomes and GO suspension).

Conclusions: Nanoethosomes was a promising carrier for dermal delivery of GO and consequently had superior anti-aging effect.     

Wakefulness in young and elderly subjects driving at night in a car simulator

Young drivers are over-represented in nighttime traffic accidents and several studies have suggested that many accidents are associated with elevated sleepiness levels. It has been suggested that there may be a connection between lowered wake capacity and functional sensory motor skills on the one hand and sleep deprivation at the circadian low in young drivers on the other.Performance during a 45/min evening and night drive among young (n = 10, age range 18–24 years) and elderly (n = 10, age range 55–64 years) subjects was studied using a moving base driving simulator. EEG was measured continuously. Every 5 min, subjects were rated on the Karolinska Sleepiness Scale (KSS). Saliva cortisol was assessed before and after each drive.The results showed that sleepiness increased across each drive and was higher among young drivers at night. Relative EEG power increased among older drivers for frequencies of 10–16 Hz. The sigma 1 frequency band (12–14 Hz) proved particularly sensitive to sustained driving, and was elevated among subjects in the elderly group. Cortisol levels before and after the evening and night drive showed higher mean levels for elderly subjects.The present study has demonstrated that young drivers were more sleepy while driving at night. The effects could represent a mobilization of effort and a reorganization of brain firing pattern among older subjects, possibly reflecting better ability and effort to resist sleepiness.     

Differential effects of COVID-19 lockdowns on well-being: interaction between age,gender and chronotype

The unprecedented restrictions imposed due to the COVID-19 pandemic altered our daily habits and severely affected our well-being and physiology. The effect of these changes is yet to be fully understood. Here, we analysed highly detailed data on 169 participants for two to six months, before and during the second COVID-19 lockdown in Israel. We extracted 12 well-being indicators from sensory data of smartwatches and from self-reported questionnaires, filled daily using a designated mobile application. We found that, in general, lockdowns resulted in significant changes in mood, sleep duration, sport duration, social encounters, resting heart rate and number of steps. Examining subpopulations, we found that younger participants (aged 20–40 years) suffered from a greater decline in mood and number of steps than older participants (aged 60–80 years). Likewise, women suffered from a higher increase in stress and reduction in social encounters than men. Younger early chronotypes did not increase their sleep duration and exhibited the highest drop in mood. Our findings underscore that while lockdowns severely impacted our well-being and physiology in general, greater damage has been identified in certain subpopulations. Accordingly, special attention should be given to younger people, who are usually not in the focus of social support, and to women.     

Sir Alan Cottrell: an appreciation

Abstract

The effect of iron additions in the range 5–15 wt-%Fe inclusive on the microstructure and properties of a Ni–Cr–Mo–Si wear resistant alloy (Tribaloy T7 00) has been investigated. Iron additions were found to stabilise the hexagonal type structure of the Laves phase and to decrease the volume fraction of the primary Laves phase. These microstructural modifications reduced the hardness, slightly improved the toughness, and significantly enhanced the strength of the as cast alloys. Unlike T700, the alloys containing iron were not stable when heat treated at 700°C, and an increase in hardness was observed. The mechanical properties of T700 have been compared with those of the cobalt base Tribaloy alloys (T400 and T8 00).

MST/1936