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Biomedical subjects

I Macdonald

Publications and source records attributed to I Macdonald.

At least 19 recordsLinked to original sources

Rest breaks and accident risk.

Regular rest breaks are recommended to prevent accumulation of accident risk during sustained activities. We examined the effect of rest breaks on temporal trends in industrial accident risk, by assessment of accident records from a large engineering company, obtained over 3 years. In 2 h of continuous work, relative risk of an accident in the last half-hour of a shift was 2.08 (95% CI 1.73-2.43) higher than in the first half-hour. Trends in risk did not seem to differ between three 2-h work periods. Regular rest breaks seem to be an effective way to control accumulation of risk during industrial shift-work.

Accidents, Occupational↗

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↗

Mechanical valve thrombosis during pregnancy.

Mechanical valve thrombosis is a life-threatening event, and prevention with meticulous anticoagulation is crucial. Pregnancy is associated with a hypercoagulable state that further emphasizes the importance of adequate anticoagulation. A case of mechanical mitral valve thrombosis in a pregnant woman due to suboptimal anticoagulation is presented. Methods of anticoagulation, as well as thrombolytic and surgical therapies, are discussed.

Adult↗

A method for the preparation of highly purified adeno-associated virus using affinity column chromatography, protease digestion and solvent extraction.

Recombinant adeno-associated virus (AAV) is becoming the vector of choice for many gene therapy protocols. There has been much recent progress made toward increasing AAV titres but a continuing problem in using AAV has been that it is relatively difficult to concentrate and purify. Traditional methods, such as caesium chloride (CsCl) gradients, have drawbacks, notably extended purification times and the ability to process only limited volumes. Where the target cells of interest require a high multiplicity of infection (MOI), or to complete in vivo experiments, there is a requirement for both the production of high titre and a large volume of virus. This is laborious to obtain using traditional methods. A simple technique is described here for purifying AAV, involving affinity chromatography, protease digestion and solvent extraction that retains both the high yields and titres obtained using CsCl gradients. In addition, this technique displays a fast throughput and may be used to purify AAV from larger volumes than CsCl gradients. The high yield and purity of these virus preparations has allowed us to achieve good levels of expression in the target cell types tested. The purification technique described here will be applicable to any protocol that requires high titre, high purity recombinant AAV (rAAV).

Blotting, Western↗

The sympathetic nervous system and obesity: role in aetiology and treatment.

The sympathetic nervous system (SNS) is an important component of the autonomic nervous system, and thus plays a major role in the maintenance of homeostasis. The SNS is of particular importance in the control of the cardiovascular system and of a number of metabolic processes. Alterations in SNS effects on metabolism have been implicated in the development and maintenance of obesity, and the SNS is a potential therapeutic target in the treatment of obesity. This review provides an overview of the anatomical and physiological aspects of the SNS, before considering the evidence showing a role for the SNS in the development or treatment of obesity.

Basal Metabolism↗

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↗

Effects of direction of rotation in continuous and discontinuous 8 hour shift systems.

OBJECTIVES: Previous research has produced conflicting evidence on the relative merits of advancing and delaying shift systems. The current study assessed the effects of the direction of shift rotation within 8 hour systems, upon a range of measures including sleep, on shift alertness, physical health, and psychological wellbeing. METHODS: An abridged version of the standard shiftwork index which included retrospective alertness ratings was completed by four groups of industrial shiftworkers on relatively rapidly rotating 8 hour systems (n=611). Two groups worked continuous systems that were either advancing or delaying; the other two groups worked discontinuous systems that were either advancing or delaying. RESULTS: Few effects were found of direction of rotation on chronic measures of health and wellbeing, even when the systems incorporated "quick returns" (a break of only 8 hours when changing from one shift to another). This was despite the use of measures previously shown to be sensitive to the effects of a broad range of features of shift systems. However, advancing continuous systems seemed to be associated with marginally steeper declines in alertness across the shift (F (3,1080)=2.87, p<0.05). They were also associated with shorter sleeps between morning shifts (F (1,404)=4.01, p<0.05), but longer sleeps between afternoons (F (1,424)=4.16, p<0.05). CONCLUSIONS: The absence of negative effects of advancing shifts upon the chronic outcome measures accorded with previous evidence that advancing shifts may not be as harmful as early research indicated. However, this interpretation is tempered by the possibility that difficult shift systems self select those workers most able to cope with their deleterious effects. The presence of quick returns in advancing continuous systems seemed to impact upon some of the acute measures such as duration of sleep, although the associated effects on alertness seemed to be marginal.

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↗

A process model of shiftwork and health.

The authors developed and tested a process model of adaptation to shiftwork, which hypothesizes that various individual and situational variables influence the development of sleep and social and domestic disturbances. Both types of disturbances trigger various types of coping behavior, leading to several proximal outcomes. The end result is the development of chronic health problems in the form of digestive and cardiovascular symptoms. The model was tested with survey data collected from 2 samples of nurses (N = 1,532) in the United Kingdom and was cross-validated against a 3rd sample of industrial workers (N = 370). Results indicate support for the model across the 3 samples, although some sample-specific and subgroup effects were found. Results have direct implications for the development of shiftwork theory and interventions.

Adaptation, Psychological↗

Distribution of rest days in 12 hour shift systems: impacts on health, wellbeing, and on shift alertness.

OBJECTIVES: To investigate of the effects of distribution of rest days in 12 hour shift systems. Although several studies have examined the effects of compressing work schedules by comparing 8 and 12 hour shift systems, there is little published research examining the various forms of 12 hour shift system. METHODS: An abridged version of the standard shiftwork index which included retrospective alertness ratings was completed by a large sample of industrial shiftworkers. The respondents worked 12 hour shift systems that either did or did not incorporate breaks of > 24 hours between the blocks of day and night shifts. For the purposes of the analysis, each of these two groups were further subdivided into those who started their morning shift at 0600 and those who started at 0700. RESULTS: Systems which incorporated rest days between the day and night shifts were associated with slightly higher levels of on shift alertness, slightly lower levels of chronic fatigue, along with longer sleep durations when working night shifts and between rest days. Early changeovers were associated with shorter night sleeps between successive day shifts, but longer and less disturbed day sleeps between night shifts. These effects of changeover time were broadly in agreement with previous research findings. CONCLUSIONS: The distribution of rest days in 12 hour shift systems had only limited effects on the outcome measures, although the few modest differences that were found favoured systems which incorporated rest days between the day and night shifts. It is conceded that the design of the study may have obscured some subtle differences between the shift systems. Nevertheless, it is concluded that the impact of distribution of rest days seems to be minor relative to previously found effects of other features of shift systems--for example, shift duration.

Adult↗

Beyond the three-process model of alertness: estimating phase, time on shift, and successive night effects.

This paper starts by summarizing the development and refinement of the additive three-process model of alertness first published by Folkard and Akerstedt in 1987. It reviews some of the successes that have been achieved by the model in not only predicting variations in subjective alertness on abnormal sleep-wake schedules but also in accounting for objective measures of sleep latency and duration. Nevertheless, predictions derived from the model concerning alertness on different shifts, and over successive night shifts, are difficult to reconcile with published data on accident risk. In light of this, we have examined two large sets of alertness ratings with a view to further refining the model and identifying additional factors that may influence alertness at any given point in time. Our results indicate that, at least for the range of sleep durations and wake-up times commonly found on rotating shift systems, we may assume the phase of the endogenous circadian component of alertness (process C) to be "set" by the time of waking. Such an assumption considerably enhanced the predictive power of the model and yielded remarkably similar phase estimates to those obtained by maximizing the post-hoc fit of the model. We then examined the manner in which obtained ratings differed from predicted values over a complete 8-day cycle of two, 12-h shift systems. This revealed a pronounced "first night compensation effect" that resulted in shift workers rating themselves as progressively more alert than would be predicted over the course of the first night shift. However, this appeared to be achieved only at the cost of lowered ratings on the second night shift. Finally, we were able to identify a "time on shift" effect whereby, with the exception of the first night shift, alertness ratings decreased over the course of each shift before showing a modest "end effect." We conclude that the identification of these additional components offers the possibility that in the future we may be able to predict trends in accident risk on abnormal sleep-wake schedules.

Animals↗

Lack of evidence that feedback from lifestyle alters the amplitude of the circadian pacemaker in humans.

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

Activity Cycles↗

The effect of activity on the waking temperature rhythm in humans.

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

Adolescent↗

Light of domestic intensity produces phase shifts of the circadian oscillator in humans.

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

Adult↗

Industrial shift systems.

This technical report describes the identification of shift systems worked by industrial shiftworkers in England, Scotland and Wales. A diverse range of shift systems were reported to be in operation across 27 industrial sectors. Companies employed up to 14 different shift systems at a particular site. The numbers of shiftworkers on a given shift schedule ranged from 1 to 2977. Most systems employed fewer than 100 people. The majority of rotas were regular, rotating systems. The most common shift durations were 8 or 12 h. Compared to earlier surveys of shiftwork prevalence in certain industries there appeared to be a substantial increase over the past 3 decades in the proportion of the workforce who work shifts. Information about the average numbers of hours worked per week on major system types is given. In addition, data for the range of shifts per cycle, the distribution of shifts and distributions of their start and end times are presented.

Humans↗

The impact of early and late shift changeovers on sleep, health, and well-being in 8- and 12-hour shift systems.

The effects on industrial shift workers of the timing of the changeover from the night to morning shift and of the length of the shift were examined. Two groups changed over at 6 a.m. and worked either 8-hr or 12-hr shift systems; the other 2 groups changed over at 7 a.m., working either 8- or 12-hr systems. Night sleeps between consecutive shifts that started at 6 a.m. were shorter and more disrupted than those starting at 7 a.m. Day sleeps following night shifts that finished at 6 a.m. were longer and less disrupted than those finishing at 7 a.m. Early starts were associated with poorer psychological and physical health. These effects of changeover time are considered in relation to the circadian rhythms in sleep duration and propensity. Although several measures favored 12-hr shifts, physical health indicators appeared to favor 8-hr systems, especially in combination with late changeovers. However, the observed effects of shift length on chronic outcome measures are somewhat inconsistent with previous research findings.

Adaptation, Psychological↗

Work shift duration: a review comparing eight hour and 12 hour shift systems.

OBJECTIVES: Shiftwork is now a major feature of working life across a broad range of industries. The features of the shift systems operated can impact on the wellbeing, performance, and sleep of shiftworkers. This paper reviews the current state of knowledge on one major characteristic of shift rotas-namely, shift duration. Evidence comparing the relative effects of eight hour and 12 hour shifts on fatigue and job performance, safety, sleep, and physical and psychological health are considered. At the organisational level, factors such as the mode of system implementation, attitudes towards shift rotas, sickness absence and turnover, overtime, and moonlighting are discussed. METHODS: Manual and electronic searches of the shiftwork research literature were conducted to obtain information on comparisons between eight hour and 12 hour shifts. RESULTS: The research findings are largely equivocal. The bulk of the evidence suggests few differences between eight and 12 hour shifts in the way they affect people. There may even be advantages to 12 hour shifts in terms of lower stress levels, better physical and psychological wellbeing, improved durations and quality of off duty sleep as well as improvements in family relations. On the negative side, the main concerns are fatigue and safety. It is noted that a 12 hour shift does not equate with being active for only 12 hours. CONCLUSIONS: There can be considerable extension of the person's time awake either side of the shift. However, the effects of longer term exposure to extended work days have been relatively uncharted in any systematic way. Longitudinal comparative research into the chronic impact of the compressed working week is needed.

Absenteeism↗