Neuronal circadian clock protein oscillations are similar in behaviourally rhythmic forager honeybees and in arrhythmic nurses.

Internal clocks driving rhythms of about a day (circadian) are ubiquitous in animals, allowing them to anticipate environmental changes. Genetic or environmental disturbances to circadian clocks or the rhythms they produce are commonly associated with illness, compromised performance or reduced survival. Nevertheless, some animals including Arctic mammals, open sea fish and social insects such as honeybees are active around-the-clock with no apparent ill effects. The mechanisms allowing this remarkable natural plasticity are unknown. We generated and validated a new and specific antibody against the clock protein PERIOD of the honeybee Apis mellifera (amPER) and used it to characterize the circadian network in the honeybee brain. We found many similarities to Drosophila melanogaster and other insects, suggesting common anatomical organization principles in the insect clock that have not been appreciated before. Time course analyses revealed strong daily oscillations in amPER levels in foragers, which show circadian rhythms, and also in nurses that do not, although the latter have attenuated oscillations in brain mRNA clock gene levels. The oscillations in nurses show that activity can be uncoupled from the circadian network and support the hypothesis that a ticking circadian clock is essential even in around-the-clock active animals in a constant physical environment.

The influence of various graphical and numeric trend display formats on the detection of simulated changes.

Integration of a large amount of information is important in anaesthesia but there is little research to guide the development of data displays. Anaesthetists from two hospitals participated in five related screen based simulation studies comparing various formats for display of historical or 'trend' data. Participants were asked to indicate when they first noticed a change in each displayed variable. Accuracy and latency (i.e. delay) in detection of changes were recorded. Latency was shorter with a graphic display of historical data than with a numeric display. Increasing number of variables or reduction of y-axis height increased the latency of detection. If the same number of data points were included, there was no difference between graphical and numerical displays of historical data. There was no difference in accuracy between graphical or numerical displays. These results suggest that the way trend data is presented can influence the speed of detection of changes.

The impact of trained assistance on error rates in anaesthesia: a simulation-based randomised controlled trial.

Trained assistance for the anaesthetist appears likely to improve safety in anaesthesia. However, there are few objective data to support this assumption, and the requirement for a trained assistant is not universally enforced. We applied a simulation-based model developed in previous work to test the hypothesis that the presence of a trained assistant reduces error in anaesthesia. Ten randomly selected anaesthetists, five trained anaesthetic technicians and five theatre nurses without training in anaesthesia participated in two simulated emergencies, with anaesthetists working alternately with a technician or a nurse. The mean (SD) error rate per scenario was 4.75 (2.9). There were significantly fewer errors in the technician group than the nurse group (33 vs 62, p = 0.01) and this difference remained significant when errors were weighted for severity. This provides objective evidence supporting the requirement for trained assistance to the anaesthetist, and furthermore, demonstrates that a simulation-based model can provide rigorous evidence on safety interventions in anaesthesia.

A simulation design for research evaluating safety innovations in anaesthesia*.

SUMMARY: It is notoriously difficult to obtain evidence from clinical randomised controlled trials for safety innovations in healthcare. We have developed a research design using simulation for the evaluation of safety initiatives in anaesthesia. We used a standard and a modified scenario in a human-patient simulator, involving a potentially life-threatening problem requiring prompt attention--either a cardiac arrest or a failure in oxygen supply. The modified scenarios involved distractions such as loud music, a demanding and uncooperative surgeon, telephone calls and frequent questions from a medical student. Twenty anaesthetics were administered by 10 anaesthetists. A mean (SD) of 11.3 (2.8) errors per anaesthetic were identified in the oxygen failure scenarios, compared with 8.0 (3.4) in the cardiac arrest scenarios (ANOVA: p = 0.04). The difference between the combined standard scenarios and the combined modified scenarios was not significant. The mean rate of errors overall was 9.7 per simulation, with a pooled SD of 4.46, so in future studies 21 subjects would provide 80% statistical power to show a reduction in error rate of 30% from baseline with p

The effect of time of day on the duration of neuromuscular blockade elicited by rocuronium.

In a prospective, observational trial, we investigated the influence of time of day on the duration of neuromuscular blockade (NMB) elicited by rocuronium. Forty-nine patients scheduled for surgery between 08:00 and 02:00 were enrolled after giving written informed consent. Time to neuromuscular recovery was measured following three doses: (1) a fat-free-mass (FFM) related induction dose (0.6 mg x kg(-1): n = 47); (2) a maintenance dose (20% of the induction dose: n = 42); and (3) a standard 10-mg dose (n = 35). The extent of NMB was dependent on the time of administration (p = 0.038 General Linear Model Analysis). The maximum effect of 50 min (95% CI 41-59 min) was elicited between 08:00 and 11:00 and the minimum duration of 29 min (95% CI 23-35 min) between 14:00 and 17:00 (p = 0.005). A similar pattern was observed for the maintenance dose. The duration of action of rocuronium is influenced by time of day and this effect is of potential clinical significance and practical relevance to research.

Anaphylaxis with associated fibrinolysis, reversed with tranexamic acid and demonstrated by thrombelastography.

In the surgical setting, fibrinolysis can be a serious complication of anaphylaxis. We present four cases of anaphylaxis that were associated with fibrinolysis during anaesthesia, and the use of the thrombelastograph to demonstrate this haemostatic defect and its correction using tranexamic acid.

Circadian neuroendocrine physiology and electromagnetic field studies: precautions and complexities.

The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis'. has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock.

Acute exposure to circularly polarized 50-Hz magnetic fields of 200-300 microT does not affect the pattern of melatonin secretion in young men.

Environmental exposure to time-varying (alternating current) magnetic fields (MFs) produced by electrical current flow is a perceived public health risk. Several epidemiological studies report correlations between MF exposure and carcinogenesis. It has been hypothesized that MF-induced suppression of melatonin could provide the mechanism by which this effect is mediated. Here, we describe results from a controlled laboratory-based study designed to detect changes in human melatonin secretion after a 2-h exposure to 200-300 microTesla, 50 Hz circularly polarized MF. Exposure was timed to occur before or during the nightly melatonin rise, and levels administered were some 4-6 times higher than the commonly encountered maximum levels. Results from 19 male subjects aged between 18 and 35 yr indicate that acute exposure to 50 Hz MFs of this nature does not result in significant suppression, alteration of peak levels, or a change in timing of the nighttime melatonin rise. We conclude that acute exposure to 50 Hz MFs does not have a significant effect on the normal nighttime production of melatonin in young men.

Circularly polarised MF (500 micro T 50 Hz) does not acutely suppress melatonin secretion from cultured Wistar rat pineal glands.

Magnetic fields (MF, 50 Hz) have been proposed to affect melatonin production in mammals; however, there is very little data about the mechanism by which this possible interaction may occur. Here we describe results from the first study in which circularly polarised 50 Hz MF have been administered to isolated pineals in highly controlled conditions. Melatonin release from isolated Wistar rat pineal glands, dissected 2 h after light onset ZT 2, was measured in a flow through culture system, during and after exposure to a 4 h MF similar in nature and magnitude to that produced in extremely close proximity to a high voltage power line (500 micro T 50 Hz circularly polarised). Melatonin release from isolated pineals was comparable to that observed in previous studies, plateauing to approximately 100 pg/ml/30 min. No significant alterations in pineal melatonin release were caused by exposure to the MF when compared to sham exposure (< 1 micro T). These results suggest that if the circadian system is acutely responsive to MF exposure of this nature, an intact circadian axis may be necessary in order to observe an effect on the production on melatonin from the pineal gland

Analysis of the circadian clock gene period in the sheep blow fly Lucilia cuprina.

We have isolated a homologue of the period (per) gene from the Australian sheep blow fly, Lucilia cuprina, as part of a comparative approach to the analysis of dipteran circadian systems. Sequence analysis of the 4 kb per cDNA revealed the conservation of three functional domains, namely the PAS dimerization motif, and the nuclear and cytoplasmic localization domains. A fourth domain, the threonine-glycine (TG) repeat region, is also conserved in L. cuprina per but has been severely truncated. No length variation was found in the TG repeat of L. cuprina or L. sericata collected from several different latitudinal zones. Expression analysis indicated a diel oscillation in per mRNA in LD 12:12 with a period of 24 h and a peak at Zt 12. PER-immunoreactive protein oscillations were also demonstrated, with peak immunoreactivity lagging approximately 3 h behind peak mRNA levels. These results show the existence of a Drosophila-like circadian system in a calliphorid fly. They also provide evidence for the conservation of per function across the Diptera, and confirm the relevance of the Drosophila system as a model for fly circadian rhythms.

Description of the photoperiodic control of larval burrowing in the blowfly Lucilia cuprina: a novel index for photoperiodic research.

The photoperiodic control of larval burrowing depth in the Australian sheep blowfly Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) was investigated by measuring burrowing depth under controlled laboratory photoperiods. The results demonstrated that larvae exposed to long photoperiods (LD 18 : 6) burrowed to deeper depths than those in shorter photoperiods (LD 12 : 12), and that this behavior was induced during the third instar stage. The ecological significance of this behavior is discussed, as are the ways in which daylength is measured and depth assessed. The use of burrowing depth could prove to be a novel index of a photoperiodic response and provide a far simpler approach to the study of photoperiodism in certain insect species.