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The circadian clock regulates multiple aspects of human physiology including immunity. People have a circadian preference termed chronotype. Those with an evening preference may be better suited to shift work, but also carry higher risk of adverse health. Shift work leads to misalignment of circadian rhythms and is associated with increased risk of inflammatory disease such as asthma and cancer. Here, we investigate the association between chronotype, shift work, and rheumatoid arthritis (RA). The associations between exposures of shift work and chronotype on risk of RA were studied in up to 444,210 U.K. Biobank participants. Multivariable logistic regression models were adjusted for covariates: age, sex, ethnicity, alcohol intake, smoking history, Townsend Deprivation Index (TDI), sleep duration, length of working week, and body mass index (BMI). After adjusting for covariates, individuals with a morning chronotype had lower odds of having rheumatoid arthritis (RA; odds ratio [OR]: 0.93, 95% confidence interval [CI]: 0.88-0.99) when compared to intermediate chronotypes. The association between morning chronotype and RA persisted with a more stringent RA case definition (covariate-adjusted OR: 0.89, 95% CI: 0.81-0.97). When adjusted for age, sex, ethnicity, and TDI, shift workers had higher odds of RA (OR: 1.22, 95% CI: 1.1-1.36) compared to day workers that attenuated to the null after further covariate adjustment (OR: 1.1, 95% CI: 0.98-1.22). Morning chronotypes working permanent night shifts had significantly higher odds of RA compared to day workers (OR: 1.89, 95% CI: 1.19-2.99). These data point to a role for circadian rhythms in RA pathogenesis. Further studies are required to determine the mechanisms underlying this association and understand the potential impact of shift work on chronic inflammatory disease and its mediating factors. [ABSTRACT FROM AUTHOR]

Many chronic disease symptomatologies involve desynchronized sleep-wake cycles, indicative of disrupted biorhythms. This can be interrogated using body temperature rhythms, which have circadian as well as sleep-wake behavior/environmental evoked components. Here, we investigated the association of wrist temperature amplitudes with a future onset of disease in the UK Biobank one year after actigraphy. Among 425 disease conditions (range n = 200-6728) compared to controls (range n = 62,107-91,134), a total of 73 (17%) disease phenotypes were significantly associated with decreased amplitudes of wrist temperature (Benjamini-Hochberg FDR q < 0.05) and 26 (6.1%) PheCODEs passed a more stringent significance level (Bonferroni-correction α < 0.05). A two-standard deviation (1.8° Celsius) lower wrist temperature amplitude corresponded to hazard ratios of 1.91 (1.58-2.31 95% CI) for NAFLD, 1.69 (1.53-1.88) for type 2 diabetes, 1.25 (1.14-1.37) for renal failure, 1.23 (1.17-1.3) for hypertension, and 1.22 (1.11-1.33) for pneumonia (phenome-wide atlas available at http://bioinf.itmat.upenn.edu/biorhythm%5fatlas/). This work suggests peripheral thermoregulation as a digital biomarker. Many chronic diseases present with desynchronized sleep-wake cycles, indicative of disrupted biorhythms. Here, the authors propose peripheral thermoregulation as a digital biomarker based on the association between lower temperature rhythms measured from wearable activity trackers with future onset of disease, such as type 2 diabetes, non-alcoholic fatty liver disease, hypertension and pneumonia. [ABSTRACT FROM AUTHOR]

A number of studies suggest that pilots are at twice the risk of melanoma and keratinocyte skin cancers than the general population, and that they have a raised mortality from melanoma. No conclusive links with in-flight exposure to ionising radiationor circadian rhythm disruption due to the pilots' shift work were found. Possible over-exposure to ultraviolet radiation (UVR) may be implicated as pilots may be exposed to higher UV-A levels at cruise altitude compared with those at ground levels. The direct method of making in-flight spectral measurements has been carried out on a limited number of flights, but this technique is challenging; the use of small wearable sensors may be more appropriate but there are a few issues that should be addressed for their use in cockpit measurements. While the spectral response of sensors for erythema effective values usually closely matches the corresponding weighting function, the response of UV-A sensors may not be spectrally flat, which, if not corrected to account for the transmission of the aircraft windshield, could potentially result in large errors. In this paper, the spectral correction method was applied to the UV-A sensor of the Genesis-UV unit to measure UVR exposure of commercial pilots on 312 flights to a range of destinations from four UK airports from September 2016 to August 2017. [ABSTRACT FROM AUTHOR]

The optical radiation safety of various seasonal affective disorder (SAD) treatment lamps, sunrise simulators and daylight bulbs available on the UK market have been assessed using recognised guidelines. An analysis is included of the photometry of circadian entrainment by bright light therapy, with a justification for a melanopsin-based action spectrum for treatment efficacy. Parameters relating to both efficacy and phototoxicity risk, which are potentially relevant to bright light therapy treatment regimes, are considered. Unpredictable variations are highlighted which lead to the conclusion that several relevant photometric variables of treatment lamps need to be characterised to predict efficacy and potential hazards. [ABSTRACT FROM AUTHOR]

Shift work causes disruption to circadian physiological processes in the human body, and desynchronization from the natural day-and-night rhythm. Circadian disruption is thought to explain the associations between shift work and various long-term diseases; light is an unrivalled synchronizer (or Zeitgeber) of circadian processes and inappropriate light exposure plausibly plays a critical role in the development of health impairments. As published measurement data on the actual light environments encountered by shift workers are sparse, nurses working in two hospitals in London (UK) and Dortmund (Germany) wore light-logging dosimetry devices to measure personal light exposures continuously over a week in three different seasons. The study identifies and quantifies several of the characteristics of light exposure related to different working patterns in winter, spring, and summer, and quantifies interindividual variations. These data enable informed design of light exposure interventions or changes to shifts to reduce unwanted effects of disruptive light exposure profiles. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a global pandemic. Measures to reduce transmission of the virus have altered usual activities, routines, and livelihoods, and have had a significant impact on mental health. The current study aims to examine the potential alterations in psychological wellbeing, mental health, sleep and diurnal preference due to the COVID-19 pandemic. A cross sectional online questionnaire-based study with n = 200 participants (aged 18–62; 7.86.0% female, 93.0% white, 92.5% UK-based, 73.5% students). Data were collected between 15th April and 8 June 2020. Participants answered questions on lifestyle changes and their concerns and worries about COVID-19, and completed the SCI, PHQ9, GAD7, PWB18, UCLA3 and MEQ. Results showed self-isolation was linked to lower psychological well-being, and increased loneliness, anxiety and depression. Home-working was related to a shift in diurnal preference. Reduced work/income was related to decreased psychological well-being and sleep quality and increased anxiety, depression, loneliness and. Intensity of worried thoughts and concerns about COVID-19 were positively correlated with anxiety, depression and negatively with sleep quality. In conclusion, the social, occupational and economic disruption due to COVID19 has had a negative impact on psychological well-being. However, the transition to home-working may have been somewhat beneficial for some individuals in terms of sleep. These findings should be taken into account by policy makers during the transition to the 'new normal' post-pandemic. [ABSTRACT FROM AUTHOR]

Summary: Despite the strong evidence on circadian rhythm disruption in shift workers and consequent increased vulnerability for infection, longitudinal association between shift work and COVID‐19 infection is unexplored. In this study, data from UK Biobank participants who were tested for COVID‐19 infection (16 March to 7 September 2020) were used to explore the link between shift work and COVID‐19 infection. Using the baseline occupational information, participants were categorised as non‐shift workers, day shift workers, mixed shift workers and night shift workers. Multivariable regression models were used to assess the association between shift work and COVID‐19 infection. Among the 18,221 participants (9.4% positive cases), 11.2% were health workers, and 16.4% were involved in shift‐work‐based jobs. Ethnic minorities (18%) and people in night‐shift‐based jobs (18.1%) had a significantly higher prevalence of COVID‐19 infection than others. Adjusted logistics regression model suggest that, compared with their counterparts, people employed in a night‐shift‐based job were 1.85‐fold (95% CI: 1.42–2.41) more likely to have COVID‐19 infection. Sensitivity analysis focusing on people working in a non‐healthcare setting suggests that people in shift‐work‐based jobs had 1.81‐fold (95% CI: 1.04%–3.18%) higher odds of COVID‐19 infection than their counterparts. Shift workers, particularly night shift workers, irrespective of their occupational group, seem to be at high risk of COVID‐19 infection. If similar results are obtained from other studies, then it would mandate to revisit the criteria for defining high‐risk groups for COVID‐19 and implementing appropriate interventions to protect people in shift‐based jobs. [ABSTRACT FROM AUTHOR]

Drawing on three sets of data provided by 338 Anglican clergy serving in the Church in Wales, 484 Presbyterian clergy serving in the Church of Scotland, and 422 Salvation Army Officers serving in the UK, this study reports the development of a 10-item instrument designed to provide independent measures of preference for morning activity (the Lark preference) and preference for evening activity (the Owl preference) appropriate for use among clergy. The thesis is then tested that these preferences predict individual differences in clergy work-related psychological health, as assessed by the Francis Burnout Inventory, after taking into account the effects of personal factors (sex and age) and personality factors (extraversion and neuroticism). The data demonstrated that clergy who displayed the Lark preference were less likely to suffer from emotional exhaustion, suggesting a clear and consistent linkage between preferences for mornings and lower vulnerability to burnout. [ABSTRACT FROM AUTHOR]

Individual variability in diurnal preference or chronotype is commonly assessed with self-report scales such as the widely used morningness–eveningness questionnaire (MEQ). We sought to investigate the MEQ's internal consistency by applying exploratory factor analysis (EFA) to determine the number of underlying latent factors in four different adult samples, two each from the United Kingdom and Brazil (total N = 3,457). We focused on factors that were apparent in all samples, irrespective of particular sociocultural diversity and geographical characteristics, so as to show a common core reproducible structure across samples. Results showed a three-factor solution with acceptable to good model fit indexes in all studied populations. Twelve of the 19 MEQ items in the three-correlated factor solution loaded onto the same factors across the four samples. This shows that the scale measures three distinguishable, yet correlated constructs: (1) items related to how people feel in the morning, which we termed efficiency of dissipation of sleep pressure (recovery process) (items 1, 3, 4, 5, 7, 9, 13, and 19); (2) items related to how people feel before sleep, which we called sensitivity to buildup of sleep pressure (items 2, 10, and 12); and (3) peak time of cognitive arousal (item 11). Although the third factor was not regarded as consistent since only one item was common among all samples, it might represent subjective amplitude. These results suggested that the latent constructs of the MEQ reflect dissociable homeostatic processes in addition to a less consistent propensity for cognitive arousal at different times of the day. By analyzing answers to MEQ items that compose these latent factors, it may be possible to extract further knowledge of factors that affect morningness–eveningness. [ABSTRACT FROM AUTHOR]

Wearable devices have been increasingly used in research to provide continuous physical activity monitoring, but how to effectively extract features remains challenging for researchers. To analyze the generated actigraphy data in large-scale population studies, we developed computationally efficient methods to derive sleep and activity features through a Hidden Markov Model-based sleep/wake identification algorithm, and circadian rhythm features through a Penalized Multi-band Learning approach adapted from machine learning. Unsupervised feature extraction is useful when labeled data are unavailable, especially in large-scale population studies. We applied these two methods to the UK Biobank wearable device data and used the derived sleep and circadian features as phenotypes in genome-wide association studies. We identified 53 genetic loci with p<5×10−8 including genes known to be associated with sleep disorders and circadian rhythms as well as novel loci associated with Body Mass Index, mental diseases and neurological disorders, which suggest shared genetic factors of sleep and circadian rhythms with physical and mental health. Further cross-tissue enrichment analysis highlights the important role of the central nervous system and the shared genetic architecture with metabolism-related traits and the metabolic system. Our study demonstrates the effectiveness of our unsupervised methods for wearable device data when additional training data cannot be easily acquired, and our study further expands the application of wearable devices in population studies and genetic studies to provide novel biological insights. Author summary: While wearable devices have been increasingly used in research for objective and continuous activity monitoring, how to effectively extract sleep and rest-activity circadian rhythm features remains the major obstacle for researchers, especially in population studies where labeled outcome data such as sleep diaries are unavailable and thus existing supervised methods cannot be applied. Here, we developed unsupervised feature extraction methods based on machine learning without the need for labeled outcome data. We applied the methods to population wearable device data to extract sleep and circadian features, and we further identified novel associated loci and the key roles of the central nervous system and the metabolic system. The findings are essential for understanding the underlying shared genetic architecture of sleep and circadian rhythms with physical and mental health, and the proposed methods can largely expand and promote the use of wearable device data in population and genetic studies. [ABSTRACT FROM AUTHOR]

Information about several studies discussed during the meeting of the Royal Society of Medicine Section of Occupational Medicine that was held in Great Britain on February 19, 1980 is presented. Studies revealed that shift work can cause various diseases such as insomnia, fatigue, loss of appetite and gastrointestinal disorders. Other studies in applied psychology indicated that circadian rhythms can affect the worker's job performance.

Life on earth has evolved during the past several billion years under relatively bright days and dark night conditions. The wide-spread adoption of electric lights during the past century exposed animals, both human and non-human, to significant light at night for the first time in their evolutionary history. Endogenous circadian clocks depend on light to entrain to the external daily environment and seasonal rhythms depend on clear nightly melatonin signals to assess time of year. Thus, light at night can derange temporal adaptations. Indeed, disruption of naturally evolved light-dark cycles results in several physiological and behavioural changes with potentially serious implications for physiology, behaviour and mood. In this review, data from night-shift workers on their elevated risk for metabolic disorders, as well as data from animal studies will be discussed. Night-shift workers are predisposed to obesity and dysregulated metabolism that may result from disrupted circadian rhythms. Although studies in human subjects are correlative, animal studies have revealed several mechanisms through which light at night may exert its effects on metabolism by disrupting circadian rhythms that are associated with inflammation, both in the brain and in the periphery. Disruption of the typical timing of food intake is a key effect of light at night and subsequent metabolic dysregulation. Strategies to avoid the effects of light at night on body mass dysregulation should be pursued. [ABSTRACT FROM AUTHOR]

Presently, about 12% of the population is 65 years or older and by the year 2030 that figure is expected to reach 21%. In order to promote the well-being of the elderly and to reduce the costs associated with health care demands, increased longevity should be accompanied by ageing attenuation. Energy restriction, which limits the amount of energy consumed to 60-70% of the daily intake, and intermittent fasting, which allows the food to be available ad libitum every other day, extend the life span of mammals and prevent or delay the onset of major age-related diseases, such as cancer, diabetes and cataracts. Recently, we have shown that well-being can be achieved by resetting of the circadian clock and induction of robust catabolic circadian rhythms via timed feeding. In addition, the clock mechanism regulates metabolism and major metabolic proteins are key factors in the core clock mechanism. Therefore, it is necessary to increase our understanding of circadian regulation over metabolism and longevity and to design new therapies based on this regulation. This review will explore the present data in the field of circadian rhythms, ageing and metabolism. [ABSTRACT FROM AUTHOR]

Daylight savings time represents a public good with costs and benefits. We provide the first comprehensive examination of the welfare effects of the spring and autumn transitions for the UK and Germany. Using individual-level data and a regression discontinuity design, we estimate the effect of the transitions on life satisfaction. Our results show that individuals in both the UK and Germany experience deteriorations in life satisfaction in the first week after the spring transition. We find no effect of the autumn transition. We attribute the negative effect of the spring transition to the reduction in the time endowment and the process of adjusting to the disruption in circadian rhythms. The effects are particularly strong for individuals with young children in the household. We conclude that the higher the shadow price of time, the more difficult is adjustment. Presumably, an increase in flexibility to reallocate time could reduce the welfare loss for individuals with binding time constraints. [ABSTRACT FROM AUTHOR]

There has been a worldwide epidemic of obesity in recent decades. In animal studies, there is convincing evidence that light exposure causes weight gain, even when calorie intake and physical activity are held constant. Disruption of sleep and circadian rhythms by exposure to light at night (LAN) might be one mechanism contributing to the rise in obesity, but it has not been well-investigated in humans. Using multinomial logistic regression, we examined the association between exposure to LAN and obesity in questionnaire data from over 100,000 women in the Breakthrough Generations Study, a cohort study of women aged 16 years or older who were living in the United Kingdom and recruited during 2003–2012. The odds of obesity, measured using body mass index, waist:hip ratio, waist:height ratio, and waist circumference, increased with increasing levels of LAN exposure (P < 0.001), even after adjustment for potential confounders such as sleep duration, alcohol intake, physical activity, and current smoking. We found a significant association between LAN exposure and obesity which was not explained by potential confounders we could measure. While the possibility of residual confounding cannot be excluded, the pattern is intriguing, accords with the results of animal experiments, and warrants further investigation. [ABSTRACT FROM PUBLISHER]

How to cite this article Daly A., Gokmen-Ozel H., MacDonald A., Preece M.A., Davies P., Chakrapani A. & McKiernan P. (2012) Diurnal variation of phenylalanine concentrations in tyrosinaemia type 1: should we be concerned? J Hum Nutr Diet. 25, 111-116 Abstract Background: Tyrosinaemia type 1 (HT1) is treated with a tyrosine and phenylalanine-restricted diet, amino acids free of phenylalanine and tyrosine, and nitisinone (NTBC). Treatment guidelines recommend plasma tyrosine between 200-400 μ m and phenylalanine at least >30 μ m. There is little information on the diurnal variation of plasma tyrosine or phenylalanine in HT1. Low plasma phenylalanine <30 μ m may be associated with poor growth and cognitive delay. The present study aimed to document diurnal variation of tyrosine and phenylalanine plasma concentrations and growth in children with HT1. Methods: Median tyrosine and phenylalanine plasma concentrations were reviewed retrospectively over 3 years in 11 subjects (median age 4 years) with HT1. Subjects routinely collected morning fasting blood samples but afternoon nonfasted samples were taken in the clinic (<10% of samples). Growth Z-scores were calculated. Results: The percentage of all plasma phenylalanine concentrations <30 μ m was 8.6% and <40 μ m was 13.6%. Only 2% of fasting morning phenylalanine concentrations were <30 μ m, compared to 83% of nonfasting afternoon samples. All but one child had a height Z-score <0. Conclusions: Blood phenylalanine concentrations were consistently lower in the afternoon. Taking blood samples at variable time points in the day may lead to variation in interpreting dietary control. A detailed study is necessary to examine the 24-h diurnal variation of plasma phenylalanine and tyrosine in HT1. It is possible that phenylalanine concentrations may be very low for a substantive time over 24 h and the potential impact that this may have on cognitive development and growth in children is unknown. [ABSTRACT FROM AUTHOR]

Background: The circadian locomotor output cycles kaput (CLOCK) gene encodes protein regulation circadian rhythm and also plays some roles in neural transmitter systems including the dopamine system. Several lines of evidence implicate a relationship between attention-deficit hyperactivity disorder (ADHD), circadian rythmicity and sleeping disturbances. A recent study has reported that a polymorphism (rs1801260) at the 3'-untranslated region of the CLOCK gene is associated with adult ADHD. Methods: To investigate the association between the polymorphism (rs1801260) in ADHD, two samples of ADHD probands from the United Kingdom (n = 180) and Taiwan (n = 212) were genotyped and analysed using withinfamily transmission disequilibrium test (TDT). Bonferroni correction procedures were used to just for multiple comparisons. Results: We found evidence of increased transmission of the T allele of the rs1801260 polymorphism in Taiwanese samples (P = 0.010). There was also evidence of preferential transmission of the T allele of the rs1801260 polymorphism in combined samples from the Taiwan and UK (P = 0.008). Conclusion: This study provides evidence for the possible involvement of CLOCK in susceptibility to ADHD. [ABSTRACT FROM AUTHOR]