Do the effects of high intensity 40 km cycling upon left ventricular function and cardiac biomarker during recovery vary with time of day?

Twelve healthy participants performed two identical high-intensity 40 km cycling trials (morning and evening) under controlled laboratory conditions. Echocardiograms and venous blood samples were collected before and after each exercise bout. Cardiac electro-mechanical-delay (cEMD) was measured as QRS-complex onset to peak systolic (S') and early diastolic (E') tissue velocities. Myocardial strain and strain rates were assessed in longitudinal, circumferential and radial planes at the left ventricular apex and base. Cardiac troponin I (cTnI) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) were assessed as biomarkers of cardiomyocyte damage and wall stress. cEMD was lengthened after both morning (S': 160 ± 30 vs. 193 ± 27; E': 478 ± 60 vs. 620 ± 87, P < 0.05) and evening (S': 155 ± 29 vs. 195 ± 31; E': 488 ± 42 vs. 614 ± 61, P < 0.05) trials. A reduction in peak S' (morning: 6.96 ± 1.12 vs. 6.66 ± 0.89; evening: 7.09 ± 0.94 vs. 7.02 ± 0.76) was correlated with cEMD (r = -0.335, P < 0.05). Peak longitudinal strain was reduced, atrial strain rates were sporadically increased in both trials post-cycling. cTnI was elevated in only two participants (0.04 µg · L(-1), 0.03 µg · L(-1)), whilst NT-proBNP was below the clinical cut-off point in all participants. Prolonged-cycling resulted in a lengthening of cEMD, small changes in aspects of left ventricular deformation and sporadic increases in cardiac biomarkers. None of these effects were moderated by time-of-day.

Geographical Variation in Underlying Social Deprivation, Cardiovascular and Other Comorbidities in Patients with Potentially Curable Cancers in England: Results from a National Registry Dataset Analysis.

AIMS: To describe the prevalence of cardiovascular disease (CVD), multiple comorbidities and social deprivation in patients with a potentially curable cancer in 20 English Cancer Alliances. MATERIALS AND METHODS: This National Registry Dataset Analysis used national cancer registry data and CVD databases to describe rates of CVD, comorbidities and social deprivation in patients diagnosed with a potentially curable malignancy (stage I-III breast cancer, stage I-III colon cancer, stage I-III rectal cancer, stage I-III prostate cancer, stage I-IIIA non-small cell lung cancer, stage I-IV diffuse large B-cell lymphoma, stage I-IV Hodgkin lymphoma) between 2013 and 2018. Outcome measures included observation of CVD prevalence, other comorbidities (evaluated by the Charlson Comorbidity Index) and deprivation (using the Index of Multiple Deprivation) according to tumour site and allocation to Cancer Alliance. Patients were allocated to CVD prevalence tertiles (minimum: <33.3rd percentile; middle: 33.3rd to 66.6th percentile; maximum: >66.6th percentile). RESULTS: In total, 634 240 patients with a potentially curable malignancy were eligible. The total CVD prevalence for all cancer sites varied between 13.4% (CVD n = 2058; 95% confidence interval 12.8, 13.9) and 19.6% (CVD n = 7818; 95% confidence interval 19.2, 20.0) between Cancer Alliances. CVD prevalence showed regional variation both for male (16-26%) and female patients (8-16%) towards higher CVD prevalence in northern Cancer Alliances. Similar variation was observed for social deprivation, with the proportion of cancer patients being identified as most deprived varying between 3.3% and 32.2%, depending on Cancer Alliance. The variation between Cancer Alliance for total comorbidities was much smaller. CONCLUSION: Social deprivation, CVD and other comorbidities in patients with a potentially curable malignancy in England show significant regional variations, which may partly contribute to differences observed in treatments and outcomes.

The unknown third - Hydrogen isotopes in tree-ring cellulose across Europe.

This is the first Europe-wide comprehensive assessment of the climatological and physiological information recorded by hydrogen isotope ratios in tree-ring cellulose (δ2Hc) based on a unique collection of annually resolved 100-year tree-ring records of two genera (Pinus and Quercus) from 17 sites (36°N to 68°N). We observed that the high-frequency climate signals in the δ2Hc chronologies were weaker than those recorded in carbon (δ13Cc) and oxygen isotope signals (δ18Oc) but similar to the tree-ring width ones (TRW). The δ2Hc climate signal strength varied across the continent and was stronger and more consistent for Pinus than for Quercus. For both genera, years with extremely dry summer conditions caused a significant 2H-enrichment in tree-ring cellulose. The δ2Hc inter-annual variability was strongly site-specific, as a result of the imprinting of climate and hydrology, but also physiological mechanisms and tree growth. To differentiate between environmental and physiological signals in δ2Hc, we investigated its relationships with δ18Oc and TRW. We found significant negative relationships between δ2Hc and TRW (7 sites), and positive ones between δ2Hc and δ18Oc (10 sites). The strength of these relationships was nonlinearly related to temperature and precipitation. Mechanistic δ2Hc models performed well for both genera at continental scale simulating average values, but they failed on capturing year-to-year δ2Hc variations. Our results suggest that the information recorded by δ2Hc is significantly different from that of δ18Oc, and has a stronger physiological component independent from climate, possibly related to the use of carbohydrate reserves for growth. Advancements in the understanding of 2H-fractionations and their relationships with climate, physiology, and species-specific traits are needed to improve the modelling and interpretation accuracy of δ2Hc. Such advancements could lead to new insights into trees' carbon allocation mechanisms, and responses to abiotic and biotic stress conditions.

The intrusion of polluted Fly River mud into Torres Strait.

There is a concern that the Fly River plume from Papua New Guinea (PNG) may be delivering mine-derived polluted mud along the southern PNG coast into the northern Torres Strait, which is the northernmost extent of the Great Barrier Reef. To quantify this threat, the mud transport dynamics along the southern PNG coast were studied using the SLIM model. The model was qualitatively verified using historical field data on sediment dynamics and compared with more recent satellite-derived turbidity data. During strong south east winds and spring tides, about 5.4% of the Fly River mud discharge enters the Torres Strait, in agreement with previous field-derived results. The annual net movement of mud is westward, thus polluted Fly River mud progressively intrudes into Torres Strait. This intrusion is slow and may take a century to reach in significant quantities at Saibai Island, the nearest Australian island to the Fly River. Field data are needed to fully validate the model and provide greater confidence in these results.

Effects of music tempo upon submaximal cycling performance.

In an in vivo laboratory controlled study, 12 healthy male students cycled at self-chosen work-rates while listening to a program of six popular music tracks of different tempi. The program lasted about 25 min and was performed on three occasions--unknown to the participants, its tempo was normal, increased by 10% or decreased by 10%. Work done, distance covered and cadence were measured at the end of each track, as were heart rate and subjective measures of exertion, thermal comfort and how much the music was liked. Speeding up the music program increased distance covered/unit time, power and pedal cadence by 2.1%, 3.5% and 0.7%, respectively; slowing the program produced falls of 3.8%, 9.8% and 5.9%. Average heart rate changes were +0.1% (faster program) and -2.2% (slower program). Perceived exertion and how much the music was liked increased (faster program) by 2.4% and 1.3%, respectively, and decreased (slower program) by 3.6% and 35.4%. That is, healthy individuals performing submaximal exercise not only worked harder with faster music but also chose to do so and enjoyed the music more when it was played at a faster tempo. Implications of these findings for improving training regimens are discussed.

Exercise at altitude.

Altitude poses physiological challenges to the sports participant in excess of those encountered at sea level. The main problem is hypoxia and the reduction in oxygen transport capacity, which is linked to the fall in alveolar oxygen tension. Training at altitude is imperative as preparation for competing there in aerobic events. The acute adaptations on exposure to moderate altitudes may be beneficial for subsequent performance at sea level, and this has led to the use of altitude training camps, though their advantages have not been conclusively demonstrated. The benefits of altitude training depend on a variety of factors, including individual characteristics and environmental training variables.

The impact of free-time activities on sleep, recovery and well-being.

We compared the effects of different types of free-time activity on subjective and objective indices of sleep, recovery and well-being in an experimental field study. Twelve participants spent four consecutive evenings after work in each of three conditions: pursuing quiet leisure activities at home; undertaking active leisure pursuits; doing additional work. Ratings of rest and recuperation, and of satisfaction, were lowest in the additional work condition. There were few other differences between conditions. However, being satisfied with one's evening activities (regardless of which experimental condition was being undertaken) was associated with improved subsequent sleep (self-reported). Evening activities involving lower mental effort were also associated with better-rated sleep, as well as improved recuperation and fatigue the next day. It is concluded that the nature of activity per se may be less important than (1) whether the activity accords with individual preference and (2) the cumulative demands of daytime and evening activities.

Fine sediment and particulate organic matter: A review and case study on ridge-to-reef transport, transformations, fates, and impacts on marine ecosystems.

Studies documenting the effects of land-derived suspended particulate matter (SPM, i.e., particulate organic matter and mineral sediment) on marine ecosystems are typically disconnected from terrestrial studies that determine their origin, transport and fate. This study reviews sources, transport, transformations, fate and effects of SPM along the 'ridge-to-reef' continuum. We show that some of the SPM can be transported over long distances and transformed into large and easily resuspendible organic-rich sediment flocs. These flocs may lead to prolonged reductions in water clarity, impacting upon coral reef, seagrass and fish communities. Using the Great Barrier Reef (NE Australia) as a case study, we identify the latest research tools to determine thresholds of SPM exposure, allowing for an improved appreciation of marine risk. These tools are used to determine ecologically-relevant end-of-basin load targets and reliable marine water quality guidelines, thereby enabling enhanced prioritisation and management of SPM export from ridge-to-reef.

The circadian body temperature rhythm in the elderly: effect of single daily melatonin dosing.

The present study is part of a more extensive investigation dedicated to the study and treatment of age-dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self-chosen sleep-wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age-dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra- and inter-individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38+/-0.19 degrees C vs. 36.17+/-0.21 degrees C) and circadian amplitude (0.33+/-0.01 degrees C vs. 0.26+/-0.01 degrees C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19+/-1.66 vs. 16.93+/-3.08 h). However, the inter-individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter-daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1 degrees C and the amplitude increased to 0.34+/-0.01 degrees C, a similar value to that found in young adults. This was probably due to the increase of the inter-daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter-individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age-dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep-improving effects.

Some chronobiological considerations related to physical exercise.

Variables associated with physical activity show circadian rhythms in resting subjects; these rhythms have both exogenous (due to the individual's lifestyle and environment) and endogenous (due to the "body clock") components. During exercise, many of the rhythms persist, even though some show decreasing amplitude with increasing severity of exercise. Whilst the value of physical fitness is not disputed (for elite athletes, for individuals who just want to be physically fit, or for patients undertaking physical rehabilitation regimens), there are certain times of the day when special care is needed. These times are soon after waking--when there is the possibility of an increased risk of cardiovascular morbidity and damage to the spine--and late in the day--when there is an increased risk of respiratory difficulties. Since physical exercise is inextricably linked with thermoregulation, there are special considerations to bear in mind when exercise takes place in cold or hot environments. Further, due to the effects of the body clock, exercise and activity during night work and after time-zone transitions presents problems peculiar to these circumstances. In addition, the menstrual cycle affects physical performance, and these circatrigintan rhythms interact with the circadian ones. Bearing in mind these factors, advice that is based upon knowledge of circadian and circatrigintan rhythms can be given to all those contemplating physical activity. Chronobiologically, there is advantage in undertaking physical activity programmes towards the middle of the waking day and not at times when a sleep or nap has just been taken.

An Unusual "Collision Tumour" of the Prostate Gland and Rectum.

Collision tumours of two different histopathological processes are rare. We describe a case of a patient with known low grade prostate adenocarcinoma developing a rectal GIST, which was diagnosed with combined imaging modalities of MR and ultrasound and confirmed by transrectal ultrasound guided biopsy.

The circadian system and the therapeutics of the affective disorders.

Establishing that a circadian rhythm is abnormal tells us little about the cause, which can arise from changes in the patient's lifestyle, irregularities of the body clock or a malfunction in the process of entrainment of the clock. In a clinical context, such a range of possible explanations implies differences in the most appropriate mode of treatment. Against this background, the conventional view that the underlying abnormality in endogenous depression is due to a disorder of the body clock is challenged. The challenge is based on difficulties of interpretation of the clinical data and the results of studies on circadian rhythms in patients. It is suggested that the state of the circadian system in depression resembles its state in healthy individuals after time-zone transitions or in shift work maladaptation syndrome and that this disturbance should be seen as resulting from changes in the phasing of external zeitgebers rather than from an abnormality in the clock itself.

Circadian rhythms: principles and measurement.

The physiological basis of rhythmic processes is explained, and the influence of rhythmicity on pathological processes and pharmacological responses is outlined. Methods of data collection and analysis are described, and the importance of taking account of, and even exploiting, rhythmicity in experimental design is discussed.

Complex interaction of the sleep-wake cycle and circadian phase modulates mood in healthy subjects.

BACKGROUND: Several studies of healthy volunteers have revealed that subjective mood may vary with the duration of prior wakefulness and with the time of day. However, in these studies, the effects of extended wakefulness and circadian phase remained confounded, and the interaction of these 2 processes could not be assessed quantitatively. METHODS: In the present study, a total of 24 healthy young subjects (16 men, 8 women) lived on a 30-hour sleep-wake schedule for 19 to 23 days or on a 28-hour sleep-wake schedule for 33 to 36 days; both schedules induced desynchrony between the subjects' sleep-wake cycle and their endogenous circadian pacemaker. Subjective mood was assessed by 2 types of visual analog scales, which were administered twice every 2 hours and every 20 minutes, respectively, during all scheduled wakefulness episodes. A circadian phase and an interval elapsed since awakening were attributed to each data point, and circadian and wake-dependent fluctuations of mood were assessed. RESULTS: A significant variation of mood with circadian phase was observed, but no reliable main effect of the duration of prior wakefulness was found. A statistically significant interaction of circadian and wake-dependent fluctuations was evident; when the analysis was restricted to specific circadian phases, mood improved, deteriorated, or remained stable with the duration of prior wakefulness. CONCLUSIONS: These results indicate that, in healthy young subjects, subjective mood is influenced by a complex and nonadditive interaction of circadian phase and duration of prior wakefulness. The nature of this interaction is such that moderate changes in the timing of the sleep-wake cycle may have profound effects on subsequent mood.

Marked 24-h rest/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status.

The rest/activity circadian cycle has been used as a reference for chemotherapy administration at specific times to improve tolerability and efficacy. Because cancer processes may be associated with alterations of circadian rhythms, the rest/activity cycle was monitored noninvasively to assess its relationship with tumor response, survival, and quality of life in 200 patients with metastatic colorectal cancer. Patients wore an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days before receiving chronomodulated chemotherapy. The circadian rhythms in activity were estimated by two robust parameters: the autocorrelation coefficient at 24 h (r24), and the dichotomy index (I

Circadian rhythms in sports performance--an update.

We discuss current knowledge on the description, impact, and underlying causes of circadian rhythmicity in sports performance. We argue that there is a wealth of information from both applied and experimental work, which, when considered together, suggests that sports performance is affected by time of day in normal entrained conditions and that the variation has at least some input from endogenous mechanisms. Nevertheless, precise information on the relative importance of endogenous and exogenous factors is lacking. No single study can answer both the applied and basic research questions that are relevant to this topic, but an appropriate mixture of real-world research on rhythm disturbances and tightly controlled experiments involving forced desynchronization protocols is needed. Important issues, which should be considered by any chronobiologist interested in sports and exercise, include how representative the study sample and the selected performance tests are, test-retest reliability, as well as overall design of the experiment.

Deriving a "phase response curve" from adjustment to simulated time zone transitions.

Thirty-eight subjects in groups of two to four have been subjected to simulated time zone transitions of 8 hr eastward, 8 hr westward, or 12 hr; all experiments have taken place in a temporal isolation unit, in which the light intensity during the waking periods was 250-300 lux. Circadian rhythms of rectal temperature have been used as a marker of the process of adjustment, the data being analyzed before (raw) and after "purification." Conventional results have been obtained, but when the data have been treated appropriately, they have produced a relationship between shift of the sleep-activity cycle and shift of the temperature rhythms that shows many characteristics of a phase response curve. Even though the factor or factors causing such adjustment are unknown, the results confirm that changes of a consonant set of "weak" zeitgebers is sufficient for entrainment to a new time zone to occur.

Effects upon circadian rhythmicity of an alteration to the sleep-wake cycle: problems of assessment resulting from measurement in the presence of sleep and analysis in terms of a single shifted component.

Experiments were performed upon groups of three or four human subjects in an isolation chamber (total n = 14). Subjects lived initially on a conventional lifestyle and then delayed their hours of sleep by 8 hr (so mimicking some aspects of nightwork) for 2 or 5 days. They also performed two constant routines--protocols designed to minimize any effects due to the environment, mealtimes, and activity. Regular samples of urine were taken when subjects were awake, and were analyzed for sodium, potassium, and chloride; rectal temperature was measured and logged at 6-min intervals throughout. Shifts in circadian rhythms produced by the change in sleep time were assessed by cosinor and cross-correlation techniques. The protocol enabled these assessments to be made on days when sleep was allowed and under constant-routine conditions, so that masking and behavioral effects could be investigated also. The results confirmed that adjustment to the change in sleep time was slow and only partial, and that assessments made on days when sleep was allowed overestimated this adjustment. Furthermore, it was concluded that, whereas cosinor and cross-correlation techniques using only one shifting component were equally useful in describing the observed changes, both were inferior to a cross-correlation technique that made use of two shifting components. Some practical and theoretical implications of these results are discussed.

"Demasking" the temperature rhythm after simulated time zone transitions.

Simulated time zone transitions were performed in an isolation unit upon groups of one to four human subjects. In the first series of experiments, the adjustment of the circadian rhythm of body temperature, measured in the presence of sleep and other masking factors, was assessed by cosinor analysis and by cross-correlation methods. These methods modeled the circadian timing system either as a single component or as the sum of two components, those due to exogenous and endogenous influences. The one-component models described a more rapid adjustment of the temperature rhythm to the time zone transition than did the two-component models; we attribute this difference to the masking effects of the exogenous component. In a second series of experiments, we showed that the shift of the endogenous component, as assessed by the two-component models, was not significantly different from that measured during constant routines. The results also showed that, if the zeitgebers were phased in advance of the endogenous component, then advances of the endogenous component were produced only if this mismatch was less than about 10 hr. Mismatches greater than this, and cases where the zeitgebers were delayed with respect to the endogenous component, both produced delays of the endogenous component. We conclude that the two-component cross-correlation methods can be used to estimate shifts of the endogenous component of a circadian rhythm in the presence of masking factors. They are therefore an alternative to constant routines when these latter are impracticable to carry out.

West Midlands Oncology Association trial of adjuvant chemotherapy in node-negative breast cancer.

Between 1976 and 1984, 574 patients with operable breast cancer and histologically negative axillary lymph nodes were randomly assigned after mastectomy to receive either no further treatment or chemotherapy with oral LMF (fluorouracil, 500 mg, methotrexate, 25 mg, and chlorambucil, 10 mg, on day 1; fluorouracil, 500 mg, and chlorambucil, 10 mg, on day 2). There is no overall survival or relapse-free survival benefit at a median follow-up of 10 years and 8 years, respectively. There are significantly more local relapses in the control group (P less than .01), but an excess of distant relapses in the treated group is not statistically significant (P = .24). A positive treatment effect in small tumors (relapse-free survival, odds ratio = 0.55, P = .01) and a negative effect in progesterone receptor-positive tumors (survival, odds ratios = 2.04, P = .04) is probably ascribable to chance. Analysis of various prognostic factors shows that tumor size and histological grade have a clear effect on both relapse-free interval and survival.