The Ecology of Human Sleep (EcoSleep) Cohort Study: Protocol for a longitudinal repeated measurement burst design study to assess the relationship between sleep determinants and outcomes under real-world conditions across time of year.

The interplay of daily life factors, including mood, physical activity, or light exposure, influences sleep architecture and quality. Laboratory-based studies often isolate these determinants to establish causality, thereby sacrificing ecological validity. Furthermore, little is known about time-of-year changes in sleep and circadian-related variables at high resolution, including the magnitude of individual change across time of year under real-world conditions. The Ecology of Human Sleep (EcoSleep) cohort study will investigate the combined impact of sleep determinants on individuals' daily sleep episodes to elucidate which waking events modify sleep patterns. A second goal is to describe high-resolution individual sleep and circadian-related changes across the year to understand intra- and inter-individual variability. This study is a prospective cohort study with a measurement-burst design. Healthy adults aged 18-35 years (N = 12) will be enrolled for 12 months. Participants will continuously wear actimeters and pendant-attached light loggers. A subgroup will also measure interstitial fluid glucose levels (six paticipants). Every 4 weeks, all participants will undergo three consecutive measurement days of four ecological momentary assessments each day ('bursts') to sample sleep determinants during wake. Participants will also continuously wear temperature loggers (iButtons) during the bursts. Body weight will be captured before and after the bursts in the laboratory. The bursts will be separated by two at-home electroencephalogram recordings each night. Circadian phase and amplitude will be estimated during the bursts from hair follicles, and habitual melatonin onset will be derived through saliva sampling. Environmental parameters (bedroom temperature, humidity, and air pressure) will be recorded continuously.

Validation of the Munich Actimetry Sleep Detection Algorithm for estimating sleep-wake patterns from activity recordings.

Periods of sleep and wakefulness can be estimated from wrist-locomotor activity recordings via algorithms that identify periods of relative activity and inactivity. Here, we evaluated the performance of our Munich Actimetry Sleep Detection Algorithm. The Munich Actimetry Sleep Detection Algorithm uses a moving 24-h threshold and correlation procedure estimating relatively consolidated periods of sleep and wake. The Munich Actimetry Sleep Detection Algorithm was validated against sleep logs and polysomnography. Sleep-log validation was performed on two field samples collected over 54 and 34 days (median) in 34 adolescents and 28 young adults. Polysomnographic validation was performed on a clinical sample of 23 individuals undergoing one night of polysomnography. Epoch-by-epoch analyses were conducted and comparisons of sleep measures carried out via Bland-Altman plots and correlations. Compared with sleep logs, the Munich Actimetry Sleep Detection Algorithm classified sleep with a median sensitivity of 80% (interquartile range [IQR] = 75%-86%) and specificity of 91% (87%-92%). Mean onset and offset times were highly correlated (r = .86-.91). Compared with polysomnography, the Munich Actimetry Sleep Detection Algorithm reached a median sensitivity of 92% (85%-100%) but low specificity of 33% (10%-98%), owing to the low frequency of wake episodes in the night-time polysomnographic recordings. The Munich Actimetry Sleep Detection Algorithm overestimated sleep onset (~21 min) and underestimated wake after sleep onset (~26 min), while not performing systematically differently from polysomnography in other sleep parameters. These results demonstrate the validity of the Munich Actimetry Sleep Detection Algorithm in faithfully estimating sleep-wake patterns in field studies. With its good performance across daytime and night-time, it enables analyses of sleep-wake patterns in long recordings performed to assess circadian and sleep regularity and is therefore an excellent objective alternative to sleep logs in field settings.

Early Neolithic pastoral land use at Alsónyék-Bátaszék, Hungary (Starcevo culture): New insights from stable isotope ratios.

The earliest introduction of livestock (cattle, goats, sheep, pigs) into the Carpathian Basin was an important step towards farming expansion into continental Europe. This spread beyond the environments of the southern Balkans was accompanied by a reduction in the spectrum of cultivated crops, changes in the relative representation of different domestic animals, and, most likely, adaptations of husbandry practices. How the earliest farmers in the Carpathian Basin kept their domestic stock is still understudied. We explored early animal management and land use strategies at the Starcevo settlement at Alsónyék-Bátaszék, Hungary (Early Neolithic, ca. 5800-5600 cal BC). Settled at the intersection of wide alluvial plains, waterlogged meadows and marshes to the east, and forested hills to the west, early farmers at Alsónyék had a wide variety of options for nourishing their livestock. We performed stable isotope ratio analysis of bone collagen (n = 99; δ13C, δ15N) and tooth enamel (nteeth = 28, sequentially sampled for δ13C and δ18O) from wild and domestic animals to locate them in the landscape and investigate herding practices on a seasonal scale. The bone collagen isotope ratios mostly indicate feeding in open environments. However, results from the sequential analysis of cattle and sheep enamel suggest diverse dietary strategies for winters, including consumption of forest resources, consumption of summer hay and grazing in an open environment. Most pigs appear to have had herbivorous diets, but several individuals likely supplemented their diet with animal protein. Stable isotope ratio results from the Lengyel phase at Alsónyék (ca. 4800-4300 cal BC) suggest more access to animal protein for pigs, and feeding in more open areas by wild boar, red deer and cattle compared to the Starcevo phase. This study's results demonstrate considerable variability in early animal husbandry practices at Alsónyék.

School start times and academic achievement - A systematic review on grades and test scores.

Early school times clash with the late sleep of adolescents, leading to wide-spread sleep restriction in students. Evidence suggests that delaying school starts is beneficial for sleep and recent studies investigated whether this also translates into improved academic achievement. We thus conducted a systematic review of the literature on school start times, grades and test scores in middle and high-school students. We reviewed 21 studies following the PRISMA guidelines and assessed the evidence quality using a pre-defined risk of bias tool. Nine studies reported no association of later starts with achievement, while the remaining reported mixed (5), positive (5), negative (1) or unclear (1) results. Considering the heterogeneity in academic outcomes, study types, amount of delay and exposure, and the substantial risk of bias, a meta-analysis was not warranted - instead we provide grouped reviews and discussion. Overall, no generalisable improvements in achievement with later starts emerge beyond the level of single studies. This does not necessarily preclude improvements in students' learning but highlights shortcomings of the literature and the challenges of using grades and test scores to operationalise academic achievement. Given other previously reported positive outcomes, our results suggest that schools could start later while achievement is likely maintained.

A 4-year longitudinal study investigating the relationship between flexible school starts and grades.

The mismatch between teenagers' late sleep phase and early school start times results in acute and chronic sleep reductions. This is not only harmful for learning but may reduce career prospects and widen social inequalities. Delaying school start times has been shown to improve sleep at least short-term but whether this translates to better achievement is unresolved. Here, we studied whether 0.5-1.5 years of exposure to a flexible school start system, with the daily choice of an 8 AM or 8:50 AM-start, allowed secondary school students (n = 63-157, 14-21 years) to improve their quarterly school grades in a 4-year longitudinal pre-post design. We investigated whether sleep, changes in sleep or frequency of later starts predicted grade improvements. Mixed model regressions with 5111-16,724 official grades as outcomes did not indicate grade improvements in the flexible system per se or with observed sleep variables nor their changes-the covariates academic quarter, discipline and grade level had a greater effect in our sample. Importantly, our finding that intermittent sleep benefits did not translate into detectable grade changes does not preclude improvements in learning and cognition in our sample. However, it highlights that grades are likely suboptimal to evaluate timetabling interventions despite their importance for future success.

Sleep improvements on days with later school starts persist after 1 year in a flexible start system.

Early school times fundamentally clash with the late sleep of teenagers. This mismatch results in chronic sleep deprivation posing acute and long-term health risks and impairing students' learning. Despite immediate short-term benefits for sleep, the long-term effects of later starts remain unresolved. In a pre-post design over 1 year, we studied a unique flexible school start system, in which 10-12th grade students chose daily between an 8:00 or 8:50AM-start. Missed study time (8:00-8:50) was compensated for during gap periods or after classes. Based on 2 waves (6-9 weeks of sleep diary each), we found that students maintained their ~ 1-h-sleep gain on later days, longitudinally (n = 28) and cross-sectionally (n = 79). This gain was independent of chronotype and frequency of later starts but attenuated for boys after 1 year. Students showed persistently better sleep quality and reduced alarm-driven waking and reported psychological benefits (n = 93) like improved motivation, concentration, and study quality on later days. Nonetheless, students chose later starts only infrequently (median 2 days/week), precluding detectable sleep extensions in the flexible system overall. Reasons for not choosing late starts were the need to make up lost study time, preference for extra study time and transport issues. Whether flexible systems constitute an appealing alternative to fixed delays given possible circadian and psychological advantages warrants further investigation.

Later school start times in a flexible system improve teenage sleep.

Sleep deprivation in teenage students is pervasive and a public health concern, but evidence is accumulating that delaying school start times may be an effective countermeasure. Most studies so far assessed static changes in schools start time, using cross-sectional comparisons and one-off sleep measures. When a high school in Germany introduced flexible start times for their senior students-allowing them to choose daily between an 8 am or 9 am start (≥08:50)-we monitored students' sleep longitudinally using subjective and objective measures. Students (10-12th grade, 14-19 y) were followed 3 weeks prior and 6 weeks into the flexible system via daily sleep diaries (n = 65) and a subcohort via continuous wrist-actimetry (n = 37). Satisfaction and perceived cognitive outcomes were surveyed at study end. Comparisons between 8 am and ≥9 am-starts within the flexible system demonstrated that students slept 1.1 h longer when starting school later-independent of gender, grade, chronotype, and frequency of later starts; sleep offsets were delayed but, importantly, onsets remained unchanged. Sleep quality was increased and alarm-driven waking reduced. However, overall sleep duration in the flexible system was not extended compared to baseline-likely because students did not start later frequently enough. Nonetheless, students were highly satisfied with the flexible system and reported cognitive and sleep improvements. Therefore, flexible systems may present a viable alternative for implementing later school starts to improve teenage sleep if students can be encouraged to use the late-option frequently enough. Flexibility may increase acceptance of school start changes and speculatively even prevent delays in sleep onsets through occasional early starts.

Inhibition of somatosensory mechanotransduction by annexin A6.

Mechanically activated, slowly adapting currents in sensory neurons have been linked to noxious mechanosensation. The conotoxin NMB-1 (noxious mechanosensation blocker-1) blocks such currents and inhibits mechanical pain. Using a biotinylated form of NMB-1 in mass spectrometry analysis, we identified 67 binding proteins in sensory neurons and a sensory neuron-derived cell line, of which the top candidate was annexin A6, a membrane-associated calcium-binding protein. Annexin A6-deficient mice showed increased sensitivity to mechanical stimuli. Sensory neurons from these mice showed increased activity of the cation channel Piezo2, which mediates a rapidly adapting mechano-gated current linked to proprioception and touch, and a decrease in mechanically activated, slowly adapting currents. Conversely, overexpression of annexin A6 in sensory neurons inhibited rapidly adapting currents that were partially mediated by Piezo2. Furthermore, overexpression of annexin A6 in sensory neurons attenuated mechanical pain in a mouse model of osteoarthritis, a disease in which mechanically evoked pain is particularly problematic. These data suggest that annexin A6 can be exploited to inhibit chronic mechanical pain.