An observational study of sleep characteristics in elite endurance athletes during an altitude training camp at 1800 m

Objectives - To observe changes in sleep from baseline and during an altitude training camp in elite endurance athletes. Design - Prospective, observational. Setting - Baseline monitoring at Participants - Thirty-three senior national-team endurance athletes (mean age 25.8 ± S.D. 2.8 years, 16 women). Measurements - Daily measurements of sleep (using a microwave Doppler radar at baseline and altitude), oxygen saturation (SpO2), training load and subjective recovery (at altitude). Results - At altitude vs. baseline, sleep duration (P = .036) and light sleep (P Conclusion - This is the first study to document changes in sleep from near-sea-level baseline and during a training camp at 1800 m in elite endurance athletes. Ascending to altitude reduced total sleep time and light sleep, while deep sleep and respiration rate increased. SpO2 and training load at altitude were associated with these responses. This research informs our understanding of the changes in sleep occurring in elite endurance athletes attending training camps at competition altitudes

High-performance fixed-bed in situ mass analyzer - ISMA

We demonstrate a newly developed high-performance fixed-bed reactor combined with an in situ mass analyzer (ISMA). The ISMA is particularly relevant to sub-second time-resolved studies where mass changes occur due to, e.g., chemical reactions and process conditions such as choice of solid, temperature, gas atmosphere, and pressure. The mass is determined from the optically measured oscillation frequency of a quartz element, yielding a mass resolution below 10 μg—typically 2–3 μg—for samples up to ∼500 mg. By placing the quartz element and optical sensor inside stainless steel pipes and providing heat from the outside, the instrument is applicable up to ∼62 bars and 700 °C. By surrounding this core part of the instrument with a suitable feed system and product analysis instruments, in combination with computer control and logging, time-resolved studies are enabled. The instrument with surrounding feed and product analysis infrastructure is fully automated. Emphasis has been put on making the instrument robust, safe, operationally simple, and user-friendly. We demonstrate the ISMA instrument on selected samples.acceptedVersio

Phenology of the avian spring migratory passage in Europe and North America : Asymmetric advancement in time and increase in duration

Climate change has been shown to shift the seasonal timing (i.e. phenology) and distribution of species. The phenological effects of climate change on living organisms have often been tested using first occurrence dates, which may be uninformative and biased. More rarely investigated is how different phases of a phenological sequence (e.g. beginning, central tendency and end) or its duration have changed over time. This type of analysis requires continuous observation throughout the phenological event over multiple years, and such data sets are rare. In this study we examined the impact of temperature on long-term change of passage timing and duration of the spring migration period in birds, and which species' traits explain species-specific variation. Data used covered 195 species from 21 European and Canadian bird observatories from which systematic daily sampling protocols were available. Migration dates were negatively associated with early spring temperature and timings had in general advanced in 57 years. Short-distance migrants advanced the beginning of their migration more than long-distance migrants when corrected for phylogenic relatedness, but such a difference was not found in other phases of migration. The advancement of migration has generally been greater for the beginning and median phases of migration relative to the end, leading to extended spring migration seasons. Duration of the migration season increased with increasing temperature. Phenological changes have also been less noticeable in Canada even when corrected for rate of change in temperature. To visualize long-term changes in phenology, we constructed the first multi-species spring migration phenology indicator to describe general changes in median migration dates in the northern hemisphere. The indicator showed an average advancement of one week during five decades across the continents (period 1959-2015). The indicator is easy to update with new data and we therefore encourage future research to investigate whether the trend towards longer periods of occurrence or emergence in spring is also evident in other migratory populations. Such phenological changes may influence detectability in monitoring schemes, and may have broader implications on population and community dynamics.Peer reviewe

Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis

Objective: To compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults. Design: Systematic review and network meta-analysis. Data sources: Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, as well as websites of regulatory agencies and pharmaceutical companies without language restrictions until 24 June 2023. Methods: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Random effects network meta-analyses were conducted for the primary analyses. The primary outcomes were the proportion of participants who were pain-free at two hours post-dose and the proportion of participants with sustained pain freedom from two to 24 hours post-dose, both without the use of rescue drugs. Certainty of the evidence was graded using the confidence in network meta-analysis (CINeMA) online tool. Vitruvian plots were used to summarise findings. An international panel of clinicians and people with lived experience of migraine co-designed the study and interpreted the findings. Eligibility criteria for selecting studies: Double blind randomised trials of adults (≥18 years) with a diagnosis of migraine according to the International Classification of Headache Disorders. Results: 137 randomised controlled trials comprising 89 445 participants allocated to one of 17 active interventions or placebo were included. All active interventions showed superior efficacy compared with placebo for pain freedom at two hours (odds ratios from 1.73 (95% confidence interval (CI) 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan), and most of them also for sustained pain freedom to 24 hours (odds ratios from 1.71 (1.07 to 2.74) for celecoxib to 7.58 (2.58 to 22.27) for ibuprofen). In head-to-head comparisons between active interventions, eletriptan was the most effective drug for pain freedom at two hours (odds ratios from 1.46 (1.18 to 1.81) to 3.01 (2.13 to 4.25)), followed by rizatriptan (1.59 (1.18 to 2.17) to 2.44 (1.75 to 3.45)), sumatriptan (1.35 (1.03 to 1.75) to 2.04 (1.49 to 2.86)), and zolmitriptan (1.47 (1.04 to 2.08) to 1.96 (1.39 to 2.86)). For sustained pain freedom, the most efficacious interventions were eletriptan and ibuprofen (odds ratios from 1.41 (1.02 to 1.93) to 4.82 (1.31 to 17.67)). Confidence in accordance with CINeMA ranged from high to very low. Sensitivity analyses on Food and Drug Administration licensed doses only, high versus low doses, risk of bias, and moderate to severe headache at baseline confirmed the main findings for both primary and secondary outcomes. Conclusions: Overall, eletriptan, rizatriptan, sumatriptan, and zolmitriptan had the best profiles and they were more efficacious than the recently marketed drugs lasmiditan, rimegepant, and ubrogepant. Although cost effectiveness analyses are warranted and careful consideration should be given to patients with a high risk cardiovascular profile, the most effective triptans should be considered as preferred acute treatment for migraine and included in the WHO List of Essential Medicines to promote global accessibility and uniform standards of care. Systematic review registration: Open Science Framework https://osf.io/kq3ys/

An Integrated Disease/Pharmacokinetic/Pharmacodynamic Model Suggests Improved Interleukin-21 Regimens Validated Prospectively for Mouse Solid Cancers

Interleukin (IL)-21 is an attractive antitumor agent with potent immunomodulatory functions. Yet thus far, the cytokine has yielded only partial responses in solid cancer patients, and conditions for beneficial IL-21 immunotherapy remain elusive. The current work aims to identify clinically-relevant IL-21 regimens with enhanced efficacy, based on mathematical modeling of long-term antitumor responses. For this purpose, pharmacokinetic (PK) and pharmacodynamic (PD) data were acquired from a preclinical study applying systemic IL-21 therapy in murine solid cancers. We developed an integrated disease/PK/PD model for the IL-21 anticancer response, and calibrated it using selected “training” data. The accuracy of the model was verified retrospectively under diverse IL-21 treatment settings, by comparing its predictions to independent “validation” data in melanoma and renal cell carcinoma-challenged mice (R2>0.90). Simulations of the verified model surfaced important therapeutic insights: (1) Fractionating the standard daily regimen (50 µg/dose) into a twice daily schedule (25 µg/dose) is advantageous, yielding a significantly lower tumor mass (45% decrease); (2) A low-dose (12 µg/day) regimen exerts a response similar to that obtained under the 50 µg/day treatment, suggestive of an equally efficacious dose with potentially reduced toxicity. Subsequent experiments in melanoma-bearing mice corroborated both of these predictions with high precision (R2>0.89), thus validating the model also prospectively in vivo. Thus, the confirmed PK/PD model rationalizes IL-21 therapy, and pinpoints improved clinically-feasible treatment schedules. Our analysis demonstrates the value of employing mathematical modeling and in silico-guided design of solid tumor immunotherapy in the clinic