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The Last Interglacial (129–116 thousand years ago (ka)) represents one of the warmest climate intervals of the past 800,000 years and the most recent time when sea level was metres higher than today. However, the timing and magnitude of the peak warmth varies between reconstructions, and the relative importance of individual sources that contribute to the elevated sea level (mass gain versus seawater expansion) during the Last Interglacial remains uncertain. Here we present the first mean ocean temperature record for this interval from noble gas measurements in ice cores and constrain the thermal expansion contribution to sea level. Mean ocean temperature reached its maximum value of 1.1 ± 0.3 °C warmer-than-modern values at the end of the penultimate deglaciation at 129 ka, which resulted in 0.7 ± 0.3 m of thermosteric sea-level rise relative to present level. However, this maximum in ocean heat content was a transient feature; mean ocean temperature decreased in the first several thousand years of the interglacial and achieved a stable, comparable-to-modern value by ~127 ka. The synchroneity of the peak in mean ocean temperature with proxy records of abrupt transitions in the oceanic and atmospheric circulation suggests that the mean ocean temperature maximum is related to the accumulation of heat in the ocean interior during the preceding period of reduced overturning circulation.

Introduction: Return to Sport tests with functional hop tests are often used to decide when a person is ready to return to sport after an anterior cruciate ligament (ACL) injury. Poor movement quality, such as knee valgus, hip adduction and hip internal rotation is considered a risk factor for ACL injury. However, it is unclear whether existing tests adequately cover the aspect of movement quality. This study aims to investigate whether there is a relationship between the calculated limb symmetry index (LSI) of hop tests as an indication of performance and the total score of the "Quality First" assessment (movement quality). The second aim is to examine the reliability of the newly developed "Quality First" assessment for evaluating movement quality in hop tests., Methods: The cross-sectional study recruited 34 patients with an ACL reconstruction. The vertical hop, single-leg hop for distance, and side hop tests were performed and recorded. The video recordings were assessed using the "Quality First" assessment. The Spearman correlation coefficient was calculated using the LSI and the "Quality First" total score. Intraclass correlation coefficients (ICC) and standard error of measurements (SEM) were used to calculate intra- and interrater reliability. In addition, the minimal detectable change (MDC) was determined., Results: The correlation test between the LSI and the "Quality First" total score showed no correlation for all three jumps ( r  = -0.1-0.02/ p -value = 0.65-0.93). The interrater reliability of the "Quality First" assessment showed fair to good reliability (ICC 2 : 0.45-0.60), with SEM ranging from 1.46 to 1.73 and the MDC from 4.06 to 4.8. Intrarater reliability was good to excellent (ICC 3 : 0.73-0.85), with SEM values ranging from 0.89 to 1.09 and the MDC from 2.47 to 3.01., Conclusion: The quality of movement, measured with the "Quality First" assessment, indicated no correlation with the calculated LSI from jump performance, therefore movement quality should also be examined in Return to Sport tests. The "Quality First" assessment shows fair to good reliability when used by different raters. When used multiple times by the same rater, the assessment has good to excellent reliability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Weber, Müller, Mathieu-Kälin, Caminada, Häberli and Baur.)

Introduction: Current approaches fail to adequately identify sport readiness after anterior cruciate ligament (ACL) rehabilitation. Altered landing biomechanics after ACL reconstruction are associated with increased risk of a noncontact ACL reinjury. There is a lack of objective factors to screen for deficient movement patterns. Therefore, the aim of this study was to investigate content validity, interpretability, and internal consistency for the newly developed "Quality First" assessment to evaluate movement quality during hop tests in patients after ACL rehabilitation., Method: Participants in this cross-sectional study were recruited in collaboration with the Altius Swiss Sportmed Center in Rheinfelden, Switzerland. After a successful ACL reconstruction, the movement quality of 50 hop test batteries was evaluated between 6 and 24 months postoperatively with the "Quality First" assessment. Content validity was assessed from the perspective of professionals. To check the interpretability, classical test theory was employed. Cronbach's α was calculated to evaluate internal consistency., Results: Content validity resulted in the inclusion of three different hop tests (single-leg hop for distance, vertical hop, and side hop). The "Quality First" assessment is enabled to evaluate movement quality in the sagittal, vertical, and the transversal plane. After the exclusion process, the "Quality First" assessment was free from floor and ceiling effects and obtained a sufficient Cronbach's α . The final version consists of 15 items, rated on a 4-point scale., Discussion: By means of further validations, the "Quality First" assessment could offer a possibility to evaluate movement quality after ACL rehabilitation during hop tests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Mathieu-Kälin, Müller, Weber, Caminada, Häberli and Baur.)

The energy imbalance at the top of the atmosphere determines the temporal evolution of the global climate, and vice versa changes in the climate system can alter the planetary energy fluxes. This interplay is fundamental to our understanding of Earth's heat budget and the climate system. However, even today, the direct measurement of global radiative fluxes is difficult, such that most assessments are based on changes in the total energy content of the climate system. We apply the same approach to estimate the long-term evolution of Earth's radiative imbalance in the past. New measurements of noble gas-derived mean ocean temperature from the European Project for Ice Coring in Antarctica Dome C ice core covering the last 40,000 y, combined with recent results from the West Antarctic Ice Sheet Divide ice core and the sea-level record, allow us to quantitatively reconstruct the history of the climate system energy budget. The temporal derivative of this quantity must be equal to the planetary radiative imbalance. During the deglaciation, a positive imbalance of typically +0.2 W⋅m -2 is maintained for ∼10,000 y, however, with two distinct peaks that reach up to 0.4 W⋅m -2 during times of substantially reduced Atlantic Meridional Overturning Circulation. We conclude that these peaks are related to net changes in ocean heat uptake, likely due to rapid changes in North Atlantic deep-water formation and their impact on the global radiative balance, while changes in cloud coverage, albeit uncertain, may also factor into the picture., Competing Interests: The authors declare no conflict of interest.

The effect of dynamic shape switching of hydrogel bilayers on the performance of self-folding microrobots is investigated for navigation in body orifices and drug release on demand. Tubular microrobots are fabricated by coupling a thermoresponsive hydrogel nanocomposite with a poly(ethylene glycol)diacrylate (PEGDA) layer, to achieve spontaneous and reversible folding from a planar rectangular structure. Graphene oxide (GO) or silica-coated superparamagnetic iron oxide nanoparticles are dispersed in the thermoresponsive hydrogel matrix to provide near-infrared (NIR) light sensitivity or magnetic actuation, respectively. The NIR light-responsive microstructures are fabricated for triggered drug delivery while magnetic nanocomposite-based microrobots are used to analyze the role of shape in locomotion. Experimental analysis and computational simulations of tubular structures show that drug release and motility can be optimized through controlled shape change. These concepts are finally applied to helical microrobots to show a possible way to achieve autonomous behavior.

The origin and maintenance of polymorphism in major histocompatibility complex (MHC) genes in natural populations is still unresolved. Sexual selection, frequency-dependent selection by parasites and pathogens, and heterozygote advantage have been suggested to explain the maintenance of high allele diversity at MHC genes. Here we argue that there are two (non-exclusive) strategies for MHC-related sexual selection, representing solutions to two different problems: inbreeding avoidance and parasite resistance. In species prone to inadvertent inbreeding, partners should prefer dissimilar MHC genotypes to similar ones. But if the goal is to maximize the resistance of offspring towards potential infections, the choosing sex should prefer mates with a higher diversity of MHC alleles. This latter strategy should apply when there are several MHC loci, as is the case in most vertebrates. We tested the relative importance of an 'allele counting' strategy compared to a disassortative mating strategy using wild-caught three-spined sticklebacks (Gasterosteus aculeatus) from an interconnected system of lakes. Here we show that gravid female fish preferred the odour of males with a large number of MHC class-IIB alleles to that of males with fewer alleles. Females did not prefer male genotypes dissimilar to their own.

A high-throughput screening strategy is described that involves the acquisition of two-dimensional 15N/1H correlation spectra in less than 10 min on 50 microM protein samples using cryogenic NMR probe technology. By screening at these concentrations, small organic molecules can be tested in mixtures of 100, which dramatically increases the throughput of the NMR-based assay. Using this strategy, libraries of more than 200 000 compounds can be tested in less than 1 month. There are many advantages of high-throughput NMR-based screening compared to conventional assays, such as the ability to identify high-affinity ligands for protein targets with no known function. This suggests that the method will be extremely useful for screening the large number of targets derived from genomics research.

The reversible and highly selective monoamine oxidase B (MAO-B) inhibitor Ro 19-6327, a picolinic acid derivative, was selected for the development of new radiopharmaceuticals, whereby in place of Cl either 123I or 18F was introduced. The respective labelling procedures have been described earlier. In this study, some metabolic properties were investigated. Blood and urine samples were analysed, and halogenated picolinylglycine, a more hydrophilic compound, was identified as the main metabolite. This shows that the amine is oxidised to the respective carboxylate, but the intermediate imine or aldehyde that was proposed earlier could not be detected. First experiments with single photon emission tomography and positron emission tomography (PET) showed that the iodo compound can be used to investigate MAO-B in vivo while the fluoro compound is accumulated in the brain to such a low degree that no PET studies can be performed. We conclude that the main reason for the poor uptake of the fluoro compound is its lower lipophilicity as compared to the iodo compound and, to a lesser degree, its metabolism, which is similar for both compounds.

After the successful 123I-labelling of Ro 43-0463 the new radiopharmaceutical was tested in animals and humans. Both investigations proved the binding of the labelled compound to cerebral MAO-B. SPECT investigations resulted in an imaging of the MAO-B distribution in the human brain. This prompted us to develop the labelling of this type of MAO-B inhibitor with 18F enabling us to transfer our results to PET.