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Abstract Galilean and Carrollian algebras acting on two-dimensional Newton-Cartan and Carrollian manifolds are isomorphic. A consequence of this property is a duality correspondence between one-dimensional Galilean and Carrollian fluids. We describe the dynamics of these systems as they emerge from the relevant limits of Lorentzian hydrodynamics, and explore the advertised duality relationship. This interchanges longitudinal and transverse directions with respect to the flow velocity, and permutes equilibrium and out-of-equilibrium observables, unveiling specific features of Carrollian physics. We investigate the action of local hydrodynamic-frame transformations in the Galilean and Carrollian configurations, i.e. dual Galilean and Carrollian local boosts, and comment on their potential breaking. Emphasis is laid on the additional geometric elements that are necessary to attain complete systems of hydrodynamic equations in Newton-Cartan and Carroll spacetimes. Our analysis is conducted in general Cartan frames as well as in more explicit coordinates, specifically suited to Galilean or Carrollian use.

We review how the international modelling community, encompassing integrated assessment models, global and regional Earth system and climate models, and impact models, has worked together over the past few decades to advance understanding of Earth system change and its impacts on society and the environment and thereby support international climate policy. We go on to recommend a number of priority research areas for the coming decade, a timescale that encompasses a number of newly starting international modelling activities, as well as the IPCC Seventh Assessment Report (AR7) and the second UNFCCC Global Stocktake. Progress in these priority areas will significantly advance our understanding of Earth system change and its impacts, increasing the quality and utility of science support to climate policy. We emphasize the need for continued improvement in our understanding of, and ability to simulate, the coupled Earth system and the impacts of Earth system change. There is an urgent need to investigate plausible pathways and emission scenarios that realize the Paris climate targets – for example, pathways that overshoot 1.5 or 2 °C global warming, before returning to these levels at some later date. Earth system models need to be capable of thoroughly assessing such warming overshoots – in particular, the efficacy of mitigation measures, such as negative CO2 emissions, in reducing atmospheric CO2 and driving global cooling. An improved assessment of the long-term consequences of stabilizing climate at 1.5 or 2 °C above pre-industrial temperatures is also required. We recommend Earth system models run overshoot scenarios in CO2-emission mode to more fully represent coupled climate–carbon-cycle feedbacks and, wherever possible, interactively simulate other key Earth system phenomena at risk of rapid change during overshoot. Regional downscaling and impact models should use forcing data from these simulations, so impact and regional climate projections cover a more complete range of potential responses to a warming overshoot. An accurate simulation of the observed, historical record remains a fundamental requirement of models, as does accurate simulation of key metrics, such as the effective climate sensitivity and the transient climate response to cumulative carbon emissions. For adaptation, a key demand is improved guidance on potential changes in climate extremes and the modes of variability these extremes develop within. Such improvements will most likely be realized through a combination of increased model resolution, improvement of key model parameterizations, and enhanced representation of important Earth system processes, combined with targeted use of new artificial intelligence (AI) and machine learning (ML) techniques. We propose a deeper collaboration across such efforts over the coming decade. With respect to sampling future uncertainty, increased collaboration between approaches that emphasize large model ensembles and those focussed on statistical emulation is required. We recommend an increased focus on high-impact–low-likelihood (HILL) outcomes – in particular, the risk and consequences of exceeding critical tipping points during a warming overshoot and the potential impacts arising from this. For a comprehensive assessment of the impacts of Earth system change, including impacts arising directly as a result of climate mitigation actions, it is important that spatially detailed, disaggregated information used to generate future scenarios in integrated assessment models be available for use in impact models. Conversely, there is a need to develop methods that enable potential societal responses to projected Earth system change to be incorporated into scenario development. The new models, simulations, data, and scientific advances proposed in this article will not be possible without long-term development and maintenance of a robust, globally connected infrastructure ecosystem. This system must be easily accessible and useable by modelling communities across the world, allowing the global research community to be fully engaged in developing and delivering new scientific knowledge to support international climate policy.

Abstract Background Mechanobiological mechanisms of osteoarthritis (OA) are unclear. Our objectives were to explore: 1) changes in knee joint physiology using a large panel of synovial fluid biomarkers from before to one year after high tibial osteotomy (HTO) surgery, and 2) the association of changes in the synovial fluid biomarkers with the changes in MRI measures of knee effusion-synovitis and articular cartilage composition. Methods Twenty-six patients with symptomatic knee OA and varus alignment underwent synovial fluid aspirations and 3 T MRI before and one year after medial opening wedge HTO. Cytokine and growth factor levels in synovial fluid were measured with multiplex assays. Ontology and pathway enrichment was assessed using data protein sets with gene set enrichment analysis (GSEA), and analyzed using linear mixed effects models. MRIs were analyzed for effusion-synovitis and T2 cartilage relaxation time using manual segmentations. Changes in biomarker concentrations were correlated to changes in MRI effusion-synovitis volume and articular cartilage T2 relaxation times. Results Decreased enrichment in Toll-like receptor and TNF-α signalling was detected one year after HTO. The leading contributors to this reduction included IL-6, TNF-α and IL-1β, whereas the highest contributors to positive enrichment were EGF, PDGF-BB and FGF-2. Effusion-synovitis volume decreased (mean [95%CI]) one year after HTO (-2811.58 [-5094.40, -528.76mm3]). Effusion-synovitis volume was moderately correlated (r [95% CI]) with decreased MMP-1 (0.44 [0.05; 0.71]), IL-7 (0.41 [0.00; 0.69]) and IL-1β (0.59 [0.25; 0.80]) and increased MIP-1β (0.47 [0.10; 0.73]). Medial tibiofemoral articular cartilage T2 relaxation time decreased (mean [95% CI]) one year after HTO (-0.33 [-2.69; 2.05]ms). Decreased T2 relaxation time was moderately correlated to decreased Flt-3L (0.61 [0.28; 0.81]), IL-10 (0.47 [0.09; 0.73]), IP-10 (0.42; 0.03–0.70) and increased MMP-9 (-0.41 [-0.7; -0.03]) and IL-18 (-0.48 [-0.73; -0.10]). Conclusions Decreased aberrant knee mechanical loading in patients with OA is associated with decreased biological and imaging measures of inflammation (measured in synovial fluid and on MRI) and increased anabolic processes. These exploratory findings suggest that improvement in knee loading can produce long-term (one year) improvement in joint physiology.

The Copernicus Atmosphere Monitoring Service (CAMS) provides daily analyses and forecasts of the composition of the atmosphere, including the reactive gases such as O3, CO, NO2, HCHO and SO2; aerosol species; and greenhouse gases. The global CAMS analysis system (IFS-COMPO) is based on the ECMWF Integrated Forecasting System (IFS) for numerical weather prediction (NWP) and assimilates a large number of composition satellite products on top of the meteorological observations ingested in IFS. The CAMS system receives regular upgrades, following the upgrades of IFS. The last upgrade, Cy48R1, operational since 27 June 2023, was major with a large number of code changes, both for IFS-COMPO and for NWP. The main IFS-COMPO innovations include the introduction of full stratospheric chemistry; a major update of the emissions; a major update of the aerosol model, including the representation of secondary organic aerosol; several updates of the dust life cycle and optics; updates to the inorganic chemistry in the troposphere; and the assimilation of Visible Infrared Imaging Radiometer Suite (VIIRS) aerosol optical depth (AOD) and TROPOspheric Monitoring Instrument (TROPOMI) CO. The CAMS Cy48R1 upgrade was validated using a large number of independent measurement datasets, including surface in situ, surface remote sensing, routine aircraft, and balloon and satellite observations. In this paper we present the validation results for Cy48R1 by comparing them with the skill of the previous operational system (Cy47R3), with the independent observations as reference, for the period October 2022 to June 2023, during which daily forecasts from both cycles are available. Major improvements in skill are found for the ozone profile in the lower–middle stratosphere and for stratospheric NO2 due to the inclusion of full stratospheric chemistry. Stratospheric trace gases compare well with the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) observations between 10 and 200 hPa, with larger deviations between 1 and 10 hPa. The impact of the updated emissions is especially visible over East Asia and is beneficial for the trace gases O3, NO2 and SO2. The CO column assimilation is now anchored by the Infrared Atmospheric Sounding Interferometer (IASI) instead of the Measurements Of Pollution in The Troposphere (MOPITT) instrument, which is beneficial for most of the CO comparisons, and the assimilation of TROPOMI CO data improves the model CO field in the troposphere. In general the aerosol optical depth has improved globally, but the dust evaluation shows more mixed results. The results of the 47 comparisons are summarised in a scorecard, which shows that 83 % of the evaluation datasets show a neutral or improved performance of Cy48R1 compared to the previous operational CAMS system, while 17 % indicate a (slight) degradation. This demonstrates the overall success of this upgrade.

Beryllium-10 cosmic-ray exposure (CRE) dating has revolutionized our understanding of glacier fluctuations around the globe. A key prerequisite for the successful application of this dating method is the determination of regional production rates of in situ accumulated 10Be, usually inferred at independently dated calibration sites. Until now, no calibration site has been available for the mid-elevation mountain ranges of central Europe. We fill this gap by determining in situ 10Be concentrations in large boulders on moraines and by applying radiocarbon and infrared-stimulated luminescence (IRSL) dating to stratigraphically younger lake sediments in the southern Black Forest, SW Germany. The dating methods yielded concordant results, and, based on age–depth modelling with 14C ages, the age of a cryptotephra, and IRSL ages, we deduced a regional 10Be production rate in quartz. Calibrating the Black Forest production rate (BFPR) in the Cosmic-Ray Exposure program (CREp) resulted in a spallogenic sea-level and high-latitude (SLHL) production rate of 3.64±0.11 atoms 10Be g−1 quartz a−1 when referring to time-dependent Lal–Stone scaling, the European Reanalysis (ERA)-40 atmosphere model, and the atmospheric 10Be-based geomagnetic database in CREp. The BFPR turned out to be ∼11 % lower than both those at the nearest calibration site in the Alps (4.10±0.10 atoms 10Be g−1 quartz a−1 at SLHL) and the canonical global 10Be production rate (4.11±0.19 atoms 10Be g−1 quartz a−1 at SLHL) in CREp. A stronger weathering and snow cover bias and a higher impact of forest, soil, moss, and shrub cover at the study site likely explain this discrepancy.

The climate science community aims to improve our understanding of climate change due to anthropogenic influences on atmospheric composition and the Earth's surface. Yet not all climate interactions are fully understood, and uncertainty in climate model results persists, as assessed in the latest Intergovernmental Panel on Climate Change (IPCC) assessment report. We synthesize current challenges and emphasize opportunities for advancing our understanding of the interactions between atmospheric composition, air quality, and climate change, as well as for quantifying model diversity. Our perspective is based on expert views from three multi-model intercomparison projects (MIPs) – the Precipitation Driver Response MIP (PDRMIP), the Aerosol Chemistry MIP (AerChemMIP), and the Radiative Forcing MIP (RFMIP). While there are many shared interests and specializations across the MIPs, they have their own scientific foci and specific approaches. The partial overlap between the MIPs proved useful for advancing the understanding of the perturbation–response paradigm through multi-model ensembles of Earth system models of varying complexity. We discuss the challenges of gaining insights from Earth system models that face computational and process representation limits and provide guidance from our lessons learned. Promising ideas to overcome some long-standing challenges in the near future are kilometer-scale experiments to better simulate circulation-dependent processes where it is possible and machine learning approaches where they are needed, e.g., for faster and better subgrid-scale parameterizations and pattern recognition in big data. New model constraints can arise from augmented observational products that leverage multiple datasets with machine learning approaches. Future MIPs can develop smart experiment protocols that strive towards an optimal trade-off between the resolution, complexity, and number of simulations and their length and, thereby, help to advance the understanding of climate change and its impacts.

The Marine Isotope Stage 11c (MIS-11c) interglacial is an enigmatic period characterized by a long duration of relatively weak insolation forcing, but it is thought to have been coincident with a large global sea-level rise of 6–13 m. The configuration of the Greenland Ice Sheet during the MIS-11c interglacial highstand is therefore of great interest. Given the constraints of limited data, model-based analysis may be of use but only if model uncertainties are adequately accounted for. A particularly under-addressed issue in coupled climate and ice-sheet modeling is the coupling of surface air temperatures to the ice model. Many studies apply a uniform “lapse rate” accounting for the temperature differences at different altitudes over the ice surface, but this uniformity neglects both regional and seasonal differences in near-surface temperature dependencies on altitude. Herein we provide the first such analysis for MIS-11c Greenland that addresses these uncertainties by comparing one-way coupled Community Earth System Model (CESM) and ice-sheet model results from several different downscaling methodologies. In our study, a spatially and temporally varying temperature downscaling method produced the greatest success rate in matching the constraints of limited paleodata, and it suggests a peak ice volume loss from Greenland during MIS-11c of approximately 50 % compared to present day (∼ 3.9 m contribution to sea-level rise). This result is on the lower bound of existing data- and model-based studies, partly as a consequence of the applied one-way coupling methodology that neglects some feedbacks. Additional uncertainties are examined by comparing two different present-day regional climate analyses for bias correction of temperatures and precipitation, a spread of initialization states and times, and different spatial configurations of precipitation bias corrections. No other factor exhibited greater influence over the simulated Greenland ice sheet than the choice of temperature downscaling scheme.

Background: An olecranon stress fracture (OSF) is a rare injury most commonly seen in high-level overhead throwing athletes with no clear consensus on surgical treatment. The most common surgical treatment described in the literature is cannulated screw fixation but there have been high rates of reported hardware irritation and need for subsequent hardware removal. Hypothesis/Purpose: This study describes a novel surgical technique in the treatment of OSFs in high-level throwing athletes using retrograde headless compression screws. We hypothesized that patients would have excellent outcomes and decreased rates of hardware irritation postoperatively. Methods: A retrospective review of competitive-level throwing athletes who sustained OSFs that were treated operatively using a novel technique using retrograde cannulated headless compression screws to avoid disruption of the triceps tendon. Postoperative outcome measures obtained included the Disabilities of the Arm, Shoulder and Hand score, Mayo Elbow Performance Score, Simple Elbow Test score, Single Assessment Numerical Evaluation score, Visual Analog Scale, arch of motion, and time to return to sport as well as level returned to. Radiographs were obtained routinely at 2-week, 6-week, 12-week, 6-month, 1-year, and 2-year follow-up. Results: Five of 5 patients who met inclusion criteria were available for final follow-up. Mean age at time of surgery was 20 years (range 17-24). Mean follow-up was 17 months (range 4-33). All patients were baseball players, 4 of which were pitchers and 1 position player. All patients were able to return to sport at the same level or higher at a mean of 5.8 months (range 3-8). Postoperatively, mean arch of motion was 138°, Visual Analog Scale score was 0, Single Assessment Numerical Evaluation score was 90, Disabilities of the Arm, Shoulder and Hand score was 2.0, Mayo Elbow Performance Score was 100, and Simple Elbow Test score was 12. There was no incidence of hardware removal. Conclusion: This study presents a novel surgical technique in the treatment of OSFs in high-level throwing athletes. The results presented demonstrate that this technique is safe and effective for getting athletes back to play quickly without any complications of hardware irritation which has previously shown to be a significant problem in prior literature.

Advancements in digitalisation with cardiac implantable electronic devices (CIEDs) allow patients opportunities for improved autonomy, quality of life, and a potential increase in life expectancy. However, with the digital and functional practicalities of CIEDs, there exists also cyber safety issues with transferring wireless information. If a digital network were to be hacked, a CIED patient could experience both the loss of sensitive data and the loss of functional control of the CIED due to an unwelcome party. Moreover, if a CIED patient were to become victim of a cyber attack, which resulted in a serious or lethal event, and if this information were to become public, the trust in healthcare would be impacted and legal consequences could result. A cyber attack therefore poses not only a direct threat to the patient's health but also the confidentiality, integrity, and availability of the CIED, and these cyber threats could be considered "patient-targeted threats." Informed consent is a key component of ethical care, legally concordant practice, and promoting patient-as-partner therapeutic relationships [1]. To date, there are no standardised guidelines for listing cybersecurity risks within the informed consent or for discussing them during the consent process. Providers are responsible for adhering to the ethical principles of autonomy, beneficence, non-maleficence, and justice, both in medical practice generally and the informed consent process specifically. At present, the decision to include cybersecurity risks is mainly left to the provider's discretion, who may also have limited cyber risk information. Without effective and in-depth communication about all possible cybersecurity risks during the consent process, CIED patients can be left unaware of the privacy and physical risks they possess by carrying such a device. Therefore, cyber risk factors should be covered within the patients' informed consent and reviewed on an ongoing basis as new risk information becomes available. By including cyber risk information in the informed consent process, patients are given the autonomy to make the best-informed decision.

Anthropogenic emissions of aerosols and precursor compounds are known to significantly affect the energy balance of the Earth–atmosphere system, alter the formation of clouds and precipitation, and have a substantial impact on human health and the environment. Global models are an essential tool for examining the impacts of these emissions. In this study, we examine the sensitivity of model results to the assumed height of SO2 injection, seasonality of SO2 and black carbon (BC) particulate emissions, and the assumed fraction of SO2 emissions that is injected into the atmosphere as particulate phase sulfate (SO4) in 11 climate and chemistry models, including both chemical transport models and the atmospheric component of Earth system models. We find large variation in atmospheric lifetime across models for SO2, SO4, and BC, with a particularly large relative variation for SO2, which indicates that fundamental aspects of atmospheric sulfur chemistry remain uncertain. Of the perturbations examined in this study, the assumed height of SO2 injection had the largest overall impacts, particularly on global mean net radiative flux (maximum difference of −0.35 W m−2), SO2 lifetime over Northern Hemisphere land (maximum difference of 0.8 d), surface SO2 concentration (up to 59 % decrease), and surface sulfate concentration (up to 23 % increase). Emitting SO2 at height consistently increased SO2 and SO4 column burdens and shortwave cooling, with varying magnitudes, but had inconsistent effects across models on the sign of the change in implied cloud forcing. The assumed SO4 emission fraction also had a significant impact on net radiative flux and surface sulfate concentration. Because these properties are not standardized across models this is a source of inter-model diversity typically neglected in model intercomparisons. These results imply a need to ensure that anthropogenic emission injection height and SO4 emission fraction are accurately and consistently represented in global models.

Abstract Background Health care has the intrinsic obligation to preserve health. This concept is also applicable to planetary health. Nitrous oxide (N2O) lacks clinical indications in modern anaesthesia, while it is a high-potential greenhouse gas. Its seemingly low cost contrasts with the consequential externalised socio-economic costs due to its contribution to the climate crisis, which is approximately €698 per emitted ton of CO2 equivalent. This difference can be internalised through emission taxation. In this study, we aim to evaluate how much N2O – total amount and converted to CO2 equivalent – is used at a German university hospital and compare this amount to that used at European hospitals. Furthermore, how the cost of N2O usage changes under different emission taxation scenarios is calculated. Methods This trial was a retrospective observational study at a German university hospital with approximately 1,250 beds between 2016 and 2020. Additionally, five European hospitals from the Health Care Without Harm Network were used for comparison from a European perspective. The main outcome parameters were the amount of N2O used, in total and converted to CO2 equivalent, and the total cost at emission taxation of €0, €25, €55 and €698 per ton CO2 equivalent. Results At the peak, 2,104 tCO2 equivalent in N2O was emitted in 2019. The actual cost was €14,040 in this year, while the corresponding socio-economic damage due to the climate crisis was almost €1.5 million. Other European hospitals showed comparable amounts of emissions. Conclusions The annual peak amount of emitted N2O corresponded to the total annual greenhouse gas emission of 188 people in Germany. To achieve a drastic reduction in use, the abandonment of recommendations by anaesthesiologic societies appears necessary, in addition to an internalisation of future costs via emission taxation, which will cause inadequate cost for a medication without relevant benefit or indication. To that end, the inclusion of health sector emissions within national or international greenhouse gas taxation, for example, the European Union Emissions Trading System, appears necessary and expedient in view of the urgent need to address the ecological transformation. Trial registration The trial was registered with the German Clinical Trials Register, identifier DRKS00024973 on 12/04/2021.

Abstract Background Informal workplace learning (WPL) has no concrete learning objective and takes place without a responsible supervisor, which makes it difficult to assess its learning outcomes. Formal learning situations, as they are known from universities or schools, do not exist in this context and make a conventional assessment of learning goals and achievements impossible. Informal learning in the workplace is of central importance, and the assessment of informal learning outcomes in medical education is an under-researched area. The aim of our study was to adapt and validate an informal WPL questionnaire (originally developed for social workers) to assess learning outcomes due to informal WPL in residency training. Methods A total of 528 residents (n = 339 female; age: M = 29.79; SD = 3.37 years) completed an adapted questionnaire on informal WPL outcomes and the Freiburg Questionnaire to Assess Competencies in Medicine (i.e. medical knowledge, communication, and scholarship). Exploratory factor analysis was used to determine the underlying factor structure. The reliability of the factors was tested using McDonald’s omega, and the correlation between the factors and the three subscales of the Freiburg questionnaire was tested using Spearman’s rho correlation coefficient. To investigate construct validity, a structural equation model was calculated to examine the relationships between medical competencies and informal learning outcomes. Results The exploratory factor analysis yielded a four-factor solution that best fit the data. The scores of all four factors (GLO-CD: generic learning outcomes—competence development, GLO-R: generic learning outcomes—reflection, JSLO: job-specific learning outcomes, and OLLO: organisational learning outcomes) showed good internal consistency (Ω ≥ .69). The structural equation model showed that "medical expertise" had an impact on all four factors of informal learning at work. “Scholarship” seemed to predict GLO-CD and GLO-R. Conclusions Our four-factor model reveals meaningful determinants of informal WPL in relation to residency training. The instrument is therefore the first promising attempt to assess informal WPL in the broader context of medical education during residency, thus supporting its construct validity.

Introduction: Misfolding of amyloidogenic proteins is a molecular hallmark of neurodegenerative diseases in humans. A detailed understanding of the underlying molecular mechanisms is mandatory for developing innovative therapeutic approaches. The bovine PI3K-SH3 domain has been a model system for aggregation and fibril formation.Methods: We monitored the fibril formation kinetics of low pH-denatured recombinantly expressed [U-13C, 15N] labeled bovine PI3K-SH3 by a combination of solution NMR, high-resolution magic angle spinning (HR-MAS) NMR and solid-state NMR spectra. Solution NMR offers the highest sensitivity and, therefore, allows for the recording of two-dimensional NMR spectra with residue-specific resolution for individual time points of the time series. However, it can only follow the decay of the aggregating monomeric species. In solution NMR, aggregation occurs under quiescent experimental conditions. Solid-state NMR has lower sensitivity and allows only for the recording of one-dimensional spectra during the time series. Conversely, solid-state NMR is the only technique to detect disappearing monomers and aggregated species in the same sample by alternatingly recoding scalar coupling and dipolar coupling (CP)-based spectra. HR-MAS NMR is used here as a hybrid method bridging solution and solid-state NMR. In solid-state NMR and HR-MAS NMR the sample is agitated due to magic angle spinning.Results: Good agreement of the decay rate constants of monomeric SH3, measured by the three different NMR methods, is observed. Moderate MAS up to 8 kHz seems to influence the aggregation kinetics of seeded fibril formation only slightly. Therefore, under sufficient seeding (1% seeds used here), quiescent conditions (solution NMR), and agitated conditions deliver similar results, arguing against primary nucleation induced by MAS as a major contributor. Using solid-state NMR, we find that the amount of disappeared monomer corresponds approximately to the amount of aggregated species under the applied experimental conditions (250 µM PI3K-SH3, pH 2.5, 298 K, 1% seeds) and within the experimental error range. Data can be fitted by simple mono-exponential conversion kinetics, with lifetimes τ in the 14–38 h range. Atomic force microscopy confirms that fibrils substantially grew in length during the aggregation experiment. This argues for fibril elongation as the dominant growth mechanism in fibril mass (followed by the CP-based solid-state NMR signal).Conclusion: We suggest a combined approach employing both solution NMR and solid-state NMR, back-to-back, on two aliquots of the same sample under seeding conditions as an additional approach to follow monomer depletion and growth of fibril mass simultaneously. Atomic force microscopy images confirm fibril elongation as a major contributor to the increase in fibril mass.

Despite a large number of studies, out of all drivers of radiative forcing, the effect of aerosols has the largest uncertainty in global climate model radiative forcing estimates. There have been studies of aerosol optical properties in climate models, but the effects of particle number size distribution need a more thorough inspection. We investigated the trends and seasonality of particle number concentrations in nucleation, Aitken, and accumulation modes at 21 measurement sites in Europe and the Arctic. For 13 of those sites, with longer measurement time series, we compared the field observations with the results from five climate models, namely EC-Earth3, ECHAM-M7, ECHAM-SALSA, NorESM1.2, and UKESM1. This is the first extensive comparison of detailed aerosol size distribution trends between in situ observations from Europe and five earth system models (ESMs). We found that the trends of particle number concentrations were mostly consistent and decreasing in both measurements and models. However, for many sites, climate models showed weaker decreasing trends than the measurements. Seasonal variability in measured number concentrations, quantified by the ratio between maximum and minimum monthly number concentration, was typically stronger at northern measurement sites compared to other locations. Models had large differences in their seasonal representation, and they can be roughly divided into two categories: for EC-Earth and NorESM, the seasonal cycle was relatively similar for all sites, and for other models the pattern of seasonality varied between northern and southern sites. In addition, the variability in concentrations across sites varied between models, some having relatively similar concentrations for all sites, whereas others showed clear differences in concentrations between remote and urban sites. To conclude, although all of the model simulations had identical input data to describe anthropogenic mass emissions, trends in differently sized particles vary among the models due to assumptions in emission sizes and differences in how models treat size-dependent aerosol processes. The inter-model variability was largest in the accumulation mode, i.e. sizes which have implications for aerosol–cloud interactions. Our analysis also indicates that between models there is a large variation in efficiency of long-range transportation of aerosols to remote locations. The differences in model results are most likely due to the more complex effect of different processes instead of one specific feature (e.g. the representation of aerosol or emission size distributions). Hence, a more detailed characterization of microphysical processes and deposition processes affecting the long-range transport is needed to understand the model variability.

Anthropogenic aerosols exert a cooling influence that offsets part of the greenhouse gas warming. Due to their short tropospheric lifetime of only several days, the aerosol forcing responds quickly to emissions. Here, we present and discuss the evolution of the aerosol forcing since 2000. There are multiple lines of evidence that allow us to robustly conclude that the anthropogenic aerosol effective radiative forcing (ERF) – both aerosol–radiation interactions (ERFari) and aerosol–cloud interactions (ERFaci) – has become less negative globally, i.e. the trend in aerosol effective radiative forcing changed sign from negative to positive. Bottom-up inventories show that anthropogenic primary aerosol and aerosol precursor emissions declined in most regions of the world; observations related to aerosol burden show declining trends, in particular of the fine-mode particles that make up most of the anthropogenic aerosols; satellite retrievals of cloud droplet numbers show trends in regions with aerosol declines that are consistent with these in sign, as do observations of top-of-atmosphere radiation. Climate model results, including a revised set that is constrained by observations of the ocean heat content evolution show a consistent sign and magnitude for a positive forcing relative to the year 2000 due to reduced aerosol effects. This reduction leads to an acceleration of the forcing of climate change, i.e. an increase in forcing by 0.1 to 0.3 W m−2, up to 12 % of the total climate forcing in 2019 compared to 1750 according to the Intergovernmental Panel on Climate Change (IPCC).

Three time-slice carbon cycle simulations for the last glacial maximum (LGM) constrained by the CO2 concentration in the atmosphere and the increase in the mean concentration of dissolved inorganic carbon in the deep ocean were carried out with a fully coupled comprehensive climate model (the Community Earth System Model version 1.2). The three modelled LGM ocean states yielded different physical features in response to artificial freshwater forcing, and, depending on the physical states, suitable amounts of carbon and alkalinity were added to the ocean to satisfy constraints from paleo-data. In all the simulations, the amount of carbon added was in line with the inferred transfers of carbon among various reservoirs during the evolution from the LGM to the pre-industrial (PI) period, suggesting that the simulated glacial ocean states are compatible with the PI one in terms of the carbon budget. The increase in total alkalinity required to simulate ocean states that were deemed appropriate for the LGM was in broad quantitative accord with the scenario of post-glacial shallow water deposition of calcium carbonate, although a more precise assessment would demand further studies of various processes such as the land chemical weathering and deep-sea burial of calcium carbonates, which have affected the alkalinity budget throughout history since the LGM. On the other hand, comparisons between the simulated distributions of paleoceanographic tracers and corresponding reconstructions clearly highlighted the different water-mass geometries and favoured a shallower Atlantic meridional overturning circulation (AMOC) for the LGM as compared to PI.

Abstract Probainognathia is a derived lineage of cynodonts which encompass Mammalia as their crown-group. The rich record of probainognathians from the Carnian of Argentina contrasts with their Norian representation, with only one named species. Here we describe a new probainognathian, Tessellatia bonapartei gen. et sp. nov., from the Norian Los Colorados Formation of the Ischigualasto-Villa Unión Basin of Argentina. The new taxon, represented by a partial cranium with associated lower jaws, was analyzed through neutron and X-rays micro-tomography (μCT). The high-resolution neutron μCT data allowed the identification of a unique character combination, including features inaccessible through traditional techniques. We constructed the largest phylogenetic data matrix of non-mammalian cynodonts. The new species and its sister taxon, the Brazilian Therioherpeton cargnini, are recovered as probainognathians, closely related to Mammaliamorpha. We conducted the first quantitative paleobiogeographic analysis of non-mammalian cynodonts, focusing in probainognathians. The results indicate that Probainognathia and Mammaliamorpha originated in southwestern Gondwana (in the Brazilian Paraná Basin), which was an important center of diversification during the Triassic. Finally, the Chinese Lufeng Basin is identified as the ancestral area of Mammaliaformes. These new findings, besides adding to the knowledge of the poorly represented Norian cynodonts from the Los Colorados Formation, are significant to improve our understanding of probainognathian diversity, evolution, and paleobiogeographic history.

The unique alignment of orbital precession and obliquity during the Marine Isotope Stage 11 (MIS-11) interglacial produced perhaps the longest period of planetary warmth above preindustrial conditions in the past 800 kyr. Reconstructions point to a significantly reduced Greenland ice sheet volume during this period as a result, although the remaining extent and volume of the ice sheet are poorly constrained. A series of time slice simulations across MIS-11 using a coupled climate model indicates that boreal summer was particularly warm around Greenland and the high latitudes of the Atlantic sector for a period of at least 20 kyr. This state of reduced atmospheric baroclinicity, coupled with an enhanced and poleward-shifted intertropical convergence zone and North African monsoon, favored weakened high-latitude winds and the emergence of a single, unified midlatitude jet stream across the North Atlantic sector during boreal summer. Consequent reductions in the lower-tropospheric meridional eddy heat flux over the North Atlantic therefore emerge as negative feedback to additional warming over Greenland. The relationship between Greenland precipitation and the state of the North Atlantic jet is less apparent, but slight changes in summer precipitation appear to be dominated by increases during the remainder of the year. Such a dynamic state is surprising, as it bears stronger resemblance to the unified-jet state postulated as typical for glacial states than to the modern-day interglacial state.

We report on Precambrian microfossils from igneous rocks of the Volyn pegmatite district, associated with the Paleoproterozoic Korosten pluton, northwestern Ukraine. The fossils were recovered from meter-sized miarolitic cavities and show a well-preserved 3D morphology, mostly filamentous but with a large variety of types and also in irregular, flaky shapes reminiscent of former biofilms, as well as rare spherical objects. Based on literature data, pyrolysis experiments, and reflected light microscopy results, the organic matter (OM) is characterized as (oxy-)kerite. Further investigations with microscopic techniques, including scanning and transmission electron microscopy, and electron microprobe analysis show that fossilization likely occurred during a hydrothermal, post-pegmatitic event by silicification dominantly in the outermost 1–2 µm of the microfossils. The hydrothermal fluid, derived from the pegmatitic environment, was enriched in SiF4, Al, Ca, Na, K, Cl, and S. The OM shows O enrichment in which N and S content is low, indicating simultaneous N and S loss during anaerobic oxidation. Mineralization with Al silicates starts at the rim of the microfossils, continuing in its outer parts into identifiable encrustations and intergrowths of clay minerals, feldspar, Ca sulfate, Ca phosphate, Fe sulfide, and fluorite. Breccias, formed during collapse of some the miarolitic cavities, contain decaying OM, which released high concentrations of dissolved NH4+, responsible for the late-stage formation of tobelite-rich muscovite and buddingtonite. The age of the fossils can be restricted to the time between the pegmatite formation, at ∼1.760 Ga, and the breccia formation at ∼1.49 Ga. As the geological environment for the growth of the microorganisms and fossilization, we assume a geyser system in which the essential biological components C, N, S, and P for growth of the organisms in the miarolitic cavities were derived from microorganisms at the surface. Fossilization was induced by magmatic SiF4-rich fluids. The Volyn occurrence is a distinct and uncommon example of Precambrian fossils, and the results underline the importance of cavities in granitic rocks as a possible habitat for microorganisms preserved in the deep biosphere.

A sensor based on a piezoelectric single crystal enables operation even under harsh environmental conditions. In addition to the sensor element, the packaging technology is crucial for sensor performance. In this paper, a suitable assembly and interconnection technology concept of Ca3TaGa3Si2O14 (CTGS) resonators for high-temperature applications is presented as a platform for future sensor assemblies. The concept described here has already been functionally tested as a temperature sensor (Schulz et al., 2021). The concept includes a sapphire base plate, a housing lid, and a spacer made from aluminium oxide (Al2O3). The substrate is metallised with platinum manufactured into thin film and thick film technology. The ceramic components are fused with glass solder. The connection of the resonator to the conductive tracks is realised by thermosonic bonding with 25 µm platinum wire. Initially, the stability of the metallisation must be investigated before subsequent electrical testing under high temperature. Diffusion processes play a major role in this temperature range, and the stability of the layer is a necessary condition for subsequent investigations. A suitable set of bonding parameters and the strength of the platinum bonds prior to and after thermal load is analysed. Shear tests are used to evaluate the quality of the ceramic materials fused with glass solder after thermal ageing. The dielectrical properties of sapphire and glass solder such as the isolation resistance, the relative permittivity, and the loss factor at high temperatures are evaluated using interdigital structures. The loss factor is measured on both bare interdigital structures and the samples coated with glass solder to make an estimation about the conductive behaviour up to 1000 ∘C. A ceramic lid for the sensor housing is attached by a high-temperature stable glass solder. Since platinum conductors are fed through this glass solder connection, the electrical conductivity of the glass solder is characterised at high temperature. Furthermore, the hermeticity of the assemblies is verified by means of helium leakage tests. These investigations are the basis for the implementation of an assembly and interconnection technology that is suitable for reliable operation under extreme temperature conditions. The packaging technology also offers further possibilities for pressure or chemical sensors that can withstand high-temperature loads.

Synucleinopathies like Parkinson's disease are neurodegenerative diseases which are associated with the deposition of fibrillar aggregates of the endogenous protein α-synuclein (α-syn). The inhibition of the elongation of α-syn fibrils is of great scientific interest and an option in the design of therapeutic strategies. Previously, we developed a disulfide-containing mutant of α-syn, called CC48, which inhibits fibril elongation by blocking of fibril ends. Surprisingly, wildtype (WT) α-syn molecules supported the blocked state, and a fusion of CC48 with WT α-syn, denoted WT-CC48, exhibited increased inhibitory potential. Here, we studied which regions of WT-CC48 are responsible for the strong inhibitory effect. To this end, we investigated a set of truncated versions of WT-CC48 by kinetic elongation assays, density gradient centrifugation, and atomic force microscopy. We show that in both the WT and the CC48 part of the fusion construct the hairpin region (residue 32–60) and NAC region (61–95), but not N- and C-terminal regions, are required for strong inhibition of fibril elongation. The required regions correspond to the segments forming the β-sheet core of α-syn fibrils. As α-syn fibrils typically consist of two protofilaments, the dimeric construct WT-CC48 provides the critical regions sufficient to cover the full β-sheetcore interface exposed at the fibril end, which can explain its high inhibitory efficiency. We suggest a mechanistic model of CC48-mediated inhibition of fibril elongation in which CC48 and WT α-syn cooperatively form an oligomer-like cap at the amyloid fibril end.

The presence of atypical cytoskeletal dynamics, structures, and associated morphologies is a common theme uniting numerous diseases and developmental disorders. In particular, cytoskeletal dysregulation is a common cellular feature of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. While the numerous activators and inhibitors of dysregulation present complexities for characterizing these elements as byproducts or initiators of the disease state, it is increasingly clear that a better understanding of these anomalies is critical for advancing the state of knowledge and plan of therapeutic attack. In this review, we focus on the hallmarks of cytoskeletal dysregulation that are associated with cofilin-linked actin regulation, with a particular emphasis on the formation, monitoring, and inhibition of cofilin-actin rods. We also review actin-associated proteins other than cofilin with links to cytoskeleton-associated neurodegenerative processes, recognizing that cofilin-actin rods comprise one strand of a vast web of interactions that occur as a result of cytoskeletal dysregulation. Our aim is to present a current perspective on cytoskeletal dysregulation, connecting recent developments in our understanding with emerging strategies for biosensing and biomimicry that will help shape future directions of the field.

ImportanceMost healthcare institutions require employees to be vaccinated against SARS-CoV-2 and many also require at least one booster.ObjectiveWe determine the impact of vaccine type, demographics, and health conditions on COVID-19 vaccine side effects in healthcare professionals.DesignA COVID-19 immunity study was performed at the 2021 American Association for Clinical Chemistry Annual Scientific meeting. As part of this study, a REDCap survey with cascading questions was administered from September 9, 2021 to October 20, 2021. General questions included participant demographics, past and present health conditions, smoking, exercise, and medications. COVID-19 specific questions asked about SARS-CoV-2 vaccine status and type, vaccine-associated side effects after each dose including any boosters, previous infection with COVID-19, diagnostic testing performed, and type and severity symptoms of COVID-19.ResultsThere were 975 participants (47.1% male, median age of 50 years) who completed the survey. Pfizer was the most commonly administered vaccine (56.4%) followed by Moderna (32.0%) and Johnson & Johnson (7.1%). There were no significant differences in vaccine type received by age, health conditions, smoking, exercise, or type or number of prescription medications. Side effects were reported more frequently after second dose (e.g., Moderna or Pfizer) (54.1%) or single/only dose of Johnson & Johnson (47.8%). Males were significantly more likely to report no side effects (p < 0.001), while females were significantly more likely to report injection site reactions (p < 0.001), fatigue (p < 0.001), headache (p < 0.001), muscle pain (p < 0.001), chills (p = 0.001), fever (p = 0.007), and nausea (p < 0.001). There was a significant upward trend in participants reporting no side effects with increasing age (p < 0.001). There were no significant trends in side effects among different races, ethnicities, health conditions, medications, smoking status or exercise. In multivariate logistic regressions analyses, the second dose of Moderna was associated with a significantly higher risk of side effects than both the second dose of Pfizer and the single dose of Johnson & Johnson.Conclusions and relevanceYounger people, females, and those receiving the second dose of Moderna had more COVID-19 vaccine side effects that per self-report led to moderate to severe limitations. As reported in other studies, the increase in side effects from Moderna may be explained by higher viral mRNA concentrations but be associated with additional protective immunity.

In spring 2020, many U.S. colleges and universities rapidly shifted to online instruction and implemented social distancing policies to respond to the COVID-19 pandemic. Students experienced unprecedented disruption of their interpersonal academic and social networks due to the loss of physical proximity. We used egocentric network analysis and latent profile analysis with survey data from April 2020 and conducted follow-up interviews in September 2020 to examine some of the pandemic’s immediate effects on student interpersonal network change. We found the disappearance of interpersonal network patterns featuring coworkers and academic ties, as well as reductions in students’ overall number of connections and the role diversity of their networks. Results suggest potential ongoing reduction of peer academic relationships, implying that institutional personnel may need to pay particular attention to academic connections in online spaces and to regenerating students’ academic networks when on-campus physical spaces may again be used to support learning.

We report neutron depolarization measurements of the suppression of long-range ferromagnetism and the concomitant emergence of magnetic irreversibilities and spin freezing in CePd_{1−x}Rh_{x} around x^{*}≈0.6. Tracking the temperature versus field history of the neutron depolarization, we find clear signatures of long-range Ising ferromagnetism below a Curie temperature T_{C} for x=0.4 and a spin freezing of ferromagnetic clusters below a freezing temperature T_{F1} for x>x^{*}. Under zero-field-cooling/field-heating and for x>x^{*} a reentrant temperature dependence of the neutron depolarization between T_{F2}