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Membrane lipids of ammonia-oxidizing Thaumarchaeota, in particular isoprenoidal glycerol dialkyl glycerol tetraethers (isoGDGTs) and hydroxylated isoGDGTs (OH-isoGDGTs), have been used as biomarkers and as proxies in various environments. Controlled growth experiments have been used to investigate the factors that influence the composition of these lipids, in particular on how these factors affect the TEX86 temperature proxy, which is based on the degree of cyclization of isoGDGTs. Recently, the ring index of OH-isoGDGTs (RI-OH′), based on cyclization patterns of OH-isoGDGTs, and the abundance of OH-isoGDGTs relative to summed abundances of OH-isoGDGTs and regular isoGDGTs (% OH) have emerged as promising temperature proxies. Here, we examined the impact of growth temperature and growth phase on the distribution of OH-isoGDGTs and their associated proxies using cultures of two thaumarchaeotal strains. Analysis of core lipids and headgroup compositions of isoGDGTs and OH-isoGDGTs showed no consistent differences between the mid-exponential and stationary phases for both strains. Nitrosopumilus adriaticus NF5 shows a substantially higher relative abundance of OH-isoGDGTs (∼ 49 %) compared to Nitrosopumilus piranensis D3C (∼ 5 %) and also relative to observations reported for core lipids in the marine environment (< 17 %), indicating large variations in % OH values even among closely related species. Unlike in the marine environment, the % OH did not decrease with increasing temperatures in either of the strains, possibly reflecting a threshold below 15 °C for this response in the natural environment. The RI-OH′ increases with increasing temperature in cultures of both strains, similar to the ring index of regular isoGDGTs. The relative abundances of the headgroups varied between strains and did not respond to changes in temperature or growth phase. The % OH and RI-OH′ calculated from intact polar lipids with different headgroups revealed large differences between the distinct intact polar lipids, similar to that previously observed for regular isoGDGTs. Together, our findings suggest that growth temperature has a pronounced effect on the degree of cyclization in isoGDGTs and OH-isoGDGTs, in contrast to the relative abundance of OH-isoGDGTs, which mainly exhibits interspecies variability.

Iron (Fe) is a key limiting nutrient for Southern Ocean phytoplankton. Input of Fe into the Southern Ocean is projected to change due to global warming, yet the combined effects of a concurrent increase in temperature with dissolved Fe (dFe) addition on phytoplankton growth and community composition have not been extensively studied. To improve our understanding of how Antarctic phytoplankton communities respond to Fe and enhanced temperature, we performed four full factorial onboard bioassays under trace-metal-clean conditions with phytoplankton communities from different regions of the Weddell Sea and the Amundsen Sea in the Southern Ocean. Treatments consisted of 2 nM Fe addition with 2 °C warming (TF), Fe addition at in situ temperature (F) +2 °C warming with no Fe addition (T) and a control at in situ temperature with no Fe addition (control, C). Temperature had a limited effect by itself but boosted the positive response of the phytoplankton to Fe addition. Photosynthetic efficiency, phytoplankton abundances and chlorophyll a concentrations typically increased (significantly) with Fe addition (F and/or TF treatment), and the phytoplankton community generally shifted from haptophytes to diatoms upon Fe addition. The < 20 µm phytoplankton fraction displayed population-specific growth responses, resulting in a pronounced shift in community composition and size distribution (mainly towards larger-sized phytoplankton) for the F and TF treatments. Such a distinct enhanced impact of dFe supply with warming on Antarctic phytoplankton size, growth and composition will likely affect trophic transfer efficiency and ecosystem structure, with potential significance for the biological carbon pump.

In this paper, we present the results of an investigation into the effects of engaging with robotic telescopes during an Astronomy 101 (Astro101) course in the United States and Canada on the self-efficacy of students. Using an astronomy self-efficacy survey that measures both astronomy personal self-efficacy and instrumental self-efficacy, the authors probed their covariance with the respondents' experience of an Astro101 course that uses robotic telescopes to collect astronomical data. Strong effects on both self-efficacy scales were seen over the period of a semester utilizing a scalable educational design using robotic telescopes. After participation in the course, the results show that the gender gap in self-efficacy between self-identified men and women is largely reduced to statistically insignificant differences compared to the initial large significant difference.

Abstract Digitisation has increasingly become a feature of education. Educational policy, too, has increasingly focused on digital processes and structures. Digital data opens up opportunities to improve the governance of continuing education given the inadequacy of existing statistics in the field of continuing education and training (CET). In this paper we use the InfoWeb Weiterbildung (IWWB) to demonstrate how CET search portals could be used as a data source to map available supply of CET. Using trends in CET delivery formats (online vs. face-to-face) and the regional distribution of offers as examples, potential practical applications of digitally-sourced data are illustrated. Requirements and limitations are discussed and research perspectives are drawn.

The policy of merging education institutions to improve efficiency and reduce public expenditure has gained popularity in many European countries. However, although this phenomenon is observed in adult education, there is currently a paucity of evidence on the subject within this field. We integrated novel data from 101 mergers of adult education centres in Germany between 1995 and 2017 with longitudinal performance data (n = 21,032) and used Poisson pseudo-marginal-likelihood fixed effects analysis to examine the impact of institutional mergers on funding levels, educational provision, and efficiency. Our results show that those institutions that were involved in a merger experienced significant reductions in institutional funding and hours of educational provision post-merger. However, the effects were smaller when we controlled for organisation-specific trends, suggesting that some of the reductions were a continuation of pre-merger consolidation trends rather than solely due to mergers. In terms of efficiency, positive effects were observed in the short run, but estimates for the medium and long run were relatively small and not statistically significant. Moreover, there was considerable variation in efficiency estimates, highlighting the heterogeneity of outcomes across cases. Thus, our study provides limited evidence to support the hypothesis that the analysed mergers have led to improved efficiency.

Marine biogenic calcium carbonate production plays a role in the exchange of CO2 between ocean and atmosphere. The effect of increased CO2 on calcification and on the resulting chemistry of shells and skeletons, however, is only partly understood. Foraminifera are among the main marine CaCO3 producers and the controls on element partitioning and isotope fractionation is the subject of many recent investigations. The enzyme carbonic anhydrase (CA) was, for example, shown to be vital for CaCO3 deposition in benthic foraminifera and indicates their ability to manipulate their intracellular inorganic carbon chemistry. Here, we tested whether CA affects the partitioning of Na, Mg and Sr in the perforate, large benthic, symbiont-bearing foraminifer Amphistegina lessonii by addition of the inhibitor acetazolamide (AZ). The effect of dissolved CO2 on the effect of CA on element partitioning was also determined using a culturing setup with controlled atmospheric carbon dioxide levels (400–1,600 ppm). Results show that inhibition by AZ reduces calcification greatly and that CO2 has a small, but positive effect on the amount of calcite formed during the incubations. Furthermore, the inhibition of CA activity has a positive effect on element partitioning, most notably Mg. This may be explained by a (n indirect) coupling of inorganic carbon uptake and inward calcium ion pumping.

Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial.

The isotopic and elemental composition of the fossil shells of foraminifera are often used for reconstructing past environments and climates. These so-called proxy relations are based on the effect of environmental conditions (e.g. seawater temperature, pH) on the isotopic ratio (e.g. δ11B or δ18O) or partitioning of elements (commonly expressed as El/Ca or DEl) during calcification. Whereas many studies focused on proxy-calibrations of divalent cations, incorporation of monovalent cations are less well constrained. Here we calibrate shell potassium content (K/Cacc) as a function of 1) seawater K+ concentration, 2) the ratio of potassium and calcium in seawater (K/Casw) and 3) temperature. Moreover, we analyze Na+ incorporation into the calcite as a function of seawater K+ and Ca2+ concentrations. First, we cultured specimens of the larger benthic foraminifer Amphistegina lessonii at four different seawater [Ca2+] and constant [K+], resulting in a range of K/Casw. Secondly, we cultured specimens of the same species at four different [Ca2+]sw and [K+]sw while keeping the ratio between these two ions constant. Finally, we tested the effect of temperature (from 18 to 28°C) on K-incorporation in this species. Measured K/Cacc values are not notably affected by [Ca2+]sw, while seawater [K+] positively influences potassium incorporation, resulting in a positive correlation between seawater K/Ca values and K/Cacc. Although the [Na+] in the culture media was constant throughout both experiments, incorporated Na responded positively to decreasing [Ca2+]sw, resulting in a positive correlation between sea water Na/Ca and Na/Cacc. The difference in the controls on K- and Na-incorporation suggests that the (biological) control on these ions differs. Part of the observed variability in element partitioning may be explained by differences in chemical speciation and crystallographic coordination in the calcite lattice.

Abstract Contextual embeddings, derived from deep language models (DLMs), provide a continuous vectorial representation of language. This embedding space differs fundamentally from the symbolic representations posited by traditional psycholinguistics. We hypothesize that language areas in the human brain, similar to DLMs, rely on a continuous embedding space to represent language. To test this hypothesis, we densely record the neural activity patterns in the inferior frontal gyrus (IFG) of three participants using dense intracranial arrays while they listened to a 30-minute podcast. From these fine-grained spatiotemporal neural recordings, we derive a continuous vectorial representation for each word (i.e., a brain embedding) in each patient. Using stringent zero-shot mapping we demonstrate that brain embeddings in the IFG and the DLM contextual embedding space have common geometric patterns. The common geometric patterns allow us to predict the brain embedding in IFG of a given left-out word based solely on its geometrical relationship to other non-overlapping words in the podcast. Furthermore, we show that contextual embeddings capture the geometry of IFG embeddings better than static word embeddings. The continuous brain embedding space exposes a vector-based neural code for natural language processing in the human brain.

Abstract Aims Cardiomyopathies (CMPs) are a heterogeneous group of diseases that are defined by structural and functional abnormalities of the cardiac muscle. Dilated cardiomyopathy (DCM), the most common CMP, is defined by left ventricular dilation and impaired contractility and represents a common cause of heart failure. Different phenotypes result from various underlying genetic and acquired causes with variable effects on disease development and progression, prognosis, and response to medical treatment. Current treatment algorithms do not consider these different aetiologies, due to lack of insights into treatable drivers of cardiac failure in patients with DCM. Our study aims to precisely phenotype and genotype the various subtypes of DCM and hereby lay the foundation for individualized therapy. Methods and results The Geno‐ And Phenotyping of PrImary Cardiomyopathy (GrAPHIC) is a currently ongoing prospective observational monocentric cohort study that recruits patients with DCM after exclusion of other causes such as coronary artery disease, valvular dysfunction, myocarditis, exposure to toxins, and peripartum CMP. Patients are enrolled at our heart failure outpatient clinic or during hospitalization at the University Hospital Hamburg. Clinical parameters, multimodal imaging and functional assessment, cardiac biopsies, and blood samples are obtained to enable an integrated genomic, functional, and biomarker analysis. Conclusions The GrAPHIC will contribute to a better understanding of the heterogeneous nature of primary CMPs focusing on DCM and provide improved prognostic approaches and more individualized therapies.

BackgroundThe differentiation of high-grade glioma and brain tumors of an extracranial origin is eminent for the decision on subsequent treatment regimens. While in high-grade glioma, a surgical resection of the tumor mass is a fundamental part of current standard regimens, in brain metastasis, the burden of the primary tumor must be considered. However, without a cancer history, the differentiation remains challenging in the imaging. Hence, biopsies are common that may help to identify the tumor origin. An additional tool to support the differentiation may be of great help. For this purpose, we aimed to identify a biomarker panel based on the expression analysis of a small sample of tissue to support the pathological analysis of surgery resection specimens. Given that an aberrant glutamate signaling was identified to drive glioblastoma progression, we focused on glutamate receptors and key players of glutamate homeostasis.MethodsBased on surgically resected samples from 55 brain tumors, the expression of ionotropic and metabotropic glutamate receptors and key players of glutamate homeostasis were analyzed by RT-PCR. Subsequently, a receiver operating characteristic (ROC) analysis was performed to identify genes whose expression levels may be associated with either glioblastoma or brain metastasis.ResultsOut of a total of 29 glutamatergic genes analyzed, nine genes presented a significantly different expression level between high-grade gliomas and brain metastases. Of those, seven were identified as potential biomarker candidates including genes encoding for AMPA receptors GRIA1, GRIA2, kainate receptors GRIK1 and GRIK4, metabotropic receptor GRM3, transaminase BCAT1 and the glutamine synthetase (encoded by GLUL). Overall, the biomarker panel achieved an accuracy of 88% (95% CI: 87.1, 90.8) in predicting the tumor entity. Gene expression data, however, could not discriminate between patients with seizures from those without.ConclusionWe have identified a panel of seven genes whose expression may serve as a biomarker panel to discriminate glioblastomas and brain metastases at the molecular level. After further validation, our biomarker signatures could be of great use in the decision making on subsequent treatment regimens after diagnosis.

BackgroundRecent advancements in Artificial Intelligence (AI) contributed significantly to suicide assessment, however, our theoretical understanding of this complex behavior is still limited.ObjectiveThis study aimed to harness AI methodologies to uncover hidden risk factors that trigger or aggravate suicide behaviors.MethodsThe primary dataset included 228,052 Facebook postings by 1,006 users who completed the gold-standard Columbia Suicide Severity Rating Scale. This dataset was analyzed using a bottom-up research pipeline without a-priory hypotheses and its findings were validated using a top-down analysis of a new dataset. This secondary dataset included responses by 1,062 participants to the same suicide scale as well as to well-validated scales measuring depression and boredom.ResultsAn almost fully automated, AI-guided research pipeline resulted in four Facebook topics that predicted the risk of suicide, of which the strongest predictor was boredom. A comprehensive literature review using APA PsycInfo revealed that boredom is rarely perceived as a unique risk factor of suicide. A complementing top-down path analysis of the secondary dataset uncovered an indirect relationship between boredom and suicide, which was mediated by depression. An equivalent mediated relationship was observed in the primary Facebook dataset as well. However, here, a direct relationship between boredom and suicide risk was also observed.ConclusionIntegrating AI methods allowed the discovery of an under-researched risk factor of suicide. The study signals boredom as a maladaptive ‘ingredient’ that might trigger suicide behaviors, regardless of depression. Further studies are recommended to direct clinicians’ attention to this burdening, and sometimes existential experience.

Abstract Reconstruction of the marine inorganic carbon system relies on proxy signal carriers, such as element/calcium (El/Ca) ratios in foraminiferal shells. Concentrations of boron, lithium, strontium, and sulfur have been shown to vary with carbonate system parameters, but when comparing individual proxy reconstructions based on these elements, they are rarely in complete agreement. This is likely caused by the simultaneous effects of multiple environmental factors on element incorporation. Culture experiments with benthic foraminifera have revealed that the shell's S/Ca reflects the carbon chemistry and can potentially be used as a proxy for seawater [CO32−]. Aiming to investigate the application potential of sulfur incorporation for carbonate speciation reconstruction, we present S/Ca ratios in five planktonic foraminiferal species, namely Globigerina bulloides, Globigerinoides ruber albus, Globigerinoides ruber ruber, Trilobatus sacculifer, and Neogloboquadrina incompta from core‐top sediments in regions with contrasting [CO32−], [HCO3−], temperature, and salinity. Analyses of B/Ca and Mg/Ca ratios are included here since these elements have been shown to depend to a certain degree on carbon system parameters (e.g., calcite saturation state and pH, respectively) as well. Moreover, foraminiferal Mg/Ca values covary with S/Ca values and thereby might compromise its proxy application. In contrast to previously published results, this new data set shows a positive correlation between the incorporation of sulfur in the foraminifer's shell and seawater [CO32−]. As the incorporation of sulfur and magnesium are positively correlated, S/Mg values of the same foraminifera may be used to improve inorganic carbon system reconstructions.

Sedimentary bulk organic matter and various molecular organic components exhibit strong CO2-dependent carbon isotope fractionation relative to dissolved inorganic carbon sources. This fractionation (εp) has been employed as a proxy for paleo-pCO2. Yet, culture experiments indicate that CO2-dependent εp is highly specific at genus and even species level, potentially hampering the use of bulk organic matter and non-species-specific organic compounds. In recent years, significant progress has been made towards a CO2 proxy using controlled growth experiments with dinoflagellate species, also showing highly species-specific εp values. These values were, however, based on motile specimens, and it remains unknown whether these relations also hold for the organic-walled resting cysts (dinocysts) produced by these dinoflagellate species in their natural environment. We here analyze dinocysts isolated from core tops from the Atlantic Ocean and Mediterranean Sea, representing several species (Spiniferites elongatus, S. (cf.) ramosus, S. mirabilis, Operculodinium centrocarpum sensu Wall and Dale (1966) (hereafter referred to as O. centrocarpum) and Impagidinium aculeatum) using laser ablation–nano-combustion–gas-chromatography–isotope ratio mass spectrometry (LA/nC/GC-IRMS). We find that the dinocysts produced in the natural environment are all appreciably more 13C-depleted compared to the cultured motile dinoflagellate cells, implying higher overall εp values, and, moreover, exhibit large isotope variability. Where several species could be analyzed from a single location, we often record significant differences in isotopic variance and offsets in mean δ13C values between species, highlighting the importance of single-species carbon isotope analyses. The most geographically expanded dataset, based on O. centrocarpum, shows that εp correlates significantly with various environmental parameters. Importantly, O. centrocarpum shows a CO2-dependent εp above ∼ 240 µatm pCO2. Similar to other marine autotrophs, relative insensitivity at low pCO2 is in line with active carbon-concentrating mechanisms at low pCO2, although we here cannot fully exclude that we partly underestimated εp sensitivity at low pCO2 values due to the relatively sparse sampling in that range. Finally, we use the relation between εp and pCO2 in O. centrocarpum to propose a first pCO2 proxy based on a single dinocyst species.

The chemical composition of foraminiferal shells is a well-known tool in paleoceanography to reconstruct past environments and climate. Their application is based on the relation between environmental variables and the concentration of elements incorporated or stable isotope fractionation during calcification. The vast majority of these so-called proxy relationships are based on the foraminiferal order of the Rotaliida, which, for example, encompasses all living planktonic species. However, there are more orders of foraminifera with calcifying members, some of which have fundamentally different biomineralization pathways, such as the Nodosariida, the Polymorphinida and the Vaginulinida. All these belong to the class of the Nodosariata and produce calcite shells, which may serve as carriers of paleoenvironmental and climate signals. The microstructures of these shells and overall morphology of these foraminifera strongly deviate from the Rotaliida, suggesting that their elemental and stable isotopic composition do not necessarily respond similarly to environmental parameters. A potential advantage of the Nodosariata is that they appear considerably earlier in the fossil record (Carboniferous) than the Rotaliida (Jurassic), thereby possibly extending the range of foraminifer-based paleoceanographic reconstructions considerably. To test the potential application of Nodosariata foraminifera as paleoproxies, we investigated incorporation of 5 elements in 11 species as a function of environmental parameters from a transect sampled in the Gulf of Mexico. Their element composition (B / Ca, Na / Ca, Mg / Ca, Sr / Ca and Ba / Ca) shows a distinct geochemical signature for these foraminifera, different to that of members of other foraminiferal orders. Results also show an increase in Mg / Ca values with increasing temperature, similar to that known for the Rotaliida, which suggest that Nodosariata shells might be useful for paleotemperature reconstructions. The difference in Mg / Ca–temperature calibration in Nodosariata compared to Rotaliida, with the large differences in their morphology, shell microstructures and overall geochemical composition, suggests that the Mg / Ca-to-temperature relationship is partly independent of the exact calcification mechanism. We compare Mg / Ca–temperature sensitivities across foraminiferal orders and describe a relationship between the average Mg / Ca and the sensitivity of the Mg / Ca–temperature calibration. For other elements, the variability across orders is smaller compared to that in Mg / Ca, which results in more similar El / Ca–environmental calibrations.

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint.

Abstract Background About 50% of older patients with acute myeloid leukemia (AML) fail to attain complete remission (CR) following cytarabine plus anthracycline-based induction therapy. Salvage chemotherapy regimens are based on high-dose cytarabine (HiDAC), which is frequently combined with mitoxantrone (HAM regimen). However, CR rates remain low, with less than one-third of the patients achieving a CR. FLT3-ITD has consistently been identified as an unfavorable molecular marker in both relapsed and refractory (r/r)-AML. One-quarter of patients who received midostaurin are refractory to induction therapy and relapse rate at 2 years exceeds 40%. The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is a very selective FLT3 inhibitor, has a high capacity for sustained FLT3 inhibition, and has an acceptable toxicity profile. Methods In this multicenter, upfront randomized phase II trial, all patients receive quizartinib combined with HAM (cytarabine 3g/m2 bidaily day one to day three, mitoxantrone 10mg/m2 days two and three) during salvage therapy. Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach with achievement of CR, complete remission with incomplete hematologic recovery (CRi), or complete remission with partial recovery of peripheral blood counts (CRh) as primary endpoint. During consolidation therapy (chemotherapy and allogeneic hematopoietic cell transplantation), patients receive either prophylactic quizartinib therapy or measurable residual disease (MRD)-triggered preemptive continuation therapy with quizartinib according to up-front randomization. The matched threshold crossing approach is a novel study-design to enhance the classic single-arm trial design by including matched historical controls from previous clinical studies. It overcomes common disadvantages of single-armed and small randomized studies, since the expected outcome of the observed study population can be adjusted based on the matched controls with a comparable distribution of known prognostic and predictive factors. Furthermore, balanced treatment groups lead to stable statistical models. However, one of the limitations of our study is the inability to adjust for unobserved or unknown confounders. Addressing the primary endpoint, CR/CRi/CRh after salvage therapy, the maximal sample size of 80 patients is assessed generating a desirable power of the used adaptive design, assuming a logistic regression is performed at a one-sided significance level α=0.05, the aspired power is 0.8, and the number of matching partners per intervention patient is at least 1. After enrolling 20 patients, the trial sample size will be recalculated in an interim analysis based on a conditional power argument. Conclusion Currently, there is no commonly accepted standard for salvage chemotherapy treatment. The objective of the salvage therapy is to reduce leukemic burden, achieve the best possible remission, and perform a hemopoietic stem-cell transplantation. Thus, in patients with FLT3-ITD mutation, the comparison of quizartinib with intensive salvage therapy versus chemotherapy alone appears as a logical consequence in terms of efficacy and safety. Ethics and dissemination Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings. Trial registration ClinicalTrials.gov NCT03989713; EudraCT Number: 2018-002675-17.

The chemical composition of mollusk shells is a useful tool in (paleo)climatology since it captures inter- and intra-annual variability in environmental conditions. Trace element and stable isotope analysis with improved sampling resolution now allows in situ determination of the composition of mollusk shell volumes precipitated at daily to sub-daily time intervals. Here, we discuss hourly resolved Mg / Ca, Mn / Ca, Sr / Ca, and Ba / Ca profiles measured by laser ablation inductively coupled plasma – mass spectrometry (ICP-MS) through shells of the photosymbiotic giant clams (Tridacna maxima, T. squamosa, and T. squamosina) and the non-photosymbiotic scallop Pecten maximus. Precise sclerochronological age models and spectral analysis allowed us to extract daily and tidal rhythms in the trace element composition of these shells. We find weak but statistically significant expressions of these periods and conclude that this cyclicity explains less than 10 % of the sub-annual variance in trace element profiles. Tidal and diurnal rhythms explain variability of, at most, 0.2 mmol mol−1 (∼ 10 % of mean value) in Mg / Ca and Sr / Ca, while ultradian Mn / Ca and Ba / Ca cyclicity has a median amplitude of less than 2 µmol mol−1 mol mol−1 (∼ 40 % and 80 % of the mean of Mn / Ca and Ba / Ca, respectively). Daily periodicity in Sr / Ca and Ba / Ca is stronger in Tridacna than in Pecten, with Pecten showing stronger tidal periodicity. One T. squamosa specimen which grew under a sunshade exhibits among the strongest diurnal cyclicity. Daily cycles in the trace element composition of giant clams are therefore unlikely to be driven by variations in direct insolation but rather reflect an inherent biological rhythmic process affecting element incorporation. Finally, the large amount of short-term trace element variability unexplained by tidal and daily rhythms highlights the dominance of aperiodic processes in mollusk physiology and/or environmental conditions over shell composition at the sub-daily scale. Future studies should aim to investigate whether this remaining variability in shell chemistry reliably records weather patterns or circulation changes in the animals' environment.

Since the industrial revolution the ocean has become noisier. The global increase in shipping is one of the main contributors to this. In some regions, shipping contributed to an increase in ambient noise of several decibels, especially at low frequencies (10 to 100 Hz). Such an increase can have a substantial negative impact on fish, invertebrates, marine mammals and birds interfering with key life functions (e.g. foraging, mating, resting, etc.). Consequently, engineers are investigating ways to reduce the noise emitted by vessels when designing new ships. At the same time, since the industrial revolution (starting around 1760) greenhouse gas emissions have increased the atmospheric carbon dioxide fraction x(CO2) by more than 100 μmol mol-1. The ocean uptake of approximately one third of the emitted CO2 decreased the average global surface ocean pH from 8.21 to 8.10. This decrease is modifying sound propagation, especially sound absorption at the frequencies affected by shipping noise lower than 10 kHz, making the future ocean potentially noisier. There are also other climate change effects that may influence sound propagation. Sea surface warming might alter the depth of the deep sound speed channel, ice melting could locally decrease salinity and more frequent storms and higher wind speed alter the depth of the thermocline. In particular, modification of the sound speed profile can lead to the appearance of new ducts making specific depths noisier. In addition, ice melting and the increase in seawater temperature will open new shipping routes at the poles increasing anthropogenic noise in these regions. This review aims to discuss parameters that might change in the coming decades, focusing on the contribution of shipping, climate change and economic and technical developments to the future underwater soundscape in the ocean. Examples are given, contrasting the open ocean and the shallow seas. Apart from the changes in sound propagation, this review will also discuss the effects of water quality on ship-radiated noise with a focus on propeller cavitation noise.

Previous research has identified maladaptive emotion regulation as a key factor in psychopathology. Thus, addressing emotion regulation via scalable, low-threshold digital interventions – such as smartphone-based Cognitive Bias Modification (CBM) – holds important therapeutic potential. Using a randomized-controlled crossover trial, we tested the efficacy of an integrated CBM module within the Affect Regulation Training (ART, i.e., CBM-ART) that targeted emotion regulation through elements of appraisal-based and approach avoidance training.Undergraduate students reporting elevated stress were randomized to a one-week active intervention (Mindgames; including psychoeducation, a quiz, and CBM-ART; n = 40), active control training (Emo Shape; including placebo psychoeducation, a quiz, and a placebo swiping task; n = 36) or waitlist (n = 25). Before and after the intervention, we assessed emotion regulation, interpretation bias, stress and depression. We further tested post-training stress reactivity using an anagram task.Results indicated that the active intervention improved negative (OR = 0.35) and positive (OR = 2.40) interpretation biases and symptom measures (d = 0.52–0.87). However, active control training showed attenuated concurrent pre-post changes on interpretation biases (i.e., OR = 0.53 for negative, and OR = 1.49 for positive interpretations) and symptom measures (d = 0.26–0.91). The active intervention was rated positively in terms of acceptability and usability.These findings provide initial evidence for the efficacy and acceptability of an integrated app-based CBM intervention for emotion regulation in reducing interpretation biases and psychopathological symptoms, including stress. However, future studies should disentangle specific mechanisms underlying interventional effects.

We report the study of a huge optical intraday flare on 2021 November 12 at 2 a.m. UT in the blazar OJ 287. In the binary black hole model, it is associated with an impact of the secondary black hole on the accretion disk of the primary. Our multifrequency observing campaign was set up to search for such a signature of the impact based on a prediction made 8 yr earlier. The first I -band results of the flare have already been reported by Kishore et al. (2024). Here we combine these data with our monitoring in the R -band. There is a big change in the R – I spectral index by 1.0 ± 0.1 between the normal background and the flare, suggesting a new component of radiation. The polarization variation during the rise of the flare suggests the same. The limits on the source size place it most reasonably in the jet of the secondary BH. We then ask why we have not seen this phenomenon before. We show that OJ 287 was never before observed with sufficient sensitivity on the night when the flare should have happened according to the binary model. We also study the probability that this flare is just an oversized example of intraday variability using the Krakow data set of intense monitoring between 2015 and 2023. We find that the occurrence of a flare of this size and rapidity is unlikely. In machine-readable Tables 1 and 2, we give the full orbit-linked historical light curve of OJ 287 as well as the dense monitoring sample of Krakow.

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.

Since the industrial revolution, oceans have become substantially noisier. The noise increase is mainly caused by increased shipping, resource exploration, and infrastructure development affecting marine life at multiple levels, including behavior and physiology. Together with increasing anthropogenic noise, climate change is altering the thermal structure of the oceans, which in turn might affect noise propagation. During this century, we are witnessing an increase in seawater temperature and a decrease in ocean pH. Ocean acidification will decrease sound absorption at low frequencies (500 km). In the case of the Northeast Atlantic Ocean, this sub-surface duct will only be present during winter, leading to similar total mean square pressure level (SPLtot) values in the summer for both (2018 to 2022) and (2094 to 2098). We observed a strong and similar correlation for the two climate change scenarios, with an increase of the top 200 m SPLtot and a slowdown of Atlantic Meridional Overturning Circulation (AMOC) leading to an increase of SPLtot at the end of the century by 7 dB.