Die Schulschließungen während der COVID-19-Pandemie hatten substantielle negative Effekte für Familien und Kinder. Wir zeigen, dass ein höherer Frauenanteil in nationalen europäischen Regierungen mit einer signifikant geringeren Wahrscheinlichkeit von Schulschließungen einherging. Dies unterstreicht die Bedeutung einer vielfältigeren politischen Repräsentation. Gleichzeitig plädieren wir dafür, zukünftige politische Entscheidungen in Krisen auf eine umfassendere, evidenzbasierte Abwägung der mittel- und langfristigen Kosten und Nutzen von Schulschließungen zu stützen.

Forests in eastern Germany are already experiencing the detrimental effects of droughts, exemplified by the severe conditions of the 2018 drought year. With climate change, such extreme events are expected to become more frequent and severe. Previous work suggests that mixed forests exhibit greater resilience against droughts than monocultures. Our study aims to investigate the impact of increased frequency of extreme droughts, such as those seen in 2018, on biomass, structure, and traits of forests in the eastern German federal states of Berlin and Brandenburg. Utilizing the flexible-trait dynamic global vegetation model LPJmL-FIT, we simulate the growth and competition of individual trees in both pine monoculture forests and mixed forests. The trees belong to different plant functional types or in the case of pine forests are parametrized as Pinus sylvestris . We create drought scenarios from high-resolution climate input data by re-shuffling the contemporary climate with increased frequencies of the extreme drought year 2018. For each scenario, we simulated vegetation dynamics over 800 simulation years which, allowed us to analyze shorter-term impacts in the first decades of the drought scenarios, as well as the long-term adaptation of the two forest types to those new climate normals. We evaluated the resulting long-term changes in biomass, plant functional traits, and forest structure to examine the new equilibrium state emerging for each scenario. Our findings revealed nuanced responses to increased drought frequency. In pine monoculture forests, increased drought frequency reduced biomass and increased biomass variance, indicating higher system instability. Conversely, in mixed forests, biomass initially declined in scenarios with increased drought frequency but eventually recovered and even exceeded baseline levels after 100–150 years. We explain recovery and increase in biomass through two forest adaptation mechanisms; first, we saw a shift in the plant community towards broadleaved trees, and second, plant traits shifted towards increased average wood density, decreased average tree height, and increased average tree age. However, for the most extreme scenario with drought occurring each year, the adaptive capacity of the mixed forest was exceeded, and the biomass halved compared to the baseline scenario. In our study, for the first time LPJmL-FIT is used with a resolution as high as 2 ×2 km 2 , which allows us to observe spatial heterogeneity drought impacts within the Berlin–Brandenburg area. Pine monocultures suffered, especially in the warmer urban areas, and mixed forests in the central–western part of Brandenburg benefitted in the long term. This study highlights the capacity of natural mixed forests in contrast to pine monocultures to adapt to increasing drought frequency up to a certain limit. The results underscore the importance of considering biodiversity in forest management strategies, especially with regard to more frequent dry periods under climate change.

Background Off-label antipsychotic use is not uncommon in youth with anorexia nervosa (AN), aiming to enhance suboptimal weight restoration, yet its efficacy remains debated, especially in youth. Methods Retrospective chart review of consecutively admitted inpatients (ages 8-18 years) with restricting/bingepurge AN, comparing youth with versus without antipsychotic treatment regarding baseline factors, treatment, and anthropometric outcome characteristics including all patients and matched subgroups. Matched subsamples were also compared regarding faster versus slower weight change (median split). Furthermore, within-subject analyses compared weight gain trajectories before versus after antipsychotic use in antipsychotic-treated youth. These results were then compared in a pre-/post design with the matched control group without antipsychotic treatment, using the mean duration until antipsychotic use in the antipsychotic-treated group as the dividing timeline, controlling for a potential order effect, in that later rather than earlier antipsychotic treatment for AN may be more successful. Results Of 294 youth with AN (median age = 15.2 (interquartile range = 14.0, 16.6) years, females = 96.6%, restricting subtype = 81.0%, hospitalization duration = 98.2 +/- 43.2 days), 44 (15.0%) underwent 52 antipsychotic trials (olanzapine = 63.5%). In multivariable analyses, antipsychotic use was independently associated with younger age, childhood physical abuse history, comorbid borderline personality traits, and lower pre-antipsychotic weight gain (p < 0.0001). In unmatched groups, antipsychotic-treated versus non-treated youth had significantly lower discharge anthropometric parameters, longer inpatient treatment, and lower weight change/week (p < 0.001-p = 0.005), without significant differences between olanzapine and non-olanzapine antipsychotics (p = 0.27-0.44). Non-significant antipsychotic effects on weight outcomes were confirmed in (1) matched subgroups of antipsychotic-treated versus non-treated youth (n = 43 each), (2) youth with faster versus slower weight gain (n = 21 vs. n = 22), and (3) antipsychotic-treated youth when comparing weight change before versus after antipsychotic use (n = 31). Moreover, in antipsychotic-treated youth, weight change/week remained significantly lower versus matched non-antipsychotic-treated youth (n = 31) both before (p = 0.053) and after (p = 0.006) the median time (5 weeks) until antipsychotic use. Conclusions In this naturalistic study, clinician's antipsychotic choice, given to a more severely ill subgroup of adolescents with AN, did not significantly improve overall worse weight change trajectories during inpatient treatment,

BackgroundDiagnostic accuracy is one of the major cornerstones of appropriate and successful medical decision-making. Clinical decision support systems (CDSSs) have recently been used to facilitate physician's diagnostic considerations. However, to date, little is known about the potential assets of CDSS for medical students in an educational setting. The purpose of our study was to explore the usefulness of CDSSs for medical students assessing their diagnostic performances and the influence of such software on students' trust in their own diagnostic abilities.MethodsBased on paper cases students had to diagnose two different patients using a CDSS and conventional methods such as e.g. textbooks, respectively. Both patients had a common disease, in one setting the clinical presentation was a typical one (tonsillitis), in the other setting (pulmonary embolism), however, the patient presented atypically. We used a 2x2x2 between- and within-subjects cluster-randomised controlled trial to assess the diagnostic accuracy in medical students, also by changing the order of the used resources (CDSS first or second).ResultsMedical students in their 4(th) and 5(th) year performed equally well using conventional methods or the CDSS across the two cases (t(164) = 1,30; p = 0.197). Diagnostic accuracy and trust in the correct diagnosis were higher in the typical presentation condition than in the atypical presentation condition (t(85) = 19.97; p < .0001 and t(150) = 7.67; p < .0001).These results refute our main hypothesis that students diagnose more accurately when using conventional methods compared to the CDSS.ConclusionsMedical students in their 4(th) and 5(th) year performed equally well in diagnosing two cases of common diseases with typical or atypical clinical presentations using conventional methods or a CDSS. Students were proficient in diagnosing a common disease with a typical presentation but underestimated their own factual knowledge in this scenario. Also, students were aware of their own diagnostic limitations when presented with a challenging case with an atypical presentation for which the use of a CDSS seemingly provided no additional insights.

BackgroundIn older adults, epidemiological data on incidence rates (IR) of hospital-acquired acute kidney injury (AKI) are scarce. Also, little is known about trajectories of kidney function before hospitalization with AKI.MethodsWe used data from biennial face-to-face study visits from the prospective Berlin Initiative Study (BIS) including community-dwelling participants aged 70+ with repeat estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. Primary outcome was first incident of hospital-acquired AKI assessed through linked insurance claims data. In a nested case-control study, kidney function decline prior to hospitalization with and without AKI was investigated using eGFR trajectories estimated with mixed-effects models adjusted for traditional cardiovascular comorbidities.ResultsOut of 2020 study participants (52.9% women; mean age 80.4 years) without prior AKI, 383 developed a first incident AKI, 1518 were hospitalized without AKI, and 119 were never hospitalized during a median follow-up of 8.8 years. IR per 1000 person years for hospital-acquired AKI was 26.8 (95% confidence interval (CI): 24.1-29.6); higher for men than women (33.9 (29.5-38.7) vs. 21.2 (18.1-24.6)). IR (CI) were lowest for persons aged 70-75 (13.1; 10.0-16.8) and highest for & GE; 90 years (54.6; 40.0-72.9). eGFR trajectories declined more steeply in men and women with AKI compared to men and women without AKI years before hospitalization. These differences in eGFR trajectories remained after adjustment for traditional comorbidities.ConclusionAKI is a frequent in-hospital complication in individuals aged 70 + showing a striking increase of IR with age. eGFR decline was steeper in elderly patients with AKI compared to elderly patients without AKI years prior to hospitalization emphasising the need for long-term kidney function monitoring pre-admission to improve risk stratification.

With the late 18th and early 19th century the movement of speculative antiquarianism in France and Great Britain reached its peak. Figures like Charles Dupuis, Jean-Sylvain Bailly, Jacob Bryant, or Georges Stanley Faber might have been different in the final aims of their theoretical architecture, but they nevertheless had many objects in common. One key figure of the early 18th century was Charles Vallancey (1731–1812), who with immense efforts tried to demonstrate how a primordial European religion was created by the Druids. His student was the freemason Godfrey Higgins (1772–1838), who in his intentions was even more ambitious than his predecessor. In his Celtic Druids (1827) and especially in his two-volume Anacalypsis (1836) Higgins, according to his opinion, consistently demonstrated how the oldest of all religions was based on a simple model of astral-religious Buddhism, and especially Jews were the heirs of this tradition. Christian Kabbalah was forming a key instrument to support this theory, by laying open the inner – Buddhistic – sense of the Pentateuch. The paper aims to give a survey of Higgins complex synthesis and exemplifies his use of Christian Kabbalah in his Anacalypis.

Porcine reproductive and respiratory syndrome virus (PRRSV), an Arteriviridae family enveloped RNA virus, is a major swine pathogen. Using yeast transformation-associated recombination (TAR) cloning, we efficiently generated infectious PRRSV and GFP-expressing clones, identifying transcription-regulating sequences as essential for stable foreign gene expression. Screening SARS-CoV-2 antivirals showed potent inhibition by the multitarget drug ribavirin, the polymerase inhibitors remdesivir and its metabolite GS-441524. Molnupiravir, targeting the polymerase by a different mechanism, showed reduced efficacy against PRRSV, while the protease inhibitor GC376 was ineffective. The AlphaFold-predicted structure of the PRRSV polymerase revealed conserved catalytic architecture with the SARS-CoV-2 polymerases, explaining cross-family inhibitor activity. In contrast, structural divergence in proteases correlated with GC376’s inefficacy. These findings underscore the utility of the TAR cloning for arterivirus engineering, with potential applications in vector vaccine development.

Management of malignant hemispheric stroke (MHS) after cardiothoracic surgery (CTS) remains difficult as decision-making needs to consider severe cardiovascular comorbidities and complex coagulation management. The results of previous randomized controlled trials on decompressive surgery for MHS cannot be generally translated to this patient population and the expected outcome might be substantially worse. Here, we analyzed mortality and functional outcome in patients undergoing decompressive hemicraniectomy (DC) for MHS following CTS and assessed the impact of perioperative coagulation management on postoperative hemorrhagic and cardiovascular complications. All patients that underwent DC for MHS resulting as a complication of CTS between June 2012 and November 2021 were included in this observational cohort study. Outcome was determined according to the modified Rankin Scale (mRS) score at 1 and 3-6 months. Clinical and demographic data, anticoagulation management and postoperative hemorrhagic and thromboembolic complications were assessed. In order to evaluate a predictive association between clinical and radiological parameters and the outcome, we used a multivariate logistic regression analysis. Twenty-nine patients undergoing DC for MHS after CTS with a female-to-male ratio of 1:1.9 and a median age of 60 (IQR 49-64) years were identified out of 123 patients undergoing DC for MHS. Twenty-four patients (83%) received pre- or intraoperative substitution. At 30 days, the in-hospital mortality rate and neurological outcome corresponded to 31% and a median mRS of 5 (5-6), which remained stable at 3-6 months [Mortality: 42%, median mRS: 5 (4-6)]. Postoperatively, 15/29 patients (52%) experienced new hemorrhagic lesions and Bayesian logistic regression predicting mortality (mRS = 6) after imputing missing data demonstrated a significantly increased risk for mortality with longer aPPT (OR = 13.94, p = .038) and new or progressive hemorrhagic lesions after DC (OR = 3.03, p = .19). Notably, all but one hemorrhagic lesion occurred before discontinued anticoagulation and/or platelet inhibition was re-initiated. Despite perioperative discontinuation of anticoagulation and/or platelet inhibition, no coagulation-associated cardiovascular complications were noted. In conclusion, Cardiothoracic surgery patients suffering MHS will likely experience severe neurological disability after DC, which should remain a central aspect during counselling and decision-making. The complex coagulation situation after CTS, however, should not per se rule out the option of performing life-saving surgical decompression.

Magnetic resonance imaging (MRI) is widely used for ischemic stroke lesion detection in mice. A challenge is that lesion segmentation often relies on manual tracing by trained experts, which is labor-intensive, time-consuming, and prone to inter- and intra-rater variability. Here, we present a fully automated ischemic stroke lesion segmentation method for mouse T2-weighted MRI data. As an end-to-end deep learning approach, the automated lesion segmentation requires very little preprocessing and works directly on the raw MRI scans. We randomly split a large dataset of 382 MRI scans into a subset (n = 293) to train the automated lesion segmentation and a subset (n = 89) to evaluate its performance. We compared Dice coefficients and accuracy of lesion volume against manual segmentation, as well as its performance on an independent dataset from an open repository with different imaging characteristics. The automated lesion segmentation produced segmentation masks with a smooth, compact, and realistic appearance that are in high agreement with manual segmentation. We report dice scores higher than the agreement between two human raters reported in previous studies, highlighting the ability to remove individual human bias and standardize the process across research studies and centers.

Intrahepatic cholangiocarcinoma (iCCA) is a rare, understudied primary hepatic malignancy with dismal outcomes. Aiming to identify prognostically relevant single-nucleotide polymorphisms, we analyzed 11 genetic variants with a role in tumor-promoting inflammation (VEGF, EGF, EGFR, IL-1B, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A and PTGS2 (COX-2) genes) and their association with disease-free (DFS) and overall survival (OS) in patients undergoing curative-intent surgery for iCCA. Genomic DNA was isolated from 112 patients (64 female, 48 male) with iCCA. Germline polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism protocols. The IL-1B +3954 C/C (73/112, hazard ratio (HR) = 1.735, p = 0.012) and the IL-8 -251 T/A or A/A (53/112 and 16/112, HR = 2.001 and 1.1777, p = 0.026) genotypes were associated with shorter OS in univariable and multivariable analysis. The IL-1B +3954 polymorphism was also associated with shorter DFS (HR = 1.983, p = 0.012), but this effect was not sustained in the multivariable model. A genetic risk model of 0, 1 and 2 unfavorable alleles was established and confirmed in multivariable analysis. This study supports the prognostic role of the IL-1B C+3954T and the IL-8 T-251A variant as outcome markers in iCCA patients, identifying patient subgroups at higher risk for dismal clinical outcomes.

BackgroundMechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ss pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC.MethodsFor 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection.ResultsHigh EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504-0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352-0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression.ConclusionsEVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity.

Different theories explain how subjective experience arises from brain activity1,2. These theories have independently accrued evidence, but have not been directly compared3. Here we present an open science adversarial collaboration directly juxtaposing integrated information theory (IIT)4,5 and global neuronal workspace theory (GNWT)6,7,8,9,10 via a theory-neutral consortium11,12,13. The theory proponents and the consortium developed and preregistered the experimental design, divergent predictions, expected outcomes and interpretation thereof12. Human participants (n = 256) viewed suprathreshold stimuli for variable durations while neural activity was measured with functional magnetic resonance imaging, magnetoencephalography and intracranial electroencephalography. We found information about conscious content in visual, ventrotemporal and inferior frontal cortex, with sustained responses in occipital and lateral temporal cortex reflecting stimulus duration, and content-specific synchronization between frontal and early visual areas. These results align with some predictions of IIT and GNWT, while substantially challenging key tenets of both theories. For IIT, a lack of sustained synchronization within the posterior cortex contradicts the claim that network connectivity specifies consciousness. GNWT is challenged by the general lack of ignition at stimulus offset and limited representation of certain conscious dimensions in the prefrontal cortex. These challenges extend to other theories of consciousness that share some of the predictions tested here14,15,16,17. Beyond challenging the theories, we present an alternative approach to advance cognitive neuroscience through principled, theory-driven, collaborative research and highlight the need for a quantitative framework for systematic theory testing and building.

Sub-Neptunes, the most common planet type, remain poorly understood. Their atmospheres are expected to be diverse, but their compositions are challenging to determine, even with JWST. Here, we present the first JWST spectroscopic study of the warm sub-Neptune GJ 3090 b (2.13 R⊕, Teq,A = 0.3 ∼ 700 K), which orbits an M2V star, making it a favorable target for atmosphere characterization. We observed four transits of GJ 3090 b: two each using JWST NIRISS/SOSS and NIRSpec/G395H, yielding wavelength coverage from 0.6 to 5.2 μm. We detect the signature of the 10833 Å metastable helium triplet at a statistical significance of 5.5σ with an amplitude of 434 ± 79 ppm, marking the first such detection in a sub-Neptune with JWST. This amplitude is significantly smaller than predicted by solar-metallicity forward models, suggesting a metal-enriched atmosphere that decreases the mass-loss rate and attenuates the helium feature amplitude. Moreover, we find that stellar contamination, in the form of the transit light source effect, dominates the NIRISS transmission spectra, with unocculted spot and faculae properties varying across the two visits separated in time by approximately 6 months. Free retrieval analyses on the NIRSpec/G395H spectrum find tentative evidence for highly muted features and a lack of CH4. These findings are best explained by a high-metallicity atmosphere (>100× solar at 3σ confidence for clouds at ∼μbar pressures) using chemically consistent retrievals and self-consistent model grids. Further observations of GJ 3090 b are needed for tighter constraints on the atmospheric abundances and to gain a deeper understanding of the processes that led to its potential metal enrichment.

The availability of nitrogen (N) and phosphorus (P) is essential for soil microbial activity and growth, yet global patterns of N and P limitation in soil microbial metabolism remain largely unknown. We modeled ecoenzyme stoichiometry data from 5,259 field observations of natural ecosystems to assess microbial N and P limitation in global surface soils. We found that microbial P limitation, which was especially strong at low latitudes, was more prevalent globally than microbial N limitation, which prevailed in cold environments. We also found widespread N and P colimitation in soil microorganisms in the tropics, contradicting the long-held paradigm that P, and not N, is the primary limiting nutrient at low latitudes. This colimitation could be attributable to elevated microbial N demand for the synthesis of P-acquiring enzymes under P limitation. Upscaling (0.1 × 0.1° spatial resolution) suggested that soil microorganisms were limited by N and P in 39% and 57%, respectively, of natural terrestrial surface areas, with 21% of areas with N and P colimitation. As a global assessment of spatial variation in microbial N and P limitation, our results highlight the importance of N availability in supporting microbial P acquisition at low latitudes and improve our understanding of microbial nutrient limitation on a global scale.

Conservation flagships are an effective approach to mobilize support for conservation. The flagship concept has recently been expanded beyond species, to include also fleets, protected areas, ecosystems, individuals, and events. Here, we present a unifying framework of flagship categories and their use, provide a roadmap for flagship selection, and give recommendations for their use in conservation practice. We also propose the flexible encompassing term ‘flagship entity’, broadly defined as a unique and recognizable entity that can be easily communicated for conservation purposes. Flagship entities are characterized by their biological and ecological organization level, temporal state, geographical reach, current level of use, and effectiveness. Flagship selection should be driven by sound knowledge and a clear understanding of the target audience’s conscious and subconscious preferences and its intended use. Further work is needed to evaluate the effectiveness of various flagship categories and concepts, and the positive and negative economic outcomes of flagship strategies.

Deep ocean circulation modulated glacial–interglacial climates through feedbacks to the carbon cycle and energy distribution. Past work has suggested that contraction of well-ventilated North Atlantic Deep Water during glacial times facilitated carbon storage in the deep ocean and drawdown of atmospheric CO2 levels. However, the spatial extent and properties of different water masses remain uncertain, in part due to conflicting palaeoceanographic proxy reconstructions. Here we combine five independent proxies to increase confidence and reconstruct Atlantic deep water distributions during the Last Glacial Maximum (around 21 thousand years ago) and the following Heinrich Stadial 1—a time when massive ice rafting in the North Atlantic interfered with deep water formation and caused global climate shifts. We find that North Atlantic Deep Water remained widespread in both periods, although its properties shifted from a cold, well-ventilated mode to a less-ventilated, possibly warmer, mode. This finding implies a remarkable persistence of deep water formation under these cold boundary conditions, sustained by compensation between the two formation modes. Our constraints provide an important benchmark for evaluating Earth system models, which can enhance confidence in future climate projections.