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Abstract Background Intragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI. Methods We retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany. Results Seven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits. Conclusion Our study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.

Abstract The peak-to-average power ratio (PAPR), commonly used to describe the amplitude variations of an OFDM (orthogonal frequency-division multiplex) signal, does not accurately reflect its impact on the system performance. This paper applies the mutual information as a metric to assess the effects of nonlinear PAPR reduction schemes on the performance of OFDM systems. Evaluation of the achieved mutual information shows that a significant capacity loss from clipping occurs only at high SNR (signal-to-noise ratio) and a simple compression/expansion technique is proposed to achieve close to optimal performance in this regime. The effectiveness of this method is validated through WER (word error rate) simulations with several modulation and coding schemes.

Abstract Background The first 24 h of infection represent a critical time window in interactions between pathogens and host tissue. However, it is not possible to study such early events in human lung during natural infection due to lack of clinical access to tissue this early in infection. We, therefore, applied RNA sequencing to ex vivo cultured human lung tissue explants (HLTE) from patients with emphysema to study global changes in small noncoding RNA, mRNA, and long noncoding RNA (lncRNA, lincRNA) populations during the first 24 h of infection with influenza A virus (IAV), Mycobacterium bovis Bacille Calmette-Guerin (BCG), and Pseudomonas aeruginosa. Results Pseudomonas aeruginosa caused the strongest expression changes and was the only pathogen that notably affected expression of microRNA and PIWI-associated RNA. The major classes of long RNAs (> 100 nt) were represented similarly among the RNAs that were differentially expressed upon infection with the three pathogens (mRNA 77–82%; lncRNA 15–17%; pseudogenes 4–5%), but lnc-DDX60-1, RP11-202G18.1, and lnc-THOC3-2 were part of an RNA signature (additionally containing SNX10 and SLC8A1) specifically associated with IAV infection. IAV infection induced brisk interferon responses, CCL8 being the most strongly upregulated mRNA. Single-cell RNA sequencing identified airway epithelial cells and macrophages as the predominant IAV host cells, but inflammatory responses were also detected in cell types expressing few or no IAV transcripts. Combined analysis of bulk and single-cell RNAseq data identified a set of 6 mRNAs (IFI6, IFI44L, IRF7, ISG15, MX1, MX2) as the core transcriptomic response to IAV infection. The two bacterial pathogens induced qualitatively very similar changes in mRNA expression and predicted signaling pathways, but the magnitude of change was greater in P. aeruginosa infection. Upregulation of GJB2, VNN1, DUSP4, SerpinB7, and IL10, and downregulation of PKMYT1, S100A4, GGTA1P, and SLC22A31 were most strongly associated with bacterial infection. Conclusions Human lung tissue mounted substantially different transcriptomic responses to infection by IAV than by BCG and P. aeruginosa, whereas responses to these two divergent bacterial pathogens were surprisingly similar. This HLTE model should prove useful for RNA-directed pathogenesis research and tissue biomarker discovery during the early phase of infections, both at the tissue and single-cell level.

Abstract Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the human brain, has long been considered essential in human behavior in general and learning in particular. GABA concentration can be quantified using magnetic resonance spectroscopy (MRS). Using this technique, numerous studies have reported associations between baseline GABA levels and various human behaviors. However, regional GABA concentration is not fixed and may exhibit rapid modulation as a function of environmental factors. Hence, quantification of GABA levels at several time points during the performance of tasks can provide insights into the dynamics of GABA levels in distinct brain regions. This review reports on findings from studies using repeated measures (n = 41) examining the dynamic modulation of GABA levels in humans in response to various interventions in the perceptual, motor, and cognitive domains to explore associations between GABA modulation and human behavior. GABA levels in a specific brain area may increase or decrease during task performance or as a function of learning, depending on its precise involvement in the process under investigation. Here, we summarize the available evidence and derive two overarching hypotheses regarding the role of GABA modulation in performance and learning. Firstly, training-induced increases in GABA levels appear to be associated with an improved ability to differentiate minor perceptual differences during perceptual learning. This observation gives rise to the ‘GABA increase for better neural distinctiveness hypothesis’. Secondly, converging evidence suggests that reducing GABA levels may play a beneficial role in effectively filtering perceptual noise, enhancing motor learning, and improving performance in visuomotor tasks. Additionally, some studies suggest that the reduction of GABA levels is related to better working memory and successful reinforcement learning. These observations inspire the ‘GABA decrease to boost learning hypothesis’, which states that decreasing neural inhibition through a reduction of GABA in dedicated brain areas facilitates human learning. Additionally, modulation of GABA levels is also observed after short-term physical exercise. Future work should elucidate which specific circumstances induce robust GABA modulation to enhance neuroplasticity and boost performance.

Abstract Hole spins in Ge/SiGe heterostructures have emerged as an interesting qubit platform with favourable properties such as fast electrical control and noise-resilient operation at sweet spots. However, commonly observed gate-induced electrostatic disorder, drifts, and hysteresis hinder reproducible tune-up of SiGe-based quantum dot arrays. Here, we study Hall bar and quantum dot devices fabricated on Ge/SiGe heterostructures and present a consistent model for the origin of gate hysteresis and its impact on transport metrics and charge noise. As we push the accumulation voltages more negative, we observe non-monotonous changes in the low-density transport metrics, attributed to the induced gradual filling of a spatially varying density of charge traps at the SiGe-oxide interface. With each gate voltage push, we find local activation of a transient low-frequency charge noise component that completely vanishes again after 30 hours. Our results highlight the resilience of the SiGe material platform to interface-trap-induced disorder and noise and pave the way for reproducible tuning of larger multi-dot systems.

Abstract Urban green spaces (UGS) provide mechanisms through which people connect and interact with each other, strengthening social relationships as well as human‐nature connections, both of high relevance for sustainable development. However, what determines urban residents' engagement in activities for the protection of UGS still lacks a systematic understanding. Our study aims to address this gap by enriching the value‐belief‐norm (VBN) theory with relational values based on a questionnaire (N = 221) among residents engaging in UGS maintenance in the city of Munich (Germany). Exploratory factor analysis and structural equation modelling showed that both individual responsibility and societal responsibility guide urban residents in their actions towards UGS protection. Furthermore, we found a direct impact of biospheric, altruistic and hedonic values on engagement for the protection of UGS. Therefore, this study signals the importance of investing in actively promoting pluralistic values among urban residents as cities today urgently need a reconnection of the human‐nature relationship and UGS stewardship actions. As we further confirm that relational values have impact on the constructs of the VBN theory, we conclude with a plea for recognizing the potential of relational values as enablers of change towards more responsible behaviours towards urban nature. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Humans modify their environment to grant or prevent others’ access to valuable resources, for example by using locks. We tested whether sanctuary-living chimpanzees (N = 10) would flexibly modify their environment to either allow or deny a dominant conspecific access to a shared food source by giving them the option to change a food reward’s pathway prior to releasing it. The food could end up in one of two locations: one was accessible to both the subject and a dominant conspecific, the other one was only accessible to the subject. We further manipulated the extent of inhibitory control needed for modifying the pathway by varying the subjects’ starting position. Our subjects reoriented the pathway competitively to monopolize food but changed the pathway less often in trials with high inhibitory demands. We further show how inhibitory task demands in a social context influence chimpanzees’ future planning. Our results show that chimpanzees will strategically manipulate their environment to maximize their own and deny a dominant conspecific access to food.

The title compound, C12H16N2O, is a hydroxy-substituted monoamine alkaloid, and the primary metabolite of the naturally occurring psychedelic compound psilocybin. Crystalline forms of psilocin are known, but their characterization by single-crystal structure analysis is limited. Herein, two anhydrous polymorphic forms (I and II) of psilocin are described. The crystal structure of polymorphic Form I, in space group P21/c, was first reported in 1974. Along with the redetermination to modern standards and unambiguous location of the acidic H atom and variable-temperature single-crystal unit-cell determinations for Form I, the Form II polymorph of the title compound, which crystallizes in the monoclinic space group P21/n, is described for the first time. The psilocin molecules are present in both forms in their phenol–amine tautomeric forms (not resolved in the 1974 report). The molecules in Forms I and II, however, feature different conformations of their N,N-dimethyl ethylene substituent, with the N—C—C—C link in Form I being trans and in Form II being gauche, allowing the latter to bend back to the hydroxyl group of the same molecule, leading to the formation of a strong intramolecular O—H...N hydrogen bond between the hydroxyl moiety and ethylamino-nitrogen group. In the extended structure of Form II, the molecules form one-dimensional strands through N—H...O hydrogen bonds from the indole group to the oxygen atom of the hydroxyl moiety of an adjacent molecule. Form II exhibits whole-molecule disorder due to a pseudo-mirror operation, with an occupancy ratio of 0.689 (5):0.311 (5) for the two components. In contrast, Form I does not feature intramolecular hydrogen bonds but forms a layered structure through intermolecular N—H...O and O—H...N hydrogen bonds.

Background: The relationship between environmental pollutants, specifically air pollution and noise, and cardiovascular disease is well-recognized. However, their combined effects on cardiovascular health are not fully explored. Objectives: To review evidence on the correlation between air pollution and noise exposure and cardiovascular disease incidence and mortality. Methods: Following the PRISMA 2020 guidelines, we identified relevant studies through multiple databases and snowballing. We focused on studies published between 2003 and 2024. Studies were selected based on a PEOS framework, with a focus on exposure to air pollution or noise and clinical cardiovascular outcomes and evaluated for bias using the ROBINS-E tool. Results: A total of 140 studies met our inclusion criteria. Most studies suggested a consistent association between long-term exposure to air pollutants and an increased risk of cardiovascular diseases, notably ischemic heart disease and stroke. While air pollution was often studied in isolation, the interaction effects between air pollution and noise exposure were less commonly investigated, showing mixed results. The majority of these studies were conducted in Western countries, which may limit the generalizability of the findings to global populations. No studies were found to use time-updated confounders, despite the long durations over which participants were followed, which could influence the accuracy of the results. Moreover, none of the studies incorporated both residential and occupational addresses in exposure assessments, suggesting a need for future studies to include these multiple exposure points to improve measurement precision and accuracy. Conclusion: Air pollution exposure is increasingly linked to cardiovascular disease risks. Although individual air pollution and noise exposures are recognized as significant risk factors, the combined interaction between these exposures needs further exploration. Registration: PROSPERO (CRD42023460443).

Abstract Vibrio cholerae, a facultative human pathogen and causative agent of the severe diarrheal disease cholera, transits between the human intestinal tract and aquatic reservoirs. Like other bacterial species, V. cholerae continuously releases bacterial extracellular vesicles (BEVs) from its surface, which have been recently characterised for their role during in vivo colonisation. However, between epidemic outbreaks, V. cholerae persists in the biofilm mode for extended periods in aquatic reservoirs, which enhances environmental fitness and host transition. In this study, we investigated the effect of V. cholerae BEVs on biofilm formation, a critical feature for ex vivo survival. In contrast to BEVs from planktonic cultures, our results show that physiological concentrations of BEVs from dynamic biofilm cultures facilitate V. cholerae biofilm formation, which could be linked to a proteinaceous factor. Comparative proteomic analyses of planktonic‐ and biofilm‐derived BEVs identified a previously uncharacterised outer membrane protein as an abundant component of dynamic biofilm‐derived BEVs, which was found to be responsible for the BEV‐dependent enhancement of biofilm production. Consequently, this protein was named outer membrane‐associated biofilm facilitating protein A (ObfA). Comprehensive molecular studies unravelled ObfA as a negative modulator of HapR activity. HapR is a key transcriptional regulator of the V. cholerae quorum sensing (QS) cascade acting as a potent repressor of biofilm formation and virulence. Consistently, obfA mutants not only exhibited reduced biofilm production but also reduced colonisation fitness. Surprisingly, our results demonstrate that ObfA does not affect HapR through the canonical QS system but via the Csr‐cascade altering the expression of the small regulatory RNAs CsrC and CsrD. In summary, this study elucidates a novel intraspecies BEV‐based communication in V. cholerae that influences biofilm formation and colonisation fitness via a new regulatory pathway involving HapR, Csr‐cascade and the BEV‐associated protein ObfA.

Introduction Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate response to NSAIDs, biological disease-modifying antirheumatic drugs (bDMARDs) should be introduced according to the recommendations of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. Until 2015, only bDMARD was recommended for axSpA in case of failure to anti-tumour necrosis factor (TNF). The 2022 Assessment of SpondyloArthritis International Society (ASAS)-EULAR recommendation proposed to start an alternative bDMARD but without advocating a switch in mode of action as proposed in rheumatoid arthritis. Since 2015, the inhibition of interleukin (IL)-17 has demonstrated efficacy in axSpA. Then, we designed a randomised multicentre clinical trial to identify the more effective treatment after a first anti-TNF failure in axSpA, comparing an anti-IL-17 to a second anti-TNF.Methods and analysis The ROC-SpA (Rotation Or Change of biotherapy after first anti-TNF treatment failure in axSpA patients) study is a prospective, randomised, multicentre, superiority open-label phase IV trial comparing an anti-IL-17 strategy (secukinumab or ixekizumab) to a second TNF blocker in a 1:1 ratio. Patients with an active axSpA (Bath Ankylosing Spondylitis Disease Activity Index >4 or ankylosing spondylitis disease activity score (ASDAS) >3.5) with inadequate 3 months response to a first anti-TNF and with a stable dose of conventional synthetic DMARDs, oral corticosteroids and/or NSAIDs for at least 1 month are included in 31 hospital centres in France and Monaco. The primary outcome is the ASAS40 response at week 24. The secondary outcomes are ASAS40 at weeks 12 and 52, other clinical scores (ASAS20, partial remission rate, ASDAS major improvement rate) at weeks 12, 24 and 52 with the drugs and anti-drugs concentrations at baseline, weeks 12, 24 and 52. The primary analysis is performed at the end of the study according to the intent-to-treat principle.Ethics and dissemination Ethics approval was obtained from the committee for the protection of persons (Comité de protection des personnes Ouest IV #12/18_1, 6 February 2018) and registered in ClinicalTrials.gov and in EudraCT. Results of this study, whether positive or negative, will be presented at national and international congresses, to national axSpA patient associations and published in a peer-reviewed journal. It could also impact the international recommendation to manage patients with axSpA.Trial registration number NCT03445845 and EudraCT2017-004700-22.

The rising demand for greenhouse cultivation poses a challenge in providing environmentally friendly energy to maintain favorable greenhouse indoor conditions. This research presents an optimization model to identify cost-optimal symbiotic pathways to replace the import of three key greenhouse crops (tomato, cucumber, lettuce) with local greenhouse production. The proposed solutions involve greenhouses that can meet these crops' heat and CO2 demands via industrial symbiosis. Switzerland is investigated as the case study, and the (waste) heat suppliers are municipal solid waste incinerators, cement production plants and biogas plants. Upgrading biomethane production plants are also considered potential CO2 suppliers. The objective is to minimize the discounted cost when replacing 25%–100 % of vegetable imports with local agricultural greenhouses, considering availability of suitable land as well as waste heat and CO2 suppliers. Optimization results suggest prioritizing northeast and west Switzerland for greenhouse development, due to the availability of suitable land and proximity of waste heat and CO2 suppliers. Waste incinerators could provide 50%–70 % of the necessary heat, while Organic Rankine cycle in cement plants could generate 63 % of the electricity of supplementary lighting demand of greenhouses. While tailored for Switzerland, the optimization framework's general formulation can be adapted also to other regions to optimize greenhouses' heat and CO2 demands. The optimization code is provided open source for associated applications.

Abstract Measuring the dynamics of microbial communities results in high-dimensional measurements of taxa abundances over time and space, which is difficult to analyze due to complex changes in taxonomic compositions. This paper presents a new method to investigate and visualize the intrinsic hierarchical community structure implied by the measurements. The basic idea is to identify significant intersection sets, which can be seen as sub-communities making up the measured communities. Using the subset relationship, the intersection sets together with the measurements form a hierarchical structure visualized as a Hasse diagram. Chemical organization theory (COT) is used to relate the hierarchy of the sets of taxa to potential taxa interactions and to their potential dynamical persistence. The approach is demonstrated on a data set of community data obtained from bacterial 16S rRNA gene sequencing for samples collected monthly from four groundwater wells over a nearly 3-year period (n = 114) along a hillslope area. The significance of the hierarchies derived from the data is evaluated by showing that they significantly deviate from a random model. Furthermore, it is demonstrated how the hierarchy is related to temporal and spatial factors; and how the idea of a core microbiome can be extended to a set of interrelated core microbiomes. Together the results suggest that the approach can support developing models of taxa interactions in the future.

Abstract Unraveling bacterial gene function drives progress in various areas, such as food production, pharmacology, and ecology. While omics technologies capture high-dimensional phenotypic data, linking them to genomic data is challenging, leaving 40–60% of bacterial genes undescribed. To address this bottleneck, we introduce Scoary2, an ultra-fast microbial genome-wide association studies (mGWAS) software. With its data exploration app and improved performance, Scoary2 is the first tool to enable the study of large phenotypic datasets using mGWAS. As proof of concept, we explore the metabolome of yogurts, each produced with a different Propionibacterium reichii strain and discover two genes affecting carnitine metabolism.

Abstract Nature's contributions to people (NCP) are essential for the production and trade of agricultural, forestry and fishery commodities. Often, there is a spatial disconnect between consumers and the natural systems where the commodities are produced. Traded agricultural products are therefore dependent on nature and NCP in their region of origin. The dependencies of agricultural products on NCP are, however, insufficiently recognised by consumers and are rarely considered in global environmental governance and trade policies along value chains. Here, we synthesise studies highlighting dependencies of agricultural products on NCP in their origin locations to identify opportunities and challenges in quantifying their contribution in sustaining trade flows. We suggest three methodological steps for quantifying NCP dependencies in international agricultural trade: spatial mapping of NCP supply and demand, linking NCP to agricultural trade flows, and tracing trade flows. Each methodological step requires further development and harmonisation to enable a complete accounting of how international agricultural trade depends on NCP. Given the lack of knowledge and data on how NCP support agricultural trade, social and environmental trade‐offs of natural resource management are currently hard to quantify. Quantifying the role of NCP dependencies of traded agricultural products can support their sustainable management, contribute to supply chain accountability and serve as input to sustainable natural resource governance and foster responsibility and equity in supply chains. Read the free Plain Language Summary for this article on the Journal blog.

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (177Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of 177Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of 177Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of 177Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies.

Abstract Two-dimensional (2D) materials are considered for numerous applications in microelectronics, although several challenges remain when integrating them into functional devices. Weak adhesion is one of them, caused by their chemical inertness. Quantifying the adhesion of 2D materials on three-dimensional surfaces is, therefore, an essential step toward reliable 2D device integration. To this end, button shear testing is proposed and demonstrated as a method for evaluating the adhesion of 2D materials with the examples of graphene, hexagonal boron nitride (hBN), molybdenum disulfide, and tungsten diselenide on silicon dioxide and silicon nitride substrates. We propose a fabrication process flow for polymer buttons on the 2D materials and establish suitable button dimensions and testing shear speeds. We show with our quantitative data that low substrate roughness and oxygen plasma treatments on the substrates before 2D material transfer result in higher shear strengths. Thermal annealing increases the adhesion of hBN on silicon dioxide and correlates with the thermal interface resistance between these materials. This establishes button shear testing as a reliable and repeatable method for quantifying the adhesion of 2D materials.

Abstract Background Neuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms. Results Twenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4–20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (

The concept of Nature-based Solutions (NbS) has gained interest as an approach to make significant contributions to the transformation towards more liveable, sustainable, and climate-resilient cities. However, the uptake of NbS into urban development practice is hindered by knowledge and governance barriers. Knowledge plays an essential role in evidence-based decision-making processes and in building the capacity to co-design sustainable pathways. In turn, governance processes can greatly support the acquisition, dissemination and application of knowledge. However, little is known about how these interactions between governance and knowledge manifest in practice. Therefore, we aim to understand the interplay between governance and monitoring & assessment (M&A) and the associated challenges and opportunities for NbS implementation in European and Latin American cities. Considering different socio-economic and cultural contexts allows us to draw from a wider range of practitioners’ experiences in different governance settings. We conducted an explorative qualitative content analysis on ten semi-structured expert interviews with thirteen city experts from local governments and academia based in seven cities: Bogota (CO), Buenos Aires (AR), Santiago (CL), São Paulo (BR), Barcelona (ES), Lisbon (PT) and Turin (IT). Our findings show that M&A provides agency for individual, institutional actors to steer political commitment and can support integrated working. The potential of collaborative M&A with non-governmental actors is still largely untapped, which requires acknowledgement of the capacities of non-governmental actors to contribute to M&A and raise awareness of the value of M&A to civil society. Furthermore, we recommend integrating more reflective learning opportunities in M&A processes, paying more attention to data sharing, and considering of more feasible M&A processes.

Abstract Surgical site infection (SSI) following osteosynthesis of trochanteric or subtrochanteric fractures is a rare but serious complication with incidence rate ranging from 1 to 3%. SSIs are associated with higher mortality and increased length of hospital stay resulting in higher healthcare costs and loss of life quality. In this retrospective analysis all patients with SSI following osteosynthesis of trochanteric or subtrochanteric fractures at the Department of Trauma Surgery were identified. We included all surgical procedures performed from 1992 to 2018, using data from electronic health records and SSI-Trauma-Registry. The aim was to describe epidemiological data, as well as to identify parameters correlating with the occurrence of SSI and mortality. Of 2753 patients, 53 (1.9%) developed SSI. Longer operative time was demonstrated among patients with SSI (P = 0.008). Mortality during the first postoperative year was significantly higher in the SSI group (32.1% vs. 19.1%; P = 0.018), with detection of methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA; HR 4.13, CI 95% 1.24–13.80; P = 0.021) or Enterococcus spp. (HR 5.58, CI 95% 1.67–18.65; P = 0.005) being independent risk factors. Male sex (HR 2.25, 95% CI 1.86–2.73; P

Urban greening has grown in significance in Europe and worldwide as a presumed “public good” initiative, delivering a range of benefits for human health and wellbeing. To redress inequalities in the distribution of such benefits, attention has turned to the potential of collaborative governance. Indicator-based frameworks have also begun to receive attention for their ability to monitor and evaluate not only the performance of greening interventions, but also the policies, practices, and norms that influence their planning and implementation, with a view to transforming governance arrangements. Extensive sets of indicators have been proposed in the literature; however, few studies have addressed the process of adapting monitoring frameworks to the limited resources and highly specific conditions of local government. We address this gap by providing an account of an early phase in developing and contextualising a framework to assess governance of urban greening in seven European cities. Following review of existing indicator sets and literature related to co-governing urban green space, we compiled a set of 126 indicators and clustered these according to normative principles underpinning successful co-governance. We then worked with city representatives to contextualise a subset of 80 indicators and link them to relevant objectives. We found that organising indicators according to principles and applying the criteria of relevance and feasibility was useful to make an abstract concept operational and to promote strategic thinking. However, we also found evidence of likely barriers to using indicators in practice, chief among them the limited agency of responsible staff, with implications for the potential to politicise indicators and thereby guide transformative change.

Background 123Iodine‐meta‐iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. Methods and Results Prospectively enrolled patients with HF (New York Heart Association class II–III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart‐to‐mediastinum ratio from 123iodine‐meta‐iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], 248 [interquartile range, 79–574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT‐proBNP, 743 [interquartile range, 250–2054] pg/dL) and 20 controls (LVEF, 65±5%; NT‐proBNP, 40 [interquartile range, 19–50] pg/dL). Delayed (4 hours) 123iodine‐meta‐iodobenzylguanidine heart‐to‐mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P

Abstract We aimed to investigate transfer of learning, whereby previously acquired skills impact new task learning. While it has been debated whether such transfer may yield positive, negative, or no effects on performance, very little is known about the underlying neural mechanisms, especially concerning the role of inhibitory (GABA) and excitatory (Glu) (measured as Glu + glutamine (Glx)) neurometabolites, as measured by magnetic resonance spectroscopy (MRS). Participants practiced a bimanual coordination task across four days. The Experimental group trained a task variant with the right hand moving faster than the left (Task A) for three days and then switched to the opposite variant (Task B) on Day4. The control group trained Task B across four days. MRS data were collected before, during, and after task performance on Day4 in the somatosensory (S1) and visual (MT/V5) cortex. Results showed that both groups improved performance consistently across three days. On Day4, the Experimental group experienced performance decline due to negative task transfer while the control group continuously improved. GABA and Glx concentrations obtained during task performance showed no significant group-level changes. However, individual Glx levels during task performance correlated with better (less negative) transfer performance. These findings provide a first window into the neurochemical mechanisms underlying task transfer.

Abstract Background Not all patients who call the ambulance service are subsequently transported to hospital. In 2018, a quarter of deployments of an emergency ambulance in Bavaria were not followed by patient transport. This study describes factors that influence patient transport rates. Method This is a retrospective cross-sectional study based on data from all Integrated Dispatch Centres of the Free State of Bavaria in 2018. Included were ambulance deployments without emergency physician involvement, which were subdivided into ambulance deployments without transport and ambulance deployments with transport. The proportion of transported patients were determined for the primary reasons for deployment and for the different community types. On-scene time was compared for calls with and without patient transport. Differences were tested for statistical significance using Chi2 tests and the odds ratio was calculated to determine differences between groups. Results Of 510,145 deployments, 147,621 (28.9%) could be classified as ambulance deployments without transport and 362,524 (71.1%) as ambulance deployments with transport.The lowest proportion of patients transported was found for activations where the fire brigade was involved (“fire alarm system” 0.6%, “fire with emergency medical services” 5.4%) and “personal emergency response system active alarm” (18.6%). The highest transport rates were observed for emergencies involving “childbirth/delivery” (96.9%) and “trauma” (83.2%). A lower proportion of patients is transported in large cities as compared to smaller cities or rural communities; in large cities, the odds ratio for emergencies without transport is 2.02 [95% confidence interval 1.98–2.06] referenced to rural communites. The median on-scene time for emergencies without transport was 20.8 min (n = 141,052) as compared to 16.5 min for emergencies with transport (n = 362,524). The shortest on-scene times for emergencies without transport were identified for activations related to “fire alarm system” (9.0 min) and “personal emergency response system active alarm” (10.6 min). Conclusion This study indicates that the proportion of patients transported depends on the reason for deployment and whether the emergency location is urban or rural. Particularly low transport rates are found if an ambulance was dispatched in connection with a fire department operation or a personal emergency medical alert button was activated. The on-scene-time of the rescue vehicle is increased for deployments without transport. The study could not provide a rationale for this and further research is needed. Trial registration This paper is part of the study “Rettungswageneinsatz ohne Transport” [“Ambulance deployment without transport”] (RoT), which was registered in the German Register of Clinical Studies under the number DRKS00017758.

This review explores how intuitive processes drive innovation, which we define as novel ideas, inventions, or artistic creations that cannot be logically derived from existing knowledge or sensory data. Although intuitive processes are not yet fully recognized as a formal area of scientific research, this paper examines current approaches to their study and modeling. It highlights the necessity of integrating unconventional modeling methods with neuroscience to gain deeper insights into these processes. Key experimental studies investigating extrasensory abilities—such as remote viewing, precognition, and telepathy—are reviewed, emphasizing their potential relevance to innovation. We propose that combining these unconventional modeling approaches with insights from systems neurology can provide new perspectives on the neural mechanisms underpinning intuition and creativity. This review emphasizes the critical need for further research into intuitive processes to address complex global challenges. It calls for a more open, interdisciplinary approach to scientific inquiry, promoting the exploration of unconventional forms of knowledge generation and their neural correlates.

Background: The regulation of cellular proliferation and genomic integrity is controlled by complex surveillance mechanisms known as cell cycle checkpoints. Disruptions in these checkpoints can lead to developmental defects and tumorigenesis. Methods: To better understand these mechanisms, computational modeling has been employed, resulting in a dataset of 414 mathematical models in the BioModels database. These models vary significantly in detail and simulated processes, necessitating a robust analytical approach. Results: In this study, we apply the chemical organization theory (COT) to these models to gain insights into their dynamic behaviors. COT, which handles both ordinary and partial differential equations (ODEs and PDEs), is utilized to analyze the compartmentalized structures of these models. COT’s framework allows for the examination of persistent subsystems within these models, even when detailed kinetic parameters are unavailable. By computing and analyzing the lattice of organizations, we can compare and rank models based on their structural features and dynamic behavior. Conclusions: Our application of the COT reveals that models with compartmentalized organizations exhibit distinctive structural features that facilitate the understanding of phenomena such as periodicity in the cell cycle. This approach provides valuable insights into the dynamics of cell cycle control mechanisms, refining existing models and potentially guiding future research in this area.

Die im Dezember 2017 in Österreich angelobte ÖVP/FPÖ-Koalition formulierte in ihrem Regierungsprogramm weitreichende Reformvorhaben im Bereich der Arbeitsmarkt- und Sozialpolitik. Während die Umsetzung vieler dieser Vorhaben am vorzeitigen Ende der Regierung im Mai 2019 scheiterte, erfuhren andere eine Realisierung. Im Rahmen des Artikels setzen wir uns mit zwei dieser Reformen in der Arbeitszeitpolitik sowie Sozialhilfepolitik auseinander. Konkret fragen wir in politikfeldvergleichender Perspektive, welche diskursiven Frames bzw. Deutungsrahmen in medialen Diskussionen um die angesprochenen Reformen eine Rolle spielten. Die medialen Diskussionen untersuchen wir anhand dreier österreichischer Tageszeitungen und mithilfe eines spezifischen diskursanalytischen Ansatzes. Dabei zeigt sich, dass die diskursive Rahmung in den zwei Politikfeldern weitreichende Differenzen aufwies. Diese interpretieren wir vor dem Hintergrund der politikwissenschaftlichen Debatte um sogenannte Populist Radical Right-Parteien und ihr sozial- und arbeitsmarktpolitisches Profil beim Eintritt in eine Koalitionsregierung mit bürgerlich-wirtschaftsliberalen Parteien.

Abstract The understanding of the impact of nitrogen (N) fertilization on the field water cycle and corresponding water use efficiency (WUE) is very important for optimizing fertilization rates and conserving stressed water resources. We modeled soil moisture dynamics of maize (Zea mays L.), finger millet (Eleusine coracana Gaertn.), and lablab [Lablab purpureus (L..) Sweet] plots using calibrated HYDRUS‐1D model on two experimental sites (rain‐fed and irrigated) for three seasons under different N treatments. The results indicate that the effects of N depended on plant specific properties such as N‐fixation and drought tolerance, and on plant available water content governed by soil structure and rainfall seasonal variability. Maize WUE of plots which received 150 kg/ha of urea (46 % N) were 10–30 kg/ha/mm higher than plots which received none; likewise, millet that received 50 kg/ha of urea had a 7–10 kg/ha/mm higher WUE than control plots in both experiments. However, differences in water cycle components were noticeable between N treatments only in the rain‐fed experiment, where higher N levels led to around 60 and 30 mm higher transpiration, 30 and 20 mm lower evaporation, and 30 and 15 mm lower percolation per season for maize and millet, respectively. In 2018, which was the driest year, the difference in maize WUE between the high and low N treatments was only 1 kg/ha/mm, which corresponded with low actual to potential transpiration ratios (

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is frequent in lung cancer patients. Here, we report a case with persistent hyponatremia, which suggested malignant SIADH and facilitated an early diagnosis of small cell lung cancer (SCLC). A combined radio-chemotherapy led to a partial remission and resolution of SIADH. An early relapse was indicated by reoccurring severe hyponatremia and increased copeptin levels, which were used as surrogate markers for the antidiuretic hormone (ADH). As palliative immunochemotherapy, together with fluid restriction and solute substitution, were unable to control hyponatremia, treatment with the ADH V2-receptor antagonist tolvaptan was initiated. Over time, the dose of tolvaptan needed to be increased, paralleled by a well-documented exponential increase of copeptin levels. In summary and conclusion, this is a rare case of a secondary failure to tolvaptan with unique documentary evidence of increasing copeptin levels. This observation supports the hypothesis that exceedingly high ADH levels may lead to competitive displacement of tolvaptan from the V2 receptor.

Introduction/Justification: The benefits of using 18F-FDG PET/CT for staging and managing treatment in patients with multiple myeloma (MM) are extensively documented. Recent studies indicate that 68Ga-PSMA PET/CT is also an excellent marker for MM lesions and may complement 18F-FDG due to the significant genetic heterogeneity observed in these patients' lesions. The involvement of bone tissue stands out as one of the most critical aspects of MM. To quantify this involvement, two quantitative parameters have recently been proposed: Percentage of Bone Involvement (PBI) and Intensity of Bone Involvement (IBI). Objectives: This study aims to compare PBI and IBI in 68Ga-PSMA and 18F-FDG PET/CT images for multiple myeloma patients. Materials and Methods: Fifteen patients were included in the study, 8 men (53.3%), with a mean age of 66.7 ± 10.7 years. The patients underwent 68Ga-PSMA and 18F-FDG PET/CT scans with a maximum interval of 8 days between images (median 4 days). The bone tissue was segmented in the images based on the Hounsfield scale of the CT image, followed by processing for closing of the volume of interest (VOI). Both PBI and IBI were calculated for the two radiotracers, with the liver SUV used as a reference for 18F-FDG and the left atrium as a reference for 68Ga-PSMA. Spearman's rank-order correlation assessed the relationship between PBI and IBI data. Results: On average, PBI values were higher for 68Ga-PSMA than for FDG, at 3.07% ± 2.5% and 1.96% ± 3.8%, respectively. The mean IBI values were similar for both radiotracers: 0.08 ± 0.13 for 18F-FDG and 0.08 ± 0.09 for 68Ga-PSMA. The median IBI calculated for 68Ga-PSMA was 0.05, higher than the 0.01 found for 18F-FDG. Despite the similarity in average values between 68Ga-PSMA and 18F-FDG, the maximum PBI and IBI values were found in different patients for both radiotracers. Additionally, the Spearman test did not indicate correlation between the variables: (r = 0.39; p = 0.16) for PBI and (r = 0.41; p = 0.13) for IBI. Conclusion: The average and maximum values of PBI and IBI for 68Ga-PSMA and 18F-FDG are close. However, no correlation was found between them, highlighting that the heterogeneous genetic profile of the disease results in different uptake patterns for both radiotracers.

Introduction/Justification: We present a case of a 71-year-old male patient diagnosed with myoepithelial carcinoma of the pelvis and perineum, who underwent fibroblast activation protein (FAP)-directed radioligand therapy and presented long lasting tumor retention as detected by late whole-body scans. Report: The patient had been previously submitted to neoadjuvant radiation therapy and surgery, with tumoral relapse at the surgical margins in the gluteal region. Lesions displayed a slow and progressive sarcomatoid growth pattern, with sacral osteolytic involvement, accompanied with obturatory and left common iliac lymph node metastases. Immunotherapy was initiated but discontinued due to grade IV diarrhea. With progressive disease evident on FDG PET/CT and no other viable chemotherapy indicated, FAPI radioligand therapy was proposed, given significant tracer uptake observed in FAP-directed PET/CT. The patient received an intravenous injection of 200 mCi of [177Lu]Lu-FAP-RTX, which was well tolerated, with no acute side effects reported. Blood tests remained within normal range. Beyond partial hair loss,no other adverse events were observed. Imaging studies including whole-body planar and SPECT/CT scans revealed intense tracer retention in the sacral mass and mild to moderate retention in the lymph node metastases up to 15 days post-treatment. Notably, indicative of a response to FAP-directed radioligand therapy, there was a resolution of drainage from a fistula in the intergluteal region. Follow-up imaging is still pending at the moment. Conclusion: This case is the first report on favorably sustained tumor retention of the radiopharmaceutical in a carcinoma patient undergoing FAP-directed radioligand therapy. With tumor response assessment still pending, longer follow-up and detailed observation is still necessary for a better understanding of potential benefits and side effects of FAP-directed radioligand therapy, especially in patients undergoing subsequent treatment cycles.

Exhausted CD8 T cells (TEX) are associated with worse outcome in cancer yet better outcome in autoimmunity. Building on our past findings of increased TIGIT+KLRG1+ TEX with teplizumab therapy in type 1 diabetes (T1D), in the absence of treatment we found that the frequency of TIGIT+KLRG1+ TEX is stable within an individual but differs across individuals in both T1D and healthy control (HC) cohorts. This TIGIT+KLRG1+ CD8 TEX population shares an exhaustion-associated EOMES gene signature in HC, T1D, rheumatoid arthritis (RA), and cancer subjects, expresses multiple inhibitory receptors, and is hyporesponsive in vitro, together suggesting co-expression of TIGIT and KLRG1 may broadly define human peripheral exhausted cells. In HC and RA subjects, lower levels of EOMES transcriptional modules and frequency of TIGIT+KLRG1+ TEX were associated with RA HLA risk alleles (DR0401, 0404, 0405, 0408, 1001) even when considering disease status and cytomegalovirus (CMV) seropositivity. Moreover, the frequency of TIGIT+KLRG1+ TEX was significantly increased in RA HLA risk but not non-risk subjects treated with abatacept (CTLA4Ig). The DR4 association and selective modulation with abatacept suggests that therapeutic modulation of TEX may be more effective in DR4 subjects and TEX may be indirectly influenced by cellular interactions that are blocked by abatacept.

Sodium vanadium triphosphate (Na3V2(PO4)3, NVP) is a promising cathode material for Na-ion batteries. Due to its intrinsically low electronic conductivity, it is usually mixed or coated with carbon. However, so far there have been no systematic studies on the ionic and electronic conductivity of carbon-coated NVP particles. In this work, NVP with varying carbon contents are prepared. The powders are sintered as single pellets or sandwiched between a solid electrolyte for measurements in an ion blocking and non-ion blocking configuration. In these two different configurations, two different electrodes are attached and several electrochemical characterization techniques are applied such as impedance spectroscopy, chronoamperometry, and four-point measurements. The NVP/C composites with carbon content >0.1 wt% show a high degree of densification and an amorphous carbon network. The conductivity of NVP in composites with carbon content 0.1 wt% show a dominance of electronic conduction in the range of 0.01–0.2 mS cm−1 because of the percolated carbon network at the grain boundaries. The ionic conductivity, however, remains almost constant in the same order of magnitude (∼6 × 10−6 S cm−1).

IntroductionInfluenza A virus (IAV) infection can cause the often-lethal acute respiratory distress syndrome (ARDS) of the lung. Concomitantly, acute kidney injury (AKI) is frequently noticed during IAV infection, correlating with an increased mortality. The aim of this study was to elucidate the interaction of IAV with human kidney cells and, thereby, to assess the mechanisms underlying IAV-mediated AKI.MethodsTo investigate IAV effects on nephron cells we performed infectivity assays with human IAV, as well as with human isolates of either low or highly pathogenic avian IAV. Also, transcriptome and proteome analysis of IAV-infected primary human distal tubular kidney cells (DTC) was performed. Furthermore, the DTC transcriptome was compared to existing transcriptomic data from IAV-infected lung and trachea cells.ResultsWe demonstrate productive replication of all tested IAV strains on primary and immortalized nephron cells. Comparison of our transcriptome and proteome analysis of H1N1-type IAV-infected human primary distal tubular cells (DTC) with existing data from H1N1-type IAV-infected lung and primary trachea cells revealed enrichment of specific factors responsible for regulated cell death in primary DTC, which could be targeted by specific inhibitors.DiscussionIAV not only infects, but also productively replicates on different human nephron cells. Importantly, multi-omics analysis revealed regulated cell death as potential contributing factor for the clinically observed kidney pathology in influenza.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Abstract Background Checklists are a powerful tool for reduction of mortality and morbidity. Checklists structure complex processes in a reproducible manner, optimize team interaction, and prevent errors related to human factors. Despite wide dissemination of the checklist, effects of checklist use in the prehospital emergency medicine are currently unclear. The aim of the study was to demonstrate that participants achieve higher adherence to guideline-recommended actions, manage the scenario more time-efficient, and thirdly demonstrate better adherence to the ABCDE-compliant workflow in a simulated ROSC situation. Methods CHIPS was a prospective randomized case–control study. Professional emergency medical service teams were asked to perform cardiopulmonary resuscitation on an adult high-fidelity patient simulator achieving ROSC. The intervention group used a checklist which transferred the ERC guideline statements of ROSC into the structure of the ‘ABCDE’ mnemonic. Guideline adherence (performance score, PS), utilization of process time (items/minute) and workflow were measured by analyzing continuous A/V recordings of the simulation. Pre- and post-questionnaires addressing demographics and relevance of the checklist were recorded. Effect sizes were determined by calculating Cohen’s d. The level of significance was defined at p

Abstract Background Helicopter emergency medical service provides timely care and rapid transport of severely injured or critically ill patients. Due to constructional or regulatory provisions at some hospitals, a remote helicopter landing site necessitates an intermediate ground transport to the emergency department by ambulance which might lengthen patient transport time and comprises the risk of disconnection or loss of vascular access lines, breathing tubes or impairment of other relevant equipment during the loading processes. The aim of this study was to evaluate if a ground intermediate transport at the hospital site prolonged patient transport times and operating times or increases complication rates. Methods A retrospective analysis of all missions of a German air rescue service between 2012 and 2020 was conducted. Need of a ground transport at the accepting hospital, transfer time from the helipad to the hospital, overall patient transport time from the emergency location or the referring hospital to the accepting hospital and duration of the mission were analyzed. Several possible confounders such as type of mission, mechanical ventilation of the patient, use of syringe infusion pumps (SIPs), day- or nighttime were considered. Results Of a total of 179,003 missions (92,773 (51,8%) primary rescue missions, 10,001 (5,6%) polytrauma patients) 86,230 (48,2%) secondary transfers) an intermediate transport by ambulance occurred in 40,459 (22,6%) cases. While transfer times were prolonged from 6.3 to 8.8 min for primary rescue cases (p

Abstract An algorithm is presented for computing a reaction-diffusion partial differential equation (PDE) system for all possible subspaces that can hold a persistent solution of the equation. For this, all possible sub-networks of the underlying reaction network that are distributed organizations (DOs) are identified. Recently it has been shown that a persistent subspace must be a DO. The algorithm computes the hierarchy of DOs starting from the largest by a linear programming approach using integer cuts. The underlying constraints use elementary reaction closures as minimal building blocks to guarantee local closedness and global self-maintenance, required for a DO. Additionally, the algorithm delivers for each subspace an affiliated set of organizational reactions and minimal compartmentalization that is necessary for this subspace to persist. It is proved that all sets of organizational reactions of a reaction network, as already DOs, form a lattice. This lattice contains all potentially persistent sets of reactions of all constrained solutions of reaction-diffusion PDEs. This provides a hierarchical structure of all persistent subspaces with regard to the species and also to the reactions of the reaction-diffusion PDE system. Here, the algorithm is described and the corresponding Python source code is provided. Furthermore, an analysis of its run time is performed and all models from the BioModels database as well as further examples are examined. Apart from the practical implications of the algorithm the results also give insights into the complexity of solving reaction-diffusion PDEs.

Nutrition research has shifted from single nutrients to examining the association of foods and dietary patterns with health. This includes recognizing that food is more than the sum of the individual nutrients and relates to the concept of the food matrix. Like other foods, dairy foods are characterized by their unique matrices and associated health effects. Although the concepts of the food matrix and/or dairy matrix are receiving increasing attention in the nutrition and health literature, there are different terms and definitions that refer to it. This article aims to provide insights into the application of the concepts of the food matrix and dairy matrix and to provide a current overview of the definitions and terminology surrounding the food matrix and dairy matrix. By analysing these aspects, we aim to illustrate the practical implications of the food matrix and dairy matrix on nutrition and health outcomes and evaluate their roles in shaping evidence-based policies for the benefit of public health. There is a need for harmonized definitions within the literature. Therefore, the International Dairy Federation put forward harmonized terms to be internationally applicable: the “dairy matrix” describes the unique structure of a dairy food, its components (e.g., nutrients and non-nutrients), and how they interact; “dairy matrix health effects” refers to the impact of a dairy food on health that extend beyond its individual components.

Aging is one of the key steps in the preparation of highly active Cu/ZnO-based catalysts for use in the production of methanol. If certain pH and temperature specifications are met, an initially amorphous precipitate transforms into the crystalline precursor phase of zincian malachite, which is characterized by a periodic arrangement of Cu and Zn atoms and has proven advantageous for the quality of the final catalyst. However, aging generally takes between 30 min and multiple hours until the desired phase transformation is completed. With our study, we show that aging can be significantly accelerated by seeding the freshly precipitated suspension with already aged zincian malachite crystals: the necessary aging time was reduced by 41% for seeding mass fractions as low as 3 wt.% and from 83 min to less than 2 min for 30 wt.% seeds. No negative influence of seeding on the phase composition, specific surface area, molar metal ratios, or the morphology of the aged precursor could be identified. Consequently, the catalyst performance in the synthesis of methanol from CO2, as well as from a CO/CO2 mixture, was identical to a catalyst from an unseeded preparation and showed small advantages compared to a commercial sample. Thus, we conclude that seeding is a vital tool to accelerate the preparation of all Cu/Zn-based catalysts while maintaining product quality, presumably also on an industrial scale.

Green urban squares are essential in densely built neighborhoods and enhance their quality of life. Investment in the greening of urban areas will have a beneficial impact, particularly regarding human thermal comfort. Smaller than parks, squares can be easily spread over the cities and should be part of any neighborhood. While the cooling effect of green squares during hot summer days is increasingly well established, microclimatic assessments during all seasons are still missing. This study aimed to determine whether it is possible to identify an optimal greenery design that maximizes human thermal comfort, as indexed by physiological equivalent temperature (PET), in temperate climates across all seasons. This study employed a “research by design” methodology, utilizing the micrometeorological simulation model ENVI-met to analyze the impact of greenery on PET improvement across different seasons. The objective was to identify the most effective combination of greenery for PET improvement. To achieve these objectives, two urban squares in Munich, Germany were selected. This selection was based on the assumption that typical greening practices, exemplified by the presence of trees, shrubs, and grass, would significantly impact urban squares and their microclimatic effects on human thermal comfort. The small square with a grass surface underneath trees, Alpenplatz, is highly influenced by the surrounding buildings, affecting the sky view factor (SVF), a crucial aspect of the urban environment. Marstallplatz, an open, large square that is not highly affected by urban morphology, was analyzed through simulation scenarios combining grass, shrubs, and trees. The results demonstrate that hot summer days are of primary concern for climate-sensitive urban square design in order to avoid health risks and thus need to be prioritized without compromising comfort for cold days. To attend to both needs, increasing the number of deciduous trees for shading during the day and the amount of grass to enhance air cooling at night are particularly effective. Nevertheless, microclimate design for the spring and autumn periods must also be considered, with the provision of adaptable opportunities for sheltered and sun-exposed spaces.

This study describes the outcome of supracondylar humerus fractures in children using crossed K-wires after closed or open reduction with the medial, lateral or bilateral approach. Patients treated between January 2000 and December 2019 were classified according to the Von Laer classification, complications were classified according to the Sink classification and clinical outcomes were classified according to modified Flynn criteria. In total, 364 patients with a mean age of 5.23 ± 2.45 years were included. The majority were type IV fractures (156; 42.9%) and 94 (60.3%) needed an open reduction for which the medial approach (53; 56.4%) was predominantly used. Overall, of 50 complications (31 using closed reduction, 19 open reduction), 17/50 (34%) needed revision surgery. An excellent clinical outcome was achieved in 348/364 (95.6%) patients. The approach used for open reduction as such had no influence on the complication rate or clinical outcome. For severely displaced fractures, the data showed that an open approach for crossed K-wires tended to result in fewer complications and better clinical outcomes than a closed reduction. If an open reduction is indicated, the required approach (medial, lateral or bilateral) should be primarily selected according to the requirements of the fracture pattern and eventual cosmetic considerations.

Abstract Climate change and particulate matter air pollution present major threats to human well-being by causing impacts on human health. Both are connected to key air pollutants such as carbon dioxide (CO $$_\text {2}$$ 2 ), primary fine particulate matter (PM $$_\text {2.5}$$ 2.5 ), sulfur dioxide (SO $$_\text {2}$$ 2 ), nitrogen oxides (NO $$_\text {x}$$ x ) and ammonia (NH $$_\text {3}$$ 3 ), which are primarily emitted from energy-intensive industrial sectors. We present the first study to consistently link a broad range of emission measurements for these substances with site-specific technical data, emission models, and atmospheric fate and effect models to quantify health impacts caused by nearly all global fossil power plants, steel mills, oil refineries and cement plants. The resulting health impact patterns differ substantially from far less detailed earlier studies due to the high resolution of included data, highlighting in particular the key role of emission abatement at individual coal-consuming industrial sites in densely populated areas of Asia (Northern and North-Eastern India, Java in Indonesia, Eastern China), Western Europe (Germany, Belgium, Netherlands) as well as in the US. Of greatest health concern are the high SO $$_\text {2}$$ 2 emissions in India, which stand out due to missing flue gas treatment and cause a particularly high share of local health impacts despite a limited number of emission sites. At the same time, the massive infrastructure and export capacity build-up in China in recent years is taking a substantial toll on regional and global health and requires more stringent regulation than in the rest of the world due to unfavorable environmental conditions and high population densities. The current phase-out of highly emitting industries in Europe is found not to have started with sites having the greatest health impacts. Our detailed site-specific emission and impact inventory is able to highlight more effective alternatives and to track future progress.

Abstract Currently arbitrary, inconsistent and non-evidence-based age cutoffs are used in the literature to classify pediatric emergencies. None of these classifications have valid medical rationale. This leads to confusion and poor comparability of the different study results. To clarify this problem, this paper presents a systematic review of the commonly used age limits from 115 relevant articles. In the literature search 6226 articles were screened. To be included, the articles had to address the following three topics: “health services research in emergency medicine”, “pediatrics” and “age as a differentiator”. Physiologic and anatomic principles with reference to emergency medicine were used to solve the problem to create a medically based age classification for the first time. The Munich Age Classification System (MACS) presented in this paper is thus consistent with previous literature and is based on medical evidence. In the future, MAC should lead to ensure that a uniform classification is used. This will allow a better comparability of study results and enable meta-analyses across studies.

The evolving research field of social studies of economics (SSE) has shown that economics as a profession has gained influence on public debate and political power in many countries and in different social contexts. The channels of influence for economists are complex and widespread, i.e., there are multiple channels through which economists are able to influence public policy issues. In this article, we provide an in-depth analysis of a sample of the 85 most published authors of trade-related research in top economics journals to characterize the social field of elite economists and show how position in that field correlates with influence and power in and outside academia. More specifically, our data include information on their academic careers, their professional social networks, and their involvement in a variety of possible intermediaries between academic economics and policymaking (e.g., institutions such as think tanks or the media). We apply multiple correspondence analysis (MCA) and cluster analysis to show how different configurations of intra-academic capital are associated to policy-relevant extra-academic capital. The overall results of this analysis are threefold. First, the biographical analysis of elite trade economists reveals a remarkable degree of concentration of different forms of capital, which indicates a strong hierarchical order within the elite segment of trade economists. Second, and in line with this, despite the overall unequal distribution of capital within this elite sample, different forms of intra-academic and extra-academic capitals become visible. Third, while the cluster analysis reveals a main “average core” of (trade-)policy-oriented economists, the group of economists with very high capital is separated into two smaller clusters: The “ivory elite” cluster consists mainly of academic capital variables, while the “public econs” cluster is also composed of non-academic variables from the policy and media channels. So, even among elite trade economists, it is only as small number, who really is successfully gaining political and societal impact.

The present study contributes to the issue of the urban heat island (UHI) effect with its possibly associated thermal stress for city dwellers and its potential mitigation during heat waves and dry spells in Central Europe. It is based on meteorological measurements along an urban transect in the city of Würzburg, Germany. Due to its topographic and structural situation, Würzburg is prone to an intense urban heat island (UHI). The measurements have started in 2018 and, hence, cover a period that was characterized by record high temperatures and long dry spells in Central Europe. Particularly on days with a maximum air temperature of more than 25 °C, an intense UHI was observed with the highest amplitude in the afternoon and, even more, during the evening hours. The highest measured difference between the densely built inner city and the outskirts was 8.2 °C. The UHI during summer is noticeably more pronounced, especially during the evening hours, when the regional background climate is anomalously warm and dry. This can be ascribed to anticyclonic weather types that prevailed over Central Europe during summertime between 2018 and 2020. The cooling effect of urban trees, in this case Tilia cordata, on near-surface air temperature amounts to partly more than 2 °C and, hence, mitigates the UHI locally, especially at noon and in the early afternoon. However, the cooling rate is only half as much when the trees suffer from water stress. Thus, an appropriate management of city's green infrastructure represents a useful strategy to mitigate the strength of the UHI and the heat stress in Central Europe.

Background: The spread of the COVID-19 pandemic and the corresponding implementation of measures such as stay-at-home orders and curfews had a major impact on health systems, including emergency medical services. This study examined the effect of the pandemic on call volumes, duration of calls and unanswered calls to the emergency number 112. Method: For this retrospective, descriptive study, 986,650 calls to seven emergency dispatch centres in Bavaria between January 01, 2019 and May 31, 2021 were analysed. The absolute number of calls and calls per 100,000 inhabitants as well as the number of unanswered calls are reported. The Mann‒Whitney U test was used to compare mean call durations between 2019 and 2020/2021 during several periods. Results: Call volume declined during the pandemic, especially during periods with strict lockdown restrictions. The largest decline (−12.9 %) occurred during the first lockdown. The largest reduction in the number of emergency calls overall (−25.3 %) occurred on weekends during the second lockdown. Emergency call duration increased, with the largest increase (+13 s) occurring during the “light” lockdown. The number of unanswered calls remained at a similar level as before the pandemic. Conclusion: This study showed that the studied Bavarian dispatch centres experienced lower call volumes and longer call durations during the first two waves of the COVID-19 pandemic (up to May 2021). Longer call durations could be the result of additional questions to identify potentially infectious patients. The fact that the number of unanswered calls hardly changed may indicate that the dispatch centres were not overwhelmed during the study period.

Abstract The subtropical free troposphere plays a critical role in the radiative balance of the Earth. However, the complex interactions controlling moisture in this sensitive region and, in particular, the relative importance of long‐range transport compared to lower‐tropospheric mixing, remain unclear. This study uses the regional COSMO model equipped with stable water isotopes and passive water tracers to quantify the contributions of different evaporative sources to the moisture and its stable isotope signals in the eastern subtropical North Atlantic free troposphere. In summer, this region is characterized by two alternating large‐scale circulation regimes: (i) dry, isotopically depleted air from the upper‐level extratropics, and (ii) humid, enriched air advected from Northern Africa within the Saharan Air Layer (SAL) consisting of a mixture of moisture of diverse origin (tropical and extratropical North Atlantic, Africa, Europe, the Mediterranean). This diversity of moisture sources in regime (ii) arises from the convergent inflow at low levels of air from different neighbouring regions into the Saharan heat low (SHL), where it is mixed and injected by convective plumes into the large‐scale flow aloft, and thereafter expelled to the North Atlantic within the SAL. Remarkably, this regime is associated with a large contribution of moisture that evaporated from the North Atlantic, which makes a detour through the SHL and eventually reaches the 850–550 hPa layer above the Canaries. Moisture transport from Europe via the SHL to the same layer leads to the strongest enrichment in heavy isotopes (δ2H correlates most strongly with this tracer). The vertical profiles over the North Atlantic show increased humidity and δ2H and reduced static stability in the 850–550 hPa layer, and smaller cloud fraction in the boundary layer in regime (ii) compared to regime (i), highlighting the key role of moisture transport through the SHL in modulating the radiative balance in this region.