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Clinical pharmacology is often the nexus in any cross‐disciplinary team that is seeking solutions for human healthcare issues. The use and application of real‐world data and artificial intelligence to better understand our ecosystem has influenced our view at the world and how we do things. This has resulted in remarkable advancements in the healthcare space and development of personalized medicines with great attributes from the application of models and simulations, contributing to a more efficient healthcare development process. A cross‐disciplinary symposium was held in December 2023, whereby experts from different scientific disciplines engaged in a high‐level discussion on the opportunities and challenges of mathematical models in different fields, possible future developments and decision making. A strong interlink amongst the disciplines represented was apparent, with clinical pharmacology identified as the one which integrates various scientific disciplines. Deliberate and strategic cross‐disciplinary dialogues are required to break out of the silos and implement integration for efficiency and cost‐effectiveness of novel interventions. [ABSTRACT FROM AUTHOR]

Background: This study focused on Ukrainian refugees and migrants, a population that, with an ongoing war, is expected to grow in Germany. Over 1 million Ukrainians with exceptional legal status and access to public insurance in Germany significantly burden governmental services, especially German healthcare. It is thus essential to facilitate their integration into the healthcare system and ensure its proper usage. Identifying the obstacles Ukrainian refugees and migrants encounter while accessing healthcare services is crucial to ease their integration. Methods: A qualitative study was conducted from February 2023 to April 2023. Thirty semi-structured interviews were performed with Ukrainian migrants and refugees. The interviews were transcribed verbatim, organized, and categorized. Thematic analysis was performed to identify barriers related to the use of German healthcare services. To assess possible differences in the experiences of Ukrainian refugees and migrants, the responses of these two groups for each topic were analysed separately. Results: Ukrainian migrants and refugees experience similar barriers while accessing German healthcare services. Predominantly, language barriers and a lack of understanding of the German healthcare system posed the main barriers in both groups. Additionally, structural challenges, such as differences in referral processes, appointment scheduling, and consultation duration, presented further challenges. Conclusion: This research study emphasizes the importance of addressing cultural and structural barriers to improve healthcare accessibility and utilization for Ukrainian refugees and migrants in Germany to better facilitate their integration into the healthcare system. [ABSTRACT FROM AUTHOR]

Introduction: Gingivitis is a common intraoral disease in patients with chronic kidney disease (CKD), which poses a particular interdisciplinary challenge. We aimed to determine the influence of an intensive oral prophylaxis program (OPP) compared to standard prevention measures on the tongue microbiome of young patients with CKD. Methods: Thirty patients with CKD (mean age 14.2 ± 5.2 years) and generalized gingivitis were included. The effects of the intensive OPP were compared with standard prophylaxis according to statutory health insurance (treatment as usual, TAU) as a control. Tongue swabs were taken from the patients at baseline (t1) and after 3 (t2) and 6 (t3) months. Next-generation sequencing of 16S rDNA genes was used to quantitatively characterize microbial communities. Results: There were no differences in the abundance, richness, or diversity of the observed genera and species between the two study groups at baseline or after 3 or 6 months. Furthermore, no change in predefined gingivitis and oral health bacterial clusters were found. At the phylum level, Firmicutes were decreased after intervention in the TAU group (t2TAU 42.9 ± 7.1 to t3TAU 34.8 ± 4.7 (npairs=14), p=0.003; false discovery rate 0.02). The decrease of Firmicutes was not significant in the OPP group. Conclusions: Despite the intensity of dental prophylaxis and decreasing clinical signs of inflammation and decreasing plaque amount, no clinically relevant changes in the tongue microbiome were observed. Our results confirm the conserved and stable nature of the tongue microbiome, even in children with CKD. [ABSTRACT FROM AUTHOR]

This study experimentally optimizes the mixing of a turbulent jet at Reynolds number 10 000 with the surrounding air by targeted shear layer actuation. The forcing is composed of superposed harmonic signals of different azimuthal wavenumber m generated by eight loudspeakers circumferentially distributed around the nozzle lip. Amplitudes and frequencies of the individual harmonic contributions serve as optimization parameters, and the time-averaged centerline velocity downstream of the potential core is used as a metric for mixing optimization. The actuation is optimized through Bayesian optimization. Three search spaces are explored—axisymmetric forcing, m = 0, superposed axisymmetric and helical forcing, m ∈ { 0 , 1 } , and axisymmetric actuation combined with two counter-rotating helical modes, m ∈ { − 1 , 0 , 1 }. High-speed particle image velocimetry (PIV) is employed to analyze the jet response to the optimized forcing. The optimization processes are analyzed by persistent data topology. In the search space of axisymmetric excitation, the routine identifies an actuation at the natural frequency of the flow to be most efficient, with the centerline velocity being decreased by 15%. The optimal solutions in both the two-mode and three-mode search space converge to a similar forcing with one axial and one helical mode combined at a frequency ratio of around 2.3. Spectral analysis of the PIV images reveals that for the identified optimal forcing frequencies, a non-linear interaction between forced and natural structures in the jet flow is triggered, leading to a reduction in centerline velocity of around 35%. The topology of the most complex search space from the discrete data reveals four basins of attractions, classified into three forcing patterns including axisymmetric, axisymmetric-helical, and axisymmetric-flapping. Two deep basins are related to the optimal pattern found as axisymmetric-helical, and the others are shallower. [ABSTRACT FROM AUTHOR]

In this paper, we introduce the first jet nozzle allowing simultaneous shape variation and distributed active control, termed "Smart Nozzle" in the sequel. Our Smart Nozzle manipulates the jet with an adjustable flexible shape via 12 equidistant stepper motors and 12 equidistantly placed inward-pointing minijets. The mixing performance is evaluated with a 7 × 7 array of Pitot tubes at the end of the potential core. The experimental investigation is carried out in three steps. First, we perform an aerodynamic characterization of the unforced round jet flow. Second, we investigate the mixing performance under five representative nozzle geometries, including round, elliptical, triangular, squared, and hexagonal shapes. The greatest mixing area is achieved with the square shape. Third, the symmetric forcing parameters are optimized for each specified nozzle shape with a machine learning algorithm. The best mixing enhancement for a symmetric active control is obtained by the squared shape, which results in a 1.93-fold mixing area increase as compared to the unforced case. Symmetrically unconstrained forcing achieves a nearly 4.5-fold mixing area increase. The Smart Nozzle demonstrates the feasibility of novel flow control techniques that combine shape variation and active control, leveraging the capabilities of machine learning optimization algorithms. [ABSTRACT FROM AUTHOR]

We propose a feature-based manifold modeling (FeMM) framework for the quasiperiodic wake dynamics of a pair of side-by-side cylinders. The key enabler is to embed the most parsimonious mean-field manifold based on the extracted features, such as force coefficients and probing data from experiments and numerical simulations. The manifold model is then identified under the mean-field constraints of the model structure, ensuring human-interpretability. The FeMM method is demonstrated with a two-dimensional incompressible flow crossing a pair of side-by-side cylinders, exhibiting a flip-flopping wake in quasiperiodic behavior. The transient and post-transient dynamics are characterized by two coupled oscillators associated with vortex shedding and gap flow oscillations. Dynamic mode decomposition analysis reveals significant modal interactions between these two flow mechanisms, posing a serious challenge to projection-based modeling approaches, such as the Galerkin projection method. Nevertheless, the FeMM approach, based on force measurements, yields an interpretable model that accounts for the mechanisms underlying the quasiperiodic dynamics, demonstrating its applicability to higher-order dynamics with multiple scales and invariant sets. This approach is expected to have broad applicability in dynamic modeling and state estimation in various real-world scenarios. [ABSTRACT FROM AUTHOR]

To optimize flapping motion for pitching foil dynamics, we significantly expand the search space to include non-periodic feedback laws through the application of the cluster-based control method, which is integrated with interpolation and machine learning optimization techniques. This approach allows for dynamic adjustment between transient and steady-state conditions, leading to an 18% increase in thrust efficiency compared to traditional sinusoidal waveforms. By clustering flow field dynamics into two cycle categories with eight clusters and optimizing closed-loop control laws, we achieve accelerated convergence to the optimal thrust cycle. The proposed approach not only refines control strategies for pitching foil dynamics but also ensures robustness and efficiency in the system performance. [ABSTRACT FROM AUTHOR]

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Objectives: CT-derived fractional flow reserve (CT-FFR) can improve the specificity of coronary CT-angiography (cCTA) for ruling out relevant coronary artery disease (CAD) prior to transcatheter aortic valve replacement (TAVR). However, little is known about the reproducibility of CT-FFR and the influence of diffuse coronary artery calcifications or segment location. The objective was to assess the reliability of machine-learning (ML)-based CT-FFR prior to TAVR in patients without obstructive CAD and to assess the influence of image quality, coronary artery calcium score (CAC), and the location of measurement within the coronary tree. Methods: Patients assessed for TAVR, without obstructive CAD on cCTA were evaluated with ML-based CT-FFR by two observers with differing experience. Differences in absolute values and categorization into hemodynamically relevant CAD (CT-FFR ≤ 0.80) were compared. Results in regard to CAD were also compared against invasive coronary angiography. The influence of segment location, image quality, and CAC was evaluated. Results: Of the screened patients, 109/388 patients did not have obstructive CAD on cCTA and were included. The median (interquartile range) difference of CT-FFR values was −0.005 (−0.09 to 0.04) (p = 0.47). Differences were smaller with high values. Recategorizations were more frequent in distal segments. Diagnostic accuracy of CT-FFR between both observers was comparable (proximal: Δ0.2%; distal: Δ0.5%) but was lower in distal segments (proximal: 98.9%/99.1%; distal: 81.1%/81.6%). Image quality and CAC had no clinically relevant influence on CT-FFR. Conclusions: ML-based CT-FFR evaluation of proximal segments was more reliable. Distal segments with CT-FFR values close to the given threshold were prone to recategorization, even if absolute differences between observers were minimal and independent of image quality or CAC. [ABSTRACT FROM AUTHOR]

We optimize jet mixing using large eddy simulations (LES) at a Reynolds number of $3000$. Key methodological enablers consist of Bayesian optimization, a surrogate model enhanced by deep learning and persistent data topology for physical interpretation. The mixing performance is characterized by an equivalent jet radius ($R_{eq}$) derived from the streamwise velocity in a plane located $8$ diameters downstream. The optimization is performed in a 22-dimensional actuation space that comprises most known excitations. This search space parameterizes the distributed actuation imposed on the bulk flow and at the periphery of the nozzle in the streamwise and radial directions. The momentum flux measures the energy input of the actuation. The optimization quadruples the jet radius $R_{eq}$ with a $7$ -armed blooming jet after around $570$ evaluations. The control input requires $2\,\%$ momentum flux of the main flow, which is one order of magnitude lower than an ad hoc dual-mode excitation. Intriguingly, a pronounced suboptimum in the search space is associated with a double-helix jet, a new flow pattern. This jet pattern results in a mixing improvement comparable to the blooming jet. A state-of-the-art Bayesian optimization converges towards this double-helix solution. The learning is accelerated and converges to another better optimum by including a deep-learning-enhanced surrogate model trained along the optimization. Persistent data topology extracts the global and many local minima in the actuation space. These minima can be identified with flow patterns beneficial to the mixing. [ABSTRACT FROM AUTHOR]

Appropriate digestate management is crucial for economic as well as ecologic optimization of biomethane production. Here, we present the production of a lignin-based phenol formaldehyde adhesive and its application to plywood from lignin separated after H3PO4 disintegration of digestate. Together with the work of Schroedter et al. (Microorganisms 9:1810, 2021), a full valorization of solid digestate is demonstrated. The separated sulfur-free LXP-lignin had high purity of above 90% lignin with a carbohydrate content of < 3%, an ash content below 2%, and a molecular weight of 6163 Da. The depolymerization of the LXP-lignin reduced the molecular weight to 3838 Da. The prepared lignin-based phenol formaldehyde resin has a viscosity of 350 mPa*s and a comparable tensile shear strength to the reference resin produced with the kraft lignin Indulin AT. Testing of nine-layer (500 × 500 mm) birch plywood panels showed promising results using standard resin recipes. [ABSTRACT FROM AUTHOR]

Fan-array wind generators (FAWGs) are being employed for unmanned aerial vehicle testing. Such testing requires uniform blowing generated from the FAWGs. However, achieving uniform blowing is impeded by the wall effects within the enclosed room. These wall effects also lead to complex flow circulations. Understanding the room flow circulations can provide insight into restoring the uniformity of FAWG blowing. In this study, a coarse-graining characterization methodology is proposed to extract the room flow circulations. The key enabler is discretizing the flow domain into regular boxes as coarse-grained units and reducing the continuous flow field to flow transfers among the units. The flow circulation structure is characterized by kinematic features, i.e., the flow loop paths. The methodology is demonstrated on a numerical simulation of the room flow generated by the world's largest FAWG in the Shenzhen unmanned aerial vehicle test center. First, an analysis of the room flow kinematics shows a deflection and velocity decay of the jet-like flow. Second, two- and three-dimensional kinematic feature identifications indicate that horizontal circulations dominate the room flow. Third, two triangular prisms are introduced to manipulate the whole room circulations to improve the flow characteristics in the drone testing region. The right-angle prism reduces the flow deflection and enhances the flow activity in the test region by orienting flow circulations from horizontal to vertical. Meanwhile, the acute-angle prism creates complex flow circulations. The proposed methodology facilitates the identification and improvement of kinematic features and contributes to the physical understanding of a flow circulation structure in complex configurations. [ABSTRACT FROM AUTHOR]

With conflict prevention as a commonplace agenda of international organisations, numerous instruments for gathering knowledge about potential armed conflict have emerged. This article focuses on the mode of knowing war through quantification in the form of fatality statistics or 'death counts', which are taken by analysts and policymakers to indicate the severity and extent of conflicts. Drawing on official documents and interviews, I argue that fatality numbers are productive of the reality of violent conflict as they shape what counts as conflict and what does not. In the reporting by prevention actors, such numbers indicate past and future trends of armed violence and, in this way, bolster the imperative to prevent by creating quantified futures of conflict. However, fatality numbers also normalise deadly violence as a baseline criterion, thus also limiting the scope of what is known as future conflict and omitting lived experiences from the abstractions behind such numbers. [ABSTRACT FROM AUTHOR]

This research examined how migrant care workers in eldercare institutions in Germany were affected by the COVID-19 pandemic, focusing on their personal experiences. The research is theoretically grounded in intersectionality and the prisoner of love framework. Drawing on 15 qualitative interviews with migrant care workers (MCWs) from Poland and Bosnia–Herzegovina, the main findings highlight that intersecting social positions play an important role in stratifying experiences for MCWs. Migrant workers with high skill levels and job security stressed similarities to their non-migrant colleagues in their day-to-day work experiences during the pandemic, foregrounding their shared professional self-image and creating solidarity between workers of all backgrounds. Strong workplace relationships, emphasising their professional identity, and adapting career plans were ways to mitigate the negative effects of the pandemic. The study's results emphasise the need for a more balanced portrayal of the pandemic's impact on migrant workers. [ABSTRACT FROM AUTHOR]

Background: The number of children experiencing postnatal situations of neurological risk (such as psycho-motor developmental disorders and delays) after birth has increased in recent years. These infants often require multiple pediatric interventions to address functional problems that might generate stress, anxiety, and discomfort. The aim of the present study is to determine whether the level of salivary cortisol, as a stress marker, increases after hydrotherapy and land-based therapy in children at risk of or currently presenting delayed psycho-motor development. Methods: Saliva samples were collected from 25 children (aged 3–36 months) between June 2022 and January 2023 at the Rehabilitation and Physical Medicine Clinical Management Unit of the Virgen de las Nieves University Hospital, Granada, Spain. Three samples were collected from each child, representing baseline, post-hydrotherapy and post-land-based therapy. Result: All salivary cortisol levels were within the normal range. Resting values were the highest, and both modes of therapy decreased salivary cortisol levels. There were no statistically significant differences between the two therapies. Conclusions: Both therapies appear to be useful for treating children with psychomotor developmental disorders without increasing stress during physiotherapy sessions. Although cortisol levels were slightly higher with hydrotherapy than with land-based therapy, this may be due to the small sample size. [ABSTRACT FROM AUTHOR]

Die Schaffung neuer Arbeitsplätze in Behörden und Einrichtungen des Bundes in den deutschen Kohleausstiegsregionen ist ein zentraler Baustein des Investitionsgesetzes Kohleregionen (InvKG). Die etwa 5 000 entstehenden Arbeitsplätze sollen attraktive Beschäftigung in die Reviere bringen, die durch das Ende der Kohleverstromung einen Transformationsprozess durchlaufen. Die Ergebnisse einer Organisationsbefragung im Lausitzer Revier zeigen, dass die Ansiedlung von Behörden und Einrichtungen des Bundes regional bis dato eine gewisse Zuzugswirkung entfaltet. Diese liegt allerdings noch unter den Erwartungen eines deutlichen Fachkräftezuzugs, die eine gelingende Transformation voraussetzt. Spürbar positive Effekte zeigen die Behördenansiedlungen bei ihrer regionalen Verankerung sowie für Bleibeperspektiven von Lausitzer Frauen, die überproportional von diesen Jobs profitieren. [ABSTRACT FROM AUTHOR]

This research focuses on the improvement of porosity distribution within the electrode of an all‐vanadium redox flow battery (VRFB) and on optimizing novel cell designs. A half‐cell model, coupled with topology and shape optimization framework, is introduced. The multiobjective functional in both cases aims to minimize pressure drop while maximizing reaction rate within the cell. Topology optimization results reveal dependencies on initial value, porosity constraint, and flow rate. The distribution with lower porosity is preferred downstream of the inlet manifold. This design enhances active surface area, thus facilitating more effective conversion of incoming educts and improving mass transport of products. Compared to homogeneous electrodes, two‐part design demonstrates superior performance at specific porosity values. For combined porosities of 0.7 and 0.95, optimized distribution results in 81 % reduction in pressure drop, while conversion rate decreases by 7%. As regards various cell designs, optimization suggests a need to reconsider the vertical format of a rectangular cell. Horizontal cells are favored for nearly all porosities and flow rates. Trapezoidal and radial designs characterized by reduced downstream cross sections lead to higher pressure drops and are not preferred. This work provides further valuable insight into optimizing VRFB electrodes and challenges conventional cell design assumptions. [ABSTRACT FROM AUTHOR]

Credit markets and property rights are fundamental for modern economies, but their implications for the commons are unknown. Using a dynamic model of competitive resource extraction, we show that improving property right security unambiguously increases conservation incentives, but the effect of credit markets on resource extraction effort hinges on the security of property rights. We test these predictions using data on global fisheries, credit markets, and the largest ever marine property rights assignment. We find that property right security reduces resource extraction and that credit market development increases resource extraction under insecure property rights but reduces resource extraction under secure property rights. [ABSTRACT FROM AUTHOR]

Background: The efficacy of different cardioplegia solutions on outcomes of complex cardiac operations such as triple valve surgery (TVS) is scarce. Here we compared the outcomes in TVS patients receiving either crystalloid (Bretschneider) or blood (Calafiore) cardioplegia. Methods: Screening of our institutional database with prospectively entered data identified 471 consecutive patients (mean age 70.3 ± 9.2 years; 50.9% male), who underwent TVS (replacement or repair of aortic, mitral and tricuspid valve) between December 1994 and January 2013. In 277 patients, cardiac arrest was induced with HTK-Bretschneider solution (HTK, n = 277, 58.8%), whereas 194 received cold blood cardioplegia (BCP) according to Calafiore (n = 194, 41.2%). Comparisons of perioperative and follow up outcomes were made between cardioplegia groups. Results: Preoperative patient characteristics and comorbidities were equally balanced between groups. 30-days mortality was similar between groups (HTK: 16.2%; BCP: 18.2%; p = 0.619). Incidence of the cumulative endpoint (30days mortality, myocardial infarction (MI), arrhythmia, low cardiac output syndrome or need for permanent pacemaker implantation) was also comparable (HTK: 47.6%; BCP: 54.8%, p = 0.149). In patients with reduced left ventricular ejection fraction (LVEF <40%), 30days mortality was higher in the HTK group (HTK 18/71 22.5%; BCP 5/50 10%; p = 0.037). Five-year survival was similar between groups (52 ± 6% for HTK and 55 ± 5% for BCP patients). In-Hospital mortality was best predicted by length of surgery and reperfusion ratio. Decreased age, shorter bypass time, preserved LVEF and concomitant surgical procedures have been found to be protective from long-term mortality. Conclusions: Myocardial protection with HTK shows equivalent outcomes compared to BCP during TVS. Patients with reduced left ventricular function may benefit from BCP during TVS. [ABSTRACT FROM AUTHOR]

In this study we propose a novel data-driven reduced-order model for complex dynamics, including nonlinear, multi-attractor, multi-frequency and multiscale behaviours. The starting point is a fully automatable cluster-based network model (CNM) (Li et al., J. Fluid Mech., vol. 906, 2021, A21) that kinematically coarse grains the state with clusters and dynamically predicts the transitions in a network model. In the proposed dynamics-augmented CNM (dCNM) the prediction error is reduced with trajectory-based clustering using the same number of centroids. The dCNM is first exemplified for the Lorenz system and then demonstrated for the three-dimensional sphere wake featuring periodic, quasi-periodic and chaotic flow regimes. For both plants, the dCNM significantly outperforms the CNM in resolving the multi-frequency and multiscale dynamics. This increased prediction accuracy is obtained by stratification of the state space aligned with the direction of the trajectories. Thus, the dCNM has numerous potential applications to a large spectrum of shear flows, even for complex dynamics. [ABSTRACT FROM AUTHOR]

This study proposes a self-learning algorithm for closed-loop cylinder wake control targeting lower drag and lower lift fluctuations with the additional challenge of sparse sensor information, taking deep reinforcement learning (DRL) as the starting point. The DRL performance is significantly improved by lifting the sensor signals to dynamic features (DFs), which predict future flow states. The resulting DF-based DRL (DF-DRL) automatically learns a feedback control in the plant without a dynamic model. Results show that the drag coefficient of the DF-DRL model is 25% less than the vanilla model based on direct sensor feedback. More importantly, using only one surface pressure sensor, DF-DRL can reduce the drag coefficient to a state-of-the-art performance of approximately 8% at Reynolds number (Re) = 100 and significantly mitigates lift coefficient fluctuations. Hence, DF-DRL allows the deployment of sparse sensing of the flow without degrading the control performance. This method also exhibits strong robustness in flow control under more complex flow scenarios, reducing the drag coefficient by 32.2% and 46.55% at Re = 500 and 1000, respectively. Additionally, the drag coefficient decreases by 28.6% in a three-dimensional turbulent flow at Re = 10 000. Since surface pressure information is more straightforward to measure in realistic scenarios than flow velocity information, this study provides a valuable reference for experimentally designing the active flow control of a circular cylinder based on wall pressure signals, which is an essential step toward further developing intelligent control in a realistic multi-input multi-output system. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) directly affects oral health. Yet data about halitosis in young CKD patients and the impact of dental prophylaxis is limited. Therefore, as part of this randomized clinical trial, halitosis in young CKD patients undergoing intensive or standard oral preventive procedures was to be explored. Methods: Three volatile sulfur compounds (hydrogen sulfide, methyl mercaptan and dimethyl sulfide) were measured in 30 young patients with CKD (mean age 14.2 years; 16 males, 14 females). Breath samples were taken after 3 and 6 months and analyzed with selective gas chromatography (OralChroma). Tongue coating (Winkel Index) and clinical indices to determine local inflammation or oral hygiene (Papillary Bleeding Index and Quigley-Hein Index) were assessed. Within an extended anamnesis, patients and their mothers and nurses were questioned about the perceived halitosis. Corresponding quotes were noted verbatim. Patients were randomized to either intensive need-related oral health care measures (oral preventative program, OPP) or a one-stage standard prevention (treatment as usual, TAU). Results: While there were no differences in volatile sulfur compound levels between TAU and OPP at the three time points of measurements (p > 0.05), there was a tendency towards a reduction in dimethyl sulfide and hydrogen sulfide of affected patients within the OPP group over time. Looking at potential differences between both groups with regard to tongue coating, significant differences were observed between baseline and 3 months after study start in the OPP group, and between baseline and 6 months after study start in the TAU group (p < 0.05). The burden of halitosis was frequently reported by patients' mothers and nurses. Conclusions: Young CKD patients regularly suffered from halitosis and dimethyl sulfide was its main source. Preventive measures mainly resulted in a reduction of tongue coating. Trial registration: The German Clinical Trial Register (# DRKS00010580). [ABSTRACT FROM AUTHOR]

Although the effects of elections and measures of direct democracy on policy outcomes have been well researched, their indirect "educative value" has received less attention, particularly in relation to political engagement of young people. This study examined the activating effect of the national elections in Germany (2009), Czech Republic (2010), and Sweden (2014) on young voters' political engagement. Young voters (Germany: N = 388; Czech Republic: N = 196, and Sweden: N = 246) were surveyed several months before (T1), shortly after (T2), and several months after (T3) the respective national elections. For all three countries, the results revealed significant increases in political engagement during the election period, followed by significant declines after the election. The post-election declines were smaller compared to the election increases, suggesting a persistence of elections' activating effects. With the exception of German young adults who were less engaged or first-time voters and showed higher increases in engagement during the election period, there were few interindividual differences. The findings suggest that major political events such as national elections can have activating effects on youth's political engagement. They support the idea of the socializing value of election participation and of late adolescence and young adulthood as a window of opportunity for reaching young voters during politicized times. [ABSTRACT FROM AUTHOR]

We propose new confidence sets (CSs) for the regression discontinuity parameter in fuzzy designs. Our CSs are based on local linear regression, and are bias‐aware, in the sense that they take possible bias explicitly into account. Their construction shares similarities with that of Anderson–Rubin CSs in exactly identified instrumental variable models, and thereby avoids issues with "delta method" approximations that underlie most commonly used existing inference methods for fuzzy regression discontinuity analysis. Our CSs are asymptotically equivalent to existing procedures in canonical settings with strong identification and a continuous running variable. However, they are also valid under a wide range of other empirically relevant conditions, such as setups with discrete running variables, donut designs, and weak identification. [ABSTRACT FROM AUTHOR]

Point defects in two-dimensional materials are of key interest for quantum information science. However, the parameter space of possible defects is immense, making the identification of high-performance quantum defects very challenging. Here, we perform high-throughput (HT) first-principles computational screening to search for promising quantum defects within WS2, which present localized levels in the band gap that can lead to bright optical transitions in the visible or telecom regime. Our computed database spans more than 700 charged defects formed through substitution on the tungsten or sulfur site. We found that sulfur substitutions enable the most promising quantum defects. We computationally identify the neutral cobalt substitution to sulfur (Co S 0 ) and fabricate it with scanning tunneling microscopy (STM). The Co S 0 electronic structure measured by STM agrees with first principles and showcases an attractive quantum defect. Our work shows how HT computational screening and nanoscale synthesis routes can be combined to design promising quantum defects. Point defects in 2D semiconductors have potential for quantum computing applications, but their controlled design and synthesis remains challenging. Here, the authors identify and fabricate a promising quantum defect in 2D WS2 via high-throughput computational screening and scanning tunnelling microscopy. [ABSTRACT FROM AUTHOR]

Achieving cost-competitive bio-based processes requires development of stable and selective biocatalysts. Their realization through in vitro enzyme characterization and engineering is mostly low throughput and labor-intensive. Therefore, strategies for increasing throughput while diminishing manual labor are gaining momentum, such as in vivo screening and evolution campaigns. Computational tools like machine learning further support enzyme engineering efforts by widening the explorable design space. Here, we propose an integrated solution to enzyme engineering challenges whereby ML-guided, automated workflows (including library generation, implementation of hypermutation systems, adapted laboratory evolution, and in vivo growth-coupled selection) could be realized to accelerate pipelines towards superior biocatalysts. Achieving cost-competitive bio-based processes requires development of stable and selective biocatalysts. In this Perspective, the authors propose an integrated solution combining growth-coupled selection with machine learning and automated workflows to accelerate development pipelines. [ABSTRACT FROM AUTHOR]

Limiting the suspension stroke in vehicles holds critical and conceivable benefits. It is crucial for the safety, stability, ride comfort, and overall performance of the vehicle. Furthermore, it improves the reliability of suspension components and maintains consistent handling during regular and rough driving conditions. Hence, the design of a safety-critical controller to limit the suspension stroke for active suspension systems is of high importance. In this study, we employed a quarter-car model that incorporates a suspension spring with cubic nonlinearity. The proposed safety-critical controller is the control Lyapunov function–control barrier function–quadratic programming (CLF-CBF-QP). Initially, we designed the reference controller as a linear quadratic regulator (LQR) controller based on the linearized quarter-car model. The reference state-feedback LQR controller simplified the design of the control Lyapunov function. Consequently, from the nonlinear model, we construct a simple control Lyapunov function that relies only on the sprung mass velocity to have a relative degree of one. The CLF intends to improve the performance by considering the nonlinearity and via online optimization. We then formulate the control barrier function to restrict the suspension stroke from breaching its limits. To assess the effectiveness of the proposed controller, we present two challenging road inputs for the nonlinear quarter-car model when employing CLF-CBF-QP and LQR controllers. The CLF-CBF-QP findings surpassed the LQR controller in terms of safety and performance. This study highlights the immense potential of CLF-CBF-QP for suspension systems, improving the time-domain performance, limiting the suspension stroke, and guaranteeing safety. [ABSTRACT FROM AUTHOR]

Background: Narcissism has been implied as a putative risk factor for substance use disorders (SUDs). However, previous research did not disentangle the degree of substance use from substance-related problems, the symptoms of SUDs. This preregistered study addressed the open question whether grandiose and vulnerable narcissism and their constituent traits convey specific SUD risk, that is, explain substance-related problems beyond the degree of use. Furthermore, we tested whether impulsivity or substance use motives linked to narcissistic self-regulation mediate this association. Methods: Narcissism, impulsivity, substance use motives, past-year substance use, and substance-related problems were assessed in 139 (poly-)substance users, 121 of whom completed a one-year follow-up. For significant longitudinal associations between narcissism factors and substance-related problems controlled for the degree of use, we tested impulsivity and substance use motives as mediators. Results: Grandiose narcissism (r =.24, p =.007) and its constituent factors antagonistic (r =.27, p =.003) and agentic narcissism (r =.18, p =.050), but not vulnerable narcissism, prospectively predicted substance-related problems beyond the degree of substance use. Associations of grandiose narcissism and antagonistic narcissism with substance-related problems were fully mediated by impulsivity, but not substance use motives. Impulsivity explained roughly one third of the association of both grandiose (P̂M = 0.30) and antagonistic narcissism (P̂M = 0.26) with substance-related problems. Discussion: We demonstrate that grandiose narcissism– particularly antagonistic but also agentic narcissism– is specifically linked to substance-related problems beyond the degree of substance use. The mediating effect of impulsivity but not substance use motives suggests that impulsivity may be a more important mechanism than narcissistic self-regulation in promoting SUD in narcissism. However, future studies may use more targeted measures than substance use motives to further probe the role of self-regulation. Similar result patterns for alcohol compared to all substances together indicate that mechanisms may be alike across substances. In conclusion, narcissistic individuals may not use substances more but have a higher SUD risk, informing prevention and treatment. [ABSTRACT FROM AUTHOR]

We numerically investigate the fluidic pinball under symmetric forcing and find seven flow regimes under different rotation speeds. The fluidic pinball consists of three rotatable cylinders placed at the vertices of an equilateral triangle pointing upstream in a uniform oncoming flow. The starting point is the unforced asymmetric periodic vortex shedding at Reynolds number Re = 100 based on the cylinder diameter. The flow is symmetrically actuated by rotating the two rear cylinders at constant speed |b| up to three times the oncoming velocity in both directions. Counterclockwise (b > 0) and clockwise (b < 0) rotation of the bottom cylinder correspond to boat tailing and base bleeding, respectively. A total of seven distinct flow regimes are observed, including a steady flow, three symmetric/asymmetric periodic types of shedding, two symmetric/asymmetric quasi-periodic behaviors, and a chaotic dynamics. The vortex shedding features multiple coupled oscillator modes, including in-phase, anti-phase, and out-of-phase synchronization and non-synchronization. These shedding regimes are analyzed employing the temporal evolution of the aerodynamic forces and a dynamical mode decomposition of the wake flow. The kaleidoscope of unforced and forced dynamics promotes the fluidic pinball as a challenging modeling and control benchmark. [ABSTRACT FROM AUTHOR]

A rectangular cylinder, with an aspect ratio of 5, is a widely used bluff body in engineering practice. It undergoes intricate dynamical behavior in response to minute alterations in the flow angle of attack (α). These modifications invariably precipitate the failure of wake control for classical flow control methods with various α values. In this study, global linear instability, adjoint method, and sensitivity analysis are employed to identify the optimal position for flow control. It is found that the sensitive region gradually transitions from the leeward side to the downwind side of the model as α and Reynolds number (Re) increase. So, we set up airflow orifices for flow control in both positions. Jet flow control on the leeward side effectively inhibits vortex shedding (α ≤ 2°). High-order dynamic mode decomposition is employed to reveal the inherent mechanism of control. Suction control on the downside effectively mitigates the shear layer separation phenomenon induced by the altered spatial structure associated with higher α. A novel zero-net-mass-flux wake control, bionics-based breathe-valve control (BVC), is proposed to optimize the control effect. BVC is applicable for various α and Re, with optimal effectiveness achievable through jet velocity adjustments. The prediction-control approach in this investigation provides a targeted method to mitigate flow-induced vibration. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES In this study, we evaluated if modified Del Nido cardioplegia delivers comparable cardiac protection in comparison to Custodiol® in patients undergoing isolated minimally invasive mitral valve repair. METHODS From January 2018 to October 2021, all patients undergoing non-emergent isolated minimally invasive mitral valve repair were included in this study. The cardioplegia was chosen at the surgeons' discretion. The primary end points of this study were peak postoperative cardiac enzyme levels. Secondary end points were in-hospital mortality, hospital stay, occurrence of cardiac arrhythmias, pacemaker implantations, postoperative lactate and sodium levels and postoperative incidence of renal failure requiring dialysis. RESULTS A total of 355 patients were included in this study. The mean age of patients was 57. After propensity score matching, a total of 156 pairs were identified. There was no difference in cross-clamp time between both groups. Postoperative creatine kinase levels were higher in patients receiving Custodiol on the 1st and 2nd postoperative days. Creatine kinase isoenzyme MB levels were higher in patients receiving Custodiol on the 2nd postoperative day (0.5 ± 0.2 vs 0.4 ± 0.1 µmol/l s; P  < 0.001). Postoperative Troponin T concentrations were similar between both groups. Maximum lactate concentrations were higher in patients receiving Custodiol on the day of surgery (2.4 ± 1.9 vs 2.0 ± 1.1 mmol/l; P  = 0.04). The overall hospital stay was longer in patients receiving Del Nido cardioplegia (10.6 ± 3.2 vs 8 ± 4.1 days; P  < 0.01). CONCLUSIONS Modified Del Nido cardioplegia based on Ionosteril® solution offers equivalent protection compared to Custodiol for isolated minimally invasive mitral valve repair. [ABSTRACT FROM AUTHOR]

Although implicated in unsuccessful treatment, psychomotor deficits and their neurobiological underpinnings in bipolar (BD) and unipolar (UD) depression remain poorly investigated. Here, we hypothesized that motor performance deficits in depressed patients would relate to basal functional coupling of the hand primary motor cortex (M1) and the posterior cingulate cortex (PCC) with the supplementary motor area (SMA). We performed a longitudinal, naturalistic study in BD, UD and matched healthy controls comprising of two resting-state functional MRI measurements five weeks apart and accompanying assessments of motor performance using a finger tapping task (FTT). A subject-specific seed-based analysis describing functional connectivity between PCC-SMA as well as M1-SMA was conducted. The basal relationships with motor performance were investigated using linear regression models and all measures were compared across groups. Performance in FTT was impaired in BD in comparison to HC in both sessions. Behavioral performance across groups correlated significantly with resting state functional coupling of PCC–SMA, but not of M1-SMA regions. This relationship was partially reflected in a reduced PCC–SMA connectivity in BD vs HC in the second session. Exploratory evaluation of large-scale networks coupling (SMN–DMN) exhibited no correlation to motor performance. Our results shed new light on the association between the degree of disruption in the SMA–PCC anticorrelation and the level of motor impairment in BD. [ABSTRACT FROM AUTHOR]

Seoul orthohantavirus (SEOV) is a rat-borne zoonotic virus that is transmitted via inhalation of aerosolized infectious excreta, and can cause hemorrhagic fever with renal syndrome (HFRS) in humans worldwide. In rats, SEOV predominantly exists as a persistent infection in the absence of overt clinical signs. Lack of disease in rats is attributed to downregulation of pro-inflammatory and upregulation of regulatory host responses. As lung microvascular endothelial cells (LMECs) represent a primary target of infection in both human and rats, infections in these cells provide a unique opportunity to study the central role of LMECs in the dichotomy between pathogenicity in both species. In this study, host responses to SEOV infection in primary human and rat LMECs were directly compared on a transcriptional level. As infection of rat LMECs was more efficient than human LMECs, the majority of anti-viral defense responses were observed earlier in rat LMECs. Most prominently, SEOV-induced processes in both species included responses to cytokine stimulus, negative regulation of innate immune responses, responses to type I and II interferons, regulation of pattern recognition receptor signaling and MHC-I signaling. However, over time, in the rat LMECs, responses shifted from an anti-viral state towards a more immunotolerant state displayed by a PD-L1, B2M-, JAK2-focused interaction network aiding in negative regulation of cytotoxic CD8-positive T cell activation. This suggests a novel mechanism by which species-specific orthohantavirus-induced endothelium and T cell crosstalk may play a crucial role in the development of acute disease in humans and persistence in rodents. Author summary: Seoul orthohantavirus is a rat-borne zoonotic virus that can cause hemorrhagic fever with renal syndrome in humans worldwide while it generally leads to persistent infection in absence of clinical signs in the natural reservoir host, the Norway rat. It is believed that persistent infection in reservoir hosts is due to downregulation of pro-inflammatory immune responses and upregulation of regulatory responses, while in humans excessive immune responses contribute to disease. Endothelial cells in the lungs are of particular interest as they represent a primary target during Seoul orthohantavirus infection in both species. So far, it remains incompletely understood how the responses of these cells to Seoul orthohantavirus contribute to the development of disease in humans and the prevention of such in rats. In this study, we compared the host responses of human and rat lung endothelial cells to Seoul orthohantavirus infection and found that anti-viral responses from both species are comparable, but differ in timing. Additionally, we identified a novel protein interaction network during later phases of acute infection in rat cells, which may play a crucial role in the development of disease in humans and persistence in rodents. [ABSTRACT FROM AUTHOR]

The Gaussian process (GP) is a popular statistical technique for stochastic function approximation and uncertainty quantification from data. GPs have been adopted into the realm of machine learning (ML) in the last two decades because of their superior prediction abilities, especially in data-sparse scenarios, and their inherent ability to provide robust uncertainty estimates. Even so, their performance highly depends on intricate customizations of the core methodology, which often leads to dissatisfaction among practitioners when standard setups and off-the-shelf software tools are being deployed. Arguably, the most important building block of a GP is the kernel function, which assumes the role of a covariance operator. Stationary kernels of the Matérn class are used in the vast majority of applied studies; poor prediction performance and unrealistic uncertainty quantification are often the consequences. Non-stationary kernels show improved performance but are rarely used due to their more complicated functional form and the associated effort and expertise needed to define and tune them optimally. In this perspective, we want to help ML practitioners make sense of some of the most common forms of non-stationarity for Gaussian processes. We show a variety of kernels in action using representative datasets, carefully study their properties, and compare their performances. Based on our findings, we propose a new kernel that combines some of the identified advantages of existing kernels. [ABSTRACT FROM AUTHOR]

In the near future, urban air mobility (UAM) will let an old dream of human society come true: affordable and fast air transportation for almost everyone. Among the various existing designs, the multicopter configuration best combines the advantages of compactness, simplicity, and maturity. These aspects are important for actual use, particularly during the early stage of this market. This study elaborates on the design principles of UAM multicopters by examining existing models in terms of their configuration, weight, and range specifications. In particular, the weights of the different components are estimated based on empirical models, aerodynamic fundamentals for the analysis of UAM multicopters are derived from momentum theory, and the power and energy requirements for hovering and cruise flight are evaluated, thereby enabling estimation of the maximum hovering time and flight range. Finally, a sizing method is introduced and validated against an actual UAM design. [ABSTRACT FROM AUTHOR]

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The configuration of rotors significantly impacts the aerodynamic efficiency and noise emission of multicopters. To date, there are no general guidelines regarding how many blades a rotor should use for optimal aerodynamic performance and minimum noise emission. From the perspectives of aerodynamics and acoustics during the hovering condition, two key parameters, i.e., figure of merit (FM) and overall sound pressure level (OASPL), are evaluated to determine the optimal blade number (BN). The number of blades chosen in this study is BN = 2–6, which is largely observed in commercial multicopters. A genetic algorithm was developed to optimize blade design for each BN-rotor configuration. The individuals are evaluated by steady computational fluid dynamics (CFD) simulations and acoustic analogy for optimizations, and the detailed analyses of optimal ones are further explored by unsteady CFD simulations. The planform of the baseline blade is maintained, and the radial distribution of twist angles is the parameter for optimization. While generating the same thrust, the value of FM keeps increasing as the number of blades increases from 2 to 4, after which the FM value reaches a plateau. The value of OASPL keeps decreasing as the number of blades increases. The reason for the FM and OASPL value trends vs blade number is explained with the numerical simulation results, and a general design rule is suggested at the end. [ABSTRACT FROM AUTHOR]

Periodontitis is associated with significant alveolar bone loss. Patients with iron overload suffer more frequently from periodontitis, however, the underlying mechanisms remain largely elusive. Here, we investigated the role of transferrin receptor 2 (Tfr2), one of the main regulators of iron homeostasis, in the pathogenesis of periodontitis and the dental phenotype under basal conditions in mice. As Tfr2 suppresses osteoclastogenesis, we hypothesized that deficiency of Tfr2 may exacerbate periodontitis‐induced bone loss. Mice lacking Tfr2 (Tfr2−/−) and wild‐type (Tfr2+/+) littermates were challenged with experimental periodontitis. Mandibles and maxillae were collected for microcomputed tomography and histology analyses. Osteoclast cultures from Tfr2+/+ and Tfr2−/− mice were established and analyzed for differentiation efficiency, by performing messenger RNA expression and protein signaling pathways. After 8 days, Tfr2‐deficient mice revealed a more severe course of periodontitis paralleled by higher immune cell infiltration and a higher histological inflammation index than Tfr2+/+ mice. Moreover, Tfr2‐deficient mice lost more alveolar bone compared to Tfr2+/+ littermates, an effect that was only partially iron‐dependent. Histological analysis revealed a higher number of osteoclasts in the alveolar bone of Tfr2‐deficient mice. In line, Tfr2‐deficient osteoclastic differentiation ex vivo was faster and more efficient as reflected by a higher number of osteoclasts, a higher expression of osteoclast markers, and an increased resorptive activity. Mechanistically, Tfr2‐deficient osteoclasts showed a higher p38‐MAPK signaling and inhibition of p38‐MAPK signaling in Tfr2‐deficient cells reverted osteoclast formation to Tfr2+/+ levels. Taken together, our data indicate that Tfr2 modulates the inflammatory response in periodontitis thereby mitigating effects on alveolar bone loss. [ABSTRACT FROM AUTHOR]

Background: Industrial by-products accrue in most agricultural or food-related production processes, but additional value chains have already been established for many of them. Crude glycerol has a 60% lower market value than commercial glucose, as large quantities are produced in the biodiesel industry, but its valorisation is still underutilized. Due to its high carbon content and the natural ability of many microorganisms to metabolise it, microbial upcycling is a suitable option for this waste product. Results: In this work, the use of crude glycerol for the production of the value-added compound itaconate is demonstrated using the smut fungus Ustilago maydis. Starting with a highly engineered strain, itaconate production from an industrial glycerol waste stream was quickly established on a small scale, and the resulting yields were already competitive with processes using commercial sugars. Adaptive laboratory evolution resulted in an evolved strain with a 72% increased growth rate on glycerol. In the subsequent development and optimisation of a fed-batch process on a 1.5-2 L scale, the use of molasses, a side stream of sugar beet processing, eliminated the need for other expensive media components such as nitrogen or vitamins for biomass growth. The optimised process was scaled up to 150 L, achieving an overall titre of 72 g L− 1, a yield of 0.34 g g− 1, and a productivity of 0.54 g L− 1 h− 1. Conclusions: Pilot-scale itaconate production from the complementary waste streams molasses and glycerol has been successfully established. In addition to achieving competitive performance indicators, the proposed dual feedstock strategy offers lower process costs and carbon footprint for the production of bio-based itaconate. [ABSTRACT FROM AUTHOR]

This article discusses the use of a preoperative intestinal preconditioning protocol to prevent postoperative vasoplegia following tricuspid valve surgery. The protocol involves administering an oral antibiotic and laxatives 24 hours before surgery to reduce intestinal bacterial translocation. A retrospective analysis of patients who underwent tricuspid valve surgery between 2017 and 2021 was conducted, comparing outcomes between those who received preconditioning and those who did not. The study found that patients who received preconditioning had a lower incidence of vasoplegia and shorter ICU stays. The authors conclude that preoperative intestinal preconditioning is safe and effective in reducing the occurrence of vasoplegia in patients undergoing tricuspid valve surgery. [Extracted from the article]

Rural to urban migration (RUM) is a key component of economic development, but its environmental consequences are not well understood. Here, we study the impacts of RUM on agriculture and land use using household panel data in combination with tree cover data from Uganda. Our results show that the labor loss and the inflow of remittances from RUM lead to a reduction in crop diversity but no shift toward less labor‐intensive crops or crops with a high up‐front investment. In addition to those results at the intensive margin, we find a reduction of cultivated area at the household level, which translates into reduced tree cover loss at the district level. These results suggest an important but nuanced role of RUM for land use change. [ABSTRACT FROM AUTHOR]

Commercial electrolyte for vanadium flow batteries is modified by dilution with sulfuric and phosphoric acid so that series of electrolytes with total vanadium, total sulfate, and phosphate concentrations in the range from 1.4 to 1.7 m, 3.8 to 4.7 m, and 0.05 to 0.1 m, respectively, are prepared. The electrolyte samples of the series for positive and negative half‐cells at various state‐of‐charges are produced by electrolysis and are investigated for stability in the range of temperatures from −20 to +65 °C. It is attempted to reveal a correlation between initial electrolyte formulation in terms of total vanadium and total sulfate concentrations, which are measurable parameters in practice, and electrolyte thermal stability properties. The study of negative electrolyte samples by headspace online mass spectrometry enables to detect hydrogen gas, which evolves by chemical reaction of vanadium(II) species with protons during thermally induced aging. The battery with vanadium electrolyte at 1.4 m total vanadium, 4.7 m total sulfate, and 0.1 m phosphate concentrations displays more stable operation in terms of capacity decay during galvanostatic charge–discharge cycles than the battery with electrolyte at 1.7 m vanadium, 3.8 m sulfate, and 0.05 m phosphate concentrations under the same conditions. [ABSTRACT FROM AUTHOR]