Ludwig-Maximilians-University of Munich

We investigate the causes of energetic proton (80‐540 keV) depletions measured during the two most distant flybys of Europa by Galileo, E17 and E25A, which encountered the Alfvén wings. First, by simulating the proton flux with a Monte Carlo particle tracing code we investigate the effect of: electromagnetic field perturbations, the induced dipole, atmospheric charge exchange and plumes. Inhomogeneous fields associated with the Alfvén wings and the ionosphere strongly affect the depletions. For homogeneous fields the depletion along the trajectory is focused on a narrow pitch angle range and has no structure, whereas the depletion for perturbed (inhomogeneous) fields represents a wider and complex structure. Furthermore, also the induced dipole alters the depletion structure. The effect of plumes (density 2.5 × 10 ¹⁵ m ⁻³ ) and charge exchange on the proton depletion is minor. Secondly, we compare the simulations to the proton measurements. The simulations with inhomogeneous fields describe the data qualitatively better than the homogeneous case, suggesting that indeed field perturbations are responsible for the measured losses. We attribute discrepancies between the simulations and the proton measurements to discrepancies between the simulated and real fields. We argue that simulating the fields along the trajectory is a good first step, but that ideally the energetic ion flux is reconstructed well to gain confidence in the interpretation of the simulated magnetic field. In conclusion, energetic ion observations along distant flybys through the Alfvén wings are suitable for isolating the characteristics of the global configuration of the magnetospheric interaction region of Europa (or other moons).

Little to no knowledge exists about television’s role in the sexual socialization of adolescents from the perspective of remembrance and resonance of narratives dealing with sexuality. The current study aims to fill this gap in the literature by using three-wave data of 703 respondents (51.5% assigned female at birth, M age = 15.44; SD = 1.43). We explored reciprocal relations between adolescents’ remembrance of resonating positive and negative messages included in sexual narratives on television and their positive sexuality components (e.g. sexual self-acceptance). Structural equation modeling showed that a respectful approach to different sexual expressions was related to the remembering of negative sexual television messages five months later. No other significant relations were found. Further, no differences were found based on adolescents’ sexual experiences. The findings are discussed in the realm of the potential of using the biographic resonance theory (BRT) of eudaimonic entertainment media to further explore the socializing potential of sexual television narratives.

Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31⁺ endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects. Graphical abstract Mechanical stress increases VEGF expression in endothelial AVM cells, possibly causing the VEGF upregulation in the microenvironment of AVM cells. The resulting RAS/RAF/MEK/ERK signaling in leads to progression of fast-flow malformations. The monoclonal VEGF-A antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. Sporadically occurring slow-flow malformations (LMs, VMs) have mutations in TEK or PIK3CA. TEK encodes the endothelial receptor tyrosine kinase TIE2. Sporadic extracranial fast-flow malformations (AVMs) show mutations in KRAS, BRAF and MAP2K1, which encodes the dual specificity mitogen-activated protein kinase MEK1. Combined targeting of the molecular causes of the disease could be key to achieve symptom control and reduce lesion growth. Orange: gain-of-function; Blue, circled with orange: enhanced signaling.

The significant increase in patients during the COVID-19 pandemic presented the healthcare system with a variety of challenges. The intensive care unit is one of the areas particularly affected in this context. Only through extensive infection control measures as well as an enormous logistical effort was it possible to treat all patients requiring intensive care in Germany even during peak phases of the pandemic, and to prevent triage even in regions with high patient pressure and simultaneously low capacities. Regarding pandemic preparedness, the German Parliament passed a law on triage that explicitly prohibits ex post (tertiary) triage. In ex post triage, patients who are already being treated are included in the triage decision and treatment capacities are allocated according to the individual likelihood of success. Legal, ethical, and social considerations for triage in pandemics can be found in the literature, but there is no quantitative assessment with respect to different patient groups in the intensive care unit. This study addressed this gap and applied a simulation-based evaluation of ex ante (primary) and ex post triage policies in consideration of survival probabilities, impairments, and pre-existing conditions. The results show that application of ex post triage based on survival probabilities leads to a reduction in mortality in the intensive care unit for all patient groups. In the scenario close to a real-world situation, considering different impaired and prediseased patient groups, a reduction in mortality of approximately 15% was already achieved by applying ex post triage on the first day. This mortality-reducing effect of ex post triage is further enhanced as the number of patients requiring intensive care increases.

Positional vertigo poses a diagnostic challenge in people with multiple sclerosis (MS). The characteristics of positional nystagmus and its response to repositioning manoeuvres are usually sufficient to diagnose benign paroxysmal positional vertigo (BPPV). However, certain BPPV variants respond poorly to repositioning manoeuvres and their nystagmus pattern can resemble that of central positional vertigo caused by infratentorial demyelination. This diagnostic difficulty is particularly challenging if positional vertigo occurs during an MS relapse. We describe a woman with MS who developed a sixth nerve palsy and gaze-evoked nystagmus, caused by demyelination near or within areas classically involved in central positional vertigo. However, she also had positional vertigo from coincident BPPV (and not central positional vertigo). This was initially a treatment resistant-posterior semicircular canal cupulolithiasis but it later progressed to a posterior semicircular canal canalolithiasis, with symptoms promptly resolving after a repositioning manoeuvre.

There is robust evidence that people with higher incomes tend to have higher self-esteem, but little is known about how changes in income and self-esteem are related within individuals. Some theories predict that increased earnings lead to higher self-esteem, others that increased self-esteem leads to higher earnings, and still others that there should be no within-person associations between these variables. We tested these theories in 4-year longitudinal data from more than 4,000 adult participants from a Dutch representative sample. Results indicated significant between-person associations between income and self-esteem, consistent with prior research. Within-person effects suggested that increases in self-esteem are a function of previous increases in income more than the other way around. These links held when analyses controlled for employment status, and they generalized across gender, age, and educational background. Overall, the findings provide evidence for theories that consider self-esteem as both a source and a consequence of personal earnings.

All-optical Compton sources combine laser-wakefield accelerators and intense scattering pulses to generate ultrashort bursts of backscattered radiation. The scattering pulse plays the role of a small-period undulator ( ${\sim }1\,\mathrm {\mu }{\rm m}$ ) in which relativistic electrons oscillate and emit X-ray radiation. To date, most of the working laser-plasma accelerators operate preferably at energies of a few hundreds of megaelectronvolts and the Compton sources developed so far produce radiation in the range from hundreds of kiloelectronvolts to a few megaelectronvolts. However, for such applications as medical imaging and tomography the relevant energy range is 10–100 keV. In this article, we discuss different scattering geometries for the generation of X-rays in this range. Through numerical simulations, we study the influence of electron beam parameters on the backscattered photons. We find that the spectral bandwidth remains constant for beams of the same emittance regardless of the scattering geometry. A shallow interaction angle of $30^{\circ }$ or less seems particularly promising for imaging applications given parameters of existing laser-plasma accelerators. Finally, we discuss the influence of the radiation properties for potential applications in medical imaging and non-destructive testing.

Two-dimensional chiral metasurfaces seem to contradict Lord Kelvin's geometric definition of chirality since they can be made to coincide by performing rotational operations. Nevertheless, most planar chiral metasurface designs often use complex meta-atom shapes to create flat versions of three-dimensional helices, although the visual appearance does not improve their chiroptical response but complicates their optimization and fabrication due to the resulting large parameter space. Here we present one of the geometrically simplest two-dimensional chiral metasurface platforms consisting of achiral dielectric rods arranged in a square lattice. Chirality is created by rotating the individual meta-atoms, making their arrangement chiral and leading to chiroptical responses that are stronger or comparable to more complex designs. We show that resonances depending on the arrangement are robust against geometric variations and behave similarly in experiments and simulations. Finally, we explain the origin of chirality and behavior of our platform by simple considerations of the geometric asymmetry and gap size.

The average age of our population is increasing, resulting in a high incidence of chronic degenerative knee pathologies. Several treatment options, including surgical procedures are available to help mitigate these pathologies. However, the percentage of subjects with chronic post-surgical knee pain is still estimated at 16–20%. Neuromodulation techniques such as spinal cord stimulation and dorsal root ganglion stimulation (DRGS) are treatment options for subjects with chronic knee pain. The evidence for peripheral nerve stimulation (PNS) is minimal due to a limited number of neuromodulation systems capable of targeting the distal part of the lower limbs. This study aimed to investigate the safety and efficacy externally powered PNS systems for the treatment of chronic intractable knee pain targeting the saphenous nerve. Patients suffering from chronic intractable post-surgical knee pain received landmark-guided peripheral nerve stimulation of the branches of the saphenous nerve. All implants were performed with an externally powered PNS system to avoid lead migration as a result of cross-joint lead positions tunneling towards an Implantable Pulse Generator to the trunk. Data were collected retrospectively. Subject-reported outcome was measured via numerical rating scale values on a 10-point scale measuring pain intensity at rest and in motion. Additional data were collected for the subjects treated at the Charité location, including quality of life with the SF-36 form, quality of sleep with the Pittsburgh Sleep Quality Index and mood states with the short form of the General Depression Scale. Thirty-three patients received direct to permanent implant, landmark- guided peripheral nerve stimulation of the saphenous nerve branches. Six (18.2%) subjects reported non-sufficient initial benefit from the therapy and were explanted. Two subjects were explanted due to wound infections. The total study population reported included 25 patients. These subjects reported significant improvements related to pain, quality of life, mood quality, and quality of sleep. Additionally, subjects were able to reduce their opioid medication significantly after PNS therapy. Externally powered PNS at the saphenous nerve branches is a straightforward, selective and safe technique for patients with chronic knee pain. The landmark-guided implantation technique is less invasive than classical neuromodulation techniques such as spinal cord or DRGS and complication rates remain low. Short-term results are promising and show considerable reductions in pain scores and opioid intake. Long-term results are pending.

Employees want to be able to telework and organisations want to provide the ideal environment to make it a success story. While some teleworkers experience telework success, that is, are satisfied and perform well, others do not. To understand the drivers of successful and unsuccessful telework, we used a mixed methods approach, taking a stress‐theoretic and configurational perspective. In Study 1, we conducted a quantitative analysis of data collected in a survey of 375 teleworkers to identify configurations of information and communication technology (ICT), work and family related challenge and hindrance stressors that lead to high and low telework success. In Study 2, we analysed qualitative data collected in interviews with 52 teleworkers to shed light on the interplay among ICT, work and family related challenge and hindrance stressors in the configurations that lead to high and low telework success. We contribute to telework research by showing that high and low telework success results from configurations of ICT, work and family related challenge and hindrance stressors. We extend the literature by showing that teleworkers benefit from challenge stressors only when they do not experience hindrance stressors. Methodologically, we provide a blueprint for an innovative approach using deductive fsQCA to refine, extend and delimit theory.

Background Feline lower airway disease (FLAD) is frequently associated with radiographic abnormalities. Objectives To evaluate whether radiographic changes in cats with naturally occurring FLAD improve with treatment and if radiographic changes correlate with clinical signs. Animals Twenty‐four client‐owned cats newly diagnosed with FLAD, based on medical history, typical clinical signs, radiographic findings, and examination of bronchoalveolar lavage fluid, were included in the prospective study. Methods At 2 examination time points (days 0 and 60), an owner questionnaire, clinical examination, and thoracic radiography were carried out. Information from the questionnaire and clinical examination were evaluated on the basis of a 12‐point clinical score. Radiographs were assessed using a 10‐point radiographic score. Individual treatment was given to all cats over the study period, based on severity of the disease and compliance of the cat. Clinical and radiographic scores were compared statistically for both examination time points and evaluated for correlation. Results All cats showed radiographic abnormalities at initial presentation. In addition to significant improvement in clinical variables, the total radiographic score improved significantly ( P = .01) during the study period, with significant improvement in the severity of bronchial ( P = .01) and interstitial lung pattern ( P = .04). Improvement of the clinical and radiographic score was not correlated. Conclusion and Clinical Importance In addition to clinical signs, repeated radiographic examination can be used as a diagnostic tool to evaluate treatment response in cats with FLAD.

Objective To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe. Methods This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case–control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching. Results A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure. Conclusions This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections. Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017).

Zusammenfassung Patienten mit einem schweren kombinierten Immundefekt (SCID) erkranken aufgrund einer fehlenden bzw. gestörten T‑Zell-Immunität meist innerhalb der ersten Lebensmonate an schweren, oft letal verlaufenden Infektionen oder Zeichen der Immunfehlregulation. Nur durch die Korrektur des Immunsystems – in der Regel durch eine hämatopoetische Stammzelltransplantation (HSZT) – ist eine Heilung möglich. Pilotstudien und nationale Programme in den USA und Europa konnten zeigen, dass betroffene Kinder bereits im asymptomatischen Stadium durch das Neugeborenenscreening erkannt werden können. Dies ermöglicht es, Patienten mit SCID noch vor Auftreten schwerer Komplikationen zu behandeln, was den Erfolg der Therapiemaßnahmen wie HSZT erheblich verbessert. Einem Bewertungsverfahren im Gemeinsamen Bundesausschuss (G-BA) folgend wurde 2019 auch in Deutschland ein Neugeborenenscreening auf SCID eingeführt. Die ersten Ergebnisse des Screenings (Trockenblutkarten von ca. 2 Mio. Neugeborenen im Zeitraum August 2019 bis Februar 2022) wurden vor Kurzem veröffentlicht. Neben klassischen SCID-Erkrankungen (Inzidenz 1:54.000) wurden, wie erwartet, auch Patienten mit einer syndromalen Grunderkrankung und T‑Zell-Lymphopenie identifiziert. Bei allen Patienten mit klassischem SCID wurde eine kurative Therapie geplant; 21 von 25 Patienten waren zum Zeitpunkt der Datenauswertung bereits transplantiert. Nur einer der 21 transplantierten Patienten verstarb an vorbestehenden Infektionen. Ein Vergleich des implementierten Screenings mit historischen Daten zeigt, dass das Screening in Deutschland erfolgreich umgesetzt wurde. Patienten mit SCID werden frühzeitig identifiziert und einer kurativen Therapie zugeführt.

The information on plasma pressure in the outer part of the inner magnetosphere is important for simulations of the inner magnetosphere and a better understanding of its dynamics. Based on 17‐year observations from both Cluster Ion Spectrometry and Research with Adaptive Particle Imaging Detector instruments onboard the Cluster mission, we used machine‐learning‐based models to predict proton plasma pressure at energies from ∼40 eV to 4 MeV in the outer part of the inner magnetosphere (L∗ ${L}^{\ast }$ = 5–9). Proton pressure distributions are assumed to be isotropic. The location in the magnetosphere, the property of stably trapped particles, and parameters of solar, solar wind, and geomagnetic activity from the OMNI database are used as predictors. We trained several different machine‐learning‐based models and compared their performances with observations. The results demonstrate that the Extra‐Trees Regressor has the best predicting performance. The Spearman correlation between the observations and predictions by the model is about 70%. The most important parameter for predicting proton pressure in our model is the L∗ ${L}^{\ast }$ value, which relates to the property of stably trapped particles. The most important predictor of solar and geomagnetic activity is F10.7 index. Based on the observations and predictions by our model, we find that no matter under quiet or disturbed geomagnetic conditions, both the dusk‐dawn asymmetry at the dayside with higher pressure at the duskside and the day‐night asymmetry with higher pressure at the nightside occur. Our results have direct practical applications, for instance, inputs for simulations of the inner magnetosphere or the reconstruction of the 3‐D magnetospheric electric current system based on the magnetostatic equilibrium.

Attention makes things look brighter and more colorful. In light of these effects, representationalist philosophers propose that attentive experiences represent more determinate color properties than inattentive experiences. Although this claim is appealing, we argue that it does not hold for one of our best conceptualizations of content determinacy, according to which an experience has more determinate contents if it represents a narrower range of values within the relevant dimension. We argue that our current empirical evidence fails to show that attention has this kind of effect on color perception. We then offer an alternative, representationalist-friendly account of the attentional effects, as changes in vividness.

Climate change has already caused local extinction in many plants and animals, based on surveys spanning many decades. As climate change accelerates, the pace of these extinctions may also accelerate, potentially leading to large‐scale, species‐level extinctions. We tested this hypothesis in a montane lizard. We resurveyed 18 mountain ranges in 2021–2022 after only ~7 years. We found rates of local extinction among the fastest ever recorded, which have tripled in the past ~7 years relative to the preceding ~42 years. Further, climate change generated local extinction in ~7 years similar to that seen in other organisms over ~70 years. Yet, contrary to expectations, populations at two of the hottest sites survived. We found that genomic data helped predict which populations survived and which went extinct. Overall, we show the increasing risk to biodiversity posed by accelerating climate change and the opportunity to study its effects over surprisingly brief timescales.

When people meet, they almost instantaneously form an impression of each other. First impressions of character traits and rapport are less favourable when people with autism spectrum condition (ASC) are judged compared to non-autistic people. Little is known about the behavioural differences that drive these altered impressions. In the present study, we investigated the influence of interpersonal synchrony on impression formation of autistic and non-autistic people. Specifically, we used lagged cross-correlations to assess how much each interactant’s motion energy, a measure which can be determined from video recordings, influenced the other interactant’s motion energy. In short, silent clips of dyadic conversations, we asked non-autistic participants to rate their impression of one of the two interactants, which was solely based on the outlines of both interactants. We expected that the amount of leading of the target interactant, their diagnostic status as well as the interaction of these factors would influence impression formation. We found that while the amount of leading had a positive effect on the impressions of non-autistic interactants, this was not true for interactants with ASC. This suggests that interpersonal synchrony of motion energy is one driver of less favourable impressions of autistic compared to non-autistic people.

Taurine-respiring gut bacteria produce H2S with ambivalent impact on host health. We report the isolation and ecophysiological characterization of a taurine-respiring mouse gut bacterium. Taurinivorans muris strain LT0009 represents a new widespread species that differs from the human gut sulfidogen Bilophila wadsworthia in its sulfur metabolism pathways and host distribution. T. muris specializes in taurine respiration in vivo, seemingly unaffected by mouse diet and genotype, but is dependent on other bacteria for release of taurine from bile acids. Colonization of T. muris in gnotobiotic mice increased deconjugation of taurine-conjugated bile acids and transcriptional activity of a sulfur metabolism gene-encoding prophage in other commensals, and slightly decreased the abundance of Salmonella enterica, which showed reduced expression of galactonate catabolism genes. Re-analysis of metagenome data from a previous study further suggested that T. muris can contribute to protection against pathogens by the commensal mouse gut microbiota. Together, we show the realized physiological niche of a key murine gut sulfidogen and its interactions with selected gut microbiota members.

The PDCD1-encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells that is recurrently inactivated in T cell non-Hodgkin lymphomas (T-NHLs). The highest frequencies of PDCD1 deletions are detected in advanced disease, predicting inferior prognosis. However, the tumor-suppressive mechanisms of PD-1 signaling remain unknown. Here, using tractable mouse models for T-NHL and primary patient samples, we demonstrate that PD-1 signaling suppresses T cell malignancy by restricting glycolytic energy and acetyl coenzyme A (CoA) production. In addition, PD-1 inactivation enforces ATP citrate lyase (ACLY) activity, which generates extramitochondrial acetyl-CoA for histone acetylation to enable hyperactivity of activating protein 1 (AP-1) transcription factors. Conversely, pharmacological ACLY inhibition impedes aberrant AP-1 signaling in PD-1-deficient T-NHLs and is toxic to these cancers. Our data uncover genotype-specific vulnerabilities in PDCD1-mutated T-NHL and identify PD-1 as regulator of AP-1 activity.