Peanut allergy is a potentially life-threatening disease because it leads to severe allergic reactions, especially in children but also in adults. So far, allergen avoidance is the most effective therapy for treating peanut allergy. In this article, current developments of peanut allergy specific immunotherapy are critically discussed based on the existing literature. These include sublingual, epicutaneous and oral peanut immunotherapy. Nonspecific treatment approaches with new-targeted antibodies such as anti-IgE (omalizumab) or anti-IL-4/IL-13 receptor antibodies (dupilumab) can also be used to treat peanut allergy with regard to the mode of action of these antibodies. Multiple studies are already available for omalizumab and are currently performed with dupilumab. Whether and which therapies for the treatment of peanut allergy will be available on the market in the future is not only relevant in terms of clinical effectiveness in the sense of a long-term stable increase in the threshold level, but also in terms of the tolerability in everyday life of affected patients.View less
Background: Chronic urticaria (CU) is a common disease which represents a considerable burden for many patients. The current urticaria guideline describes the evidence-based diagnosis and treatment of CU. In addition, however, questions often arise in everyday practice that are not addressed by the guideline.
Methods: In May 2020, a digital meeting with German urticaria experts was held, in which practical aspects of CU treatment were discussed and supporting aids for everyday clinical treatment formulated. The resulting advice in this document focus on practical questions and the available literature and experiences of the participants.
Results: The diagnosis of CU can be made in a short time by means of a thorough anamnesis, a physical examination, and a basic laboratory chemical diagnosis. For this purpose, practical recommendations for everyday practice are given in this paper. An extended diagnosis is only indicated in a few cases and should always be carried out in parallel with an effective therapy. In general, CU should always be treated in the same way, regardless of whether wheals, angioedema or both occur. Symptomatic therapy should be carried out according to the treatment steps recommended by the guidelines. This publication provides practical advice on issues in everyday practice, such as the procedure in the current coronavirus disease 2019 (COVID-19) pandemic, the cardiac risk under higher dosed H1 antihistamines, the self-administration of omalizumab as well as vaccination under omalizumab therapy. In addition to treatment recommendations, topics such as documentation in the practice and family planning with urticaria will be discussed.
Discussion: These supporting treatment recommendations serve as an addendum to the current CU guideline and provide support in dealing with CU patients in everyday practice. The aim is to ensure that patients suffering from CU achieve complete freedom of symptoms with the help of an optimal therapy.View less
Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.View less
While the demand for ethical artificial intelligence (AI) systems increases, the number of unethical uses of AI accelerates, even though there is no shortage of ethical guidelines. We argue that a possible underlying cause for this is that AI developers face a social dilemma in AI development ethics, preventing the widespread adaptation of ethical best practices. We define the social dilemma for AI development and describe why the current crisis in AI development ethics cannot be solved without relieving AI developers of their social dilemma. We argue that AI development must be professionalised to overcome the social dilemma, and discuss how medicine can be used as a template in this process.View less
Terahertz (THz) radiation encompasses a wide spectral range within the electromagnetic spectrum that extends from microwaves to the far infrared (100 GHz–∼30 THz). Within its frequency boundaries exist a broad variety of scientific disciplines that have presented, and continue to present, technical challenges to researchers. During the past 50 years, for instance, the demands of the scientific community have substantially evolved and with a need for advanced instrumentation to support radio astronomy, Earth observation, weather forecasting, security imaging, telecommunications, non-destructive device testing and much more. Furthermore, applications have required an emergence of technology from the laboratory environment to production-scale supply and in-the-field deployments ranging from harsh ground-based locations to deep space. In addressing these requirements, the research and development community has advanced related technology and bridged the transition between electronics and photonics that high frequency operation demands. The multidisciplinary nature of THz work was our stimulus for creating the 2017 THz Science and Technology Roadmap (Dhillon et al 2017 J. Phys. D: Appl. Phys. 50 043001). As one might envisage, though, there remains much to explore both scientifically and technically and the field has continued to develop and expand rapidly. It is timely, therefore, to revise our previous roadmap and in this 2023 version we both provide an update on key developments in established technical areas that have important scientific and public benefit, and highlight new and emerging areas that show particular promise. The developments that we describe thus span from fundamental scientific research, such as THz astronomy and the emergent area of THz quantum optics, to highly applied and commercially and societally impactful subjects that include 6G THz communications, medical imaging, and climate monitoring and prediction. Our Roadmap vision draws upon the expertise and perspective of multiple international specialists that together provide an overview of past developments and the likely challenges facing the field of THz science and technology in future decades. The document is written in a form that is accessible to policy makers who wish to gain an overview of the current state of the THz art, and for the non-specialist and curious who wish to understand available technology and challenges. A such, our experts deliver a 'snapshot' introduction to the current status of the field and provide suggestions for exciting future technical development directions. Ultimately, we intend the Roadmap to portray the advantages and benefits of the THz domain and to stimulate further exploration of the field in support of scientific research and commercial realisation.View less
Aims. DE Boo is a unique system, with an edge-on view through the debris disk around the star. The disk, which is analogous to the Kuiper belt in the Solar System, was reported to extend from 74 to 84 AU from the central star. The high photometric precision of the Characterising Exoplanet Satellite (CHEOPS) provided an exceptional opportunity to observe small variations in the light curve due to transiting material in the disk. This is a unique chance to investigate processes in the debris disk.
Methods. Photometric observations of DE Boo of a total of four days were carried out with CHEOPS. Photometric variations due to spots on the stellar surface were subtracted from the light curves by applying a two-spot model and a fourth-order polynomial. The photometric observations were accompanied by spectroscopic measurements with the 1m RCC telescope at Piszkésteto and with the SOPHIE spectrograph in order to refine the astrophysical parameters of DE Boo.
Results. We present a detailed analysis of the photometric observation of DE Boo. We report the presence of nonperiodic transient features in the residual light curves with a transit duration of 0.3–0.8 days. We calculated the maximum distance of the material responsible for these variations to be 2.47 AU from the central star, much closer than most of the mass of the debris disk. Furthermore, we report the first observation of flaring events in this system.
Conclusions. We interpreted the transient features as the result of scattering in an inner debris disk around DE Boo. The processes responsible for these variations were investigated in the context of interactions between planetesimals in the system.View less
Context. Measurements of the occultation of an exoplanet at visible wavelengths allow us to determine the reflective properties of a planetary atmosphere. The observed occultation depth can be translated into a geometric albedo. This in turn aids in characterising the structure and composition of an atmosphere by providing additional information on the wavelength-dependent reflective qualities of the aerosols in the atmosphere.
Aims. Our aim is to provide a precise measurement of the geometric albedo of the gas giant HD 189733b by measuring the occultation depth in the broad optical bandpass of CHEOPS (350–1100 nm).
Methods. We analysed 13 observations of the occultation of HD 189733b performed by CHEOPS utilising the Python package PyCHEOPS. The resulting occultation depth is then used to infer the geometric albedo accounting for the contribution of thermal emission from the planet. We also aid the analysis by refining the transit parameters combining observations made by the TESS and CHEOPS space telescopes.
Results. We report the detection of an 24.7 ± 4.5 ppm occultation in the CHEOPS observations. This occultation depth corresponds to a geometric albedo of 0.076 ± 0.016. Our measurement is consistent with models assuming the atmosphere of the planet to be cloud-free at the scattering level and absorption in the CHEOPS band to be dominated by the resonant Na doublet. Taking into account previous optical-light occultation observations obtained with the Hubble Space Telescope, both measurements combined are consistent with a super-stellar Na elemental abundance in the dayside atmosphere of HD 189733b. We further constrain the planetary Bond albedo to between 0.013 and 0.42 at 3σ confidence.
Conclusions. We find that the reflective properties of the HD 189733b dayside atmosphere are consistent with a cloud-free atmosphere having a super-stellar metal content. When compared to an analogous CHEOPS measurement for HD 209458b, our data hint at a slightly lower geometric albedo for HD 189733b (0.076 ± 0.016) than for HD 209458b (0.096 ± 0.016), or a higher atmospheric Na content in the same modelling framework. While our constraint on the Bond albedo is consistent with previously published values, we note that the higher-end values of ~0.4, as derived previously from infrared phase curves, would also require peculiarly high reflectance in the infrared, which again would make it more difficult to disentangle reflected and emitted light in the total observed flux, and therefore to correctly account for reflected light in the interpretation of those phase curves. Lower reported values for the Bond albedos are less affected by this ambiguity.View less
Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.View less
Systemic sclerosis represents a chronic connective tissue disease featuring fibrosis, vasculopathy and autoimmunity, affecting skin, multiple internal organs, and skeletal muscles. The vasculopathy is considered obliterative, but its pathogenesis is still poorly understood. This may partially be due to limitations of conventional transmission electron microscopy previously being conducted only in single patients. The aim of our study was therefore to precisely characterize immune inflammatory features and capillary morphology of systemic sclerosis patients suffering from muscle weakness. In this study, we identified 18 individuals who underwent muscle biopsy because of muscle weakness and myalgia in a cohort of 367 systemic sclerosis patients. We performed detailed conventional and immunohistochemical analysis and large-scale electron microscopy by digitizing entire sections for in-depth ultrastructural analysis. Muscle biopsies of 12 of these 18 patients (67%) presented minimal features of myositis but clear capillary alteration, which we termed minimal myositis with capillary pathology (MMCP). Our study provides novel findings in systemic sclerosis-associated myositis. First, we identified a characteristic and specific morphological pattern termed MMCP in 67% of the cases, while the other 33% feature alterations characteristic of other overlap syndromes. This is also reflected by a relatively homogeneous clinical picture among MMCP patients. They have milder disease with little muscle weakness and a low prevalence of interstitial lung disease (20%) and diffuse skin involvement (10%) and no cases of either pulmonary arterial hypertension or renal crisis. Second, large-scale electron microscopy, introducing a new level of precision in ultrastructural analysis, revealed a characteristic capillary morphology with basement membrane thickening and reduplications, endothelial activation and pericyte proliferation. We provide open-access pan-and-zoom analysis to our datasets, enabling critical discussion and data mining. We clearly highlight characteristic capillary pathology in skeletal muscles of systemic sclerosis patients.View less
Among the hundreds of known hot Jupiters (HJs), only five have been found to have companions on short-period orbits. Within this rare class of multiple planetary systems, the architecture of WASP-47 is unique, hosting an HJ (planet-b) with both an inner and an outer sub-Neptunian mass companion (-e and -d, respectively) as well as an additional non-transiting, long-period giant (-c). The small period ratio between planets -b and -d boosts the transit time variation (TTV) signal, making it possible to reliably measure the masses of these planets in synergy with the radial velocity (RV) technique. In this paper, we present new space- and ground-based photometric data of WASP-47b and WASP-47-d, including 11 unpublished light curves from the ESA mission CHaracterising ExOPlanet Satellite (CHEOPS). We analyzed the light curves in a homogeneous way together with all the publicly available data to carry out a global N-body dynamical modeling of the TTV and RV signals. We retrieved, among other parameters, a mass and density for planet -d of Md = 15.5 ± 0.8 M⊕ and ρd = 1.69 ± 0.22 g cm−3, which is in good agreement with the literature and consistent with a Neptune-like composition. For the inner planet (-e), we found a mass and density of Me = 9.0 ± 0.5 M⊕ and ρe = 8.1 ± 0.5 g cm−3, suggesting an Earth-like composition close to other ultra-hot planets at similar irradiation levels. Though this result is in agreement with previous RV plus TTV studies, it is not in agreement with the most recent RV analysis (at 2.8σ), which yielded a lower density compatible with a pure silicate composition. This discrepancy highlights the still unresolved issue of suspected systematic offsets between RV and TTV measurements. In this paper, we also significantly improve the orbital ephemerides of all transiting planets, which will be crucial for any future follow-up.View less
Subependymomas are benign tumors characteristically encountered in the posterior fossa of adults that show distinct epigenetic profiles assigned to the molecular group "subependymoma, posterior fossa" (PFSE) of the recently established DNA methylation-based classification of central nervous system tumors. In contrast, most posterior fossa ependymomas exhibit a more aggressive biological behavior and are allocated to the molecular subgroups PFA or PFB. A subset of ependymomas shows epigenetic similarities with subependymomas, but the precise biology of these tumors and their potential relationships remain unknown. We therefore set out to characterize epigenetic traits, mutational profiles, and clinical outcomes of 50 posterior fossa ependymal tumors of the PFSE group. On histo-morphology, these tumors comprised 12 ependymomas, 14 subependymomas and 24 tumors with mixed ependymoma-subependymoma morphology. Mixed ependymoma-subependymoma tumors varied in their extent of ependymoma differentiation (2-95%) but consistently exhibited global epigenetic profiles of the PFSE group. Selective methylome analysis of microdissected tumor components revealed CpG signatures in mixed tumors that coalesce with their pure counterparts. Loss of chr6 (20/50 cases), as well as TERT mutations (21/50 cases), were frequent events enriched in tumors with pure ependymoma morphology (p < 0.001) and confined to areas with ependymoma differentiation in mixed tumors. Clinically, pure ependymoma phenotype, chr6 loss, and TERT mutations were associated with shorter progression-free survival (each p < 0.001). In conclusion, our results suggest that subependymomas may acquire genetic and epigenetic changes throughout tumor evolution giving rise to subclones with ependymoma morphology (resulting in mixed tumors) that eventually overpopulate the subependymoma component (pure PFSE ependymomas).View less
Climate change, biodiversity loss, and chemical pollution are planetary-scale emergencies requiring urgent mitigation actions. As these “triple crises” are deeply interlinked, they need to be tackled in an integrative manner. However, while climate change and biodiversity are often studied together, chemical pollution as a global change factor contributing to worldwide biodiversity loss has received much less attention in biodiversity research so far. Here, we review evidence showing that the multifaceted effects of anthropogenic chemicals in the environment are posing a growing threat to biodiversity and ecosystems. Therefore, failure to account for pollution effects may significantly undermine the success of biodiversity protection efforts. We argue that progress in understanding and counteracting the negative impact of chemical pollution on biodiversity requires collective efforts of scientists from different disciplines, including but not limited to ecology, ecotoxicology, and environmental chemistry. Importantly, recent developments in these fields have now enabled comprehensive studies that could efficiently address the manifold interactions between chemicals and ecosystems. Based on their experience with intricate studies of biodiversity, ecologists are well equipped to embrace the additional challenge of chemical complexity through interdisciplinary collaborations. This offers a unique opportunity to jointly advance a seminal frontier in pollution ecology and facilitate the development of innovative solutions for environmental protection.View less
Background: Augmented reality (AR) has the potential to support complex neurosurgical interventions by including visual information seamlessly. This study examines intraoperative visualization parameters and clinical impact of AR in brain tumor surgery.
Methods: Fifty-five intracranial lesions, operated either with AR-navigated microscope (n = 39) or conventional neuronavigation (n = 16) after randomization, have been included prospectively. Surgical resection time, duration/type/mode of AR, displayed objects (n, type), pointer-based navigation checks (n), usability of control, quality indicators, and overall surgical usefulness of AR have been assessed.
Results: AR display has been used in 44.4% of resection time. Predominant AR type was navigation view (75.7%), followed by target volumes (20.1%). Predominant AR mode was picture-in-picture (PiP) (72.5%), followed by 23.3% overlay display. In 43.6% of cases, vision of important anatomical structures has been partially or entirely blocked by AR information. A total of 7.7% of cases used MRI navigation only, 30.8% used one, 23.1% used two, and 38.5% used three or more object segmentations in AR navigation. A total of 66.7% of surgeons found AR visualization helpful in the individual surgical case. AR depth information and accuracy have been rated acceptable (median 3.0 vs. median 5.0 in conventional neuronavigation). The mean utilization of the navigation pointer was 2.6 x /resection hour (AR) vs. 9.7 x /resection hour (neuronavigation); navigation effort was significantly reduced in AR (P < 0.001).
Conclusions: The main benefit of HUD-based AR visualization in brain tumor surgery is the integrated continuous display allowing for pointer-less navigation. Navigation view (PiP) provides the highest usability while blocking the operative field less frequently. Visualization quality will benefit from improvements in registration accuracy and depth impression.View less
The Hayabusa2 mission provided a unique data set of asteroid Ryugu that covers a wide range of spatial scale from the orbiter remote sensing instruments to the returned samples. The MASCOT lander that was delivered onto the surface of Ryugu aimed to provide context for these data sets by producing in situ data collected by a camera (MasCam), a radiometer (MARA), a magnetometer (MasMag) and a spectrometer (MicrOmega). In this work, we evaluate the success of MASCOT as an integrated lander to bridge the gap between orbiter and returned sample analysis. We find that MASCOT’s measurements and derivatives thereof, including the rock morphology, colour in the visible wavelengths, possible meteorite analogue, density, and porosity of the rock at the landing site are in good agreement with those of the orbiter and the returned samples. However, it also provides information on the spatial scale (sub-millimetres to centimetres) at which some physical properties such as the thermal inertia and reflectance undergo scale-dependent changes. Some of the in situ observations such as the presence of clast/inclusions in rocks and the absence of fine particles at the landing site was uniquely identified by MASCOT. Thus, we conclude that the delivery of an in situ instrument like MASCOT provides a valuable data set that complements and provides context for remote sensing and returned sample analyses.View less
Extended-spectrum cephalosporins (ESCs) are critically important antimicrobial agents for human and veterinary medicine. ESC resistance (ESC-R) genes have spread worldwide through plasmids and clonal expansion, yet the distribution and dynamics of ESC-R genes in different ecological compartments are poorly understood. Here we use whole genome sequence data of Enterobacterales isolates of human and animal origin from Europe and North America and identify contrasting temporal dynamics. AmpC β-lactamases were initially more dominant in North America in humans and farm animals, only later emerging in Europe. In contrast, specific extended-spectrum β-lactamases (ESBLs) were initially common in animals from Europe and later emerged in North America. This study identifies differences in the relative importance of plasmids and clonal expansion across different compartments for the spread of different ESC-R genes. Understanding the mechanisms of transmission will be critical in the design of interventions to reduce the spread of antimicrobial resistance.View less
The Paleogene evolution of the NW margin of the African Plate (Western External Rif Zone) was studied by means of multidisciplinary analyses of twenty-one stratigraphic logs, including tectofacies recognition, petro-mineralogical results, and thicknesses analysis. Four stratigraphic intervals were recognized separated by three unconformities coarsely aligned with the Cretaceous–Paleogene, Eocene–Oligocene and Oligocene–Miocene boundaries, respectively. Tectofacies appear from the late Ypresian being more frequents from the Oligocene as the tectonic activity increases. The petrology of detrital suites indicates recycled orogen-derived sediments, with quartz supplied from metamorphic rocks of the Atlas orogen and/or the African craton. On the basis of Mesozoic clay mineral assemblages reported in the literature, the clay mineralogy of mudstones suggests upper Jurassic to upper Cretaceous terrains from the Internal Intrarif as the main source area of the Paleocene–Eocene successions, with sediment provenance reversion during the Oligocene and additional contribution of Paleocene to lower Eocene suites. The different displacement capability of the identified aluminic-magnesic clay mineralogy enabled to deduce the relative proximity of the source area. These findings point out a complex sedimentary evolution characterized by a mixture of different lithotypes dating back to upper Jurassic. X-ray parameters helped to identify evidences of synsedimentary tectonics overprinting the inherited mineralogy during some periods with weak burial diagenesis at most. During the Paleogene a foreland basin is formed mainly in the Mesorif and Prerif sub-domains. This foredeep was represented by two ‘sub-geosynclines’ separated by a relative bulge located in the External Mesorif. The Internal Intrarif could represent the relative orogenic front, advancing on the External Intrarif. The Eocene forebulge was located in the Ridges Domain, while the Gharb Basin was the backbulge of the system. During the Oligocene the depocentral area migrated southward and a homogeneization of thicknesses took also place in the whole margin. In this new configuration, the foredeep would be located in the External Mesorif (previously a relative bulge) while the Ridges Domain and the Gharb Basin continued to act as the system forebulge and backbulge, respectively. A comparison with the Paleogene evolution of other western Tethys external margins (Betic Chain, Tunisian Tell, Sicilian Maghrebids, and Apennines) has revealed more similarities than differences. The effects of the Eo-Alpine tectonics are recognized everywhere even if they decrease both from N to S, and from W to E in the different considered margins. The evolution of the compared margins shows a common pre-foredeed (Paleocene-Eocene) and beginning of foredeep (Oligocene) stages in the foreland basins.View less
Geschichten und Theater fördern nicht nur Neugier und Motivation, sie begünstigen auch das langfristige Lernen und sind somit lohnende Bestandteile von Fremdsprachenunterricht (Bryant/Rummel 2015). Allerdings kann gerade das Auswendiglernen von Theatertexten entmutigend sein. Durch den Einsatz kodifizierter Gesten, also von Handbewegungen mit den immer gleichen Bedeutungen, können Lehrkräfte Bewegung in ihren Unterricht bringen und dabei den Lernprozess ihrer Lernenden unterstützen. Darüber hinaus verbessert der Gebrauch von Gesten die Erinnerungsleistungen und kann die Lerneffizienz steigern (Janzen Ulbricht 2020). Und schließlich eigenen sich kodifizierte Gesten auch als Brücke zwischen den unterschiedlichen Sprachen, die die Lernenden mit- und einbringen. Das Theaterprojekt A Dentist to the Rescue basiert auf dem BBC-Nachrichtenclip The Dentist Who Helped a Koala to Walk von Isabelle Rodd. Es geht darin um einen Koala mit dem Spitznamen Triumph, dem seit der Geburt ein Fuß fehlt. Das Projekt lädt dazu ein, in der Lerngruppe vorhandene Sprachen im Englischunterricht zu nutzen. Es ist für drei Unterrichtsblöcke à 90 Minuten konzipiert und schließt zwei Hausaufgaben mit ein.View less