Ludwig-Maximilians-Universität in Munich

As the first group of tetrapods to achieve powered flight, pterosaurs first appeared in the Late Triassic. They proliferated globally, and by the Late Jurassic through the Cretaceous, the majority of these taxa belonged to the clade Monofenestrata (which includes the well-known Pterodactyloidea as its major subclade), typified by their single undivided fenestra anterior to the orbit. Here, a new taxon Melkamter pateko gen. et sp. nov., represented by the specimen MPEF-PV 11530 (comprising a partial cranium and associated postcranial elements), is reported from the latest Early Jurassic (Toarcian) locality of Queso Rallado (Cañadón Asfalto Formation) and referred to the clade Monofenestrata, increasing our previously known taxonomic and geographic representations, and temporal range for this clade. This occurrence marks the oldest record of Monofenestrata globally and helps to shed critical light on the evolutionary processes undergone during the ‘non-pterodactyloid’-to-pterodactyloid transition within the Pterosauria. In addition, another single isolated tooth from the same locality shows ctenochasmatid affinities. These finds further elucidate the still-poor Gondwanan Jurassic pterosaur fossil record, underscoring that most of our current ideas about the timing and modes of pterosaur evolution during that period are largely based on (and biased by) the pterosaur fossil record of the Northern Hemisphere.

Literature on stress and intimate partner violence (IPV) has primarily focused on stress as an outcome of women’s experience of IPV. However, stress may also be a predictor of male-perpetrated IPV. To improve our understanding of how theoretical approaches to stress have been applied to IPV research, we conducted a sub-analysis of a broader systematic review to identify published literature that examines theoretical approaches to stress as a predictor of male-perpetrated IPV. We conducted a search of nine electronic databases and assessed title/abstract and full texts according to pre-defined inclusion and exclusion criteria. Two reviewers categorized included studies into different theoretical groupings and sub-groupings. Data were extracted according to a data extraction template developed for the review, establishing consistency in a pilot data extraction phase. The review identified 27 articles that addressed the following theories of stress: general stress theory, life course theory, occupational stress theory, vulnerability theory, and family stress theory. Each of these sub-theories focuses on different forms of stress, for example, life course theory specifically focuses on stressful early life experiences, including adverse childhood events, whereas occupational stress theory focuses on workplace-related stressors that may result in increased male-perpetrated IPV. Analysis of measurement of stress variables indicated that measurement of stress varies widely across studies and primarily relies on self-reports. Consideration of stress as a predictor of IPV provides important insights into preventable and modifiable targets for intervention. Additional research on mechanisms and pathways between stress and IPV is needed.

Aims In the treatment of basal thumb osteoarthritis (OA), intra-articular autologous fat transplantation has become of great interest within recent years as a minimally invasive and effective alternative to surgical intervention with regard to pain reduction. This study aims to assess its long-term effectiveness. Methods Patients diagnosed with stage one to three OA received a single intra-articular autologous fat transplantation. Fat tissue was harvested from the abdomen and injected into the trapeziometacarpal (TMC) joint under radiological guidance, followed by one week of immobilization. Patients with a minimum three-year post-procedure period were assessed for pain level (numerical rating scale), quality of life (Mental Health Quotient (MHQ)), the abbreviated version of the Disabilities of Arm, Shoulder and Hand questionnaire (QuickDASH)), and grip and pinch strength, as well as their overall impression of the treatment. Wilcoxon tests compared data from pre-intervention, and at one and three years post-intervention. Results Out of 136 treated joints, the study involved 87 patients (37 patients were loss to follow-up, and 12 patients (9%) who underwent resection arthroplasty) with a median follow-up of 4.9 years (IQR 5.4 to 5.9). Pain, both at rest and during stress, significantly improved at one year and remained stable through three years. Sex, age, and stage of disease were not associated with postoperative pain levels. Patient-reported outcome measures for QuickDASH and MHQ improved up to at least three years post-treatment. Patients reported high satisfaction and willingness to recommend the procedure. Grip and pinch strength did not significantly change over time. Conclusion The data show that autologous fat transfer has a longer-lasting effect in two-thirds of re-examined patients. If patients had an initial positive response, the pain-reducing effect lasted for at least three years. Therefore, this minimally invasive approach can offer a valuable treatment alternative for basal thumb OA.

A series of aryl‐substituted ortho‐quinone methides (oQMs) was synthesised and structurally characterised. Kinetic studies of the nucleophilic additions of carbanions (reference nucleophiles) to oQMs were used to determine second‐order rate constants k2 for the carbon‐carbon bond forming reactions (20 °C, DMSO) at the oQMs’ exocyclic π‐bond. Analysing the kinetic data by the linear free energy relationship lg k2=sN(N+E) revealed the Mayr electrophilicities E of the oQMs. The electrophilicities E of oQMs correlate linearly with Hammett substituent constants and experimentally determined reduction potentials Epred as well as with quantum‐chemically calculated methyl anion affinities (MAAs), which provides valuable tools for prediciting the reactivity of further types of oQMs. Embedding the oQMs in Mayr's reactivity scales enables to predict novel nucleophilic reaction partners for oQMs and can productively be used to prepare simple Michael adducts as well as 4+2 or 4+1 cyclisation products as demonstrated in this work by several novel reactions with neutral or negatively charged C‐, N‐, and S‐nucleophiles.

Oxide zeolites are synthesized from aqueous solutions in an established way employing hydrothermal synthesis. Transferring this approach to nitride zeolites requires a solvent providing nitrogen for which ammonia has proven to be particularly suitable. We present the successful ammonothermal synthesis of the (oxo)nitridosilicate compounds Ce3[Si6N11], Li2RE4[Si4N8]O3 (RE=La, Ce) and K1.25Ce7.75[Si11N21O2]O0.75. Within this procedure, the usage of supercritical ammonia as a solvent as well as the utilization of the mineralizers NaN3, Li3N and KN3, respectively, allowed the targeted synthesis of large single crystals. Formation of these (oxo)nitridosilicates depends mainly on the employed mineralizer despite their similar degree of condensation. The three compounds were structurally characterized using X‐ray diffraction and their crystal structures contain a wide range of different ring sizes within their tetrahedra networks. The zeolite(‐like) crystal structures are elucidated and compared to known nitridosilicate representatives of the respective structure types. Their elemental composition was investigated using energy‐dispersive X‐ray (EDX) spectroscopy and incorporation of the O rather than N−H functionality was confirmed by Fourier‐Transform infrared (FTIR) spectroscopy as well as by charge distribution (CHARDI) and bond valence sum (BVS) calculations. The presented examples demonstrate that ammonothermal synthesis provides a one‐step access from elemental starting materials towards nitride zeolites.

Zusammenfassung Die Novellierung von § 64 des Strafgesetzbuches (StGB) ist am 01.10.2023 in Kraft getreten. Es erfolgte u. a. eine Spezifizierung des „Hangs“: Gefordert sind nun das Vorliegen einer Substanzkonsumstörung und in dessen Folge eine dauernde und schwerwiegende Beeinträchtigung von Lebensgestaltung, Gesundheit, Arbeitsfähigkeit oder Leistungsfähigkeit („Hangkriterien“). In einer vorangegangenen Arbeit der Verfasser (Schwarz und Stübner 2023) wurde eine retrospektive Aktenanalyse durchgeführt bei n = 70 männlichen Patienten, deren Unterbringung gemäß § 64 StGB in der Klinik für Forensische Psychiatrie am Bezirksklinikum Ansbach (Bayern) zwischen dem 01.07.2021 und dem 30.06.2022 beendet worden war (Querschnittvollerfassung). In der hier vorliegenden explorativen Sekundäranalyse dieser Daten sollte nun ein etwaiger Zusammenhang zwischen dem Therapieergebnis (bedingte Entlassung aus der Maßregel oder vorzeitige Erledigung) und der im jeweiligen Fall vorliegenden Art und Anzahl der Hangkriterien fokussiert werden. Es zeigte sich, dass bei Patienten mit einem regulären Therapieabschluss im Durchschnitt höhere Anzahlen von Hangkriterien vorgelegen hatten, insbesondere Beeinträchtigungen der Arbeitsfähigkeit. In dieser Gruppe waren allerdings weniger schwere psychiatrische Komorbiditäten zu verzeichnen. Zwischen den einzelnen Hangkriterien wurden teils hochsignifikante Zusammenhänge ermittelt. Insgesamt deutet sich an, dass die neue Konturierung des Hangbegriffs zu einer gezielteren Zuweisung von Patienten, die von den spezifischen Therapieangeboten in einer Entziehungsanstalt profitieren, führen könnte. Zudem scheinen sich die rechtswissenschaftlich intendierten Verbesserungen mit erfahrungswissenschaftlichen Methoden abbilden zu lassen.

Here we make the case that the interment of twelve skeletons in a small Western Cape rock shelter should be viewed as a single event. We present evidence of the partially disarticulated, clearly overlapping arrangement of human remains and the radiocarbon dating results from the individuals that point to a hasty but coordinated burial at a critical moment in the prehistory of the Cape. The moment was marked by the earliest appearance of the pastoralist lifestyle in an area previously dominated by hunting and gathering (Sadr PLoS ONE 10(8):e0134215, 2015). Because, as others show (Dlamini et al., this volume), these interments are associated with peri-mortem violence, the demonstration of contemporaneity and entanglement implies a rare occurrence of so many deaths at a time when conflict between pastoralists and hunter-gatherers in the area seems likely. In describing the circumstances of bone recovery, the positioning of body parts and the associated radiocarbon ages, we lay the platform for further micro-stratigraphic, biological, genetic and isotopic studies of the twelve individuals and some contemplation on the nature of the event.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo. We also show that phenotype-specific therapeutic vulnerabilities and modes of treatment-induced phenotype reprogramming can be captured in phenotypic heterogeneity maps. Our methodology and analyses of tumour-cell heterogeneity in PDAC may guide the development of phenotype-targeted treatment strategies.

Zusammenfassung Zielsetzung Die Pathogeninaktivierung (PI) ist ein weltweit anerkanntes Verfahren zur Verbesserung der Sicherheit von Thrombozytenkonzentraten und Plasma. Diese Arbeit untersucht die Notwendigkeit und potenziellen Vorteile der Implementierung der PI für Thrombozytenkonzentrate in Deutschland. Methodik Analysiert werden sowohl Daten zur aktuellen Blutversorgung als auch zu Infektionsrisiken von Thrombozytenkonzentraten sowie bestehender Sicherheitsstandards auch im interationalen Vergleich. Ergebnisse Die Ergebnisse zeigen, dass PI die Sicherheit durch die Inaktivierung bekannter und unbekannter Pathogene verbessert, die Haltbarkeit verlängert, den Spenderkreis erweitert und die Anzahl verworfener Thrombozytenkonzentrate reduziert. Dies stabilisiert die Versorgung und senkt Kosten. Schlussfolgerung Eine Integration der PI in die deutschen Hämotherapie-Richtlinien und beschleunigte Zulassungsverfahren werden empfohlen.

BACKGROUND White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease. METHODS Structural T 2 -weighted imaging, multishell diffusion imaging, and dynamic contrast–enhanced magnetic resonance imaging were performed at 3T in 44 participants with sporadic cerebral small vessel disease and 32 participants with monogenic cerebral small vessel disease (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; 59±12 years, 41 males) between June 2017 and May 2020 as part of the prospective, multicenter (Edinburgh, the United Kingdom; Maastricht, the Netherlands; and Munich, Germany), observational INVESTIGATE-SVDs study (Imaging Neurovascular, Endothelial and Structural Integrity in Preparation to Treat Small Vessel Diseases). The mean diffusivity, free water content, and perfusion (all derived from multishell diffusion imaging), as well as the blood-brain barrier leakage and plasma volume fraction (derived from dynamic contrast–enhanced magnetic resonance imaging), were compared between deep and periventricular WMH types using paired t tests. Additional spatial analyses were performed inside and outside the WMH types to determine the internal heterogeneity and the extent of the penumbras, that is, adjacent white matter at risk for conversion to WMH. RESULTS Periventricular WMH had higher mean diffusivity, higher free water content, and more plasma volume compared with deep WMH ( P <0.001, P =0.01, and P <0.001, respectively). No differences were observed in perfusion ( P =0.94) and blood-brain barrier leakage ( P =0.65) between periventricular and deep WMHs. The spatial analyses inside WMH and the adjacent white matter revealed a gradual gradient in white matter microstructure, free water content, perfusion, and plasma volume but not in blood-brain barrier leakage. CONCLUSIONS We showed different pathophysiological heterogeneity of the 2 WMH types. Periventricular WMHs display more severe damage and fluid accumulation compared with deep WMH, whereas deep WMHs reflect stronger hypoperfusion in the lesion’s core. REGISTRATION URL: https://www.isrctn.com ; Unique identifier: ISRCTN10514229.

Rubin, Hannah, and Cailin O’Connor (2018. “Discrimination and Collaboration in Science.” Philosophy of Science 85 (3): 380–402) introduced a game-theoretic model to examine the dynamics of collaboration and discrimination in academia. They found that small minority groups face higher rates of discrimination in collaboration, despite moral and legal demands for equality. This paper extends their work by assessing the effectiveness of anti-discrimination measures, focusing on German legal provisions for discrimination in the workplace: internal complaints boards and training and organisational measures as mandated by the General Equal Treatment Act. My results show that internal boards are effective in preventing discrimination in initially fair (i.e. non-discriminatory) environments, but fall short in already discriminatory environments. In contrast, training and organisational measures significantly reduce discriminatory behaviour, even where awareness is low. This highlights the importance of proactive anti-discrimination measures.

Objectives In most countries the majority of patients are in outpatient care. In difference to hospitalized patients, their blood samples often take hours after collection to centrifugation. The study investigates the release of potassium and the development of pseudohyperkalemia in lithium heparin (Li-Hep) and serum blood collection tubes over time. Methods From 201 donors 4 serum and 4 Li-Hep blood collection tubes were taken each. After 0.5, 4, 6 and 8h whole blood was centrifuged, and potassium levels were determined. To simulate the preanalytic conditions, the samples with a storage time >0.5h were shaken on a standard shaker for 1h and stored at 4–8°C for the remaining time. Results Over time, significant more potassium was released before centrifugation from the Li-Hep plasma than from serum (1.21 vs 0.94 mmol/L). After 6h, the two groups were no longer highly statistically significantly different (potassium mean: 5.01 mmol/L in serum group, 4.92 mmol/L in Li-Hep group). In the Li-Hep group 164 donors developed a pseudohyperkalemia after 8h, compared to 76 in the serum group. Significance The decision as to which material is best suited should not only be based on which value comes closest to the physiological situation immediately after blood collection. The subsequent preanalytic circumstances must also be considered. Serum tubes appear to be at least as suitable for potassium determination as Li-Hep tubes. In terms of patient blood management, serum provides the possibility of performing a wider range of analyses in the outpatient setting.

Background The MITRA-PRO registry revealed residual mitral regurgitation (MR) to be an important predictor of survival following transcatheter edge-to-edge repair (TEER). Intraprocedural MR assessment using 3D-Vena Contracta Area (VCA) might be a feasible tool to guide mitral TEER procedures. The study aimed to assess the impact of residual MR assessed by 3D-VCA on 1-year mortality. Methods 823 patients with residual MR quantification using 3D-VCA in the MITRA-PRO registry, were included in this study. 1-year mortality, NYHA classification and major adverse events were assessed 1-year after mitral TEER. Results Patients with trace residual MR after mitral TEER were allocated to the 3D-VCA < 0.1 cm² group (27.8%), while a 3D-VCA ≥ 0.1 < 0.3 cm² (55.4%) was considered as mild and a 3D-VCA ≥ 0.3 cm² (16.8%) as relevant residual MR. One-year mortality was significantly lower in patients with non-relevant residual MR (3D-VCA < 0.1 cm²: 10.5%; ≥ 0.1 < 0.3 cm²: 16.0%; ≥ 0.3: 24.8%, p = 0.003). An increasing 3D-VCA post mitral TEER was associated with a higher 1-year mortality. At a 3D-VCA of 0.07 cm² mortality increased significantly (1-year mortality 3D-VCA post mitral TEER ≥ 0.07 cm²: 16.5% vs. < 0.07 cm²: 7.8%; p = 0.005) indicating a 3D-VCA of 0.07 cm² to be a cut-off value for survival in daily practice. Conclusions Residual MR assessed by 3D-VCA after TEER is associated with 1-year mortality. Therefore, 3D-VCA is a valuable echocardiographic tool for intraprocedural MR assessment during mitral TEER and achieving a lower 3D-VCA improve patient survival. (German Clinical Trials Register: DRKS00012288). Trial Registration Number DRKS00012288

Geological interpretations, earthquake source inversions and ground motion modeling, among other applications, require models that jointly resolve crustal and mantle structure. With the second generation of the Collaborative Seismic Earth Model (CSEM2), we present a global multi‐resolution tomographic Earth model that serves this purpose. The model evolves through successive regional‐ and global‐scale refinements. While the first generation aggregated regional models, with this study, we ensure consistency between all individual submodels, resulting in a model that accurately explains wave propagation across scales. Recent regional tomographic models were incorporated, comprising continental‐scale inversions for Asia and Africa, as well as regional inversions for the Western US, Central Andes, Iran, and Southeast Asia. Across all regional refinements, over 793,000 source‐receiver pairs contributed. Moreover, the long‐wavelength Earth model (LOWE) introduces large‐scale structures outside of pre‐existing local refinements. A full‐waveform inversion for global anisotropic P‐and S‐wave speed structure over a total of 194 iterations with a minimum period of 50 s on a large data set of 1 hr of waveform data from 2,423 earthquakes and over 6 million source‐receiver pairs ensures that regional updates in the crust and uppermost mantle translate into updates of deeper, global‐scale structure. To test the performance of CSEM2, we evaluate waveform fits between observed and synthetic seismograms at 50 s for an independent data set on the global scale, and on the regional scale for lower periods. We accurately simulate waveforms within and across regional refinements, maintaining the original resolution of the submodels embedded in the global framework.

Background To date, assistive gait devices (AGDs) for people with neuromuscular diseases (NMDs) have not been systematically evaluated. Objective This systematic review evaluated AGDs for people with NMDs. Methods Suitable tools were used to assess the study quality and the certainty of evidence. If feasible, a descriptive and quantitative synthesis was conducted. Results Forty studies were included on: gait-assisting exoskeletons (GAEs), orthopaedic footwear (OF), knee and/or ankle-foot-orthoses (AFOs) and non-invasive neuroprostheses that provide functional electrical stimulation (FES). Pairwise meta-analysis could not be performed due to a lack of homogenous data. The within-group pre-post meta-analysis in GAE studies showed an improvement in 2-min walk test (2MWT) (m) (standardized mean difference [SMD] = 0.36, 95%-CI: 0.17 to 0.54), but not in 10-meter walk test (10MWT) (sec) (SMD = 0.33, 95%-CI: −0.10 to 0.76) and in functional independence measure (FIM) (SMD = −0.002, 95%-CI: −0.21 to 0.21). In AFO studies, there was no improvement in 10MWT(m) (SMD = −0.11, 95%-CI: −0.76 to 0.53). A single session with AFO or OF vs no-AFO or OF post-intervention meta-analysis did not reveal an improvement in walking speed (m/s) (SMD = 0.39, 95%-CI: −0.03 to 0.83). Discussion GAEs seem to help patients to walk longer. The meta-analyses showed no significant results to support the effect of AFOs or OF. Neuroprostheses and knee orthoses showed no evidence. Conclusion No clear conclusions can be drawn on how AGDs affect NMDs. The positive AGD effects are based on very low certainty of evidence.

Seasonal song production in canaries is influenced by gonadal hormones, but the molecular mechanisms underlying testosterone‐induced song development in adult female canaries, which rarely sing naturally, remain poorly understood. We explored testosterone‐induced song development in adult female canaries by comparing gene regulatory networks in the song‐controlling brain area HVC at multiple time points (1 h to 14 days) post‐treatment with those of placebo‐treated controls. Females began vocalizing within 4 days of testosterone treatment, with song complexity and HVC volume increasing progressively over 2 weeks. Rapid transcriptional changes involving 2739 genes preceded song initiation. Over 2 weeks, 9913 genes—approximately 64% of the canary's protein‐coding genome—were differentially expressed, with 98% being transiently regulated. These genes are linked to various biological functions, with early changes at the cellular level and later changes affecting the nervous system level after prolonged hormone exposure. Our findings suggest that testosterone‐induced song development is accompanied by extensive and dynamic transcriptional changes in the HVC , implicating widespread neuronal involvement. These changes underpin the gradual emergence of singing behavior, providing insights into the neural basis of seasonal behavioral patterns.

While significant progress has been made in treating Parkinson's disease (PD) symptoms, disease-modifying therapies (DMTs) have consistently failed. To address the underlying molecular mechanisms of PD, two biology-based criteria have been proposed: the “Synucleinopathy-Neurodegeneration-Genetics” (SynNeurGe) and “neuronal α-synuclein disease” (NSD) frameworks. Both frameworks emphasize the importance of biological markers over clinical symptoms. They recognize α-synuclein aggregation and genetic mutations (such as SNCA) as key diagnostic elements, with α-synuclein seed amplification assays (SAA) in cerebrospinal fluid (CSF) used to detect early disease stages. Dopaminergic neurodegeneration, measured by DAT imaging, is also central to both frameworks. These shared features aim to improve early diagnosis and precision medicine for PD. However, SynNeurGe provides a broader, more flexible framework that integrates α-synuclein pathology (S), neurodegeneration (N), and genetics (G), linked to clinical features (C). It aims to accommodate the complexity of PD and related Lewy body diseases, facilitating research on targeted DMTs. In contrast, NSD focuses specifically on PD and Lewy body dementia, introducing a staging system (NSD-ISS) based on biological markers and clinical impairment, helping track disease progression from preclinical to symptomatic stages. Despite their differences, both approaches highlight the need for more specific biomarkers and prospective studies to improve early intervention and personalized treatment. Harmonizing SynNeurGe and NSD concepts will be key in creating a universally accepted framework for precise PD diagnosis and therapy development.

Industrial policy has regained political attention due to the challenges associated with global market integration, technological changes, and the need for sustainable transformation. However, the lack of a consistent understanding of industrial policy hampers systematic comparisons. This paper develops a novel concept of industrial policy portfolios that captures different dimensions of industrial policy outputs across countries and over time. We illustrate this approach by comparing the policy dynamics in the United States and Germany over the last four decades and show that despite similar dynamics of policy growth, the countries display pronounced variation in the areas and instruments they prioritized.