X-Ray Photon Correlation Spectroscopy Reveals Intermittent Aging Dynamics in a Metallic Glass

We use coherent X-rays to probe the aging dynamics of a metallic glass directly on the atomic level. Contrary to the common assumption of a steady slowing down of the dynamics usually observed in macroscopic studies, we show that the structural relaxation processes underlying aging in this metallic glass are intermittent and highly heterogeneous at the atomic scale. Moreover, physical aging is triggered by cooperative atomic rearrangements, driven by the relaxation of internal stresses. The rich diversity of this behavior reflects a complex energy landscape, giving rise to a unique type of glassy-state dynamics.Comment: 5 pages, 4 figure

Integration of a semi-automatic in-vitro RFA procedure into an experimental setup

Radiofrequency ablation (RFA) is a standard clinical procedure for treating many cardiac arrhythmias. In order to increase the success rate of this treatment, the evaluation of lesion development with the help of intracardiac electrogram (EGM) criteria has to be improved further. We are investigating in-vitro the electrophysiological characteristics of cardiac tissue by using fluorescence-optical and electrical techniques. In this project, it is intended to create ablation lesions under defined conditions in rat atria or ventricle and to determine the electrical activity in the myocardium surrounding these lesions less than 1 s after the ablation. Therefore, we developed a semi-automatic RFA procedure, which was integrated into an existing experimental setup. Firstly, a controllable protection circuit board was designed to galvanically isolate the sensitive amplifiers for measuring extracellular potentials during the ablation. Secondly, a real-time system was implemented to control and to autonomously monitor the RFA procedure. We verified each component as well as the different sequences of the RFA procedure. In conclusion, the expanded setup will be used in future in-vitro experiments to determine new EGM criteria to assess lesion formation during the RFA procedure

Microscopic evidence of the connection between liquid-liquid transition and dynamical crossover in an ultraviscous metallic glass former

Liquid-liquid transitions are interesting to many researchers since they occur in systems as diverse as monoatomic liquids, multicomponent oxides, and metallic glass formers. In some cases, the crossover is accompanied by changes in the dynamical properties. By combining state-of-the-art synchrotron techniques, we followed the structure and atomic motion during quasistatic cooling of the Au49Cu26.9Si16.3Ag5.5Pd2.3 metallic glass former from the low-temperature supercooled liquid. With this thermal protocol, we were able to lower the glass transition temperature far enough to reveal a liquid-liquid crossover between two amorphous structures corresponding to two ultraviscous liquids with different kinetic behavior. This transition is in competition with vitrification, which occurs at conventional cooling rates, and is accompanied by structural changes not affecting the average density. Our results provide a direct connection between polyamorphism and dynamical crossover, and an alternative case to add to the highly debated topic on the low-temperature divergence of the dynamics in supercooled liquids.Peer ReviewedPostprint (published version

Prognostic Value of Different CMR-Based Techniques to Assess Left Ventricular Myocardial Strain in Takotsubo Syndrome

Cardiac magnetic resonance (CMR)-derived left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information on various cardiovascular diseases but has not yet been investigated comprehensively in patients with Takotsubo syndrome (TS). This study evaluated the prognostic value of feature tracking (FT) GLS, tissue tracking (TT) GLS, and fast manual long axis strain (LAS) in 147 patients with TS, who underwent CMR at a median of 2 days after admission. Long-term mortality was assessed 3 years after the acute event. In contrast to LV ejection fraction and tissue characteristics, impaired FT-GLS, TT-GLS and fast manual LAS were associated with adverse outcome. The best cutoff points for the prediction of long-term mortality were similar with all three approaches: FT-GLS −11.28%, TT-GLS −11.45%, and fast manual LAS −10.86%. Long-term mortality rates were significantly higher in patients with FT-GLS > −11.28% (25.0% versus 9.8%; p = 0.029), TT-GLS > −11.45% (20.0% versus 5.4%; p = 0.016), and LAS > −10.86% (23.3% versus 6.6%; p = 0.014). However, in multivariable analysis, diabetes mellitus (p = 0.001), atrial fibrillation (p = 0.001), malignancy (p = 0.006), and physical triggers (p = 0.006) outperformed measures of myocardial strain and emerged as the strongest, independent predictors of long-term mortality in TS. In conclusion, CMR-based longitudinal strain provides valuable prognostic information in patients with TS, regardless of the utilized technique of assessment. Long-term mortality, however, is mainly determined by comorbidities

Mental Health in German Paralympic Athletes During the 1st Year of the COVID-19 Pandemic Compared to a General Population Sample

Introduction: The COVID-19 pandemic has huge influences on daily life and is not only associated with physical but also with major psychological impacts. Mental health problems and disorders are frequently present in elite paralympic athletes. Due to the pandemic situation, new stressors (e.g., loss of routine, financial insecurity) might act upon the athletes. Therefore, the assessment of mental health in athletes during the COVID-19 pandemic is important to identify prevalence of psychological problems and propose countermeasures. Methods: The mental health of German paralympic athletes was longitudinally monitored (starting in May 2019). The athletes completed the Patient Health Questionnaire 4 (PHQ-4) on a weekly basis and reported a stress level, training hours, and training load. During the pandemic, 8 measurement time points (March 2020 to April 2021) were used to reflect the psychological health course of the athletes. In parallel, a convenience sample of the general population was questioned about their psychological distress, including the PHQ-4. To be included in the analysis, participants of both groups had to complete at least 4 measurement time points. Matching of the para-athletes and the general population sample was prioritized upon completion of the same measurement time points, gender, and age. Results: Seventy-eight paralympic athletes (40 women, 38 men, age: 29.8 ± 11.4 years) met the inclusion criteria. Seventy-eight matched pairs of the general population (40 women; 38 men; age: 30.5 ± 10.9 years) were identified. The para-athletes had a significantly (p < 0.0001; 0.39 < r < 0.48) lower PHQ-4 value at each measurement time point compared to the matched control group. No significant age or sex differences were evident regarding the symptom burden. In para-athletes, no significant and a weak positive correlation was found between decreased training load and PHQ-4 values and Mental Health in Para-Athletes During COVID-19 a stress level, respectively. Reduced physical activity was significantly (p < 0.0001) associated with higher PHQ-4 values in the general population sample. Discussion: Lower PHQ-4 values were reported by the para-athletes compared to the general population sample. However, small sample sizes must be considered while interpreting the data. Nevertheless, adequate support for individuals suffering from severe psychopathological symptoms should be provided for para-athletes as well as for the general population

In vitro validation and characterization of pulsed inhaled nitric oxide administration during early inspiration

Purpose: Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. Methods: An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration ("pulsed delivery"), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5-40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. Results: Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 +/- 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. Conclusion: Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes

A general T-matrix approach applied to two-body and three-body problems in cold atomic gases

We propose a systematic T-matrix approach to solve few-body problems with s-wave contact interactions in ultracold atomic gases. The problem is generally reduced to a matrix equation expanded by a set of orthogonal molecular states, describing external center-of-mass motions of pairs of interacting particles; while each matrix element is guaranteed to be finite by a proper renormalization for internal relative motions. This approach is able to incorporate various scattering problems and the calculations of related physical quantities in a single framework, and also provides a physically transparent way to understand the mechanism of resonance scattering. For applications, we study two-body effective scattering in 2D-3D mixed dimensions, where the resonance position and width are determined with high precision from only a few number of matrix elements. We also study three fermions in a (rotating) harmonic trap, where exotic scattering properties in terms of mass ratios and angular momenta are uniquely identified in the framework of T-matrix.Comment: 14 pages, 4 figure

MEDBERT.de: A Comprehensive German BERT Model for the Medical Domain

This paper presents medBERTde, a pre-trained German BERT model specifically designed for the German medical domain. The model has been trained on a large corpus of 4.7 Million German medical documents and has been shown to achieve new state-of-the-art performance on eight different medical benchmarks covering a wide range of disciplines and medical document types. In addition to evaluating the overall performance of the model, this paper also conducts a more in-depth analysis of its capabilities. We investigate the impact of data deduplication on the model's performance, as well as the potential benefits of using more efficient tokenization methods. Our results indicate that domain-specific models such as medBERTde are particularly useful for longer texts, and that deduplication of training data does not necessarily lead to improved performance. Furthermore, we found that efficient tokenization plays only a minor role in improving model performance, and attribute most of the improved performance to the large amount of training data. To encourage further research, the pre-trained model weights and new benchmarks based on radiological data are made publicly available for use by the scientific community.Comment: Keno K. Bressem and Jens-Michalis Papaioannou and Paul Grundmann contributed equall

A simple approach for detecting HLA-A02 alleles in archival formalin-fixed paraffin-embedded tissue samples and an application example for studying cancer immunoediting

The HLA system represents a central component of the antigen presentation machinery. As every patient possesses a defined set of HLA molecules, only certain antigens can be presented on the cell surface. Thus, studying HLA type-dependent antigen presentation can improve the understanding of variation in susceptibility to various diseases, including infectious diseases and cancer. In archival formalin-fixed paraffin-embedded (FFPE) tissue, the HLA type is difficult to analyze because of fragmentation of DNA, hindering the application of commonly used assays that rely on long DNA stretches. Addressing these difficulties, we present a refined approach for characterizing presence or absence of HLA-A*02, the most common HLA-A allele in the Caucasian population, in archival samples. We validated our genotyping strategy in a cohort of 90 samples with HLA status obtained by an NGS-based method. 90% (n = 81) of the samples could be analyzed with the approach. For all of them, the presence or absence of HLA-A*02 alleles was correctly determined with the method, demonstrating 100% sensitivity and specificity (95% CI: 91.40%-100% and 91.19%-100%). Furthermore, we provide an example of application in an independent cohort of 73 FFPE microsatellite-unstable (MSI) colorectal cancer samples. As MSI cancer cells encompass a high number of mutations in coding microsatellites, leading to the generation of highly immunogenic frameshift peptide antigens, they are ideally suited for studying relations between the mutational landscape of tumor cells and interindividual differences in the immune system, including the HLA genotype. Overall, our method can help to promote studying HLA type-dependency during the pathogenesis of a wide range of diseases, making archival and historic tissue samples accessible for identifying HLA-A*02 alleles.Peer reviewe

A quantitative analysis on the effects of critical factors limiting the effectiveness of species conservation in future-time

The effectiveness of conservation plans depends on environmental, ecological, and socioeconomic factors. Global change makes conservation decisions even more challenging. Among others, the components of most concern in modern‐day conservation assessments are as follows: the magnitude of climate and land‐use changes; species dispersal abilities; competition with harmful socioeconomic activities for land use; the number of threatened species to consider; and, relatedly, the available budget to act. Here, we provide a unified framework that quantifies the relative effects of those factors on conservation. We conducted an area‐scheduling work plan in order to identify sets of areas along time in which the persistence expectancies of species are optimized. The approach was illustrated using data of potential distribution of ten nonvolant mammal species in Iberia Peninsula from current time up to 2080. Analyses were conducted considering possible setups among the factors that are likely to critically impact conservation success: three climate/land‐use scenarios; four species’ dispersal kernel curves; six land‐use layer types; and two planning designs, in which assessments were made independently for each species, or joining all species in a single plan. We identified areas for an array of investments levels capable to circumvent the spatial conflicts with socioeconomic activities. The effect of each factor on the estimated species persistence scores was assessed using linear mixed models. Our results evidence that conservation success is highly reliant on the resources available to abate land‐use conflicts. Nonetheless, under the same investment levels, planning design and climate change were the factors that most shaped species persistence scores. The persistence of five species was especially affected by the sole effect of planning design and consequently, larger conservation investments may retard climatic debts. For three species, the negative effects of a changing climate and of multiple‐species planning designs added up, making these species especially at risk. Integrated assessments of the factors most likely to limit species persistence are pivotal to achieve effectiveness