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The relationship between equanimity and postural stability
No full textBackground:
The main goal of this study was to examine the relation between inner (equanimity), and outer (postural stability) balance. It was expected that participants with a higher sense of equanimity, higher emotion regulation abilities, and higher executive control performance abilities would show better postural stability in an emotionally demanding situation. This hypothesis adds to the importance of emotion regulation in the assumed relation between equanimity and postural stability.
Methods:
One hundred forty-seven young, healthy participants completed a postural sway task under emotionally demanding and neutral conditions. Emotion regulation strategies were measured using the affective style questionnaire, and attentional abilities were assessed using the attention network task.
Results:
Participants with low equanimity had a higher sample entropy (higher complexity of postural stability signal) when emotion acceptance was low compared to high emotion acceptance. In participants with high equanimity, the effect reverses. However, the results were only obtained with one postural stability parameter, namely the parameter of sample entropy.
Conclusions:
Inner and outer balance are somehow related, and the emotional regulation strategy of acceptance might play an important role. However, the results depend on measuring outer balance, and further studies must investigate the relationship in more depth
Durch Jesu Gnadentrieb soll meine Orgel klingen - Die Späth-Orgeln in der St. Oswaldkirche und Dreieinigkeitskirche Regensburg
No full textDie barocke Kirchenorgel ist in der Regel das größte und kostspieligste Ausstattungsstück eines sakralen Raums, das sämtliche Gattungen der bildenden Kunst in sich vereinen kann. Dennoch ist ihre wissenschaftliche Betrachtung bisher weitgehend unter instrumentenkundlichen und musikwissenschaftlichen Aspekten erfolgt. Vorliegende Dissertation hat das Ziel, anhand der beiden von Franz Jacob Späth (1714-1786) gebauten Orgeln in der St. Oswaldkirche und Dreieinigkeitskirche Regensburg, die bisherigen Arbeiten auf diesem Gebiet durch die Auseinandersetzung mit der symbolischen Bedeutung und dem ikonographischen Inhalt des Instruments zu ergänzen und dadurch die Orgel stärker in den Fokus kunsthistorischer Forschung zu rücken. Außerdem sollten die beiden behandelten musik- und kunstgeschichtlich wertvollen Instrumente ausführlich dokumentiert werden.
Zunächst werden die allgemeingültigen symbolischen Bedeutungsebenen der Orgel referiert, die sich z.B. aus dem etymologischen Ursprung ihres Namens, ihrer Entstehungsgeschichte und ihrer technischen Besonderheiten ergeben. Ein Abriss über die süddeutsche Kirchenmusik des Barocks zeigt die Aufgaben und Funktionen der Orgel als Musikinstrument des christlichen Gottesdienstes auf. Da die beiden Werke für protestantische Kirchen gebaut wurden, wird schwerpunktmäßig das lutherische Musikverständnis dargelegt.
Darauf aufbauend werden die beiden Späthorgeln detailliert untersucht. Dies beinhaltet einen Überblick über die barocke Regensburger Orgellandschaft, die damalige Entwurfspraxis, die Biographien der am Bau beteiligten Personen, eine Beschreibung der Kirchenräume, für die die Orgeln geschaffen wurden, die Entstehungsgeschichte der Werke einschließlich bekannter Vorgängerinstrumente, nachträgliche Um- bzw. bei der Dreieinigkeitskirchenorgel auch Neubaumaßnahmen am Spielwerk sowie eine genaue Beschreibung der Gehäuse. Schwerpunkt ist die ikonographische und ikonologische Entschlüsselung des theologischen und künstlerischen Programms der Gehäuse und ihres Zierrats im Kontext zum Sakralraum. Die hier gewonnenen interpretatorischen Erkenntnisse konnten durch zeitgenössische literarische und bildliche Quellen belegt werden.
Franz Jacob Späth zählte zu den renommiertesten Instrumentenbauern seiner Zeit. Hauptsächlich im Klavierbau tätig sind aus seiner Hand nur die zwei behandelten Orgelwerke bekannt. Bei der 1750 entstandenen Orgel in der St. Oswaldkirche Regensburg handelt es sich um die einzige auch noch im Spielwerk erhaltene barocke Kirchendenkmalorgel der ehemaligen freien Reichsstadt. Von dem Instrument in der Dreieinigkeitskirche aus dem Jahr 1758 konnten lediglich das wertvolle, denkmalgeschützte Gehäuse und große Teile des Zierrats die Zeit überdauern. Das zu seiner Erbauung größte Werk Regensburgs verzichtet in seiner künstlerischen Ausgestaltung fast vollständig auf figürlichen Schmuck und nimmt auch so eine Sonderstellung ein.
Im Rahmen dieser Arbeit wird gezeigt, dass beide Orgeln über ein komplexes theologisches Bildprogramm verfügen. Das selbstbewusste Verständnis der protestantischen Kirchenmusik, das diese der Wortverkündigung gleichstellt, wurde eindrucks- und qualitätsvoll sichtbar gemacht. Besonderer Wert wurde auf die harmonische inhaltliche und architektonische Einfügung in den Kirchenraum gelegt. Die Orgel diente durch ihre Musik der Wortverkündigung, der Vermittlung von Glaubensinhalten und ermöglichte der christlichen Gemeinde eine Teilhabe an der Liturgie der Kirche. Diese immateriellen Inhalte wurden durch ihre künstlerische Gestaltung nicht nur hör- sondern auch sichtbar gemacht, wodurch die Orgeln den Rang eines vierten Prinzipalstücks des christlichen Kirchenraums erhielten
Applications of 3D models in cholangiocarcinoma
No full textThe prognosis for patients diagnosed with cholangiocarcinoma (CCA) is dismal, with an overall 5-year-mortality rate of 80%. Therapeutic approaches for this cancer are very limited and the only curative treatment is total surgical resection despite recent advancements in CCA research. However, only a minority of patients are eligible for surgery due to late-stage diagnosis. Therefore, there is an urgent need to gain a deeper understanding of CCA and to discover new treatments, which can be achieved by utilization and optimization of 3D tumor models. Traditional 2D cell culture is still undeniably important in cancer research, especially for the discovery of biomarkers and drug screening. However, classical 2D tumor models do not represent the tumor biology in its full complexity as they lack the vital interactions between cancer cells, angiogenesis, and tumor microenvironment. In recent years, 3D models, including spheroids, 3D co-culture systems, organoids, tumors-on-a-chip, and the in vivo chorioallantoic membrane (CAM) model, have been used for CCA research. These models enable the study of the tumor microenvironment, investigation of metastases, drug development and testing, cholangiocarcinogenesis and personalized therapy. This review summarizes the applications of the different 3D tumor models that have been used for the investigation of CCA. Moreover, the advantages and disadvantages of the different 3D tumor models are discussed, and suggestions for future research possibilities are described. By optimizing 3D models, the gap between basic research findings and clinical applications can be bridged, enabling the discovery of more effective therapies for CCA and other cancers
Impact of COVID-19 Lockdown on the Incidence of Common Pregnancy Complications—Is the Diagnosis of FGR Made Too Generously?
No full textPurpose: In 2020, a lockdown due to COVID-19 was ordered by the German government, resulting in population-wide restrictions. In this retrospective study, we question the extent to which health policy restrictions have influenced medical diagnoses. Methods: The incidence rates of relevant pregnancy complications during all trimesters of pregnancy were evaluated for a 6-month pre-pandemic period (April–September 2019), in comparison to the same period during the lockdown in 2020. Mothers and newborns who presented at the University Hospital St. Hedwig, Regensburg, Germany, were included in the study. The incidence rates of preeclampsia and suspected FGR (fetal growth retardation), as relevant obstetric diseases, were further compared with those in a post-pandemic period (April–September 2023). Results: A total of 5137 newborns were included, with 1709 born during the 6-month pre-pandemic period, 1806 during the 6-month lockdown period and 1687 during the 6-month post-pandemic period. During the pandemic period, significantly fewer patients were hospitalized due to hyperemesis gravidarum (1.8% vs. 0.9%, p = 0.04). No differences were observed concerning the incidence of miscarriages before and after 14 weeks of gestation (WG), preterm deliveries (<37 WG), gestational age at preterm birth and birth weight. Likewise, within the group of preterm-born babies, no difference was observed in preeclampsia among the two periods. However, in the pandemic period, the frequency of preterm-born babies with suspected FGR was significantly lower than in the pre-pandemic period (1.5% and 0.6%, p = 0.01). Regarding this point, we analyzed data of all newborns in a comparative post-pandemic period in 2023 (n = 1687). This group presented a significantly increased FGR incidence compared to that during the pandemic, therefore returning to the pre-pandemic level (1.5% and 1.4%, p = 0.145). Conclusions: During the COVID-19 pandemic, there were significantly fewer deliveries with suspected FGR. After all specific restrictions on elective and outpatient services were lifted, the incidence of suspected FGR returned to its initial level, suggesting that the diagnosis—as a solely machine-dependent and not symptom-based diagnosis—was partly exaggerated in both the pre-and post-pandemic periods
Static and Dynamic Correlations in Binary and Ternary Mixtures of TMAO, Urea, and Water
No full textForce field molecular dynamics simulations of aqueous solutions of TMAO and urea are used to investigate the delicate interactions in binary and ternary mixtures of one of the most important osmolyte systems. We explore the effect of the choice of force fields on local interactions and thermodynamics. Fully decomposed dielectric relaxation spectra from simulations are used to interpret existing experimental data and evaluate currently used fitting techniques. We show that many force field combinations describe the potential of mean force between urea and TMAO, but it is more challenging to describe thermodynamic data for the ternary system like activity coefficients
Inclusive Model-Driven Engineering for Accessible Software
No full textWhile model-driven engineering (MDE) claims to be a good development approach for cross-cutting concerns, this raises the question of why not every application created with MDE is accessible. Moreover, why are the MDE development processes and the tools themselves not more inclusive? In this vision paper, we sketch an ideal picture of how inclusivity in MDE - considered throughout tools, methods, artifacts, and processes - would intrinsically lead to more accessible software systems. We review the state-of-the-art, discuss current challenges, and present a possible future of inclusive MDE
Testung von Vistusertib im Vergleich zu Rapamycin in der RIST-Therapie in einem In-vitro-Modell des Neuroblastoms
No full textDas Neuroblastom ist der häufigste extrakranielle solide Tumor im Kindesalter. Die Amplifikation des bekannten MYCN-Onkogens in ungefähr 25 % aller Fälle korreliert mit dem Vorliegen eines Hochrisiko-Neuroblastom. Trotz intensiven Behandlungsverfahren bleibt das Outcome für Patient*innen mit rezidivierendem oder therapierefraktärem Hochrisiko-Neuroblastom schlecht und neue Therapieansätze werden dringend benötigt. Die RIST-Therapie stellt einen neuen multimodalen Therapieansatz für das Hochrisiko-Neuroblastom dar und basiert auf der metronomischen Kombination der molekular-zielgerichteten Inhibitoren (Rapamycin und Dasatinib (Sprycel®)) mit den konventionellen Zytostatika (Irinotecan und Temozolomid). Die offene, randomisierte Phase-II-Studie RIST-rNB-2011 (ClinicalTrials.gov ID: NCT01467986) zeigte eine Verbesserung des progressionsfreien Überlebens und des Gesamtüberlebens bei MYCN-amplifizierten rezidivierendem oder therapierefraktärem Neuroblastom.
Mit dem Ziel die RIST-Therapie zu verbessern, wurde im Rahmen dieser Studie der neue ATP-kompetitive mTORC1/2-Inhibitor Vistusertib (AZD2014) anstelle des allosterischen mTORC1-Inhibitors Rapamycin getestet. Bei der Ermittlung der halbmaximalen inhibitorischen Konzentration (IC50) in drei MYCN-amplifizierten Neuroblastom-Zelllinien (Kelly, SK-N-BE(2) und IMR-32) konnte gezeigt werden, dass nanomolare Konzentrationen von Vistusertib effektiv die Zellviabilität im Vergleich zu den hohen IC50-Werten von Rapamycin im mikromolaren Bereich hemmen. Die Behandlung von Neuroblastom-Zelllinien mit IC50-Werten von Vistusertib inhibierte den mTOR-Signalweg mit reduzierter Phosphorylierung der ribosomal protein S6 kinase 1 (S6K1, Thr389) und des eukaryotic translation initiation factor 4E-binding proteins 1 (4E-BP1, Ser65), welche zwei bekannte Substrate von mTORC1 sind. Zellzyklusanalysen zeigten, dass Vistusertib in allen drei Neuroblastom-Zelllinien einen G1-Phase-Arrest induziert, wohingegen keine Induktion von Apoptose bei der Testung von Caspase-3 oder PARP1-Spaltung nachgewiesen wurde. Die Doppelbehandlung mit Dasatinib plus Vistusertib inhibierte die Zellviabilität signifikant stärker als im Vergleich zur Einzelbehandlung. In einem präklinischen In-vitro-Modell zeigte die Substitution von Rapamycin durch Vistusertib in der multimodalen VIST-Therapie, dass in allen drei untersuchten Neuroblastom-Zelllinien die Zellviabilität signifikant reduziert war.
Zusammengefasst lässt sich sagen, dass Vistusertib bei deutlich niedrigeren Konzentrationen genauso effektiv wie Rapamycin in der RIST-Therapie agiert. Kürzlich durchgeführte klinische Studien mit Vistusertib bei anderen Hochrisiko-Karzinomen wiesen auf ein akzeptables Nebenwirkungsprofil hin. Deshalb könnte Vistusertib eine gute Option für die Evaluation in zukünftigen klinischen Studien bei rezidivierendem oder therapierefraktärem Hochrisiko-Neuroblastom darstellen
Incorporating historic information to further improve power when conducting Bayesian information borrowing in basket trials
No full textIn basket trials a single therapeutic treatment is tested on several patient populations simultaneously, each of which forming a basket, where patients across all baskets on the trial share a common genetic aberration. These trials allow testing of treatments on small groups of patients, however, limited basket sample sizes can result in inadequate precision and power of estimates. It is well known that Bayesian information borrowing models such as the exchangeability-nonexchangeability (EXNEX) model can be implemented to tackle such a problem, drawing on information from one basket when making inference in another. An alternative approach to improve power of estimates, is to incorporate any historical or external information available. This paper considers models that amalgamate both forms of information borrowing, allowing borrowing between baskets in the ongoing trial whilst also drawing on response data from historical sources, with the aim to further improve treatment effect estimates. We propose several Bayesian information borrowing approaches that incorporate historical information into the model. These methods are data-driven, updating the degree of borrowing based on the level of homogeneity between information sources. A thorough simulation study is presented to draw comparisons between the proposed approaches, whilst also comparing to the standard EXNEX model in which no historical information is utilized. The models are also applied to a real-life trial example to demonstrate their performance in practice. We show that the incorporation of historic data under the novel approaches can lead to a substantial improvement in precision and power of treatment effect estimates when such data is homogeneous to the responses in the ongoing trial. Under some approaches, this came alongside an inflation in type I error rate in cases of heterogeneity. However, the use of a power prior in the EXNEX model is shown to increase power and precision, whilst maintaining similar error rates to the standard EXNEX model
Entanglement properties of SU(2) gauge theory
Full text linkUnderstanding how isolated quantum systems thermalize is central to both fundamental physics and the development of quantum technologies. In this Perspective, we present recent and new results on thermalization in nonabelian gauge theory from exact real-time simulations of two-dimensional lattice models. We discuss tests of the eigenstate thermalization hypothesis, entanglement entropy dynamics, the absence of persistent non-thermal states, spectral signatures, and measures of quantum complexity. Our new results include a two-step thermalization process in localized regions and the role of higher gauge field representations. These findings suggest that thermalization in gauge theories may offer a test case for quantum advantage
In Vivo Immune Cell Responses and Long-Term Effects of Cold Atmospheric Plasma in the Upper Respiratory Tract
Full text linkCold atmospheric plasma (CAP) devices produce reactive oxygen and reactive nitrogen species, which have antimicrobial and antiviral effects, while also affecting the molecular and cellular processes in eukaryotic cells. This study investigates the effects of CAP treatment on immune responses and long-term organism health in the upper respiratory tract (URT). Using a surface-microdischarge-based plasma intensive care (PIC) device from terraplasma medical GmbH, 129Sv/Ev wildtype mice were exposed to short (single 10 min session), long (five 10 min sessions), and recovery-phase treatments (five 10 min sessions; 7 days of recovery). Bronchoalveolar lavage fluid was examined by cytospin, fluorescence-activated cell sorting, and mRNA expression analysis. Lung tissue was analyzed for morphological changes (H&E), DNA damage (γH2AX), apoptosis (TUNEL), immune cell marker alterations (CD45, Ly-6G, CD68, CD3, MCC), and fibrosis (NE). Results showed that PIC treatment increased the number of apoptotic cells and activated immune markers, such as IFN-γ, IL-6, and TNF-α, in the lungs, especially after multiple treatments. These effects largely reversed after a 7-day regeneration period. Importantly, no DNA damage or morphological lung alterations were observed across groups. The findings suggest that PIC treatment in the URT induces transient immune activation without causing tissue damage, but caution is advised for patients with cytokine release syndrome or macrophage activation syndrome due to potential cytokine surges