Editorial: Hochschulzugang und Studium nicht-traditioneller Studierender: Die Situation in Österreich, Deutschland und der Schweiz

Die strukturelle Durchlässigkeit in ein Hochschulstudium und Schaffung von Rahmenbedingungen für lebenslanges Lernen sind wichtige Ziele des Europäischen Hochschulraums. In den D-A-CH-Ländern sind sowohl Absolvent:innen der beruflichen Bildung ohne Matura/Abitur als auch Erwerbs- und Familientätige sowie „learners in later life“ wichtige Zielgruppen des Konstrukts „nicht-traditionelle Studierende“. Aus diversitäts- und ungleichheitstheoretischen Perspektiven untersuchen die Beiträge – auf Grundlage aktueller Daten – Regelungen des Hochschulzugangs, das Zeitbudget Studierender, die Effekte von Pflegeverantwortung sowie den Studienabbruch, u. a. während der Covid-19-Pandemie. Thematisiert werden ein Lernort auf See ebenso wie neue Wege in ein Studium zum Lehramt an beruflichen Schulen. Die Beiträge repräsentieren Tiefenbohrungen auf nach wie vor kleinem Terrain

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

Background/Aims The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. Methods Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA. Results BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non- significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately. Conclusion Our results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs that may sensitize NET cells to somatostatin analogs, and that if there is resistance to its action this may be overcome by combination with everolimus

Validation of the network of relationship inventory in female and male adolescents

Friendships and their different qualities have been shown to be important for adolescents\u27 socio-emotional development and psychological adjustment. In empirical research on such friendship qualities, the Network of Relationship Inventory-Relationship Quality Version (NRI-RQV) is a widely used questionnaire. Here, we conduct an extensive validation of a German version of the NRI-RQV, investigating its factor structure, reliability, and concurrent validity, in a sample of N= 679 adolescents aged 13-18 years. Applying multigroup confirmatory factor analysis, we further test whether the factor structure of the friendship quality construct holds across groups of males and females. Results showed that a structure with nine correlated first-order factors fit the data well, indicating nine distinct friendship qualities in males and females. Measurement invariance testing suggested the same underlying friendship quality construct, albeit differences in mean scores per gender. As evidence for concurrent validity, closeness and discordant friendship qualities showed expected correlations with empathy and social problems, respectively, but not with aggressive behavior. Overall, results indicate good psychometric properties for the German version of the NRI-RQV as a measure of friendship qualities in both males and females. (DIPF/Orig.

Atypical dorsolateral prefrontal activity in females with conduct disorder during effortful emotion regulation

BACKGROUND: Conduct disorder (CD), which is characterized by severe aggressive and antisocial behavior, is linked to emotion processing and regulation deficits. However, the neural correlates of emotion regulation are yet to be investigated in adolescents with CD. Furthermore, it remains unclear whether CD is associated with deficits in emotional reactivity, emotion regulation, or both. METHODS: We used functional magnetic resonance imaging to study effortful emotion regulation by cognitive reappraisal in 59 female adolescents 15 to 18 years of age (30 with a CD diagnosis and 29 typically developing (TD) control adolescents). RESULTS: Behaviorally, in-scanner self-report ratings confirmed successful emotion regulation within each group individually but significant group differences in emotional reactivity and reappraisal success when comparing the groups (CD < TD). Functional magnetic resonance imaging results revealed significantly lower activation in left dorsolateral prefrontal cortex and angular gyrus in CD compared with TD adolescents during emotion regulation, but no group differences for emotional reactivity. Furthermore, connectivity between left dorsolateral prefrontal cortex and the bilateral putamen, right prefrontal cortex, and amygdala was reduced in CD compared with TD adolescents during reappraisal. Callous-unemotional traits were unrelated to neural activation, but these traits correlated negatively with behavioral reports of emotional reactivity. CONCLUSIONS: Our results demonstrate reduced prefrontal brain activity and functional connectivity during effortful emotion regulation in female adolescents with CD. This sheds light on the neural basis of the behavioral deficits that have been reported previously. Future studies should investigate whether cognitive interventions are effective in enhancing emotion-regulation abilities and/or normalizing prefrontal and temporoparietal activity in female adolescents with CD

Immersivity: An Interdisciplinary Approach to Spaces of Immersion

This article proposes to shift the scholarly focus from the conceptually, terminologically, and methodologically fuzzy notion of “immersion” to the concept of “immersivity,” and thus from a discussion of experiences to an analysis of the productive forces that enable such experiences (aesthetic and otherwise). Using case studies from theme parks, film, and immersive theatre to video games and immersive educational spaces, we argue that immersivity is a distinct term that denotes an inherent quality of objects in general and of mediated, delineated, real and virtual spaces in particular. We assume that in all of these examples, spatial qualities and modes interact in particular ways to facilitate immersion. Elucidating these interactions requires discussing examples from different disciplinary contexts. It is precisely through this interdisciplinary approach that we take a first step towards understanding immersivity, as we pinpoint cross-disciplinary congruences wherever possible. The article thus offers the starting point for a transdisciplinary, qualitative, experimental, and analytical model of immersivity. Following a theoretical introduction to the topic of immersion, we will first conceptualize our interdisciplinary understanding of immersion and immersivity and then launch into a transdisciplinary dialogue about examples of immersive spaces.L’objectif de cet article est de réorienter l’intérêt scientifique sur la notion floue « d’immersion » vers le concept « d’immersivité », et donc de passer de l’analyse des expériences-mêmes à une analyse des efforts et circonstances de production de telles expériences (esthétiques et autres). À partir des analyses de cas sur les parcs d’attractions, les films et le théâtre immersif, les jeux vidéo et les espaces éducatifs immersifs, nous faisons le constat que « l’immersivité » est un terme distinct qui désigne une qualité inhérente aux objets en général et aux espaces médiatisés, délimités, réels et virtuels en particulier. Nous assumons que dans tous ces exemples, les qualités et les modes spatiaux interagissent à chaque fois de façon particulière pour faciliter l’immersion. Afin de comprendre et d’élucider ces exemples, il nous semble nécessaire de discuter et relayer des exemples issus de contextes disciplinaires différentes. C’est notamment par cette approche interdisciplinaire que nous comptons faire les premiers pas vers une compréhension de « l’immersivité » en identifiant les croisements et congruences interdisciplinaires à chaque point où cela semble possible. Cet article a donc pour but de poser les fondements d’un modèle transdisciplinaire, qualitatif, expérimental et analytique de l’immersivité. Après une introduction théorique sur le terme de l’immersion, nous développons d’abord notre compréhension interdisciplinaire de l’immersion et de l’immersivité, puis nous lancerons un dialogue transdisciplinaire sur des exemples d’espaces immersifs

Analysis of Lymphocytic DNA Damage in Early Multiple Sclerosis by Automated Gamma-H2AX and 53BP1 Foci Detection: A Case Control Study

Background In response to DNA double-strand breaks, the histone protein H2AX becomes phosphorylated at its C-terminal serine 139 residue, referred to as γ-H2AX. Formation of γ-H2AX foci is associated with recruitment of p53-binding protein 1 (53BP1), a regulator of the cellular response to DNA double-strand breaks. γ-H2AX expression in peripheral blood mononuclear cells (PBMCs) was recently proposed as a diagnostic and disease activity marker for multiple sclerosis (MS). Objective To evaluate the significance of γ-H2AX and 53BP1 foci in PBMCs as diagnostic and disease activity markers in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS) using automated γ-H2AX and 53BP1 foci detection. Methods Immunocytochemistry was performed on freshly isolated PBMCs of patients with CIS/early RRMS (n = 25) and healthy controls (n = 27) with γ-H2AX and 53BP1 specific antibodies. Nuclear γ-H2AX and 53BP1 foci were determined using a fully automated reading system, assessing the numbers of γ-H2AX and 53BP1 foci per total number of cells and the percentage of cells with foci. Patients underwent contrast enhanced 3 Tesla magnetic resonance imaging (MRI) and clinical examination including expanded disability status scale (EDSS) score. γ-H2AX and 53BP1 were also compared in previously frozen PBMCs of each 10 CIS/early RRMS patients with and without contrast enhancing lesions (CEL) and 10 healthy controls. Results The median (range) number of γ-H2AX (0.04 [0–0.5]) and 53BP1 (0.005 [0–0.2]) foci per cell in freshly isolated PBMCs across all study participants was low and similar to previously reported values of healthy individuals. For both, γ-H2AX and 53BP1, the cellular focus number as well as the percentage of positive cells did not differ between patients with CIS/RRMS and healthy controls. γ-H2AX and 53BP1 levels neither correlated with number nor volume of T2-weighted lesions on MRI, nor with the EDSS. Although γ-H2AX, but not 53BP1, levels were higher in previously frozen PBMCs of patients with than without CEL, γ-H2AX values of both groups overlapped and γ-H2AX did not correlate with the number or volume of CEL. Conclusion γ-H2AX and 53BP1 foci do not seem to be promising diagnostic or disease activity biomarkers in patients with early MS. Lymphocytic DNA double-strand breaks are unlikely to play a major role in the pathophysiology of MS

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

BACKGROUND/AIMS The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110\textgreeka inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. METHODS Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA. RESULTS BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately. CONCLUSION Our results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs that may sensitize NET cells to somatostatin analogs, and that if there is resistance to its action this may be overcome by combination with everolimus

Atypical Dorsolateral Prefrontal Activity in Female Adolescents With Conduct Disorder During Effortful Emotion Regulation

BACKGROUND: Conduct disorder (CD), which is characterized by severe aggressive and antisocial behavior, is linked to emotion processing and regulation deficits. However, the neural correlates of emotion regulation are yet to be investigated in adolescents with CD. Furthermore, it remains unclear whether CD is associated with deficits in emotional reactivity, emotion regulation, or both. METHODS: We used functional magnetic resonance imaging to study effortful emotion regulation by cognitive reappraisal in 59 female adolescents 15 to 18 years of age (30 with a CD diagnosis and 29 typically developing (TD) control adolescents). RESULTS: Behaviorally, in-scanner self-report ratings confirmed successful emotion regulation within each group individually but significant group differences in emotional reactivity and reappraisal success when comparing the groups (CD < TD). Functional magnetic resonance imaging results revealed significantly lower activation in left dorsolateral prefrontal cortex and angular gyrus in CD compared with TD adolescents during emotion regulation, but no group differences for emotional reactivity. Furthermore, connectivity between left dorsolateral prefrontal cortex and the bilateral putamen, right prefrontal cortex, and amygdala was reduced in CD compared with TD adolescents during reappraisal. Callous-unemotional traits were unrelated to neural activation, but these traits correlated negatively with behavioral reports of emotional reactivity. CONCLUSIONS: Our results demonstrate reduced prefrontal brain activity and functional connectivity during effortful emotion regulation in female adolescents with CD. This sheds light on the neural basis of the behavioral deficits that have been reported previously. Future studies should investigate whether cognitive interventions are effective in enhancing emotion-regulation abilities and/or normalizing prefrontal and temporoparietal activity in female adolescents with CD