Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial

Atezolizumab; Ovarian cancer; PlatinumAtezolizumab; Càncer d'ovari; PlatíAtezolizumab; Cáncer de ovario; PlatinoPURPOSE Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy. PATIENTS AND METHODS ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1–positive populations (alpha .025 for each population). RESULTS Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1–positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1–positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively). CONCLUSION ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1–positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC

The Power of Problem Based Learning beyond its Didactic Attributes

Hybrid courses with a focus on practice-orientated education and self-guided learning phases are on the rise on the higher education sector. Disciplines in Life Sciences implicate a high degree of practical laboratory expertise. The University of Applied Sciences (UAS) in Vienna, Austria, has thus been endeavoured offering students a high qualitative education integrating hybrid courses based on PBL principles, which consist of on-site (including the transmission of necessary background and practical laboratory training) and off-site (including self-study phases) sessions. As practical laboratory units are central in those courses, the restrictive measures, including the transition to a complete online teaching format due to the first Covid-19-pandemic lock-down, had severe effects on the implementation and the quality of the curriculum. According to surveys made specifically to address this problematic situation, it can be concluded that on-site practical units are fundamental for certain disciplines such as Life Sciences

Microstructure Evolution of a New Precipitation-Strengthened Fe–Al–Ni–Ti Alloy down to Atomic Scale

Ferritic materials consisting of a disordered matrix and a significant volume fraction of ordered intermetallic precipitates have recently gained attention due to their favorable properties regarding high-temperature applicability. Alloys strengthened by Heusler-type precipitates turned out to show promising properties at elevated temperatures, e.g., creep resistance. The present work aims at developing a fundamental understanding of the microstructure of an alloy with a nominal composition of 60Fe–20Al–10Ni–10Ti (in at. %). In order to determine the microstructural evolution, prevailing phases and corresponding phase transformation temperatures are investigated. Differential thermal analysis, high-temperature X-ray diffraction, and special heat treatments were performed. The final microstructures are characterized by means of scanning and transmission electron microscopy along with hardness measurements. Atom probe tomography conducted on alloys of selected heat-treated conditions allows for evaluating the chemical composition and spatial arrangement of the constituent phases. All investigated sample conditions showed microstructures consisting of two phases with crystal structures A2 and L21. The L21 precipitates grew within a continuous A2 matrix. Due to a rather small lattice mismatch, matrix–precipitate interfaces are either coherent or semicoherent depending on the cooling condition after heat treatment

Patients' perceptions of risky developments during psychotherapy

Research on risks and unwanted effects is largely missing in psychotherapy. Using exploratory factor analysis six dimensions of personal therapy situation were identified in a preliminary study, three of them were associated with risky developments during the psychotherapeutic process: (1) (poor) quality of therapeutic relationship, (2) burden caused by psychotherapy, and (3) dependency/isolation. Based on the finding of this study an online survey was performed to examine these three dimensions. Aside from these three factors another variable was associated with risky therapy developments: the online questionnaire also asked for premature terminations of psychotherapy as a consequence of risky conditions for the therapeutic development. Risky conditions were found to be associated with the following variables: (1) the combination of female patient–male therapist, (2) the therapeutic orientation (particularly with the psychodynamic approaches) and (3) the duration of therapy. Fewer humanistic and systemic psychotherapies were found among the high risk-prone group of patients who were at risk in at least three of the four variables which were associated with risky developments. Differences in the findings of the study regarding the four therapeutic orientations stress the importance of an extensive differential indication and a cooperative partnership between patient and therapist, in order to facilitate a positive patient participation towards the choice of therapy method and subsequent successful participation throughout the course of treatment. Further studies should also focus on female patient and male therapist psychotherapies

T cell stimulator cells, an efficient and versatile cellular system to assess the role of costimulatory ligands in the activation of human T cells.

It is well established that full activation of T cells requires the interaction of the TCR complex with the peptide-MHC complex (Signal 1) and additional signals (Signal 2). These second signals are generated by the interaction of costimulatory ligands expressed on antigen presenting cells with activating receptors on T cells. In addition, T cell responses are negatively regulated by inhibitory costimulatory pathways. Since professional antigen presenting cells (APC) harbour a plethora of stimulating and inhibitory surface molecules, the contribution of individual costimulatory molecules is difficult to assess on these cells. We have developed a system of stimulator cells that can give signal 1 to human T cells via a membrane bound anti-CD3 antibody fragment. By expressing human costimulatory ligands on these cells, their role in T cell activation processes can readily be analyzed. We demonstrate that T cell stimulator cells are excellent tools to study various aspects of human T cell costimulation, including the effects of immunomodulatory drugs or how costimulatory signals contribute to the in vitro expansion of T cells. T cell stimulator cells are especially suited for the functional evaluation of ligands that are implicated in costimulatory processes. In this study we have evaluated the role of the CD2 family member CD150 (SLAM) and the TNF family member TL1A (TNFSF15) in the activation of human T cells. Whereas our results do not point to a significant role of CD150 in T cell activation we found TL1A to potently costimulate human T cells. Taken together our results demonstrate that T cell stimulator cells are excellent tools to study various aspects of costimulatory processes

Die Wirkung von MOOCs und iMooX.at aus Sicht von Kursersteller:innen

iMooX.at wird im Rahmen des Projekts „MooX – Die MOOC-Plattform als Service für alle österreichischen Universitäten“ (2020–2023) als nationale Plattform für Hochschulen ausgebaut. Im Beitrag werden bisherige Ergebnisse und Wirkungen des Projekts dargestellt. So wurden bereits 70 MOOCs durchgeführt (geplant waren 33). In problemzentrierten Interviews mit fünf Kursersteller:innen wurden zudem Wirkungen von MOOCs und iMooX.at als Plattform gesammelt. Kursersteller:innen bestätigen in einer Online-Befragung (n=17) im hohen Maße, dass iMooX.at zur Verbreitung von OER beiträgt und positive Wirkungen für unterschiedliche Gruppen hat. Dieses Projekt wurde am 1. Juni 2023 im Rahmen einer Online-Veranstaltung des BMBWF präsentiert. Die Präsentationsunterlagen finden Sie hier

The Resource Curse and Rentier States in the Caspian Region : A Need for Context Analysis

Although much attention is paid to the Caspian region with regard to energy issues, the domestic consequences of the region’s resource production have so far constituted a neglected field of research. A systematic survey of the latest research trends in the economic and political causalities of the resource curse and of rentier states reveals that there is a need for context analysis. In reference to this, the paper traces any shortcomings and promising approaches in the existent body of literature on the Caspian region. Following on from this, the paper then proposes a new approach; specifically, one in which any differences and similarities in the context conditions are captured. This enables a more precise exploration of the exact ways in which they form contemporary post-Soviet Caspian rentier states.Obwohl der Region am Kaspischen Meer im Zuge von Energiediskursen große Aufmerksamkeit zuteil wird, stellen die innerstaatlichen Folgen der Ressourcenproduktion in der Region ein bislang vernachlässigtes Forschungsfeld dar. Ein systematischer Überblick über die jüngsten Forschungstrends zu wirtschaftlichen und politischen Kausalzusammenhängen des Ressourcenfluchs und zu Rentierstaaten offenbart die Notwendigkeit von Kontextanalysen. Hierauf Bezug nehmend, analysiert der Aufsatz sowohl die Mängel als auch viel versprechende Ansätze in der betreffenden Literatur zur Region am Kaspischen Meer. Der Aufsatz stellt letztendlich einen neuen Ansatz vor, der Unterschiede und Gemeinsamkeiten in den Kontextbedingungen erfasst, um zu erforschen, wie diese die gegenwärtigen post-sowjetischen Rentierstaaten in der Region am Kaspischen Meer tatsächlich prägen

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements