Palliative chemotherapy for pancreatic adenocarcinoma: a retrospective cohort analysis of efficacy and toxicity of the FOLFIRINOX regimen focusing on the older patient

Background: Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX. Methods: We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients. Results: Overall survival in our cohort was 10.2 months. Only 43% of patients did not need dose adaptations, but dose reductions did not lead to an inferior survival. We did not find evidence that patients aged 65 years and older deemed fit enough for palliative treatment had more toxicities or a worse outcome than younger patients. Conclusion: We conclude that treatment with the FOLFIRINOX protocol in patients with pancreatic cancer should not be withhold from patients solely based on their chronological age but rather be based on the patient’s performance status and comorbidities

BAW-Brief Nr. 1 – Februar 2012

610-B, Bautechnik, Überprüfung der Ermüdungsgefährdung von Hängeranschlüssen von Stabbogenbrücken im Bestand609-B, Bautechnik, Ermüdungssicherheit von geschmiedeten Hängeranschlüsse

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Fecundity selection theory: concepts and evidence

Fitness results from the optimal balance between survival, mating success and fecundity. The interactions between these three components of fitness vary importantly depending on the selective context, from positive covariation between them, to antagonistic pleiotropic relationships when fitness increases in one reduce fitness of others. Therefore, elucidating the routes through which selection shapes life history and phenotypic adaptations via these fitness components is of primary significance to understand ecological and evolutionary dynamics. However, while the fitness components mediated by natural (survival) and sexual (mating success) selection have extensively been debated from most possible perspectives, fecundity selection remains considerably less studied. Here, we review the theory, evidence and implications of fecundity selection as a driver of sex-specific adaptive evolution. Based on accumulating literature on the life-history, phenotypic and ecological aspects of fecundity, we (i) suggest that ‘fecundity’ is restricted to refer to brood size per reproductive episode, while ‘annual’ and ‘lifetime fecundity’ should not be used interchangeably with ‘fecundity’ as they represent different life history parameters; (ii) provide a generalized redefinition of fecundity selection that encompasses any traits that influence fecundity in any direction (from high to low) and in either sex; (iii) review the (macro)ecological basis of fecundity selection (e.g., ecological pressures that influence predictable spatial variation in fecundity); (iv) suggest that most ecological theories of fecundity selection should be tested in organisms other than birds; (v) argue that the longstanding fecundity selection hypothesis of female-biased sexual size dimorphism (SSD) has gained inconsistent support, that strong fecundity selection does not necessarily drive female-biased SSD, and that this form of SSD can be driven by other selective pressures; and (vi) discuss cases in which fecundity selection operates on males

The effects of mutant Ras proteins on the cell signalome

The genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells. © 2020, The Author(s)

Virtuelle Rundenzeitoptimierung mittels realistischer Rennfahrzeugsimulation

Der Einsatz von maßeschneiderten Fahrdynamik-Simulationspaketen ist Stand der Technik bei der Entwicklung von Rennfahrzeugen. Neben dem virtuellen Prototypenbau können schnelle Simulationsmodelle zu Konzeptuntersuchungen und zur Optimierung einzelner Fahrzeugkomponenten dienen. Die Entwicklung von Fahrdynamikreglern wird während des gesamten Entwicklungszyklus unterstützt, vom ersten Entwurf des Regelalgorithmus bis hin zu Funktionstests und Abstimmung des Steuergeräts in Echtzeitumgebungen, wo eine Implementierung des Reglers in Software oder Hardware mittels Sensoren und Aktuatoren mit der Vollfahrzeugsimulation verbunden ist. Zur Simulation der Rennfahrzeugdynamik wird neben einem präisen physikalischen Fahrzeugmodell ein Fahrermodell benötigt, das das virtuelle Fahrzeug im fahrdynamischen Grenzbereich präzise langs zeitoptimaler Führungsgrößen für die Ideallinie und das Geschwindigkeitsprofil führen kann. In diesem Beitrag wird eine Strategie zur Rundenzeitoptimierung vorgestellt, in der eine näherungsweise optimale Startlösung für die Sollgeschwindigkeit durch den Einsatz von nichtlinearen Optimierungsverfahren iterativ verbessert wird. Ergebnisse der Optimierung und die Grenzen der Vorgehensweise werden diskutiert