Non-Waste-Wachsschalungen: Neuartige Präzisions-Schalungen aus 100 % recycelbaren Industrie-Wachsen zur Herstellung von geometrisch komplexen Beton-Bauteilen

Die neuen 3D-Entwurfs-, Berechnungs- und Fertigungsverfahren in Kombination mit dem Werkstoff ultrahochfester Beton (UHPC) bieten das Potenzial, den Beton-Leichtbau zu revolutionieren [1]. Die Herausforderung bei der Herstellung von geometrisch komplexen und hochpräzisen UHPC-Bauteilen liegt dabei im Schalungsbau. Da bisher keine verfügbaren abfallfreien und somit nachhaltigen alternativen Schalungsmaterialien bzw. -systeme identifiziert werden konnten, wurde der Forschungsansatz entwickelt, frei geformte Schalungen für Betonbauteile unter Verwendung von CNC-gefrästen recycelbaren Industriewachsen zu verwenden. Die Erforschung dieses Ansatzes hin zu einer anwendbaren Non-Waste-Schalungstechnologie wurde in einem gemeinsamen Forschungsprojekt des Instituts für Werkzeugmaschinen und Fertigungstechnik (IWF) und des Instituts für Tragwerksentwurf (ITE) der TU Braunschweig durchgeführt. Im Folgenden werden die wesentlichen Inhalte des Vorhabens, ausgehend von der Auswahl geeigneter Wachse, über die Untersuchung der Zerspanbarkeit bis hin zur Betonierung und anschließenden Analyse der Schalungen und Abgüsse, vorgestellt und diskutiert. Grundlegende Erkenntnisse wurden u. a. bereits 2016 in [2]–[5] veröffentlicht. Diese werden hier teilweise wiedergegeben und zudem mit zusätzlichen Informationen ergänzt. Die wesentlichen Erkenntnisse aus dem Forschungsvorhaben werden zusammengefasst. Ausführliche Informationen zur Entwicklung der Non-Waste-Wachsschalungstechnologie finden sich in der 2019 veröffentlichten Dissertation von Jeldrik Mainka [6].The new 3D design, calculation and manufacturing methods in combination with ultra-high strength concrete (UHPC) off er the potential to revolutionise lightweight concrete construction [1]. The challenge in the production of geometrically complex and high-precision UHPC components lies in formwork construction. As no available waste-free and thus sustainable alternative formwork materials or systems have been identified so far, the research approach was developed to use freely shaped formwork for concrete components using CNC-milled recyclable industrial waxes. The research of this approach towards an applicable non-waste formwork technology was carried out in a joint research project of the Institute for Machine Tools and Production Engineering (IWF) and the Institute of Structural Design (ITE) of the Technical University of Braunschweig. In the following, the main contents of the project, starting with the selection of suitable waxes, the investigation of machinability up to the concreting and subsequent analysis of the formwork and castings are presented and discussed. Basic findings have already been published in 2016 in [2]–[5]. These are partly reproduced here and supplemented with additional information. The main findings of the research project are summarised. Detailed information on the development of non-waste wax formwork technology can be found in the dissertation by Jeldrik Mainka [6], published in 2019

Obesity alters endoxifen plasma levels in young breast cancer patients: A pharmacometric simulation approach

Endoxifen is one of the most important metabolites of the prodrug tamoxifen. High interindividual variability in endoxifen steady‐state concentrations (CSS,min ENDX) is observed under tamoxifen standard dosing and patients with breast cancer who do not reach endoxifen concentrations above a proposed therapeutic threshold of 5.97 ng/mL may be at a 26% higher recurrence risk compared with patients with endoxifen concentrations exceeding this value. In this investigation, 10 clinical tamoxifen studies were pooled (1,388 patients) to investigate influential factors on CSS,min ENDX using nonlinear mixed‐effects modeling. Age and body weight were found to significantly impact CSS,min ENDX in addition to CYP2D6 phenotype. Compared with postmenopausal patients, premenopausal patients had a 30% higher risk for subtarget CSS,min ENDX at tamoxifen 20 mg per day. In treatment simulations for distinct patient subpopulations, young overweight patients had a 3.1–13.8‐fold higher risk for subtarget CSS,min ENDX compared with elderly low‐weight patients. Considering ever‐rising obesity rates and the clinical importance of tamoxifen for premenopausal patients, this subpopulation may benefit most from individualized tamoxifen dosing

Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort

Tamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds are considered infeasible. Therefore, we aim to validate the association between Z-endoxifen concentration and tamoxifen treatment outcomes, and identify a Z-endoxifen concentration threshold of tamoxifen efficacy, using pharmacometric modeling and simulation. As a first step, the CYP2D6 Endoxifen Percentage Activity Model (CEPAM) cohort was created by pooling data from 28 clinical studies (&gt; 7,000 patients) with measured endoxifen plasma concentrations. After cleaning, data from 6,083 patients were used to develop a nonlinear mixed-effect (NLME) model for tamoxifen and Z-endoxifen pharmacokinetics that includes a conversion factor to allow inclusion of studies that measured total endoxifen but not Z-endoxifen. The final parent-metabolite NLME model confirmed the primary role of CYP2D6, and contributions from body weight, CYP2C9 phenotype, and co-medication with CYP2D6 inhibitors, on Z-endoxifen pharmacokinetics. Future work will use the model to simulate Z-endoxifen concentrations in patients receiving single agent tamoxifen treatment within large prospective clinical trials with long-term survival to identify the Z-endoxifen concentration threshold below which tamoxifen is less efficacious. Identification of this concentration threshold would allow personalized tamoxifen treatment to improve outcomes in patients with hormone receptor-positive breast cancer.</p