Gesellschaft für Klinische Forschung

In 2022, lung cancer had both the highest incidence and the highest mortality in both sexes combined. Image-guided and adaptive radiotherapy has emerged as a treatment option for inoperable lung cancer patients. One of the major uncertainties in radiotherapy of lung tumors is the breathing-induced motion. The current standard of care to account for breathing motion is respiratory-correlated four-dimensional computed tomography (4D-CT), which represents the three-dimensional (3D) anatomy in typically ten different breathing phases. Although magnetic resonance imaging (MRI) is increasingly used as an imaging modality for radiotherapy, no 4D-MRI methodology yet exists for MR-guided radiotherapy at MR-linac systems. The aim of this thesis was to investigate the development of a 4D-MRI methodology on the 1.5 T Unity MR-linac. This development would enable motion management on the day of treatment, which goes beyond the adaptive radiotherapy workflows currently available that are limited to correcting for daily anatomical changes based on a 3D-MRI scan. The basis of this thesis was the development of an MRI methodology consisting of the acquisition sequence and the methodology to process the images into a respiratory-correlated 4D-MRI. A standard two-dimensional (2D)-MRI sequence was modified to acquire two slices simultaneously to extend the coverage of the anatomy in the slice direction. After processing the data into a 4D-MRI, they were subsequently transformed into a time-weighted average 3D-MRI (i.e., mid-position) that is compatible with the treatment planning software. The trade-off between the spatial resolution and acquisition time resulted in a limited accuracy for treatment planning when using this mid-position. Therefore, the spatial resolution of the mid-position MRI was improved by deforming a high-resolution MRI scan to the mid-position based on 4D-MRI-derived motion information. In addition to the use for treatment planning and adaptation, it was also successfully demonstrated that the 4D-MRI methodology could be used for real-time motion estimation and target tracking during treatment (the latter in a phantom). To improve the representativeness of the 4D-MRI for the underlying average breathing and to minimize the risk of target drift, a visual biofeedback method using an internal navigator was developed. Breathing regularity and stability were drastically improved in healthy volunteers. As a result, a shorter scan time could suffice for the required amount of data to correctly represent the average breathing cycle with the 4D-MRI. In the last chapter, an improved visual biofeedback implementation was used to guide healthy volunteers and one patient during the acquisition of different 4D-MRI sequences in an international collaboration, allowing for in vivo comparisons between different 4D-MRI methods. In conclusion, the research presented in this thesis introduced a 4D-MRI methodology that enables motion estimation for treatment planning, can define the time-weighted tumor position for treatment planning, and can be used for real-time motion estimation during irradiation. When combined with visual biofeedback, breathing is regularized and stabilized, which improves the representativeness of the 4D-MRI and derived time-weighted average anatomy. All-in-all, enabling 4D-MRI as motion management at the MR-linac will further expand the patient-specific treatments in MR-guided radiotherapy and hopefully lead to improved patient outcomes.

Inguinal hernia repair with synthetic mesh became a gold standard due to durability and low recurrence rates. With the growing popularity of absorbable meshes in abdominal wall repairs, we evaluated performance of absorbable biosynthetic mesh and permanent synthetic mesh in inguinal hernia repair. A retrospective analysis of patients undergoing elective unilateral inguinal hernia operations with absorbable biosynthetic (Phasix™ Mesh and Phasix™ ST Mesh) and permanent synthetic (Bard™ Soft Mesh and Ventralight™ ST Mesh) from Herniamed was performed. Patients in both mesh groups were matched using 1:1 propensity score matching. Complications (intraoperative, general, and postoperative) and clinical outcomes at 1-year follow-up were reported and compared between matched pairs. Among 1,185,067 patients from 954 centers, 8,286 patients fit the inclusion criteria, 75 patients with absorbable mesh - Phasix group, and 8,211 patients with synthetic mesh - PP group. After propensity score matching, there were 64 matched pairs. There were no statistical differences between groups observed in intraoperative, general, or postoperative complications. At 1-year follow-up, there were no recurrences reported for either group. There were no significant differences in 1-year outcomes including pain (on exertion, at rest, and requiring treatment) between Phasix and PP groups. Complications and 1-year outcomes following inguinal hernia repair are not statistically different between absorbable biosynthetic and permanent synthetic mesh. Despite the absorbable nature of the biosynthetic mesh, the 1-year outcomes are similar to permanent synthetic mesh. However, the study was conducted on a small cohort and future studies with longer follow-up are needed to evaluate advantages, if any, over the other mesh types.

At crime scenes, apart from the detection of blood, it may be important to determine whether a person was alive at the time of blood deposition. Based on the rapid onset of fibrinolysis after death, this pathway could be considered to identify potential biomarkers for postmortem blood. Fibrinolysis is the natural process that breaks down blood clots after healing a vascular injury. One of its products, D-dimer, could be a potential biomarker for postmortem blood. SERATEC® (SERATEC® GmbH, Göttingen, Germany) has developed the PMB immunochromatographic assay to simultaneously detect human hemoglobin and D-dimer. The main goals of this study were to assess the possibility of using this test to detect postmortem blood, evaluate D-dimer levels in antemortem, menstrual, and postmortem blood, and assess the ability to obtain STR profiles from postmortem blood. Except for one degraded sample, all postmortem blood samples reacted positively for the presence of D-dimer using the SERATEC® PMB test. All antemortem blood samples from living individuals showed negative results for D-dimer detection, except for one liquid sample with a weak positive result, probably due to pre-existing health conditions. Menstrual blood samples gave variable results for D-dimer. The DIMERTEST® Latex assay was used for semi-quantitative measurement of D-dimer concentrations, with postmortem and menstrual blood yielding higher D-dimer concentrations compared to antemortem blood. Full STR profiles were developed for all postmortem samples tested except for one degraded sample, pointing to the possibility of not only detecting postmortem blood at the crime scene but also the potential identification of the victim.

This paper demonstrates the critical role of the Asset Administration Shell (AAS) as a standardized framework for data exchange within the industrial automation domain, particularly considering the discrete manufacturing roots of automation projects. To address the lack of integration and collaboration in the supply chain of automation projects, we propose a digitally assisted and efficient solution using the Factory-X project as a case study. This approach connects various tools from manufacturers and integrates them into the toolchains used by system integrators, mechanical engineers, and operators. We demonstrate how the proposed method significantly enhances productivity and the solution-finding process in automation engineering by facilitating the exchange and integration of automation component information between customers and suppliers through AAS.

Zusammenfassung Das Kapitel stellt die Zielsetzung und die Zielgruppen des Buches vor. Mit der Zusammenstellung von Fachinformationen sollen Wintersportler und Wintersportlerinnen, Seilbahnwirtschaft, Tourismusdestinationen aber auch Umwelt- und Naturschtzverbände angesprochen werden. Ziel ist es zu einem nachhaltigen Skibetrieb in den Alpen beizutragen. Weiterhin finden sich in diesem Kapitel Erläuterungen zu wichtigen Fachbegriffen.