Fuchs (Germany)

SUMMARY & CONCLUSIONSThe residual risk of safety-instrumented systems constitutes a critical non-functional requirement governed by international standards. One crucial measure is the probability of failure on demand (PFD), describing the likelihood of a safety function to be inoperable at the time when it is needed. Various approaches for quantifying safety as a function of key design parameters have been explored in the literature. However, existing methods often rely on simplifying assumptions, such as neglecting the effects of demands and proof tests, applying approximations, or restricting the analysis to the special cases of high or low demand. More complex scenarios are typically addressed using numerical techniques.This paper presents closed-form exact expressions for the average probability of failure on demand (PFD) in systems with redundant safety functions. The proposed formulas cover common multi-channel configurations, including 1oo2, 1oo3, and 2oo3 architectures, and are validated through comparison with detailed simulation results.

The remaining risk of safety-instrumented systems is an important non-functional requirement that is regulated by international standards. Several ways towards computing the safety as a function of its relevant design parameters have been studied in the literature. However, the standard approach only covers two special cases of high or low demand, which simplify the treatment by either ignoring the effects of demand rate or test interval on the safety. More detailed treatments in the literature derive Markov models, which can be numerically analyzed, or approximate solutions using Taylor series expansions etc. This paper introduces closed-form exact formulas for the average probability of failure on demand (PFD) and the resulting hazardous event frequency (HEF, or accident rate), taking into account demand rate and test interval. It integrates all cases of low, high and medium demand in one formula. The derivation is based on an analysis of the cyclostationary semi-Markov stochastic process of the safety-integrated system and its symbolic transient analysis over the test interval.

This paper discusses a navigation system solution integrating inertial sensors and evaluates the application requirements for precise underwater operations dedicated to unmanned underwater vehicles. Accordingly, the systematic design of a high-grade inertial navigation module is described consisting of a fiber optical gyroscope based inertial measurement unit and additional position-independent auxiliary sensors for measuring velocity and pressure. In this context, modularization in the form of successive filter stages consisting of kinematic and kinetic Kalman filters was carried out in order to be able to realize a holistic approach. It is the combination of commercially available and process-specific components that creates a framework for enabling precise underwater operations. For performance determination of the system, evaluation tests were conducted using an unmanned surface vehicle in the port of Rostock. Besides the integrated solution, the impact of the auxiliary sensors on the autonomous motion state estimation was determined, simulating the navigation conditions during submerged operation. A high-precision Global Navigation Satellite Systems receiver served as a position reference. Finally, automated maneuvering tests were performed using an underwater vehicle in a restricted test tank, where the accuracy of the high-grade navigation module could be demonstrated even during long-term position update independent underwater operations.

PurposeEvery year around 70,000 people in Germany suffer from an abdominal incisional hernia that requires surgical treatment. Five years after reconstruction about 25% reoccur. Incisional hernias are usually closed with mesh using various reconstruction techniques, summarized here as standard reconstruction (SR). To improve hernia repair, we established a concept for biomechanically calculated reconstructions (BCR). In the BCR, two formulas enable customized patient care through standardized biomechanical measures. This study aims to compare the clinical outcomes of SR and BCR of incisional hernias after 1 year of follow-up based on the Herniamed registry.MethodsSR includes open retromuscular mesh augmented incisional hernia repair according to clinical guidelines. BCR determines the required strength (Critical Resistance to Impacts related to Pressure = CRIP) preoperatively depending on the hernia size. It supports the surgeon in reliably determining the Gained Resistance, based on the mesh-defect-area-ratio, further mesh and suture factors, and the tissue stability. To compare SR and BCR repair outcomes in incisional hernias at 1 year, propensity score matching was performed on 15 variables. Included were 301 patients with BCR surgery and 23,220 with standard repair.ResultsBCR surgeries show a significant reduction in recurrences (1.7% vs. 5.2%, p = 0.0041), pain requiring treatment (4.1% vs. 12.0%, p = 0.001), and pain at rest (6.9% vs. 12.7%, p = 0.033) when comparing matched pairs. Complication rates, complication-related reoperations, and stress-related pain showed no systematic difference.ConclusionBiomechanically calculated repairs improve patient care. BCR shows a significant reduction in recurrence rates, pain at rest, and pain requiring treatment at 1-year follow-up compared to SR.

This contribution presents research activities on vibroacoustic metamaterials (VAMM) based on the resonance effect for application in space structures to reduce structural vibrations. The focus of this work is the development of a design process for conception, numerical simulation, and manufacturing of vibroacoustic metamaterials as well as an experimental demonstration of the vibration reduction effect. The technology of VAMM is applied to representative scaled down launcher and satellite components. The vibration reduction behavior is tailored to each component, dependant on requirements on additional mass, manufacturing considerations and frequency range. A high potential is shown for all demonstrators, giving a bright outlook for further development and implementation of VAMM components for launcher and space components.

Abstract In this contribution we present analytical results on a model for dynamic fracture in viscoelastic materials at small strains that have been obtained in full depth in [1]. In the model, the sharp crack interface is regularized with a phase‐field approximation, and for the phase‐field variable a viscous evolution with a quadratic dissipation potential is employed. A non‐smooth penalization prevents material healing. The viscoelastic momentum balance is formulated as a first order system and coupled in a nonlinear way to the non‐smooth evolution equation of the phase field. We give a full discretization in time and space using a discontinuous Galerkin method for the first‐order system. We discuss the existence of discrete solutions and, with the step size in space and time tending to zero, their convergence to a suitable notion of weak solution of the system. Eventually, we provide a numerical benchmark and compare it with simulation results found in [2].

Abstract Mit dem Erscheinen der 1. Ausgabe der Reihe IEC/EN 61508 (“Funktionale Sicherheit sicherheitsbezogener elektrischer/elektronischer/programmierbarer elektronischer Systeme”) im Jahre 2001 war der offizielle Beginn der Funktionalen Sicherheit gelegt. Doch ihre Anfänge der reichen weiter zurück und die Funktionalen Sicherheit ist in den Entwicklungsabteilungen von Pepperl+Fuchs seit fast 50 Jahren verankert.

This pilot study aimed to evaluate a continuous glucose monitoring (CGM) based approach to study the effects of a functional drink containing specific amino acids and chromium picolinate (FD) and a combination of FD with a juice (FDJ) on postprandial glucose in a close to real life setting. The predefined primary endpoint for this study was the 120-min incremental area under the glucose curve (iAUC0−120min) after meals. It was estimated that using CGM and repeated meals in 6 participants could be sufficient to match the power of the previous study in regards to the quantity of meals. Participants followed a pre-specified meal schedule over 9 days and consumed the drinks three times daily with main meals. Differences between drinks were analyzed by analysis of covariances (ANCOVA) with subject number and activity as random factors and nutrient composition as covariates. In 156 meals available for analysis, a significant 34% reduction of glucose iAUC0−120min was shown for FDJ (p < 0.001). FD did not show a significant effect on its own, but a significant reduction of 17.6% (p = 0.007) was shown in pooled data for FD and FDJ. While the differences between the two functional drinks used were not the primary focus of this study, it was sufficiently powered to detect previously described effects in 60 participants in a cross-over design under laboratory settings. The design presented defines a novel and cost-effective approach using CGM devices and app-based lifestyle tracking for studying nutritional effects on glucose at home in a close to real-life setting.

Abstract Background: Ribociclib (RIB; a selective CDK4/6 inhibitor) + endocrine therapy (ET; aromatase inhibitor or fulvestrant along with ovarian suppression in pre- and perimenopausal patients [pts]) received USFDA and EMA approval for pre-, peri- and postmenopausal pts with HR+, HER2- advanced breast cancer (ABC) based on results from phase 3 MONALEESA (ML) trials. In ML-2 trial, first-line treatment (tx) with RIB + letrozole (LET) vs placebo (PBO) + LET significantly improved median progression-free survival (mPFS) in postmenopausal pts with HR+, HER2- ABC. In ML-3 and ML-7 trials, RIB + ET vs PBO + ET showed a significant improvement in mPFS and overall survival among pts with HR+, HER2- ABC, irrespective of menopausal status, line of tx and combination partner. Real-world evidence on the effectiveness, safety, and tolerability of RIB + ET in pts with HR+, HER2- ABC would help to gain insight into routine clinical practice. Methods: RIBANNA is a prospective, noninterventional study ongoing in Germany since October 2017. Pre-, peri- and postmenopausal pts who received first-line tx with RIB + ET, or ET alone or chemotherapy (CT) for HR+, HER2- ABC in accordance with German tx guidelines were included. Data from routine clinical practice in all 3 cohorts, including further lines of sequential therapy, were collected. The third interim analysis data from RIBANNA study was presented in SABCS 2020. Fourth interim analysis data will be presented during SABCS 2021. Results: Till February 11, 2021, 2594 pts were included in the study (RIB + ET, n = 2183; ET, n = 229; CT, n = 182) and the enrollment was stopped; however, pt follow-up will be continued for an additional 4 years. For the fourth interim analysis, full analysis set (comprising all pts, except screening failures and locked pts, who received at least one dose of study medication [safety analysis set] and for whom ≥ 1 post-baseline evaluation was recorded) included 2131 pts (RIB + ET, n = 1814 [81.2%]; ET, n = 175 [73.8%]; CT, n = 142 [72.1%]), while the safety analysis set comprised 2452 pts (RIB + ET, n = 2062 [92.3%]; ET, n = 216 [91.1%]; CT, n = 174 [88.3%]). Until last patient first visit, among 2594 treated pts (including screening failures), data from first-line (1L) tx are available for 2452 pts (94.5%), from second-line (2L) tx for 343 pts (13.2%), and from third-line (3L) tx for 74 pts (2.9%, Table 1). Overall, 23.9%, 27.9%, and 43.4% of pts discontinued the study in RIB + ET, ET, and CT cohorts, respectively. The fourth interim analysis is planned in October 2021, and the final baseline demographic data as well as updated information on safety will be presented during SABCS 2021. Conclusion: RIBANNA study showed diverse population characteristics among pts who received RIB tx in a real-world setting. The data from fourth interim analysis, which is planned in October 2021, including final baseline demographic data and updated safety data will be presented. Table 1. Patient disposition following last patient first visit on February 11, 2021PatientsTotal. (N = 2594). n (%)RIB + AI/FUL (n = 2183). n (%)ET (n = 229). n (%)CT. (n = 182). n (%)Includeda2594 (100.0)2183 (100.0)229 (100.0)182 (100.0)Treated (including screening failures)2452 (94.5)2062 (94.5)216 (94.3)174 (95.6)1L therapyb2452 (94.5)2062 (94.5)216 (94.3)174 (95.6)2L therapyb343 (13.2)264 (12.1)36 (15.7)43 (23.6)3L therapyb74 (2.9)53 (2.4)10 (4.4)11 (6.0)4L therapyb7 (0.3)7 (0.3)0 (0.0)0 (0.0)Discontinued studyc664 (25.6)521 (23.9)64 (27.9)79 (43.4)aAll pts signing informed consent form, bNumber of data set available till February11, 2021, cEnd of documentation with reason other than ‘end of study. Citation Format: Diana Lüftner, Cosima Brucker, Thomas Decker, Peter Fasching, Thomas Göhler, Christian Jackisch, Jan Janssen, Andreas Köhler, Kerstin Lüdtke-Heckenkamp, Marion van Mackelenbergh, Frederik Marmé, Arnd Nusch, Beate Rautenberg, Toralf Reimer, Marcus Schmidt, Rudolf Weide, Pauline Wimberger, Naiba Nabieva, Christian Roos, Achim Wöckel. Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) locally advanced or metastatic breast cancer: Fourth interim analysis from the RIBANNA study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-15.