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Impact of CCND1 amplification on the prognosis of hormone receptor–positive, HER2-negative breast cancer patients—correlation of clinical and pathological markers
No full textPurpose The cyclin D1 gene ( CCND1 ) encodes a key cell-cycle regulatory protein. Resistance to endocrine therapy is reportedly observed more often in patients with CCND1 -amplified tumors. CCND1 amplification is known to be a driving event in breast cancer, but contradictory findings are reported for its association with prognosis. This study therefore investigated the prognostic value of CCND1 amplification in hormone receptor (HR)-positive breast cancer patients. Methods A cohort of 894 unselected breast cancer patients from the Bavarian Breast Cancer Cases and Controls (BBCC) study was included. The CCND1 amplification rate was evaluated in tissue microarrays using fluorescence in situ hybridization. A CCND1 /CEP11 ratio ≥ 2.0 was considered amplified. Statistical analysis was conducted on cases with ratios based on a range of 20–100 nuclei analyzed per case. A univariable Cox regression model was fitted with disease-free survival (DFS) and overall survival (OS). Results CCND1 gene status was assessable in 511 patients. The CCND1 amplification rate was 12.9% (66 patients). Most patients with CCND1 amplification had luminal B-Like—(51.5%, n = 34) or luminal A-Like tumors (25.8%, n = 17), 13 patients with HER2-positive disease (19.7%) and only two patients had triple-negative tumors (3.0%). Survival analysis, focused on HR-positive, HER2-negative patients, showed no statistically significant differences in the DFS and OS with and without CCND1 amplification ( P = 0.20 and 0.14, respectively, in the unadjusted analysis). Conclusions CCND1 amplification is a recurring event in breast cancer, occurring most frequently in luminal B-like and HER2-amplified subtypes. A trend toward less favorable outcomes was observed among CCND1 -amplified HR-positive, HER2-negative tumors.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Consideration of previous fatigue damage in the crash simulation of short-fibre reinforced thermoplastics
No full textParallel erschienen als Druckausgabe bei FAU University Press, ISBN: 978-3-96147-802-6Bauteile aus kurzfaserverstärkten Thermoplasten werden im Fahrzeugbau zunehmend in Funktionen eingesetzt, bei denen sie sowohl während der normalen Gebrauchsdauer beansprucht als auch ihr Verhalten im Crash von Bedeutung ist. Die durch wiederholte Beanspruchung infolge der Gebrauchslastfälle auftretende Ermüdungsschädigung führt zu einer Verschlechterung der mechanischen Eigenschaften, wird jedoch gegenwärtig in der Crashsimulation nicht berücksichtigt. Hier setzt die vorliegende Arbeit an: sie stellt einen Ansatz vor, der durch geeignete experimentelle Charakterisierungsverfahren die Materialdegradation infolge zyklischer Beanspruchung quantifizieren und ihre Auswirkungen auf crashrelevante Werkstoffeigenschaften modellieren soll. Diese veränderten Werkstoffkennwerte werden der Crashsimulation je nach vorherrschender Schädigung übergeben. Die notwendigen Modelle werden durch Betrachtungen an Zugstäben hergeleitet und in Biegeversuche an Kreuzrippenträgern validiert. Der vorgestellte Ansatz zeigt hierbei eine gute Prognosefähigkeit, deren Diskussion und Ausblick auf weitere Potentiale den Abschluss der Arbeit darstellt.Components made of short fibre-reinforced thermoplastics are increasingly being used in vehicle design in functions where they are stressed during normal service life and where their behaviour in a crash is also important. The fatigue damage caused by repeated loading as a result of service load cases leads to a deterioration of the mechanical properties, but is not currently taken into account in crash simulation. This is where the present work comes in: it presents an approach that uses suitable experimental characterisation methods to quantify material degradation due to cyclic loading and to model its effects on crash-relevant material properties. These changed material parameters are transferred to the crash simulation depending on the prevalent damage. The necessary models are derived from observations on tensile rods and validated in bending tests on cross-ribbed beams. The presented approach shows a good predictive capability, whose discussion and outlook on further potentials represent the conclusion of the work
Age-and sex-specific reference intervals of total cholesterol, LDL cholesterol, HDL cholesterol and non-HDL cholesterol. Comparison of two algorithms for the indirect estimation of reference intervals
No full textObjectives Reference intervals of total cholesterol concentrations in plasma and of their fractions low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-and non-HDL concentrations are seldom studied with respect to the relevance of age and sex. Therefore, the effect of age and sex on the reference intervals was reinvestigated with 2 indirect procedures. Methods As an indirect approach, the truncated minimum chi-square method was applied. All analyses were performed by computer programs available. The script published on the homepage of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL) allows to derive a continuous age dependency of reference intervals together with their confidence and equivalence limits. The results of this approach were compared with those obtained by an indirect method developed more recently, the refineR algorithm. Results In the present study, the upper reference limits of total cholesterol varied from 5.1 to 7.8 mmol/L (197–302 mg/dL) depending on various biological variables (as age, sex, inpatients versus outpatients). These upper limits increased with age. Differences between sexes can be neglected except for the age above 80 years. The pattern of reference limits of LDL cholesterol and non-HDL cholesterol paralleled those of total cholesterol. The reference limits of HDL cholesterol were higher in women than in men but were independent of age. Conclusions Reference limits for the concentrations of total cholesterol and their fractions LDL-, HDL-and non-HDL concentrations should be stratified for age and sex
Wall-less Flow Phantoms with 3D printed Soluble Filament for Ultrasonic Experiments
No full textTissue-mimicking materials (TMMs) typically used for ultrasound phantoms include gelatin, agarose and polyvinyl alcohol (PVA). These materials have shown sufficient similarity in ultrasound parameters compared to human tissue. Despite their extensive use for years to generate ultrasound phantoms, no simple and easily reproducible way to generate complex, wall-less ultrasound flow phantoms has been introduced. Commercially available ultrasound flow phantoms are limited to simple flow geometries that do not reflect the complex blood flow in humans. Flow phantoms with complex geometries presented in scientific publications either have walls between TMMs and the flow channel, are limited to one material, or are complicated to produce. In this contribution, we present a method using 3D printing and soluble filament that allows for the reliable and consistent production of complex flow geometries with the typical materials used for ultrasound phantoms and without any walls
Genetic underpinnings of the psoriatic spectrum
No full textThe psoriatic field includes both rare and common subtypes. Common complex forms include psoriasis vulgaris and psoriatic arthritis. In these subtypes, certain HLA alleles remain the most relevant genetic factors, although genome-wide association studies lead to the detection of more than 80 susceptibility loci. They mainly affect innate and adaptive immunity and explain over 28 % of the heritability. Pustular psoriasis comprises a group of rarer subtypes. Using exome sequencing, several disease genes were identified for mainly generalized pustular psoriasis, and an oligogenic inheritance is likely. Treatment studies based on the affected IL–36 pathway indicate a high response rate in this subtype further supporting the pathophysiological relevance of the affected gene products
Using a single inertial sensor to control exergames for children with cerebral palsy
No full textIntroduction: Children with cerebral palsy (CCP) benefit from intensive arm training. Exergames that can be played at home offer the possibility to increase the frequency of therapy but require reliable and accurate real-time motion tracking via easy-to-use sensors in unsupervised settings and magnetically disturbed environments. Method: We propose an inertial-sensor-based method with a single sensor on the wrist for real-time tracking of the inclination of the forearm. The control parameter of the game was validated with an optical marker-based ground truth system. Results: First experiments with a therapist performing training movements in a healthy and simulated spastic manner show that the forearm inclination well captures the motion dynamics. The accuracy of the inertial-sensor-based measurement is validated with respect to the reference system in three healthy subjects. Orientation offsets between the inertial sensor and the forearm marker set in the range of 2° ̶ 6° and dynamic measurement errors about 3.1° were obtained. Conclusion: This work demonstrates that the proposed method is suitable for real-time control of exergames of CCP. The validation with an optical reference system showed that the forearm inclination can be used as for feedback and therapeutic progress monitoring
Twenty years of newborn screening for congenital adrenal hyperplasia and congenital primary hypothyroidism – experiences from the DGKED/AQUAPE study group for quality improvement in Germany
No full textCongenital primary hypothyroidism (CH) and congenital adrenal hyperplasia (CAH) are targeted by the German and Austrian newborn screening. For both diseases, there are registries for quality improvement, based on standardized observational data from long-term patient follow-up, under the auspices of the DGKED study group. By September 2021, the CH registry HypoDOK includes datasets from 23,348 visits of 1,840 patients, and the CAH registry contains datasets from 36,237 visits of 1,976 patients. Here, we report on the recruitment process, patient characteristics, and research contributions from the registries, and underline that the registries are an important tool to improve patient care and outcomes. Registries for rare conditions should thus be considered as an important public health measure and they should be adequately institutionalized and funded.None declared
Ultrasound-Mediated Cavitation of Magnetic Nanoparticles for Drug Delivery Applications
No full textMagnetic nanoparticles guided by an external magnetic field can be used to deliver drugs (e.g., chemotherapeutics) to malignant regions (e.g., tumor tissue). Some nonmagnetic, sonosensitive nanoparticles are known to generate cavitation induced by focused ultrasound. This can can be used to monitor spatial/temporal particle distribution and to stimulate local drug release in target regions. Little to nothing is known about the sonosensitivity of magnetic nanoparticles. Therefore, we investigated this physical phenomenon in the present contribution. We showed that certain magnetic nanoparticles have high cavitation potential and are promising for further research in this regard
Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults
Get PDFAnti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood. In this retrospective, multinational study, real-world data were collected from 14 different sites in Germany, Austria and Switzerland on 88 patients receiving 93 2nd-generation CAR therapies. Bridging therapy was classified into the categories 1) no systemic therapy (15/93 treatments), 2) low-intensity therapy (38/93 treatments) and 3) high-intensity therapy (39/93 treatments). We analyzed the impact of bridging regimens on clinical outcome. Patients receiving a high-intensity bridging therapy had a significantly higher tumor burden at time of eligibility compared to patients treated with a low-intensity or no systemic bridging therapy. They suffered significantly more from bacterial adverse events and mucositis. Overall survival was significantly better for patients who did not receive any bridging therapy in comparison to patients who had been treated with a low- or high-intensity bridging regimen. In conclusion, in this retrospective cohort, high-intensity bridging therapy has not improved the outcome in terms of overall and progression-free survival in comparison to a low-intensity therapy. Yet, high-intensity bridging therapy was associated with more adverse events. Our study suggests that a low-intensity bridging regimen may be preferred whenever tumor burden and disease kinetics allow this treatment strategy
Charakterisierung von Flüssigkeiten für Wasserstoffspeicherung und -transport mittels Oberflächenlichtstreuung
No full textParallel erschienen als Druckausgabe bei FAU University Press, ISBN: 978-3-96147-806-4This thesis contains an extensive characterization of liquids relevant to hydrogen storage and transport with respect to their thermophysical properties over a broad range of process-relevant conditions. Surface light scattering (SLS) has been employed to simultaneously study the viscosity and interfacial tension of several hydrogen carrier liquids. A particular focus has been put on the investigation of the technically relevant bicyclic liquid organic hydrogen carrier (LOHC) systems based on diphenylmethane (DPM) or benzyltoluene (BT) at temperatures up to 573 K as well as in the presence of molecular hydrogen at pressures up to 8 MPa. Based on systematic experimental investigations involving additionally capillary viscometry, the influence of the degree of hydrogenation, LOHC composition, and process-relevant byproducts on the viscosity and interfacial tension of the DPM- and the BT-based LOHC systems is identified. Meaningful correlations, mixing rules, and prediction schemes for the viscosity and interfacial tension based on the present data are discussed and provided. The experimental results for the thermophysical properties provide a basis for an improved understanding of the structure-property relationships of bicyclic hydrocarbons that have thus far been scarcely studied.
In the context of this work, the applicability of the SLS method was further extended using a new approach for the evaluation of SLS signals recorded from propagating capillary waves close to their transition to overdamped behavior. This development allows for an accurate account of all signal contributions present in this regime and, thus, for a reliable determination of viscosity and interfacial tension at the corresponding state points. Further metrological aspects regarding the capabilities and limitations of SLS are additionally highlighted.Diese Arbeit enthält eine umfassende Charakterisierung von Flüssigkeiten, die für die Speicherung und den Transport von Wasserstoff relevant sind, hinsichtlich ihrer thermophysikalischen Eigenschaften in einem breiten Spektrum prozessrelevanter Bedingungen. Mit Hilfe der Oberflächenlichtstreuung (surface light scattering, SLS) wurden simultan die Viskosität und Grenzflächenspannung mehrerer Wasserstoffträgerflüssigkeiten untersucht. Ein besonderer Schwerpunkt lag dabei auf der Untersuchung der technisch relevanten bizyklischen flüssigen organischen Wasserstoffträger (liquid organic hydrogen carrier, LOHC)-systeme auf Basis von Diphenylmethan (DPM) oder Benzyltoluol (BT) bei Temperaturen bis 573 K sowie in Gegenwart von molekularem Wasserstoff bei Drücken bis zu 8 MPa. Basierend auf systematischen experimentellen Untersuchungen auch mit ergänzenden Kapillarviskosimeter-Messungen wird der Einfluss des Hydriergrades, der LOHC-Zusammensetzung und prozessrelevanter Nebenprodukte auf die Viskosität und Grenzflächenspannung der DPM- und BT-basierten LOHC-Systeme identifiziert. Aussagekräftige Korrelationen, Mischungsregeln und Vorhersageschemata für die Viskosität und Grenzflächenspannung auf Grundlage der vorliegenden Daten werden diskutiert und bereitgestellt. Die experimentellen Ergebnisse für die thermophysikalischen Eigenschaften bieten eine Grundlage für ein besseres Verständnis der Struktur-Eigenschafts-Beziehungen von bizyklischen Kohlenwasserstoffen, die bisher kaum untersucht wurden.
Im Rahmen dieser Arbeit wurde die Anwendbarkeit der SLS-Methode durch einen neuen Ansatz für die Auswertung von SLS-Signalen erweitert, die von fortschreitenden Kapillarwellen nahe ihres Übergangs zu übergedämpftem Verhalten aufgezeichnet wurden. Diese Entwicklung ermöglicht eine genaue Berücksichtigung aller in diesem Regime vorhandenen Signalbeiträge und damit eine zuverlässige Bestimmung von Viskosität und Grenzflächenspannung an den entsprechenden Zustandspunkten. Weitere messtechnische Aspekte hinsichtlich der Möglichkeiten und Grenzen von SLS werden darüber hinaus beleuchtet