Design, Aufbau und Inbetriebnahme eines Bestrahlungsplatzes mit aktiver dreidimensionaler Aufbereitung des Protonenstrahls

Seit 1998 werden am Helmholtz-Zentrum Berlin für Materialien und Energie GmbH (HZB) in Kooperation mit der Charité-Universitätsmedizin Berlin Augentumore mit Protonen bestrahlt. Dazu beschleunigt ein Zyklotron, welches hauptsächlich für die Therapie genutzt wird, die Protonen auf eine Energie von 68MeV. Neben dem Therapieplatz existiert auch ein Experimentierplatz zu Forschungszwecken. Die Strahlaufbereitung erfolgt in beiden Anwendungsgebieten primär durch passives Aufstreuen des Strahls mit einer einzelnen Streufolie. Dies führt jedoch zu erheblichen Strahlverlusten, die die erreichbare Strahlintensität bzw. Dosisleistung im Feld limitieren. Ziel dieser Arbeit ist es, einen Bestrahlungsplatz mit aktiver, dreidimensionaler Strahlführung aufzubauen, um eine möglichst effiziente Strahlstromnutzung zu ermöglichen und flexibel auf Anforderungen an das Bestrahlungsfeld eingehen zu können. Zu diesem Zweck wurde ein Modell entwickelt, welches unter Berücksichtigung verschiedener Parameter der Messgeometrie, Strahlcharakteristik und Felderzeugung Strahlprofile berechnet. Dieses Modell wurde im Vergleich mit Monte-Carlo Simulationen und Messungen getestet und verifiziert. Anschließend konnten Untersuchungen zur Positionierung der verwendeten Komponenten durchgeführt sowie deren Einflüsse auf Penumbra, Homogenität und Transmission der Strahlfelder analysiert werden. Es zeigte sich, dass die hohen klinischen Anforderungen für die Anwendung in der Augentumortherapie am HZB erfüllt werden können, sofern stärkere Magnetspulen verwendet werden. Mit Hilfe des Modells wurden für einen optimierten Aufbau Strahlprofile berechnet und charakterisiert. Es konnte so gezeigt werden, dass unter diesen optimierten Bedingungen eine Anwendbarkeit des aktiven Systems in der Augentumortherapie möglich ist. Des Weiteren wurde im Verlauf dieser Arbeit ein statischer Modulator für den Bestrahlungsplatz am HZB entwickelt, mit Hilfe eines 3D-Druckers hergestellt und erfolgreich getestet.Since 1998, ocular tumours have been irradiated with protons at the Helmholtz- Zentrum Berlin für Materialien und Energie GmbH (HZB) in cooperation with Charité-Universitätsmedizin Berlin. For this purpose a cyclotron is operated which accelerates protons to an energy of 68MeV and is mainly used for therapy purposes. In addition to the therapy station there is also an experimental station for research purposes. In both application areas, beam delivery is primarily achieved by passive scattering using a single scattering foil. However, this leads to considerable beam losses, which in turn limit the maximum beam intensity or dose rate in the irradiation field. The aim of this work is to construct an irradiation setup with active three-dimensional beam delivery in order to enable the most efficient possible use of beam current and to be able to respond flexibly to different irradiation field requirements. Therefore, a model was developed which calculates beam profiles taking into account various parameters of the measurement geometry, beam characteristics and field generation. This model was tested and verified in comparison with Monte Carlo simulations and measurements. Subsequently investigations into the positioning of the components used could be carried out and their influences on penumbra, homogeneity and transmission of the beam fields analysed. It was found that the high clinical requirements in terms of maximum penumbra and field homogeneity for the application in eye tumour therapy at HZB can be met if stronger magnetic coils were used. Model calculations were used to calculate and characterize different beam profiles for an optimized setup. It could be shown that under these optimized conditions an applicability of the active system in eye tumour therapy is possible. Furthermore, a static modulator for the irradiation site at HZB was developed in the course of this work, manufactured using a 3D printer and successfully tested

From the Steppe to the Desert: Survey of Band-Winged Grasshoppers from Mongolia (Orthoptera: Acrididae: Oedipodinae) Based on Material from 50 Years of Expeditions

The steppe regions of Mongolia have a rich grasshopper fauna. Especially, the short-horned (Caelifera) grasshopper family Acrididae with the subfamilies Gomphocerinae (slant-faced grasshoppers) and Oedipodinae (band-winged grasshoppers) show a high diversity and abundance. This study reviews the Mongolian fauna of band-winged grasshoppers based on collection data of 50 years of expeditions of the German-Mongolian research cooperation. These collection data (assembled between 1962 and 2019) were used to generate a faunistic overview of Oedipodinae species for the region. In total 740 specimens belonging to 16 species were reported. Based on the collected material, study of the types and the original species descriptions following species were synonymized: Bryodema gebleri mongolica ZUBOWSKY, 1900 syn. nov. with Bryodema gebleri (FISCHER von WALDHEIM, 1836), as well as Oedaleus asiaticus BEY-BIENKO, 1941 syn. nov. with Oedaleus decorus (GERMAR, 1825). Based on the generated dataset the region around Khustai National Park and the Great Lakes Depression in North-West-Mongolia were evaluated as the most species-rich spots of Oedipodinae

CLINICAL AND FUNCTIONAL CHARACTERISTICS OF NONAGENARIANS HOSPITALIZED IN A GERIATRIC UNIT: A DESCRIPTIVE STUDY

Peer reviewe

Influence of motivation and a new digitized training program on undergraduate dental students during preclinical scaling training

Background The current study evaluated whether a new digitized scaling training program (DTP: n = 30; supervisor-student-ratio 1:10) improves the performance of undergraduate dental student during a preclinical course in regard to two different instruments [sonic scalers (AIR) and Gracey curettes (GRA)] compared to a conventional training program (CTP: n = 19; supervisor-student-ratio 1:4). Methods All the participants received a two-hour lecture on both instruments, followed by a 12-week period with a weekly training program lasting 45 min (10 sessions); one group was supported by DTP. At the end of the training phase, all the participants performed the subgingival scaling of six equivalent test teeth using GRA and AIR. Treatment time, proportion of removed simulated biofilm (relative cleaning efficacy, RCE-b) and hard deposits (RCE-d) were recorded. By using a pseudonymized questionnaire with a 5-point Likert scale, self-assessment of scaling effort, handling, root surface roughness/destruction and effectiveness were evaluated. In addition, personal data such as age, gender, handedness, regularity of playing computer games/consoles and previous dental/technical or medical education were elevated and correlated with cleaning efficacy. Results The DTP participants showed higher effectiveness in RCE-b compared to those who used the CTP with GRA (71.54% vs. 67.23%, p = 0.004) and AIR (71.75% vs. 62.63%, p ≤ 0.001), and the DTP students were faster with both instruments (p ≤ 0.001). For RCE-d, there was no significant difference between the DTP and CTP groups (GRA p = 0.471; AIR p = 0.158), whereas DTP showed better RCE-d results with GRA versus AIR (84.68% vs. 77.85%, p < 0.001). According to the questionnaire, no significant differences were detected between the training groups in terms of self-assessment, handling, treatment time, root surface roughness/destruction or effectiveness of the instruments. The CTP group favored AIR compared to GRA regarding the fatigue effect. The CTP and playing computer games/consoles regularly was correlated with lower RCE-b, whereas previous education in medicine/dentistry was correlated with higher RCE-b values. Conclusions Within the limitations of the study, the DTP with a reduced supervision effort compared to the CTP resulted in higher effectiveness and lower instrumentation time for removing simulated biofilms

Neuropsychological analysis of gait disturbances during dual task in MCI patients

peer reviewedaudience: researcher, professional, studen

The Degree of t-System Remodeling Predicts Negative Force-Frequency Relationship and Prolonged Relaxation Time in Failing Human Myocardium

The normally positive cardiac force-frequency relationship (FFR) becomes flat or negative in chronic heart failure (HF). Here we explored if remodeling of the cardiomyocyte transverse tubular system (t-system) is associated with alterations in FFR and contractile kinetics in failing human myocardium. Left-ventricular myocardial slices from 13 failing human hearts were mounted into a biomimetic culture setup. Maximum twitch force (F), 90% contraction duration (CD90), time to peak force (TTP) and time to relaxation (TTR) were determined at 37 degrees C and 0.2-2 Hz pacing frequency. F-1(Hz)/F-0.(5)(Hz) and F-2(Hz)/F-0.(5)(Hz) served as measures of FFR, intracellular cardiomyocyte t-tubule distance (Delta TT) as measure of t-system remodeling. Protein levels of SERCA2, NCX1, and PLB were quantified by immunoblotting. F-1(Hz)/F-0.(5)(Hz) (R-2 = 0.82) and F-2(Hz)/F-0.(5)(Hz) (R-2 = 0.5) correlated negatively with Delta TT, i.e., samples with severe t-system loss exhibited a negative FFR and reduced myocardial wall tension at high pacing rates. PLB levels also predicted F-1(Hz)/F-0.(5)(Hz), but to a lesser degree (R-2 = 0.49), whereas NCX1 was not correlated (R-2 = 0.02). CD90 correlated positively with Delta TT (R-2 = 0.39) and negatively with SERCA2/PLB (R-2 = 0.42), indicating that both the t-system and SERCA activity are important for contraction kinetics. Surprisingly, Delta TT was not associated with TTP (R-2 = 0) but rather with TTR (R-2 = 0.5). This became even more pronounced when interaction with NCX1 expression was added to the model (R-2 = 0.79), suggesting that t-system loss impairs myocardial relaxation especially when NCX1 expression is low. The degree of t-system remodeling predicts FFR inversion and contraction slowing in failing human myocardium. Moreover, together with NCX, the t-system may be important for myocardial relaxation

Comparison of Mesenchymal Stromal Cells From Different Origins for the Treatment of Graft-vs.-Host-Disease in a Humanized Mouse Model

Mesenchymal stromal cells (MSCs) have potent immunomodulatory properties that make them an attractive tool against graft- vs.-host disease (GVHD). However, despite promising results in phase I/II studies, bone marrow (BM-) derived MSCs failed to demonstrate their superiority over placebo in the sole phase III trial reported thus far. MSCs from different tissue origins display different characteristics, but their therapeutic benefits have never been directly compared in GVHD. Here, we compared the impact of BM-, umbilical cord (UC-), and adipose-tissue (AT-) derived MSCs on T-cell function in vitro and assessed their efficacy for the treatment of GVHD induced by injection of human peripheral blood mononuclear cells in NOD-scid IL-2Rγnull HLA-A2/HHD mice. In vitro, resting BM- and AT-MSCs were more potent than UC-MSCs to inhibit lymphocyte proliferation, whereas UC- and AT-MSCs induced a higher regulatory T-cell (CD4+CD25+FoxP3+)/T helper 17 ratio. Interestingly, AT-MSCs and UC-MSCs activated the coagulation pathway at a higher level than BM-MSCs. In vivo, AT-MSC infusions were complicated by sudden death in 4 of 16 animals, precluding an analysis of their efficacy. Intravenous MSC infusions (UC- or BM- combined) failed to significantly increase overall survival (OS) in an analysis combining data from 80 mice (hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.32–1.08, P = 0.087). In a sensitivity analysis we also compared OS in control vs. each MSC group separately. The results for the BM-MSC vs. control comparison was HR = 0.63 (95% CI 0.30–1.34, P = 0.24) while the figures for the UC-MSC vs. control comparison was HR = 0.56 (95% CI 0.28–1.10, P = 0.09). Altogether, these results suggest that MSCs from various origins have different effects on immune cells in vitro and in vivo. However, none significantly prevented death from GVHD. Finally, our data suggest that the safety profile of AT-MSC and UC-MSC need to be closely monitored given their pro-coagulant activities in vitro

Urbanes Bauen: Rückbesinnung und Zukunft im urbanen Bauen mit Holz am Bespiel der Wuppertaler Nordstadt

oai:elpub.bib.uni-wuppertal.de:duepublico_mods_0000069

Swiss public health measures associated with reduced SARS-CoV-2 transmission using genome data

Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020 - the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrasted these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland's border closures de-coupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86-98% reduction in introductions during Switzerland's strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Last, we quantified local transmission dynamics once introductions into Switzerland occurred, using a phylodynamic model. We found that transmission slowed 35-63% upon outbreak detection in summer 2020, but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics