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The paper reports an investigation on whether valid results can be achieved in analyzing the structure of datasets although a large percentage of data is missing without replacement. Two types of confirmatory factor analysis (CFA) models were employed for this purpose: the missing data CFA model with an additional latent variable for representing the missing data and the semi-hierarchical CFA model that also includes the additional latent variable and reflects the hierarchical structure assumed to underlie the data. Whereas, the missing data CFA model assumes that the model is equally valid for all participants, the semi-hierarchical CFA model is implicitly specified differently for subgroups of participants with and without omissions. The comparison of these models with the regular one-factor model in investigating simulated binary data revealed that the modeling of missing data prevented negative effects of missing data on model fit. The investigation of the accuracy in estimating the factor loadings yielded the best results for the semi-hierarchical CFA model. The average estimated factor loadings for items with and without omissions showed the expected equal sizes. But even this model tended to underestimate the expected values.
Der Wald der Zukunft ... : ...braucht andere Bäume. Welche, versuchen Forscher herauszufinden
(2020)
Die Luft ist heiß und trocken, der sandige Boden hält kein Wasser: Es gibt nicht viele Wälder in Deutschland, denen es schlechter geht als dem Frankfurter Stadtwald. Für Wolfgang Brüggemann und Vera Holland ist er damit der perfekte Ort, um klimawandelresistente Bäume zu finden. Denn: Wer es hier schafft, der schafft es überall.
Die Phänomene des Traums und Träumens als allnächtliche Konfrontation mit dem Fremden und Anderen des wachen (Er-)Lebens (vgl. Engel 2003, S. 153) wie auch der wachen Persönlichkeit üben eine nachhaltige Faszination aus, die maßgeblich auf ihre ambivalente Charakteristik zurückzuführen ist. Der/die Träumende befindet sich in einem Stadium jenseits der Realität, in einem Dazwischen von Leben und Tod, und ist »mit einer Erlebenswelt und einer Erlebensweise konfrontiert, die [Manfred Engel zufolge] auf ebenso evidente wie rätselhafte Weise anders sind als die des wachen Lebens« (ebd.)...
Previous studies reported on the safety and applicability of mesenchymal stem/stromal cells (MSCs) to ameliorate pulmonary inflammation in acute respiratory distress syndrome (ARDS). Thus, multiple clinical trials assessing the potential of MSCs for COVID-19 treatment are underway. Yet, as SARS-inducing coronaviruses infect stem/progenitor cells, it is unclear whether MSCs could be infected by SARS-CoV-2 upon transplantation to COVID-19 patients. We found that MSCs from bone marrow, amniotic fluid, and adipose tissue carry angiotensin-converting enzyme 2 and transmembrane protease serine subtype 2 at low levels on the cell surface under steady-state and inflammatory conditions. We did not observe SARS-CoV-2 infection or replication in MSCs at steady state under inflammatory conditions, or in direct contact with SARS-CoV-2-infected Caco-2 cells. Further, indoleamine 2,3-dioxygenase 1 production in MSCs was not impaired in the presence of SARS-CoV-2. We show that MSCs are resistant to SARS-CoV-2 infection and retain their immunomodulation potential, supporting their potential applicability for COVID-19 treatment.
Summary We introduce fsbrain, an R package for the visualization of neuroimaging data. The package can be used to visualize vertex-wise and region-wise morphometry data, parcellations, labels and statistical results on brain surfaces in three dimensions (3D). Voxel data can be displayed in lightbox mode. The fsbrain package offers various customization options and produces publication quality plots which can be displayed interactively, saved as bitmap images, or integrated into R notebooks.
Availability and Implementation The software, source code and documentation are available under the MIT license at https://github.com/dfsp-spirit/fsbrain. Releases can be installed directly from the Comprehensive R Archive Network (CRAN).
NHC supersilyl silver complex [Ag(IPr)SitBu3] as a promising agent for substitution reactions
(2020)
The NHC supersilyl silver complex [Ag(IPr)SitBu3] (IPr = NHCIPr) was prepared by treatment of Ag(IPr)Cl with Na(thf)2[SitBu3] in benzene/thf at room temperature. X‐ray quality crystals of the NHC supersilyl silver complex [Ag(IPr)SitBu3] (monoclinic, space group P21/m) were grown from heptane at room temperature. The 29Si NMR spectrum of a solution of [Ag(IPr)SitBu3] in C6D6 revealed two doublets caused by coupling to 107Ag and 109Ag nuclei. We further investigated the possibility of a conversion of triel halides EX3 by treatment with [Ag(IPr)SitBu3]. At ambient temperature the reaction of [Ag(IPr)SitBu3] with an excess of EX3 yielded tBu3SiEX2 (E = B, Al; X = Cl, Br; E = Ga; X = Cl) and IPr·EX3 (EX3 = BCl3, BBr3, AlCl3, AlBr3, GaCl3). The identity of tBu3SiEX2 and IPr·EX3 was confirmed by comparison with authentic samples.
[1,3-Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene]triiodoborane benzene hemisolvate
(2020)
Der vorliegende Beitrag stellt die Bedeutsamkeit emotionaler und transformationaler Führungskompetenzen im Kontext inklusiver Schulentwicklung sowie allgemein im Rahmen eines transformationalen Schulmanagements dar. Daran anknüpfend werden als Praxisbeispiele zur Weiterqualifizierung ein Master-Fernstudiengang für Schulmanagement sowie ein in weiterer Entwicklung befindliches digitales Leadership-Training für Schulentwicklung vorgestellt. Letzteres fokussiert insbesondere die Förderung emotionaler und transformationaler Führungskompetenzen, welche wesentlich dazu beitragen können, inspirierend zu motivieren, kollegiale Beziehungen gewinnbringend zu gestalten und adäquat durch inklusive Schulentwicklungsprozesse zu begleiten.
Tailoring of spin state energetics of transition metal complexes and even the correct prediction of the resulting spin state is still a challenging task, both for the experimentalist and the theoretician. Apart from the complexity in the solid state imposed by packing effects, molecular factors of the spin state ordering are required to be identified and quantified on equal rights. In this work we experimentally record the spin states and SCO energies within an eight-member substitution-series of N4O2 ligated iron(II) complexes both in the solid state (SQUID magnetometry and single-crystal X-ray crystallography) and in solution (VT-NMR). The experimental survey is complemented
by exhaustive theoretical modelling of the molecular and electronic structure of the open-chain N4O2 family and its macrocyclic N6 congeners through density-functional theory methods. Ligand topology is identified as the leading factor defining ground-state multiplicity of the corresponding iron(II) complexes. Invariably the low-spin state is sterically trapped in the macrocycles, whereas subtle substitution effects allow for a molecular fine tuning of the spin state in the open-chain ligands. Factorization of computed relative SCO energies holds promise for directed design of future SCO systems.
Simple Summary
The interaction between tumors and immune cells influences tumor fate, i.e., regression, growth, or even metastases. The evaluation of tumor infiltrating lymphocytes (TILs) in human breast cancer has prognostic value. Pet rabbits develop spontaneous mammary carcinomas and have an immune system that is comparable with that of humans, so that they have the potential to provide an animal model for human breast cancer. To further substantiate this similarity, this study examined TILs in 107 pet rabbit mammary carcinomas according to criteria established for human breast cancer. For TIL evaluation routinely stained microscopic sections were examined by light microscopy. Relevant histological and immunohistochemical tumor characteristics were obtained from a data base. Results showed that increased presence of stromal TILs was statistically associated with histological tumor features indicative of a less aggressive biological behavior, i.e., reduced tumor cell proliferation and a lower histological grade. The expression by tumor cells of calponin, a presumed tumor suppressor protein, was also associated with their reduced proliferation and a higher percentage of stromal TILs. Data suggest that higher percentages of stromal TILs may have the potential to serve as favorable prognostic indicator in rabbit mammary carcinomas and support the value of pet rabbits for comparative research.
Abstract
Tumor infiltrating lymphocytes (TILs) serve as prognostic biomarker in human breast cancer. Rabbits have the potential to act as animal model for human breast cancer, and close similarities exist between the rabbit and human immune system. The aim of this study is to characterize TILs in pet rabbit mammary carcinomas and to statistically correlate results with histological and immunohistochemical tumor characteristics. Microscopic evaluation of TILs was performed in hematoxylin and eosin stained sections of 107 rabbit mammary carcinomas according to international guidelines for human breast cancer. Data on histological features of malignancy, estrogen and progesterone receptor status and calponin expression were obtained from the data base. This study revealed a statistical association between stromal TILs in the central tumor (CT) and infiltrative margin. Higher maximal percentages of stromal TILs at the CT were statistically correlated with decreased mitotic count and lower tumor grade. An increased number of calponin positive tumor cells was statistically associated with a lower mitotic count and a higher percentage of stromal TILs. Results suggest that higher percentages of stromal TILs are useful biomarkers that may point toward a favorable prognosis in rabbit mammary carcinomas and support the concept of the use of rabbits for translational research
The hidden burden of severe asthma: from patient perspective to new opportunities for clinicians
(2020)
Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the “International Course on Severe Asthma” that took place in Palermo, Italy, on May 10–11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient’s needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach.
Die Sicherstellung der hausärztlichen Versorgung ist vor allem im ländlichen Raum mit regional unterschiedlich starker Ausprägung zunehmend gefährdet. Ein wesentlicher Grund liegt in der stetig sinkenden Zahl an hausärztlich tätigen Ärzten/innen. Ursächlich hierfür sind einerseits die hohen „Bruttoabgänge“ von Hausärzten/innen, zumeist aufgrund altersbedingten Ausscheidens, und einem andererseits eklatanten Nachwuchsproblem.
Um dieser problematischen Entwicklung entgegenzuwirken, kommt der Gewinnung hausärztlichen Nachwuchses eine Schlüsselrolle zu. In Flächenländern wie Australien, Kanada oder den USA, die ähnlichen Herausforderungen schon seit längerer Zeit gegenüberstehen, existieren seit den 1970er Jahren universitäre Schwerpunktprogramme, die die Allgemeinmedizin bereits in der medizinischen Ausbildung fördern. Breit angelegte Evaluationsstudien zeigen dabei, dass die Teilnahme an longitudinalen Längsschnittcurricula einen positiven Effekt auf die Wahrscheinlichkeit hat, nach Abschluss des Studiums eine Weiterbildung im Fach Allgemeinmedizin aufzunehmen und sich darüber hinaus hausärztlich (im ländlichen Raum) niederzulassen.
Unter der Annahme, dass eine allgemeinmedizinische Schwerpunktsetzung im Studium das Interesse am selbigen Fach erhöht und darüber hinaus eine hausärztliche Karriereplanung positiv beeinflusst, soll die hier vorliegende Promotionsarbeit folgende Forschungsfrage beantworten: Wie kann ein longitudinales, fachbereichsweites Lehrangebot konzeptionell gestaltet werden, welches es Medizinstudierenden ermöglicht, Allgemeinmedizin im ländlichen Raum kennenzulernen?
Zur Beantwortung der Fragestellung wurde ein triangulierender Forschungsansatz gewählt, der aus mehreren Arbeitsschritten besteht: 1. Erarbeitung einer Übersichtarbeit bestehend aus einer Literaturrecherche und der Kontaktaufnahme zu hiesigen Experten, 2. schriftliche und telefonische Befragung aller medizinischen Fakultäten Deutschlands 3. webbasierte Befragung von Medizinstudierenden der Goethe Universität, Frankfurt, 4. konzeptionelle Entwicklung und Implementierung eines universitären Schwerpunktprogramms zur Förderung der Allgemeinmedizin in ländlichen Regionen auf Basis der in Schritt eins bis drei gewonnen Ergebnisse.
Mittels der verschiedenen methodischen Entwicklungsschritte konnte im Zeitraum von 2015 bis 2016 das longitudinale Schwerpunktprogramm „Landpartie 2.0“ konzeptionell entwickelt und ab dem Wintersemester 2016/2017 in das Medizinstudium der Goethe-Universität, Frankfurt am Main, implementiert werden.
Das entwickelte Lehrangebote richtet sich pro Jahr in der Regel an bis zu 15 Studierende ab dem klinischen Studienabschnitt. Im Kern beinhaltet das mehrsemestrige Angebot wiederkehrende Praxisphasen in ausgewählten und geschulten Hausarztpraxen in ländlichen Regionen. Begleitet werden die Praktika von vor- und nachbereitenden Seminaren an der Universität, dem Kurs Allgemeinmedizin in einer ländlichen Hausarztpraxis und einem jährlichen Tagesausflug zu innovativen Gesundheitsmodellen. Seit Einführung des Programms konnten 62 Studierende in die „Landpartie 2.0“ aufgenommen werden.
Erste Evaluationsergebnisse belegen eine sehr hohe Zufriedenheit mit den einzelnen Programmbestandteilen unter den Teilnehmenden. Langfristig sollen darüber hinaus in einer Verbleibstudie Effekte auf die Motivation für eine hausärztliche Tätigkeit (auf dem Land) sowie Karriereverläufe abgebildet werden.
Insgesamt erwies sich das gewählte methodische Vorgehen als zielführend. Mittels der einzelnen Entwicklungsschritte konnte ein abgestimmtes, umfassendes und den wissenschaftlichen Erkenntnissen berücksichtigendes Längsschnittcurriculum am Fachbereich Medizin der Goethe Universität, Frankfurt am Main, erfolgreich konzeptioniert und implementiert werden.
Obstructive Sleep Apnea is emerging as a global health epidemic, particularly due to the obesity pandemic. However, comprehensive prevalence data are still lacking and global OSA research has not yet been structurally evaluated. Using the latest comprehensive age/gender-specific BMI and obesity data, a global landscape estimating the risk/burden of OSA was created. Results were presented in relation to an in-depth analysis of OSA research and countries’ socioeconomic/scientific background. While the USA, Canada, and Japan are the highest publishing countries on OSA, Iceland, Greece, and Israel appeared at the forefront when relating the scientific output to socioeconomic parameters. Conversely, China, India, and Russia showed relatively low performances in these relations. Analysis of the estimated population at risk (EPR) of OSA showed the USA, China, India, and Brazil as the leading countries. Although the EPR and OSA research correlated strongly, major regional discrepancies between the estimated demand and actual research performances were identified, mainly in, but not limited to, developing nations. Our study highlights regional challenges/imbalances in the global activity on OSA and allows targeted measures to mitigate the burden of undiagnosed/untreated OSA. Furthermore, the inclusion of disadvantaged countries in international collaborations could stimulate local research efforts and provide valuable insights into the regional epidemiology of OSA.
Background: The feedback given to students plays an important role in their efficiency related to learning practical skills. In the present study, diverse feedback modalities have been investigated. Our hypothesis is that individualized and unsupervised video feedback can produce a similar learning experience as performing practical skills in an oral and maxillofacial surgery setting with conventional direct expert feedback (control group).
Methods: This prospective, randomized, controlled, and blinded study compared direct expert feedback (DEF), individualized video feedback (IVF) and unsupervised video feedback (UVF). The participants were fourth-year dental students from University Goethe in Frankfurt. The students were assigned to one of the three feedback methods (n = 20 per group) using simple randomization. All participants watched an instruction video for an interdental (‘Ernst’) ligature and periphery venous catheterization. Next, the students were video recorded performing the tasks by themselves (pre-test). Following this, every student received feedback using one of the above-mentioned feedback modalities. The participants then performed the same task again while being video recorded (post-test) to measure the acquired competence. Six weeks later, the students participated in an objective structured clinical examination (OSCE) to evaluate their long-term knowledge retention. All examiners were blinded regarding the students’ instructional approach and their affiliation in terms of the learning group.
Results: For the interdental ligature, we found significant improvements in performance in each feedback modality group between the pre-test and post-test (p < 0.001). UVF had the strongest effect on performance time. The comparison between each group in the post-test showed no significant differences between the three groups.
Conclusion: This study showed that IVF and UVF can be considered an alternative or adjunct to conventional methods (i.e. DEF) when learning procedural skills in oral and maxillofacial surgery. However, DEF showed to be the most effective method of feedback and therefore preferable in teaching.
Background: Recent advances in 3D printing technology have enabled the emergence of new educational and clinical tools for medical professionals. This study provides an exemplary description of the fabrication of 3D‐printed individualised patient models and assesses their educational value compared to cadaveric models in oral and maxillofacial surgery.
Methods: A single‐stage, controlled cohort study was conducted within the context of a curricular course. A patient's CT scan was segmented into a stereolithographic model and then printed using a fused filament 3D printer. These individualised patient models were implemented and compared against cadaveric models in a curricular oral surgery hands‐on course. Students evaluated both models using a validated questionnaire. Additionally, a cost analysis for both models was carried out. P‐values were calculated using the Mann‐Whitney U test.
Results: Thirty‐eight fourth‐year dental students participated in the study. Overall, significant differences between the two models were found in the student assessment. Whilst the cadaveric models achieved better results in the haptic feedback of the soft tissue, the 3D‐printed individualised patient models were regarded significantly more realistic with regard to the anatomical correctness, the degree of freedom of movement and the operative simulation. At 3.46 € (compared to 6.51 €), the 3D‐printed patient individualised models were exceptionally cost‐efficient.
Conclusions: 3D‐printed patient individualised models presented a realistic alternative to cadaveric models in the undergraduate training of operational skills in oral and maxillofacial surgery. Whilst the 3D‐printed individualised patient models received positive feedback from students, some aspects of the model leave room for improvement.
Purpose: To investigate cortical thickness and cortical quantitative T2 values as imaging markers of microstructural tissue damage in patients with unilateral high-grade internal carotid artery occlusive disease (ICAOD).
Methods: A total of 22 patients with ≥70% stenosis (mean age 64.8 years) and 20 older healthy control subjects (mean age 70.8 years) underwent structural magnetic resonance imaging (MRI) and high-resolution quantitative (q)T2 mapping. Generalized linear mixed models (GLMM) controlling for age and white matter lesion volume were employed to investigate the effect of ICAOD on imaging parameters of cortical microstructural integrity in multivariate analyses.
Results: There was a significant main effect (p < 0.05) of the group (patients/controls) on both cortical thickness and cortical qT2 values with cortical thinning and increased cortical qT2 in patients compared to controls, irrespective of the hemisphere. The presence of upstream carotid stenosis had a significant main effect on cortical qT2 values (p = 0.01) leading to increased qT2 in the poststenotic hemisphere, which was not found for cortical thickness. The GLMM showed that in general cortical thickness was decreased and cortical qT2 values were increased with increasing age (p < 0.05).
Conclusion: Unilateral high-grade carotid occlusive disease is associated with widespread cortical thinning and prolongation of cortical qT2, presumably reflecting hypoperfusion-related microstructural cortical damage similar to accelerated aging of the cerebral cortex. Cortical thinning and increase of cortical qT2 seem to reflect different aspects and different pathophysiological states of cortical degeneration. Quantitative T2 mapping might be a sensitive imaging biomarker for early cortical microstructural damage.
Rational agency is of central interest to philosophy, with evolutionary accounts of the cognitive underpinnings of rational agency being much debated. Yet one building block—our ability to argue—is less studied, except Mercier and Sperber’s argumentative theory (Mercier and Sperber in Behav Brain Sci 34(02):57–74, https://doi.org/10.1017/s0140525x10000968 [Titel anhand dieser DOI in Citavi-Projekt übernehmen] , 2011, in The enigma of reason. Harvard University Press, Cambridge, 2017). I discuss their account and argue that it faces a lacuna: It cannot explain the origin of argumentation as a series of small steps that reveal how hominins with baseline abilities of the trait in question could turn into full-blown owners of it. This paper then provides a first sketch of the desired evolutionary trajectory. I argue that reasoning coevolves with the ability to coordinate behavior. After that, I establish a model based on niche construction theory. This model yields a story with following claims. First, argumentation came into being during the Oldowan period as a tool for justifying information ‘out of sight’. Second, argumentation enabled hominins to solve collective action problems with collaborators out of sight, which stabilized argumentative practices eventually. Archeological findings are discussed to substantiate both claims. I conclude with outlining changes resultant from my model for the concept of rational agency.
Explaining humans as rational creatures—capable of deductive reasoning—remains challenging for evolutionary naturalism. Schechter (Philosophical Perspectives, 24(1)437–464, 2011, 2013) proposes to link the evolution of this kind of reasoning with the ability to plan. His proposal, however, does neither include any elaborated theory on how logical abilities came into being within the hominin lineage nor is it sufficiently supported by empirical evidence. I present such a theory in broad outline and substantiate it with archeological findings. It is argued that the cognitive makeup of any animal is constituted by being embedded in a certain way of life. Changing ways of life thus foster appearances of new cognitive abilities. Finally, a new way of life of coordinated group behavior emerged within the hominins: anticipatory group planning involved in activities like making sophisticated spears for hunting. This gave rise to human logical cognition. It turned hominins into domain-general reasoner and adherents of intersubjective norms for reasoning. However, as I argue, it did not—and most likely could not—give rise to reason by deductive logic. More likely, deductive reasoning entered our world only a few thousand years ago: exclusively as a cultural artifact.
Introns of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers independently of CLP1. Splice site recognition involves the mature domain and the anticodon-intron base pair of pre-tRNAs. The 2.1-Å resolution X-ray crystal structure of a TSEN15–34 heterodimer and differential scanning fluorimetry analyses show that PCH mutations cause thermal destabilization. While endonuclease activity in recombinant mutant TSEN is unaltered, we observe assembly defects and reduced pre-tRNA cleavage activity resulting in an imbalanced pre-tRNA pool in PCH patient-derived fibroblasts. Our work defines the molecular principles of intron excision in humans and provides evidence that modulation of TSEN stability may contribute to PCH phenotypes.
Purpose: In this study, we examined distress levels and quality of life (QoL) of patients with hematologic malignancies under treatment in an acute setting. We used external- and self-assessment instruments for distress. Additionally, we investigated the relation between distress and QoL as well as whether highly distressed patients differed from less distressed patients concerning their QoL.
Methods: A cross-sectional study with patients of the Medical Clinic II of the University Hospital Frankfurt was conducted. One hundred and nine patients were assessed with an expert rating scale and completed self-report questionnaires. Data were exploratively analyzed and group comparisons between patients who scored above the cut-off of the respective screening instruments and those who did not were conducted.
Results: Patients with hematologic malignancies experience high levels of distress and low QoL. Especially, role and social functioning are affected. Patients suffer most from fatigue, appetite loss, and insomnia. Using established cut-offs, all screening instruments were able to differentiate between patients regarding distress and QoL. Patients scoring above the cut-off were significantly more distressed and had a lower QoL. There was a medium-to-strong correlation between distress and QoL indicators.
Conclusion: Cancer-specific screening instruments seem to be able to identify treatment needs more specifically. They also allowed a better differentiation concerning QoL. The close link between distress and QoL needs to be recognized to enable a holistic approach to treatment and thereby optimize the quality of treatment.
Objective: To explore and describe exposure to suicidality in healthcare providers (HCP) working with oncological patients. Special emphasis was put on five central aspects from the HCPs perspective: Exposure, Confidence, Expertise, Distress, and Education.
Methods: A 48‐item online questionnaire was developed and distributed to HCPs working with cancer patients. Three hundred fifty‐four answered questionnaires were analyzed.
Results: Overall 83.3% of HCPs reported to have encountered at least one suicidal patient in the last year. Feeling confident in talking about suicidality was reported by 72.1% of HCPs, with 71.2% of nurses reporting feeling insecure compared with only 5.1% of psychotherapists. Similarly, 22.3% of HCPs felt overwhelmed when confronted with a patient who substantiated his suicidality during consultation. A lack of personal knowledge concerning suicidality in general and in oncological patients in particular, was reported by 39.6% and 49.8%, respectively. In total, 88.1% of HCPs reported feeling distressed when confronted with suicidality, while 81.1% of participants wanted further education regarding suicidality in cancer patients despite that 73.2% had already received some sort of psycho‐oncology education.
Conclusions: Despite the well‐documented fact of elevated suicide rates in cancer patients, there remain deficits in knowledge, which induce feelings of insecurity and helplessness in HCPs. There is a demand for further education concerning the treatment of suicidal cancer patients. Therefore, special curricula addressing this topic should be devised. A general debate about suicidality in cancer patients could help raise awareness of this problem and generate means of prevention.
Background: With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas.
Methods: We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients’ professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires.
Results: We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21–63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11–82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2–22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p < .001). Multivariable regression analysis showed that patient age < 40 years as well as occupational group and self-reported fatigue were factors independently associated with the ability to return to work.
Conclusion: The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.
In dieser Arbeit wurde der spezifische Energieverlust im TOF Detektor genutzt, um leichte Kerne zu identifizieren. Da die gemeinsame Betrachtung aller Szintillatorstäbe bei der aktuellen Kalibrierung des TOF Detektors keine eindeutige Zuordnung ermöglicht, wurde der Energieverlust der einzelnen Stäbe individuell parametrisiert. So konnten Helium und sogar Lithium Kerne selektiert werden. Die Impulskorrektur hat für zweifach geladene Kerne, abgesehen von sehr hohen Impulsen, eine erfolgreiche Korrektur der Masse ermöglicht. Bei Lithium hingegen wurde der Impuls überkorrigiert, sodass die Masse zu niedrig rekonstruiert wurde.
Durch Optimierung der Impulskorrektur könnte zusammen mit einer verbesserten Kalibrierung des TOF Detektors ein sehr hohes Auflösungsvermögen erreicht werden. Daher sollte die systematische Impulskorrektur für hohe Impulse durch weitere Simulationen verbessert und der Energieverlust vor dem Auftreffen auf den META Detektor genauer untersucht werden. Optimalerweise würde zur Kalibrierung des TOF Detektors die Abhängigkeit des Energieverlustes vom Winkel, in welchem die Teilchen auf den Detektor treffen, berücksichtigt werden. Ziel ist es, alle Stäbe pro zurückgelegter Wegstrecke zu kalibrieren, sodass weder ein Unterschied durch den Einfallwinkel der Teilchen noch durch die verschiedenen Stablängen aufkommt. Folglich wäre eine sehr spezifische Teilchenselektion möglich.
In this thesis different descriptions for the non-Abelian Landau-Pomeranchuk-Migdal (LPM) effect are studied within the partonic transport approach BAMPS (Boltzmann Approach to Multi-Parton Scatterings), which numerically solves the 3+1-dimensional Boltzmann equation for massless partons based on elastic and radiative interactions calculated in perturbative quantum chromodynamics.
The LPM effect is a coherence effect originating from the finite formation time of gluon emissions leading to characteristic dependencies of the radiative energy loss of energetic partonic projectiles, as e.g. jets in ultra-relativistic heavy-ion collisions.
Due to this non-locality of interactions, such coherence effects are difficult to describe rigorously in transport theory.
Therefore we compare in this work three different implementations for the LPM effect: i) a parametric LPM suppression based on a theta function in the radiative matrix elements, ii) a stochastic LPM approach, which explicitly simulates the elastic interactions of gluons during their formation time, and iii) the thermal gluon emission rate from the AMY formalism, which is a hard-thermal-loop calculation exactly considering the non-Abelian LPM effect by resumming ladder diagrams in the large medium limit.
After discussing the numerical implementation of the three approaches, we investigate their consequences in different jet-energy loss scenarios: first the academic scenarios of eikonal and non-eikonal jets flying through a static brick of thermal quark-gluon plasma and then jets traversing the expanding medium of ultra-relativistic heavy-ion collisions at LHC energies.
We can demonstrate that although the different LPM approaches show similarities in the radiative energy loss there are differences in the underlying gluon emission spectra, which originate from the specific treatment of divergences in the matrix elements within BAMPS.
Furthermore, based on the different LPM approaches we present simulation results for recent jet quenching observables from the LHC experiments and discuss properties of the underlying heavy-ion medium.
Replacement of a stenotic aortic valve reduces immediately the ventricular to aortic gradient and is expected to improve diastolic and systolic left ventricular function over the long term. However, the hemodynamic changes immediately after valve implantation are so far poorly understood. Within this pilot study, we performed an invasive pressure volume loop analysis to describe the early hemodynamic changes after transcatheter aortic valve implantation (TAVI) with self-expandable prostheses. Invasive left ventricular pressure volume loop analysis was performed in 8 patients with aortic stenosis (mean 81.3 years) prior and immediately after transfemoral TAVI with a self-expandable valve system (St. Jude Medical Portico Valve). Parameters for global hemodynamics, afterload, contractility and the interaction of the cardiovascular system were analyzed. Left ventricular ejection fraction, (53.9% vs. 44.8%, p = 0.018), preload recruitable stroke work (68.5 vs. 44.8 mmHg, p = 0.012) and end-systolic elastance (3.55 vs. 2.17, p = 0.036) both marker for myocardial contractility declined significantly compared to baseline. As sign of impaired diastolic function, TAU, a preload-independent measure of isovolumic relaxation (37.3 vs. 41.8 ms, p = 0.018) and end-diastolic pressure (13.1 vs. 16.4 mmHg, p = 0.015) raised after valve implantation. Contrarily, a smaller ratio of end-systolic to arterial elastance (ventricular-arterial coupling) indicates an improvement of global cardiovascular energy efficiency (1.40 vs. 0.97 p = 0.036). Arterial elastance had a strong correlation with the number of conducted rapid ventricular pacings (Pearson correlation coefficient, r = 0.772, p = 0.025). Invasive left ventricular pressure volume loop analysis revealed impaired systolic and diastolic function in the early phase after TAVI with self-expandable valve for the treatment of severe aortic stenosis. Contrarily, we found indications for early improvement of global cardiovascular energy efficiency.
Aims: Stroke is a major complication after transcatheter aortic valve implantation (TAVI). Although multifactorial, it remains unknown whether the valve deployment system itself has an impact on the incidence of early stroke. We performed a meta- and network analysis to investigate the 30-day stroke incidence of self-expandable (SEV) and balloon-expandable (BEV) valves after transfemoral TAVI.
Methods and results: Overall, 2723 articles were searched directly comparing the performance of SEV and BEV after transfemoral TAVI, from which 9 were included (3086 patients). Random effects models were used for meta- and network meta-analysis based on a frequentist framework. Thirty-day incidence of stroke was 1.8% in SEV and 3.1% in BEV (risk ratio of 0.62, 95% confidence interval (CI) 0.49–0.80, p = 0.004). Treatment ranking based on network analysis (P-score) revealed CoreValve with the best performance for 30-day stroke incidence (75.2%), whereas SAPIEN had the worst (19.0%). However, network analysis showed no inferiority of SAPIEN compared with CoreValve (odds ratio 2.24, 95% CI 0.70–7.2).
Conclusion: Our analysis indicates higher 30-day stroke incidence after transfemoral TAVI with BEV compared to SEV. We could not find evidence for superiority of a specific valve system. More randomized controlled trials with head-to-head comparison of SEV and BEV are needed to address this open question.
Background: Cerebral O2 saturation (ScO2) reflects cerebral perfusion and can be measured noninvasively by near-infrared spectroscopy (NIRS). Objectives: In this pilot study, we describe the dynamics of ScO2 during TAVI in nonventilated patients and its impact on procedural outcome. Methods and Results: We measured ScO2 of both frontal lobes continuously by NIRS in 50 consecutive analgo-sedated patients undergoing transfemoral TAVI (female 58%, mean age 80.8 years). Compared to baseline ScO2 dropped significantly during RVP (59.3% vs. 53.9%, p < .01). Five minutes after RVP ScO2 values normalized (post RVP 62.6% vs. 53.9% during RVP, p < .01; pre 61.6% vs. post RVP 62.6%, p = .53). Patients with an intraprocedural pathological ScO2 decline of >20% (n = 13) had higher EuroSCORE II (3.42% vs. 5.7%, p = .020) and experienced more often delirium (24% vs. 62%, p = .015) and stroke (0% vs. 23%, p < .01) after TAVI. Multivariable logistic regression revealed higher age and large ScO2 drops as independent risk factors for delirium. Conclusions: During RVP ScO2 significantly declined compared to baseline. A ScO2 decline of >20% is associated with a higher incidence of delirium and stroke and a valid cut-off value to screen for these complications. NIRS measurement during TAVI procedure may be an easy to implement diagnostic tool to detect patients at high risks for cerebrovascular complications and delirium.
Traumatische Verletzungen fordern jährlich über fünf Millionen Todesopfer. Sie sind bei unter 45-Jährigen die häufigste Ursache für Tod und körperliche Behinderung dar. Ein Polytrauma verursacht eine schwere Belastung für das Immunsystem und ist häufig von schweren Störungen der Immunregulation gekennzeichnet. Die Immunreaktion übersteigt bei schweren Traumata das für lokale Reparaturmechanismen notwendige Maß, und so kommt es je nach Ausmaß der Verletzungen innerhalb der ersten Minuten bis Stunden zu einer systemischen Hyperinflammation, dem sogenannten Systemischen Inflammatorischen Response- Syndrom (SIRS). Auch in nicht verletzten Organen verursacht SIRS Störungen in der Endothel-Funktion, wodurch die Mikrozirkulation in diesen Organgen beeinträchtigt ist. In der Folge kommt es zu interstitieller Ödembildung, zur Gewebsinfiltration durch Leukozyten und zu Zelluntergang. Diese Prozesse können zur Fehlfunktion von Organen bis hin zum Organversagen, und, da sie häufig in mehreren Organen gleichzeitig ablaufen, auch zum klinisch dann oft schwer beherrschbaren Multiorganversagen (MOV) führen. Auf der anderen Seite stoßen schwere Verletzungen antiinflammatorische Prozesse an, die zu einer ausgeprägten Immunsuppression führen können, dem Kompensatorischen Antiinflammatorischen Response-Syndrom (CARS), mit der Folge, dass polytraumatisierte Patienten erhöht anfällig für infektiöse Komplikationen sind. Die beschriebenen Funktionsstörungen des Immunsystems sind ein wichtiger Mortalitätsfaktor von polytraumatisierten Patienten. Während wir SIRS und seine Folgen über die letzten Jahre immer besser verstehen, mit signifikanten Fortschritten auch für die klinische Handhabung dieser Komplikationen des Polytraumas, ist CARS weit schlechter untersucht.
Während der post-traumatschen Immunantwort spielen nicht nur Zellen der angeborenen, sondern auch solche der erworbenen Immunabwehr eine wichtige Rolle. So sind regulatorische T-Zellen (Treg) entscheidend an der posttraumatischen Immunsuppression beteiligt. Treg beeinflussen die immunologische Homöostase Treg mit einem Arsenal immunsuppressiver Werkzeuge. Sie töten oder beeinflussen beispielsweise antigenpräsentierende Zellen oder T-Effektorzellen und verändern das Zytokinmilieu und metabolische Signalwege. Nach einem Trauma kann eine überschießende Aktivität von Treg die immunologische Balance so beeinträchtigen, dass eine posttraumatische Immunsuppression entsteht oder intensiviert wird. Die hier vorgestellte Studie Ziel dient daher dem besseren Verständnis der Dynamik von Treg nach einer stattgehabten traumatischen Verletzung. Dafür untersuchten wir die Verläufe verschiedener Subpopulationen von Treg im Blut schwer verletzter Patienten. Da der Forschung am Menschen in vivo enge ethische und methodologische Grenzen gesetzt sind, nehmen Tiermodelle in der Traumaforschung einen hohen Stellenwert ein. Daher verglichen wir die an Patienten erhobenen Daten über die posttraumatische Dynamik von Treg mit den Verläufen in einem adäquaten Tiermodell.
Aufgrund der guten anatomischen, physiologischen und genetischen Ähnlichkeit zum Menschen werden Tiermodelle am Schwein zunehmend beliebter. Ein Polytraumamodell am Schwein existiert erst seit wenigen Jahren. Über Treg wurde in diesem Rahmen bisher nicht geforscht. Die Charakterisierung ihres Immunphänotyps und ihrer Dynamik könnte die Anwendbarkeit des Schweine-Modells für Fragen der Trauma-Forschung verbessern und gleichzeitig unser Verständnis der Pathophysiologie posttraumatischer Komplikationen wir SIRS oder Sepsis erhöhen.
Bei 20 Traumapatienten (TP) mit einem Injury Severity Score (ISS) ≥ 16 wurde bei Ankunft in der Notaufnahme, nach einem und nach drei Tagen venöses Blut entnommen. Zehn gesunde Freiwillige (HV) fungierten in der Studie als Kontrollgruppe. Das Polytrauma im Großtiermodell am Schwein bestand aus einer Femurfraktur, einer Leberlazeration, einer Lungenkontusion und einem hämorrhagischen Schock, was einen ISS von 27 ergab. Auf die Traumainduktion folgte die Reanimationsphase und die chirurgische Versorgung der Femurfraktur nach dem damage-control-Prinzip. Die Blutentnahmen erfolgten bei den Versuchstieren vor und sofort nach Trauma, sowie nach 24 und 72 Stunden. Wir verglichen die Dynamik der Verläufe der Treg von TP mit denen von HV und mit Daten aus den Tierversuchen. Es herrscht noch kein wissenschaftlicher Konsens darüber, welche Kombination aus immunologischen Oberflächenmarkern die Identifikation von Treg zuverlässig gewährleisten kann. Dies liegt auch daran, dass Treg eine Gruppe verschiedener Unterpopulationen darstellen. Folglich analysierten wir verschiedene Kombinationen. Wir färbten Cluster of differentiation (CD) 4-positive und CD25-positive (CD4+CD25+), CD4+CD25+forkhead box P3 (FoxP3)+, CD4+CD25+CD127-negative (CD127−) und CD4+CD25+CD127−FoxP3+ Zellen mit Antikörpern und charakterisierten die jeweilige Gruppe mithilfe der Durchflusszytometrie. CD4+CD25+CD127− Treg sind beim Menschen bekannt. Beim Schwein werden sie in dieser Studie erstmalig beschrieben.
...
Let me start with a reminiscence: a few weeks ago, I was sitting in one of my preferred cafés in Paris, le Café Odéon- Théâtre de l’Europe, a vivid place near the Jardin de Luxembourg in the heart of the university quarter. I realised that the waiter was wearing a shirt with the letters "Defend Paris", which he explained to be a statement against the forces that make Paris an uneasy place to live, a defiance against the powerful and social injustice. With a mixture of rebellion and idealism, he added that he understands himself as part of a "Reclaim Your City" Movement, thus representing what is central for urban citizenship today: a republican defence against forces that make a metropolitan city a trademark to be sold to people who can afford it, but increasingly less a home for ordinary people who want to live in the city. Walking through the streets, passing a small jewelry shop, a place of distinguished understatement showing a picture of Meghan Markle wearing "rose"-earrings displayed in the window, the term "zombie urbanism" came to my mind – a term used by Jonny Aspen, professor at the Institute of Urbanism and Landscape in Oslo (See Bjerkeset and Aspen (forthcoming 2020) and here), to describe a cliché-like way of dealing with urban environment by developers and designers – a "staged urbanism", in which urban features are used as a means for selling, marketing and branding. This kind of city-marketing can prove quite successful: whereas the burning of Notre Dame mobilised hundreds of millions of donations within a short period of time, the burning of the National Museum in Rio de Janeiro soon after, extinguishing 200 years of documentation of cultural memory, mobilised only 225.000 Euros (state 1.4.2019). ...
The weather of the atmospheric boundary layer significantly affects our life on Earth. Thus, a realistic modelling of the atmospheric boundary layer is crucial. Hereby, the processes of the atmospheric boundary layer depend on an accurate representation of the land-atmosphere coupling in the model. In this context the land surface temperature (LST) plays an important role. In this thesis, it is examined if the assimilation of LST can lead to improved estimates of the boundary layer and its processes.
To properly assimilate the LST retrievals, a suitable model equivalent in the weather prediction model is necessary. In the weather forecast model of the German Weather Service used here, the LST is modelled without a vegetation temperature. To compensate for this deficit, two different vegetation parameterizations were investigated and the better one, a conductivity scheme, was implemented. In order to make optimal use of the influence of the assimilation of the LST observation on the model system, it is useful to pass on the information of the observation to land and atmosphere already in the assimilation step. For that reason, a fully coupled land-atmosphere prediction model was used. Therefore, the existing control vector of the assimilation system, a local ensemble transform Kalman filter, was extended by the soil temperature and moisture. In two-day case studies in March and August 2017, different configurations of the augmented assimilation system were evaluated based on observing system simulation experiments (OSSE).
LST was assimilated hourly over two days in the weakly and strongly coupled assimilation system. In addition, every six hours a free 24-hour forecast was simulated. The experiments were validated with the simulated truth (a high-resolution model run) and compared against an experiment without assimilation. It was shown that the prediction of the boundary layer temperature, especially during the day, and the prediction of the soil temperature, during the whole day and night, could be improved.
The best impact of LST assimilation was achieved with the fully coupled system. The humidity variables of the model benefited only partially from the LST assimilation. For this reason, covariances in the model ensemble were investigated in more detail. To check their compatibility with the high-resolution model run the ensemble consistency score was introduced. It was found that the covariances between the LST and the temperatures of the high-resolution model run were better represented in the ensemble than those between the LST and the humidity variables.
A realistic simulation of the atmospheric boundary layer (ABL) depends on an accurate representation of the land–atmosphere coupling. Land surface temperature (LST) plays an important role in this context and the assimilation of LST can lead to improved estimates of the boundary layer and its processes. We assimilated synthetic satellite LST retrievals derived from a nature run as truth into a fully coupled, state‐of‐the‐art land–atmosphere numeric weather prediction model. As assimilation system a local ensemble transform Kalman filter was used and the control vector was augmented by the soil temperature and humidity. To evaluate the concept of the augmented control vector, two‐day case‐studies with different control vector settings were conducted for clear‐sky periods in March and August 2017. These experiments with hourly LST assimilation were validated against the nature run and overall, the RMSE of atmospheric and soil temperature of the first‐guess (and analysis) were reduced. The temperature estimate of the ABL was particularly improved during daytime as was the estimate of the soil temperature during the whole diurnal cycle. The best impact of LST assimilation on the soil and the ABL was achieved with the augmented control vector. Through the coupling between the soil and the atmosphere, the assimilation of LST can have a positive impact on the temperature forecast of the ABL even after 15 hr because of the memory of the soil. These encouraging results motivate further work towards the assimilation of real satellite LST retrievals.
Increases in water demand often result in unsustainable water use, leaving insufficient amounts of water for the environment. Therefore, water-saving strategies have been introduced to the environmental policy agenda in many (semi)-arid regions. As many such interventions failed to reach their objectives, a comprehensive tool is needed to assess them. We introduced a constructive framework to assess the proposed strategies by estimating five key components of the water balance in an area: (1) Demand; (2) Availability; (3) Withdrawal; (4) Depletion and (5) Outflow. The framework was applied to assess the Urmia Lake Restoration Program (ULRP) which aimed to increase the basin outflow to the lake to reach 3.1 × 109 m3 yr−1. Results suggested that ULRP could help to increase the Outflow by up to 57%. However, successful implementation of the ULRP was foreseen to be impeded because of three main reasons: (i) decreasing return flows; (ii) increased Depletion; (iii) the impact of climate change. Decreasing return flows and increasing Depletion were expected due to the introduction of technologies that increase irrigation efficiency, while climate change could decrease future water availability by an estimated 3–15%. We suggest that to reach the intervention target, strategies need to focus on reducing water depletion rather than water withdrawals. The framework can be used to comprehensively assess water-saving strategies, particularly in water-stressed basins.
Der Mensch ist ein emotionales Tier: Gefühle beeinflussen jedes menschliche Verhalten – auch jenes von Wissenschaftler/innen. Meist wird diese Emotionalität im Dienst wissenschaftlicher Objektivität vermieden oder unterdrückt. Dabei hat sie entscheidenden Anteil an Erkenntnisprozessen sowohl in der Generierung von Daten als auch in deren Interpretation und in der Präsentation von Wissensbeständen. Dies gilt ganz besonders für die Primatologie, gerade dort, wo mit unseren nächsten Artverwandten, den anderen Affen, im Feld geforscht wird. Primatologische Erkenntnisse wiederum affizieren ein großes Publikum und können deswegen leicht popularisiert werden. - Diese Open-Access-Publikation untersucht anhand primatologischer Forschungsmemoiren die Form und Funktion von Emotionen, Affekten und Gefühlen in der Feldforschung, die Affektpoetik und Emotionsregime der Primatologie sowie die Rolle, welche Fiktionen für die Reflexion des Verhältnisses von Mensch, Affe und Affekt spielen. Sie stellt damit die Frage nach der Rolle von Emotionalität in der Primatologie als Frage nach den epistemischen, poetologischen und politischen Grundlagen einer gegenwärtigen Leitwissenschaft der Anthropologie.
SARS-CoV-2 and stroke characteristics: a report from the Multinational COVID-19 Stroke Study Group
(2020)
Background: Stroke is reported as a consequence of SARS-CoV-2 infection. However, there is a lack of regarding comprehensive stroke phenotype and characteristics
Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke (AIS), intracranial hemorrhage (ICH), and cerebral venous or sinus thrombosis (CVST) among SARS-CoV-2 infected patients. We further investigated the association of demographics, clinical data, geographical regions, and countries’ health expenditure among AIS patients with the risk of large vessel occlusion (LVO), stroke severity as measured by National Institute of Health stroke scale (NIHSS), and stroke subtype as measured by the TOAST criteria. Additionally, we applied unsupervised machine learning algorithms to uncover possible similarities among stroke patients.
Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least one eligible stroke patient. Out of 432 patients included, 323(74.8%) had AIS, 91(21.1%) ICH, and 18(4.2%) CVST. Among 23 patients with subarachnoid hemorrhage, 16(69.5%) had no evidence of aneurysm. A total of 183(42.4%) patients were women, 104(24.1%) patients were younger than 55 years, and 105(24.4%) patients had no identifiable vascular risk factors. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144(37.8%) presented to the hospital with chief complaints of stroke-related symptoms, with asymptomatic or undiagnosed SARS-CoV-2 infection. Among AIS patients 44.5% had LVO; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median NIHSS (8[3-17], versus 11 [5-17]; p=0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; p<0.001) in countries with middle to high-health expenditure when compared to countries with lower health expenditure. The unsupervised machine learning identified 4 subgroups, with a relatively large group with no or limited comorbidities.
Conclusions: We observed a relatively high number of young, and asymptomatic SARS-CoV-2 infections among stroke patients. Traditional vascular risk factors were absent among a relatively large cohort of patients. Among hospitalized patients, the stroke severity was lower and rate of mechanical thrombectomy was higher among countries with middle to high-health expenditure.
While the liver, specifically hepatocytes, are widely accepted as the main source for hepatitis C virus (HCV) production, the role of the liver/hepatocytes in the clearance of circulating HCV remains largely unknown. Here we evaluated the function of the liver/hepatocytes in clearing virus from the circulation by investigating viral clearance during liver transplantation and from culture medium in vitro. Frequent HCV kinetic data during liver transplantation were recorded from 5 individuals throughout the anhepatic (AH) phase and for 4 hours after reperfusion (RP), along with recordings of fluid balances. Using mathematical modeling, the serum viral clearance rate, c, was estimated. Analogously, we monitored the clearance rate of HCV at 37°C from culture medium in vitro in the absence and presence of chronically infected Huh7 human hepatoma cells. During the AH phase, in 3 transplant cases viral levels remained at pre-AH levels, while in the other 2 cases HCV declined (half-life, t1/2~1h). Immediately post-RP, virus declined in a biphasic manner in Cases 1-4 consisting of an extremely rapid (median t1/2=5min) decline followed by a slower decline (HCV t1/2=67min). In Case 5, HCV remained at the same level post-RP as at the end of AH. Declines in virus level were not explained by adjusting for dilution from IV fluid and blood products. Consistent with what was observed in the majority of patients in the anhepatic phase, the t1/2 of HCV in cell culture was much longer in the absence of chronically HCV-infected Huh7 cells. Therefore, kinetic and modeling results from both in vivo liver transplantation cases and in vitro cell culture studies suggest that the liver plays a major role in clearing HCV from the circulation.
Background: The prevalence of multimorbidity is increasing in recent years, and patients with multimorbidity often have a decrease in quality of life and require more health care. The aim of this study was to explore the evolution of multimorbidity taking the sequence of diseases into consideration.
Methods: We used a Belgian database collected by extracting coded parameters and more than 100 chronic conditions from the Electronic Health Records of general practitioners to study patients older than 40 years with multiple diagnoses between 1991 and 2015 (N = 65 939). We applied Markov chains to estimate the probability of developing another condition in the next state after a diagnosis. The results of Weighted Association Rule Mining (WARM) allow us to show strong associations among multiple conditions.
Results: About 66.9% of the selected patients had multimorbidity. Conditions with high prevalence, such as hypertension and depressive disorder, were likely to occur after the diagnosis of most conditions. Patterns in several disease groups were apparent based on the results of both Markov chain and WARM, such as musculoskeletal diseases and psychological diseases. Psychological diseases were frequently followed by irritable bowel syndrome.
Conclusions: Our study used Markov chains and WARM for the first time to provide a comprehensive view of the relations among 103 chronic conditions, taking sequential chronology into consideration. Some strong associations among specific conditions were detected and the results were consistent with current knowledge in literature, meaning the approaches were valid to be used on larger data sets, such as National Health care Systems or private insurers.
The extensive scholarship devoted to the congruence of mass-elite policy preferences lacks consensus about the meaning, comparison, and measurement across political settings. This makes comparisons difficult and raises obstacles to advancing the debates. This symposium aims to identify the diversity of methodological choices and to reflect systematically on several key choices of particular importance in understanding the congruence. The contributions to the symposium compare and contrast how several types of measurement fare in diverse political contexts in Eastern Europe, Latin America, North Africa, and East Asia, and what we can learn from those methodological choices.
Auf das richtige Maß kommt es an : wie beeinflussen digitale Medien unser Denken und Handeln?
(2020)
Welchen Einfluss haben digitale Technologien auf das menschliche Wahrnehmen, Denken und Handeln? Schaden Computerspiele der Entwicklung junger Gehirne? Und gibt es tatsächlich so etwas wie eine »digitale Demenz«, eine durch die Nutzung moderner Technologien bedingte wachsende Vergesslichkeit? Auf einige dieser Fragen gibt es bereits Antworten, die empirisch belegt sind.
A question of striking the right balance : how do digital media influence how we think and act?
(2020)
What influence do digital technologies have on human perception, thinking and action? Do computer games harm the development of young brains? And is there really such a thing as »digital dementia«, an increasing forgetfulness caused by the use of modern technologies? For some of these questions, answers are available that are empirically corroborated.
The requirement of the versatile signal generator has always been evident in modern RF and communication systems. The most conventional technique, voltage control oscillator (VCO), has inferior phase noise and narrow bandwidth despite its operating frequency can be up to the sub-THz regime. Its phase noise influenced by a various parameter associated with the oscillator circuit e.g. transistor size \& noise, bias current, noise leaking from the bias supply etc. The bandwidth is limited because the input voltage \& the output frequency of the VCO is not strictly linear over the tuning range. The phase noise and SFDR of the VCO output are enhanced by using the phase-lock technique. The phase-locked loop (PLL) uses the feedback system locking the reference frequency set by the VCO. However, the settling time of the PLL is higher due to a feedback control loop. The higher settling time increases the frequency switching time between PLL outputs. IG-oscillators is suitable for multi-GHz range and wide bandwidth application. Signal generation can alos be achieved by the free-electron radiation, optical lasers, Gunn diodes as well and they can operate even at the THz domain. All these signal generators suffer from slow frequency switching, lack of digital controllability, and advance modulation capability even though their frequency of operation is THz regime. Alternatively, the AWG (arbitrary wave generator) can produce a wide range of frequencies with low phase noise, including digital controllability. One of the vital components of the AWG is the direct digital synthesiser (DDS). Generally, it is composed of a phase accumulator, digital to analogue converter, sine mapping circuits and low pass filter. It needs a reference clock that acts as samples of the DDS outputs. Its output frequency can be varied by applying an appropriate digital input code. But high-speed DDS has several limitations; such as low number of output frequency points, lack of phase control unit, high power consumptions etc. This work addresses such limitations.
Purpose: Auditory functional MRI (fMRI) often uses silent inter-volume delays for stimulus presentation. However, maintaining the steady-state of the magnetization usually requires constant delays. Here, a novel acquisition scheme dubbed “pre-Saturated EPI using Multiple delays in Steady-state” (SEPIMS) is proposed, using spin saturation at a fixed delay before each volume to maintain steady-state conditions, independent of previous spin history. This concept allows for variable inter-volume delays and thus for flexible stimulus design in auditory fMRI. The purpose was to compare the signal stability of SEPIMS and conventional sparse EPI (CS-EPI). Methods: The saturation module comprises two non-selective adiabatic saturation pulses. The efficiency of the saturation and its effect on the SEPIMS signal stability is tested in vitro and in vivo. Results: Data show that SEPIMS yields the same signal stability as CS-EPI, even for extreme variations between inter-volume delay durations. However, dual saturation pulses are required to achieve sufficiently high saturation efficiency in compartments with long T1 values. Importantly, spoiler gradient pulses after the EPI readout have to be optimized to avoid eddy-current-induced image distortions. Conclusion: The proposed SEPIMS sequence maintains high signal stability in the presence of variable inter-volume durations, thus allowing for flexible stimulus design.
Simple Summary: Glioblastomas are very malignant and essentially incurable brain tumors. One problem is the extensive penetration of tumor cells into the adjacent normal brain tissue. Thus, the testing of novel drugs requires appropriate tumor models, preferentially avoiding animal studies. This paper describes so-called brain tissue slice tandem-culture systems. They consist of a slice of normal brain tissue and a second layer of tumor tissue. The microscopic analysis of these slice tandem-cultures allows for the simultaneous assessment of single cells invading into the normal brain tissue and the space occupying growth of the total tumor mass. It is shown that the direct application of test drugs onto the slices exerts inhibitory effects on both mechanisms. We thus describe a system mimicking the situation in glioblastoma patients. It reduces animal studies, allows for the direct application of test drugs and the precise quantitation of their inhibitory effects on tumor growth and invasion.
Abstract: Glioblastomas (GBMs) are the most malignant brain tumors and are essentially incurable even after extensive surgery, radiotherapy, and chemotherapy, mainly because of extensive infiltration of tumor cells into the adjacent normal tissue. Thus, the evaluation of novel drugs in malignant glioma treatment requires sophisticated ex vivo models that approach the authentic interplay between tumor and host environment while avoiding extensive in vivo studies in animals. This paper describes the standardized setup of an organotypic brain tissue slice tandem-culture system, comprising of normal brain tissue from adult mice and tumor tissue from human glioblastoma xenografts, and explore its utility for assessing inhibitory effects of test drugs. The microscopic analysis of vertical sections of the slice tandem-cultures allows for the simultaneous assessment of (i) the invasive potential of single cells or cell aggregates and (ii) the space occupying growth of the bulk tumor mass, both contributing to malignant tumor progression. The comparison of tissue slice co-cultures with spheroids vs. tissue slice tandem-cultures using tumor xenograft slices demonstrates advantages of the xenograft tandem approach. The direct and facile application of test drugs is shown to exert inhibitory effects on bulk tumor growth and/or tumor cell invasion, and allows their precise quantitation. In conclusion, we describe a straightforward ex vivo system mimicking the in vivo situation of the tumor mass and the normal brain in GBM patients. It reduces animal studies and allows for the direct and reproducible application of test drugs and the precise quantitation of their effects on the bulk tumor mass and on the tumor’s invasive properties
Background Coronavirus disease 2019 (COVID-19) represents a significant challenge to health care systems around the world. A well-functioning primary care system is crucial in epidemic situations as it plays an important role in the development of a system-wide response.
Methods 2,187 Austrian and German GPs answered an internet suvey on preparedness, testing, staff protection, perception of risk, self-confidence, a decrease in the number of patient contacts, and efforts to control the spread of the virus in the practice during the early phase of the COVID-pandemic (3rd to 30th April).
Results The completion rate of the questionnaire was high (90.9%). GPs gave low ratings to their preparedness for a pandemic, testing of suspected cases and efforts to protect staff. The provision of information to GPs and the perception of risk were rated as moderate. On the other hand, the participants rated their self-confidence, a decrease in patient contacts and their efforts to control the spread of the disease highly.
Conclusion Primary care is an important resource for dealing with a pandemic like COVID-19. The workforce is confident and willing to take an active role, but needs to be provided with the appropriate surrounding conditions. This will require that certain conditions are met.
Registration Trial registration at the German Clinical Trials Register: DRKS00021231
Risk evaluations for agricultural chemicals are necessary to preserve healthy populations of honey bee colonies. Field studies on whole colonies are limited in behavioural research, while results from lab studies allow only restricted conclusions on whole colony impacts. Methods for automated long-term investigations of behaviours within comb cells, such as brood care, were hitherto missing. In the present study, we demonstrate an innovative video method that enables within-cell analysis in honey bee (Apis mellifera) observation hives to detect chronic sublethal neonicotinoid effects of clothianidin (1 and 10 ppb) and thiacloprid (200 ppb) on worker behaviour and development. In May and June, colonies which were fed 10 ppb clothianidin and 200 ppb thiacloprid in syrup over three weeks showed reduced feeding visits and duration throughout various larval development days (LDDs). On LDD 6 (capping day) total feeding duration did not differ between treatments. Behavioural adaptation was exhibited by nurses in the treatment groups in response to retarded larval development by increasing the overall feeding timespan. Using our machine learning algorithm, we demonstrate a novel method for detecting behaviours in an intact hive that can be applied in a versatile manner to conduct impact analyses of chemicals, pests and other stressors.
Perspectives on participation in continuous vocational education training - an interview study
(2020)
In European industrialized countries, a large number of companies in the healthcare, hotel, and catering sectors, as well as in the technology sector, are affected by demographic, political, and technological developments resulting in a greater need of skilled workers with a simultaneous shortage of skilled workers (CEDEFOP, 2015, 2016). Consequently, employers have to address workers who have not been taken into account such as low-skilled workers, workers returning from a career break, people with a migrant background, older people, and jobseekers and train them, in order to guarantee the professionalization of this workforce (Festing and Harsch, 2018). Continuing vocational education and training (CVET) is seen as an indispensable tool; because CVET has advantages for both employers and employees, it helps to increase the productivity of companies (Barrett and O’Connell, 2001), to prevent the widening of socioeconomic disparities (Dieckhoff, 2007), and to open up career opportunities for the workforce (Rubenson and Desjardins, 2009). However, participation rate on CVET seems to differ, depending on institutional factors (such as sector and size of the company) and individual characteristics (such as qualification level, migration background, age and time of absence from work) (e.g., Rubenson and Desjardins, 2009; Wiseman and Parry, 2017). In contrast to previous research, our study aims to provide a holistic view of reasons for and against CVET, combining the different perspectives of employers and (potential) employees. The analysis of reasons and barriers was carried out based on semi-structured interviews. Fifty-seven employers, 73 employees, and 42 jobseekers (potential employees) from the sectors retail, healthcare and social services, hotels and catering, and technology were interviewed. Results point to considerable differences in the reasons and barriers mentioned by the disadvantaged groups. These differences are particularly significant between employees on the one side and employers, as well as jobseekers, on the other side, while the reasons to attend CVET of jobseekers are more similar to those of employers. The results can be used to tailor CVET more closely to the needs of (potential) employees and thus strengthen both the qualification and career opportunities of (potential) employees and the competitiveness and productivity of companies.
This paper summarizes key elements of the German Federal Constitutional Court’s decision on the European Central Bank’s Public Sector Asset Purchase Programme. It briefly explains how it is possible for the German Court to disagree with the ruling of the Court of Justice of the European Union. Finally, it makes suggestions concerning a practical way forward for the Governing Council of the ECB in light of these developments.
This article studies whether people want to control what information on their own past pro-social behavior is revealed to others. Participants are assigned a color that depends on their past pro-social behavior. They can spend money to manipulate the probability with which their color is revealed to another participant. The data show that participants are more likely to reveal colors with more favorable informational content. This pattern is not found in a control treatment in which colors are randomly assigned, thus revealing nothing about past pro-social behavior. Regression analysis confrms these fndings, also when controlling for past pro-social behavior. These results complement the existing empirical evidence, confrming that people strategically and, therefore, consciously manipulate their social image.
The tremendous diversity of life in the ocean has proven to be a rich source of inspiration for drug discovery, with success rates for marine natural products up to 4 times higher than other naturally derived compounds. Yet the marine biodiscovery pipeline is characterized by chronic underfunding, bottlenecks and, ultimately, untapped potential. For instance, a lack of taxonomic capacity means that, on average, 20 years pass between the discovery of new organisms and the formal publication of scientific names, a prerequisite to proceed with detecting and isolating promising bioactive metabolites. The need for “edge” research that can spur novel lines of discovery and lengthy high-risk drug discovery processes, are poorly matched with research grant cycles. Here we propose five concrete pathways to broaden the biodiscovery pipeline and open the social and economic potential of the ocean genome for global benefit: (1) investing in fundamental research, even when the links to industry are not immediately apparent; (2) cultivating equitable collaborations between academia and industry that share both risks and benefits for these foundational research stages; (3) providing new opportunities for early-career researchers and under-represented groups to engage in high-risk research without risking their careers; (4) sharing data with global networks; and (5) protecting genetic diversity at its source through strong conservation efforts. The treasures of the ocean have provided fundamental breakthroughs in human health and still remain under-utilised for human benefit, yet that potential may be lost if we allow the biodiscovery pipeline to become blocked in a search for quick-fix solutions.
The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.
Safety requirements and the need of low‐migration UV inks have received increasing attention in the packaging industry. Crucial for the development and design of low‐migration UV inkjet inks for migration‐sensitive applications is the polymerization degree. In this study, curing‐behavior of a black, high purity packaging ink (HPP‐ink) was monitored using ATR‐FTIR spectroscopy. UV irradiation of HPP‐ink led to changes in specific absorption bands of the FTIR spectra due to crosslinking reaction of double bonds. Changes in absorptions bands at 1,408 and 1,321 cm−1 permitted the determination of CC conversion of acrylic and vinyl double bond, independently of one another. In addition, a method was developed which allows the investigation of surface‐cure and deep‐cure behavior, separately.
Rodrigues Ridge connects the Réunion hotspot track with the Central Indian Ridge (CIR) and has been suggested to represent the surface expression of a sub-lithospheric flow channel. From global earthquake catalogues, the seismicity in the region has been associated mainly with events related to the fracture zones at the CIR. However, some segments of the CIR appear void of seismic events. Here, we report on the seismicity recorded at a temporary array of 10 seismic stations operating on Rodrigues Island from September 2014 to June 2016. The array analysis was performed in the time domain by time shifting and stacking the complete waveforms. Event distances were estimated based on a 1-D velocity model and the travel time differences between S and P wave arrivals. We detected and located 63 new events that were not reported by the global networks. Most of the events (51) are located off the CIR and can be classified as intraplate earthquakes. Local magnitudes varied between 1.6 and 3.7. Four seismic clusters were observed that occurred to the west of the spreading segment of the CIR. The Rodrigues Ridge appeared to be aseismic during the period of operation. The lack of seismic activity along both Rodrigues Ridge and the sections of the CIR to the east of Rodrigues may be explained by partially molten upper-mantle material, possibly in relation to the proposed material flow between the Réunion plume and the CIR.
Omkāra to Ek Onkāra
(2020)
Background: Persistent pain in breast cancer survivors is common. Psychological and sleep-related factors modulate perception, interpretation and coping with pain and may contribute to the clinical phenotype. The present analysis pursued the hypothesis that breast cancer survivors form subgroups, based on psychological and sleep-related parameters that are relevant to the impact of pain on the patients’ life.
Methods: We analysed 337 women treated for breast cancer, in whom psychological and sleep-related parameters as well as parameters related to pain intensity and interference had been acquired. Data were analysed by using supervised and unsupervised machine-learning techniques (i) to detect patient subgroups based on the pattern of psychological or sleep-related parameters, (ii) to interpret the detected cluster structure and (iii) to relate this data structure to pain interference and impact on life.
Results: Artificial intelligence-based detection of data structure, implemented as self-organizing neuronal maps, identified two different clusters of patients. A smaller cluster (11.5% of the patients) had comparatively lower resilience, more depressive symptoms and lower extraversion than the other patients. In these patients, life-satisfaction, mood, and life in general were comparatively more impeded by persistent pain.
Conclusions: The results support the initial hypothesis that psychological and sleep-related parameter patterns are meaningful for subgrouping patients with respect to how persistent pain after breast cancer treatments interferes with their life. This indicates that management of pain should address more complex features than just pain intensity. Artificial intelligence is a useful tool in the identification of subgroups of patients based on psychological factors.
Although immune checkpoint inhibitors such as anti-PD-1 antibodies have shown remarkable clinical success in many different tumor types, the proportion of patients benefiting from this treatment option remains low. Therefore, there is a need to sensitize tumors for immune checkpoint blockade. In this study two approaches were tested, a chemoimmunotherapy approach combining PD-1 checkpoint blockade with doxorubicin (DOX) chemotherapy, and ablation of the sphingosine-1-phosphate (S1P) receptor (S1PR4) based on the following rationale. Chemotherapy was shown to induce immune paralysis which contributes to tumor relapse, while PD-1 signaling was shown to facilitate the acquisition of chemoresistance. Thus, combinatorial chemoimmunotherapy is expected to be beneficial by maintaining or even activating anti-tumor immunity during chemotherapy. S1PR4 is an immune cell specific receptor, whose ablation slowed tumor progression by activating anti-tumor immunity in a mouse model that was previously insensitive to anti-PD-1 monotherapy. This suggested that S1PR4 ablation might pre-activate immunity to sensitize for anti-PD-1 therapy.
To test these combinatorial approaches, two tumor mouse models were employed, namely the MC38 murine adenocarcinoma model as well as the transgenic polyoma middle T oncogene (PyMT) breast cancer model. In the MC38 model, a mild synergistic effect of PD-1 immune checkpoint blockade and S1PR4 ablation was observed, indicated by improved tumor progression and survival as compared to the WT control, and an increased number of tumor-free mice compared to anti-PD-1 therapy alone in WT mice. These observations correlated with an enhanced natural killer (NK) cell infiltrate and increased CXCL9 and CXCL10 production in anti-PD-1 treated S1PR4 KO tumors. As noted before, the PyMT model was largely resistant to anti-PD-1 monotherapy in a therapeutic setting. S1PR4 ablation alone showed significant tumor reduction that was not further enhanced by anti-PD-1 treatment. The same was observed when chemotherapy with DOX was added, where WT tumors relapsed, while S1PR4 KO tumor did not. Addition of anti-PD-1 did only mildly increase tumor control in S1PR4 KO mice, indicating that S1PR4 KO per se very efficiently re-activated anti-tumor immunity. Since S1PR4 KO induces type I 12 interferon (IFN-1) over-production in S1PR4 KO PyMT tumors, a link between high IFN-1 levels and tumor immunity was tested by using mice deficient in the IFN-1 receptor (IFNAR1). Unexpectedly, DOX chemotherapy was most efficient in mice with IFNAR ablation only as compared to WT, S1PR4 KO or S1PR4 and IFNAR1 double KO mice, although deficiency in IFNAR signaling is predominantly regarded as tumor promoting. The underlying mechanisms need to be tested in future studies. Interestingly, chemoimmunotherapy in WT mice prevented tumor relapse to a similar extent than S1PR4 KO and was superior to chemotherapy or immune checkpoint blockade alone. To investigate mechanisms of chemoimmunotherapy success compared to monotherapy, whole transcriptome analysis was used, which identified a set of genes that were upregulated specifically upon chemoimmunotherapy. This gene signature and, more specifically, a condensed four-gene signature predicted favorable survival of human mammary carcinoma patients in the METABRIC cohort.
Moreover, PyMT tumors treated with chemoimmunotherapy contained higher levels of cytotoxic lymphocytes, particularly NK cells. Gene set enrichment analysis and ELISA measurements revealed increased IL-27 production and signaling in PyMT tumors upon chemoimmunotherapy. Moreover, IL-27 improved NK cell cytotoxicity against PyMT cells in vitro. These data supported recent clinical observations indicating a benefit of chemoimmunotherapy compared to monotherapy in breast cancer and suggested potential underlying mechanisms.
Taken together the present work revealed new strategies to reactivate tumor immunity leading to improved chemotherapy response, namely a combination with immune checkpoint blockade and ablation of S1PR4, which activated different lymphocyte compartments within tumors.
Despite the success of immune checkpoint blockade in cancer, the number of patients that benefit from this revolutionary treatment option remains low. Therefore, efforts are being undertaken to sensitize tumors for immune checkpoint blockade, which includes combining immune checkpoint blocking agents such as anti-PD-1 antibodies with standard of care treatments. Here we report that a combination of chemotherapy (doxorubicin) and immune checkpoint blockade (anti-PD-1 antibodies) induces superior tumor control compared to chemotherapy and immune checkpoint blockade alone in the murine autochthonous polyoma middle T oncogene-driven (PyMT) mammary tumor model. Using whole transcriptome analysis, we identified a set of genes that were upregulated specifically upon chemoimmunotherapy. This gene signature and, more specifically, a condensed four-gene signature predicted favorable survival of human mammary carcinoma patients in the METABRIC cohort. Moreover, PyMT tumors treated with chemoimmunotherapy contained higher levels of cytotoxic lymphocytes, particularly natural killer cells (NK cells). Gene set enrichment analysis and bead-based ELISA measurements revealed increased IL-27 production and signaling in PyMT tumors upon chemoimmunotherapy. Moreover, IL-27 signaling improved NK cell cytotoxicity against PyMT cells in vitro. Taken together, our data support recent clinical observations indicating a benefit of chemoimmunotherapy compared to monotherapy in breast cancer and suggest potential underlying mechanisms.
Activations with neutrons in the keV energy range were routinely performed at the Karlsruhe Institute of Technology (KIT) in Germany in order to simulate stellar conditions for neutron-capture cross sections. A quasi-Maxwell-Boltzmann neutron spectrum of kT = 25 keV, being of interest for the astrophysical s-process, was produced by the 7Li(p,n) reaction utilizing a 1912 keV proton beam at the Karlsruhe Van de Graaff accelerator. Activated samples resulting in long-lived nuclear reaction products with half-lives in the order of yr 100 Myr were analyzed by Accelerator Mass Spectrometry (AMS). Comparison of the obtained reaction cross sections to literature data from previous Time-of-Flight (ToF) measurements showed that the selected AMS data are systematically lower than the ToF data. To investigate this discrepancy, 54Fe(n,γ)55Fe and 35Cl(n,γ)36Cl reaction cross sections were newly measured at the Frankfurt Neutron Source (FRANZ) in Germany. To complement the existing data, an additional neutron activation of 54Fe and 35Cl at a proton energy of 2 MeV was performed. The results will give implications for the stellar environment at kT = 90 keV, reaching the not yet experimentally explored high-energy s-process range. AMS measurements of the activated samples are scheduled.
Das Ziel dieser Arbeit ist die realitätsgetreue Entwicklung eines interaktiven 3D-Stadtmodells, welches auf den ÖPNV zugeschnitten ist. Dabei soll das Programm anhand von Benutzereingaben und mit Hilfe einer Datenquelle, automatisch eine dreidimensionale Visualisierung der Gebäude erzeugen und den lokalen ÖPNV mitintegrieren. Als Beispiel der Ausarbeitung diente das ÖPNV-Netz der Stadt Frankfurt. Hierbei wurde auf die Problematik der Erhebung von Geoinformationen und der Verarbeitung von solchen komplexen Daten eingegangen. Es wurde ermittelt, welche Nutzergruppen einen Mehrwert durch eine derartige 3D Visualisierung haben und welche neuen Erweiterungs- und Nutzungspotenziale das Modell bietet.
Dem Leser soll insbesondere ein Einblick in die Generierung von interaktiven 3D-Modellen aus reinen Rohdaten verschafft werden. Dazu wurde als Entwicklungsumgebung die Spiele-Engine Unity eingesetzt, welche sich als sehr fähiges und modernes Entwicklungswerkzeug bei der Erstellung von funktionalen 3D-Visualisierungen herausgestellt hat. Als Datenquelle wurde das OpenStreetMap Projekt benutzt und im Rahmen dieser Arbeit behandelt. Anschließend wurde zur Evaluation, das Modell verschiedenen Nutzern bereitgestellt und anhand eines Fragebogens evaluiert.
Im Mittelpunkt der Dissertation steht die Untersuchung der Sprachförderkompetenz von Grundschullehrkräften aus linguistischer Perspektive. Dabei geht es um Grundschullehrkräfte, die in der vorschulischen Sprachförderung, v.a. von Kindern mit Deutsch als früher Zweitsprache (DaZ), im Rahmen sogenannter Vorlaufkurse in Hessen tätig sind. Anhand von zwei zentralen Dimensionen professioneller Kompetenz, dem Wissen und dem Handeln, werden in zwei empirischen Studien anhand einer Gruppe von 10 Lehrkräften der Umfang des sprachlichen Fachwissens und verschiedene Eigenschaften des sprachlichen Handelns in der Interaktion mit DaZ-Kindern im Vorlaufkurs untersucht. Zudem werden mögliche Zusammenhänge zwischen Wissen und Handeln sowie Unterschiede und Gemeinsamkeiten hinsichtlich beider Dimensionen zu pädagogischen Fachkräften aus dem Elementarbereich geprüft.
Macrophages acquire anti-inflammatory and proresolving functions to facilitate resolution of inflammation and promote tissue repair. While alternatively activated macrophages (AAMs), also referred to as M2 macrophages, polarized by type 2 (Th2) cytokines IL-4 or IL-13 contribute to the suppression of inflammatory responses and play a pivotal role in wound healing, contemporaneous exposure to apoptotic cells (ACs) potentiates the expression of anti-inflammatory and tissue repair genes. Given that liver X receptors (LXRs), which coordinate sterol metabolism and immune cell function, play an essential role in the clearance of ACs, we investigated whether LXR activation following engulfment of ACs selectively potentiates the expression of Th2 cytokine-dependent genes in primary human AAMs. We show that AC uptake simultaneously upregulates LXR-dependent, but suppresses SREBP-2-dependent gene expression in macrophages, which are both prevented by inhibiting Niemann–Pick C1 (NPC1)-mediated sterol transport from lysosomes. Concurrently, macrophages accumulate sterol biosynthetic intermediates desmosterol, lathosterol, lanosterol, and dihydrolanosterol but not cholesterol-derived oxysterols. Using global transcriptome analysis, we identify anti-inflammatory and proresolving genes including interleukin-1 receptor antagonist (IL1RN) and arachidonate 15-lipoxygenase (ALOX15) whose expression are selectively potentiated in macrophages upon concomitant exposure to ACs or LXR agonist T0901317 (T09) and Th2 cytokines. We show priming macrophages via LXR activation enhances the cellular capacity to synthesize inflammation-suppressing specialized proresolving mediator (SPM) precursors 15-HETE and 17-HDHA as well as resolvin D5. Silencing LXRα and LXRβ in macrophages attenuates the potentiation of ALOX15 expression by concomitant stimulation of ACs or T09 and IL-13. Collectively, we identify a previously unrecognized mechanism of regulation whereby LXR integrates AC uptake to selectively shape Th2-dependent gene expression in AAMs.
We study the influence of the baryon chemical potential μB on the properties of the Quark–Gluon–Plasma (QGP) in and out-of equilibrium. The description of the QGP in equilibrium is based on the effective propagators and couplings from the Dynamical QuasiParticle Model (DQPM) that is matched to reproduce the equation-of-state of the partonic system above the deconfinement temperature Tc from lattice Quantum Chromodynamics (QCD). We study the transport coefficients such as the ratio of shear viscosity η and bulk viscosity ζ over entropy density s, i.e., η/s and ζ/s in the (T,μ) plane and compare to other model results available at μB=0 . The out-of equilibrium study of the QGP is performed within the Parton–Hadron–String Dynamics (PHSD) transport approach extended in the partonic sector by explicitly calculating the total and differential partonic scattering cross sections based on the DQPM and the evaluated at actual temperature T and baryon chemical potential μB in each individual space-time cell where partonic scattering takes place. The traces of their μB dependences are investigated in different observables for symmetric Au + Au and asymmetric Cu + Au collisions such as rapidity and mT -distributions and directed and elliptic flow coefficients v1,v2 in the energy range 7.7 GeV ≤sNN−−−−√≤200 GeV.
Direct nanoscopic observation of plasma waves in the channel of a graphene field-effect transistor
(2020)
Plasma waves play an important role in many solid-state phenomena and devices. They also become significant in electronic device structures as the operation frequencies of these devices increase. A prominent example is field-effect transistors (FETs), that witness increased attention for application as rectifying detectors and mixers of electromagnetic waves at gigahertz and terahertz frequencies, where they exhibit very good sensitivity even high above the cut-off frequency defined by the carrier transit time. Transport theory predicts that the coupling of radiation at THz frequencies into the channel of an antenna-coupled FET leads to the development of a gated plasma wave, collectively involving the charge carriers of both the two-dimensional electron gas and the gate electrode. In this paper, we present the first direct visualization of these waves. Employing graphene FETs containing a buried gate electrode, we utilize near-field THz nanoscopy at room temperature to directly probe the envelope function of the electric field amplitude on the exposed graphene sheet and the neighboring antenna regions. Mapping of the field distribution documents that wave injection is unidirectional from the source side since the oscillating electrical potentials on the gate and drain are equalized by capacitive shunting. The plasma waves, excited at 2 THz, are overdamped, and their decay time lies in the range of 25-70 fs. Despite this short decay time, the decay length is rather long, i.e., 0.3-0.5 μm, because of the rather large propagation speed of the plasma waves, which is found to lie in the range of 3.5-7 × 106 m/s, in good agreement with theory. The propagation speed depends only weakly on the gate voltage swing and is consistent with the theoretically predicted 1/4 power law.
Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
Ein professioneller Orchestermusiker verbringt die meiste Zeit in körperlich ungünstiger Sitzhaltung beim Spielen. Die Folge ist ein Anstieg des Risikos für die Entwicklung von muskuloskelettalen Beschwerden [44, 127, 128]. Eine Verbesserung der Arbeitsbedingungen lässt sich u.a. durch den Einsatz von ergonomischen Stühlen erzielen, da sie einen Einfluss auf die Körperhaltung des Orchestermusikers besitzen. Im Mittelpunkt der vorliegenden Arbeit standen daher sechs unterschiedliche von der Firma Mey für Orchestermusiker konzipierte Stühle. Die Studie beinhaltete eine Untersuchung des Einflusses der Stühle auf die Oberkörperstatik und die Sitzdruckverteilung von Orchestermusikern und den Einfluss auf ihr Instrumentalspiel im Vergleich zur habituellen Sitzhaltung. Das Probandenkollektiv umfasste 24 Berufsmusiker des Polizeiorchesters Mainz (Rheinland-Pfalz, Deutschland) und bestand zum größten Teil aus Blasinstrumentalisten (3 Frauen, 21 Männer). Das Durchschnittsalter betrug 45 Jahre. Die Überprüfung der Oberkörperstatik erfolgte durch einen 3D-Rückenscanner (ABW GmbH, Frickenhausen, Deutschland), eine Evaluation der Druckverhältnisse im Gesäß durch eine Druckmessmatte (GeBioM GmbH, Münster, Deutschland), womit sich bei jedem Stuhl ein bestimmtes Druckmuster kennzeichnen ließ. Die Messung erfolgte pro Stuhl und Messgerät stets im Wechsel zwischen der statischen Position ohne Instrument (oI) und der statischen Position mit Instrument (mI). Bei der statistischen Auswertung kam es zur Verwendung nicht parametrischer Tests (Friedman-, Wilcoxon Matched- Pairs-Test), wobei das Signifikanzniveau bei ≤0,05 lag. Es erfolgte eine Unterteilung in einen Inter- und einen Intrastuhlvergleich.
Die Ergebnisse des Interstuhlvergleichs zeigten bezüglich der Schulterregion keine signifikanten Veränderungen, wohingegen im Hinblick auf die WS-Parameter Signifikanzen zwischen Stuhl 2 und 5 verzeichnet wurden: in der habituellen Position offenbarte die Rumpflänge D die größte Abweichung mit einem Längenunterschied von 14mm (p≤0,001), so auch die Rumpflänge S (16 mm; p≤0,001). Bezüglich dieser Stühle wiesen die restlichen WS-Parameter Abweichungen von max. 4° bzw. 3mm auf. Zwischen Stuhl 2 und 3 ergaben sich m.I. im Hinblick auf den thorakalen (p≤0,01) und lumbalen Biegungswinkel (p≤0,001) max. Diskrepanzen von 2,5°. Die größten Unterschiede in der Beckenregion zeigten sich beim Beckenabstand zwischen Stuhl 3 und 5 o.I. (7mm) und m.I. (4mm), (beide Bedingungen p≤0,001). Im Hinblick auf die Druckparameter fand sich eine Abhängigkeit zwischen belasteter Fläche und Sitzbeinhöckerdruck (SBH): eine kleine Fläche bedeutete eine schlechte Druckverteilung und umgekehrt. Stühle 1 und 4 besaßen den geringsten SBH (p≤0,001). Im Intrastuhlvergleich zeigten die Bereiche der WS, Schultern und Becken jeweils mindestens einen signifikanten Parameter auf, wie z.B. Schulterblattabstand, sagittale Rumpfneigung und Beckenabstand. Korrelationen zwischen den Parametern waren nicht zu erkennen. M.I. kommt es hinsichtlich des SBH auf der linken Hälfte im Schnitt auf allen Stühlen zu einer Druckerhöhung von 8,46%, auf der rechten zu einer von 11,11%. Im Hinblick auf den Oberschenkeldruck (OS) vollzieht sich die größte Veränderung (7,4bar) der rechten Gesäßhälfte auf Stuhl 2 mit p≤0,001. Der Interstuhlvergleich zeigt also, dass die Wahl eines Stuhls keine Auswirkung auf die Körperhaltung hat. Ursache für Diskrepanzen hinsichtlich des SBH ist die unterschiedliche Polsterung und Größe der Sitzfläche, welche eine hohe Relevanz in Bezug auf die Umverteilung des Drucks und den subjektiven Komfort besitzt. Eine gepolsterte und große Oberfläche ist gleichzusetzen mit einer günstigen Druckverteilung und einem angenehmen individuellen Sitzgefühl. Der Intrastuhlvergleich offenbart ebenfalls keine klinisch relevanten Veränderungen im Oberkörper. Ausschließlich in der Druckverteilung ist eine signifikante Variabilität hinsichtlich des OS rechts bei Stuhl 2 vorhanden (p≤0,001). Die Sitzposition der Probanden ist symmetrisch. Die Symmetrie bezieht sich sowohl auf den Schulter-, WS- und Beckenbereich, als auch auf die Druckverhältnisse im Gesäßbereich.
In der vorliegenden Studie konnte belegt werden, dass gepolsterte und breite Sitzoberflächen mit gleichmäßiger Druckverteilung und gleichzeitig hohem Komfort einhergehen. Im Hinblick auf das Musizieren über einen längeren Zeitraum ist das Vorhandensein eines hohen Komforts für den Orchestermusiker von Bedeutung. Diese Erkenntnisse sind bei der Weiterentwicklung von ergonomischen Stühlen zu berücksichtigen. Eine Analyse der Schulter- und Rumpfmuskulatur und Messung des Beckenwinkels ist in weiteren Studien zusätzlich erforderlich, um zu erforschen, inwieweit die Stühle die Fehlfunktionen des Bewegungsapparates beeinflussen.
Interdisziplinäre Ansätze erhalten in der modernen Medizin immer mehr Bedeutung. Besonders in der Forschung stellen sich viele Themen als zu komplex dar, um nur von Spezialisten erfasst und bearbeitet werden zu können. Dabei werden oft
Verknüpfungen gefunden, die in den evidenzbasierten Kontext eingeordnet, bewertet und in den Praxisalltag implementiert werden müssen. Hierbei sind gegenseitige Einflüsse vom muskuloskelettalen und craniomandibulären System schon lange bekannt aber noch nicht hinreichend systematisch populationsbezogen untersucht.
Ein großer Anteil aktuell verfügbarer Daten über Oberkörperstatik und Okklusion sowie deren Zusammenhänge beruht auf klinischen Erhebungen, die in Zusammenhang von
Diagnostik oder Therapie von Erkrankungen durchgeführt werden.
Normwerte der Oberkörperstatik von gesunden Frauen oder auch Verbindungen zur Okklusion liegen nur für Frauen im Alter von 21-30 Jahren vor, aus diesem Grund war das Ziel dieser Studie diese Interdependenz näher zu betrachten.
Hierzu wurden 101 subjektiv gesunde freiwillige Frauen im Alter von 51-60 (55,16±2,89SD) Jahren untersucht, da zu dieser Altersgruppe keine aussagekräftige Studienlage vorliegt und diese Personengruppe, obwohl sie keinen wachstumsbedingten
Veränderungen unterliegt, weitreichende körperliche Veränderungen im Rahmen der Menopause durchläuft. Es wurden allgemeinanamnestische Daten abgefragt und Wirbelsäulenparameter mittels eines Rückenscanners (backmapper miniRot Kombi, ABW GmbH, Frickenhausen, Deutschland) erhoben, dabei wurden auch Rückenparameter während einer temporären Okklusionssperre mittels Watterollen aufgezeichnet. Zur Durchführung einer Modellanalyse nach Schopf wurden Gipsmodelle der Kiefer angefertigt und vermessen. Mithilfe des Zebris WinJawAnalyzers (Isny, Deutschland) wurde eine axiographische Analyse der Grenzbewegungen der Kiefer
durchgeführt.
Es konnten Normwerte der Oberkörperstatik für die untersuchte Probandinnengruppe erstellt werden. Diese zeigen eine ausbalancierte und nur schwach ausgeprägt asymmetrische Körperhaltung der untersuchten Frauen. Im Vergleich mit Personen anderer Altersgruppen und Geschlechter ergaben sich Unterschiede, die in einen Kontext altersbedingter oder hormoneller Konstitutionsänderungen gesetzt werden konnten.
Eine Untersuchung kurzfristiger, symmetrischer Okklusionsänderung mithilfe von Watterollen im Prämolarenbereich ergab keine Änderung von Parametern der
Wirbelsäule, des Schulter- oder Beckengürtels.
Im Anamnesebogen gesammelte Angaben zu kieferorthopädischer Behandlung, Häufigkeit sportlicher Betätigung, Vorhandensein migräneinduzierter oder anderweitiger Kopfschmerzen und Kiefergelenksgeräuschen ergaben ebenfalls keine signifikanten
Zusammenhänge zur Oberkörperstatik.
Assoziationen bestehen hingegen zwischen modellanalytischen sowie axiographischen Parametern und der Oberkörperstatik. Im Folgenden werden klinisch relevante Wechselbeziehungen aufgeführt:
Bei Betrachtung des Platzangebotes der Stützzonen im Oberkiefer sind die Dornfortsätze der Wirbelkörper bei symmetrischem Platzangebot nach rechts gedreht, wenn jedoch die linke Stützzone ein größeres Platzangebot aufweist als die rechts, so sind die Dornfortsätze eher nach links rotiert.
Im Bereich der Okklusion des linken ersten Molaren wird der Schulterblattabstand und die maximale Rotation der Wirbelkörperdornfortsätze nach rechts tendenziell stärker
wenn der Molar weiter distal okkludiert.
Bei Untersuchung der Protrusion steht bei Hypomobilität des Unterkiefers die linke Schulter cranialer als die rechte, bei Hypermobilität kehrt sich dies jedoch um und die rechte Schulter befindet sich tendenziell in einer höheren Position.
Diese Assoziationen und weitere in dieser Arbeit vorgestellten subklinische Verknüpfungen liefern vielfältige Anhaltspunkte für globale Zusammenhänge zwischen dem craniomandibulären und muskuloskelettalen System. Auf- und Absteigende
Funktionsketten, myofasciale Verbindungen und neuromuskuläre Mechanismen können diesen Ergebnissen zugrunde liegen. Darüber hinaus stellen die hier vorgestellten Messergebnisse Resultate von Momentaufnahmen dar. Deshalb werden zur exakteren Eruierung dieser Ergebnisse zusätzliche Daten zu Verhaltensweisen und Merkmalskombinationen benötigt.
Mithilfe dieser Informationen können dann auch interdisziplinäre Verfahrensweisen der Medizin unterstützt und klinische Therapieansätze verbessert werden. Zum Beispiel
könnten habituell bedingte Fehlbelastungen im Rahmen von craniomandibulären oder spinalen Krankheitsbildern besser verstanden werden und Therapiekonzepte mithilfe von
Orthopäden, Zahnärzten, Physiotherapeuten und Neurologen ausgearbeitet werden.
High-pressure single-crystal to 20 GPa and powder diffraction measurements to 50 GPa, show that the structure of Pb2SnO4 strongly distorts on compression with an elongation of one axis. A structural phase transition occurs between 10 GPa and 12 GPa, with a change of space group from Pbam to Pnam. The resistivity decreases by more than six orders of magnitude when pressure is increased from ambient conditions to 50 GPa. This insulator-to-semiconductor transition is accompanied by a reversible appearance change from transparent to opaque. Density functional theory-based calculations show that at ambient conditions the channels in the structure host the stereochemically-active Pb 6s2 lone electron pairs. On compression the lone electron pairs form bonds between Pb2+ ions. Also provided is an assignment of irreducible representations to the experimentally observed Raman bands.
Digitale Technologien begünstigen den Einsatz einer dynamischen Preisgestaltung, also von Preisen, die für ein prinzipiell gleiches Produkt unangekündigt variieren. Dabei werden in der öffentlichen Diskussion unterschiedliche Ausgestaltungsformen dynamischer Preise oftmals vermischt, was eine sinnvolle Analyse der Vor- und Nachteile der dynamischen Preisgestaltung erschwert. Das Ziel des Beitrags ist die Darstellung der ökonomischen Grundlagen und die Diskussion sowie Klassifikation der Ausgestaltungsmöglichkeiten der dynamischen Preisgestaltung. Darüber hinaus erfolgt eine Bewertung der Vor- und Nachteile der dynamischen Preisgestaltung aus Käufer- und Verkäufersicht. Abschließend werden Implikationen für die betriebswirtschaftliche Forschung diskutiert.
Hintergrund: Die Tiefe Hirnstimulation ist eine etablierte Therapieoption zur Behandlung von Bewegungsstörungen. Um ein möglichst gutes Ansprechen bei geringen Nebenwirkungen zu erreichen, ist eine optimale Platzierung der Stimulationselektrode unverzichtbar. Für die Optimierung der Elektrodenposition wird in vielen Zentren eine Makrostimulation durchgeführt, die jedoch abhängig von der Mitarbeit des Patienten ist und eine Operation im Wachzustand erfordert.
Fragestellung: Ziel dieser Arbeit war es herauszufinden, ob die intraoperativ gemessenen Nebenwirkungsschwellen durch MEP oder Traktographie vorausgesagt werden können und eine Korrelation zur postoperativen Nebenwirkungsschwelle nachgewiesen werden kann.
Methoden: Eingeschlossen wurden die Daten von 42 Patienten, die sich einer Tiefen Hirnstimulation unterzogen hatten. Intraoperativ erfolge neben der Ableitung der Nebenwirkungsschwelle bei der Makrostimulation die Erfassung von MEP. Zusätzlich wurde eine Traktographie zur Darstellung der motorischen Faserbahnen durchgeführt, wobei auch die Daten der nTMS genutzt wurden. Anschließend erfolgte eine Abstandsmessung zwischen der Stimulationselektrode und der motorischen Faserbahn. Wenige Tage postoperativ wurden die Nebenwirkungsschwellen erneut im Rahmen der Ersteinstellung des Neurostimulators erhoben. Die Daten der intraoperativ gemessenen Nebenwirkungsschwelle wurden mit den Daten der MEP-Schwellenwerte, dem Faserbahnabstand und den postoperativen Schwellenwerten mittels einer linearen
Regressionsanalyse korreliert.
Ergebnisse: Eine Korrelation zwischen intraoperativer Nebenwirkungsschwelle und MEP konnte nicht nachgewiesen werden. Es ergab sich ein signifikanter Zusammenhang der Abstände der Stimulationselektrode zur motorischen Faserbahn. Die Korrelation mit den postoperativen Nebenwirkungsschwellen ergab einen signifikanten Zusammenhang.
Schlussfolgerung: Die intraoperativen Nebenwirkungsschwellen konnten durch MEP in dieser Studie nicht vorhergesagt werden. Jedoch kann die Traktographie die Makrostimulation ergänzen. Außerdem sollten die intraoperativ gemessenen Nebenwirkungsschwellen mit Vorsicht betrachtet werden, da diese zu einer Überschätzung des therapeutischen Fensters beitragen können.
Das Thema Datenschutz wird in Zeiten von Internet und künstlicher Intelligenz immer komplexer. Die Entwicklungen scheinen in manchen Bereichen kaum noch beherrschbar zu sein. Nur ein Zusammenspiel von Rechtswissenschaft und Informatik kann den Einzelnen und bestimmte gesellschaftliche Gruppen vor Diskriminierung schützen.
The issue of data security has become increasingly complex in the age of the internet and artificial intelligence. The developments seem to be almost unmanageable in some areas. Cooperation between jurisprudence and information technology is the only thing that can protect the individual and certain social groups from discrimination.
Bevor der Bundesgesundheitsminister mit der Corona-Bewältigung in das Rampenlicht der Öffentlichkeit treten konnte, versuchte er in einer Reihe von Gesetzgebungsvorhaben und Maßnahmen, die deutsche gesetzliche Krankenversicherung (GKV) zu verändern. Eine seiner Maßnahmen war das Digitale-Versorgung-Gesetz, das der Bundestag im Dezember 2019 verabschiedete (DVG, BGBl. I, S. 2562) und die medizinische Versorgung durch Digitalisierung und Innovation verbessern sollte. Es sieht u.a. vor, Gesundheits-Apps auf Rezept zu verschreiben und Videosprechstunden und Telemedizin zum Alltag werden zu lassen. Vor allem aber sollen umfangreiche medizinische Daten der Versicherten in einem Forschungsdatenzentrum zusammengeführt und effektiv ausgewertet werden, um bessere Erkenntnisse in der Gesundheitsforschung zu erlangen.
Dagegen hatte ein Versicherter Beschwerde erhoben, und das Bundesverfassungsgericht hat im Verfahren des einstweiligen Rechtsschutzes entschieden, dass Teile dieses Gesetzes – nämlich §§ 68a Abs. 5 und 303a-303f SGB V – in der Tat erhebliche verfassungsrechtliche Bedenken aufwerfen. Dennoch hat das Gericht den Vollzug dieser Regelungen nicht ausgesetzt (Rn. 6 ff.) und noch nicht einmal die hilfsweise beantragte Reduktion des Datenumgangs angeordnet. Das ist im Ergebnis, vor allem aber in seiner Begründung unter mindestens zwei Aspekten kritisch zu betrachten.
A link between populism and social media is often suspected. This paper spells out a set of possible mechanisms underpinning this link: that social media changes the communication structure of the public sphere, making it harder for citizens to obtain evidence that refutes populist assumptions. By developing a model of the public sphere, four core functions of the public sphere are identified: exposing citizens to diverse information, promoting equality of deliberative opportunity, creating deliberative transparency, and producing common knowledge. A wellworking public sphere allows citizens to learn that there are genuine disagreements among citizens that are held in good faith. Social media makes it harder to gain this insight, opening the door for populist ideology.
We investigate hadronic particle spectra and flow characteristics of heavy-ion reactions in the FAIR/NICA energy range of 1 AGeV ≤ Elab ≤ 10 AGeV within a relativistic ideal hydrodynamic one-fluid approach. The particlization is realized by sampling the Cooper-Frye distribution for a grand canonical hadron gas on a hypersurface of constant energy density. Results of the hydrodynamic calculations for different underlying equations of state are presented and compared with experimental data and microscopic transport simulations. The sensitivity of the approach to physical model inputs concerning the initial state and the particlization is studied.
Virtual reality (VR) headsets offer a large and immersive workspace for displaying visualizations with stereoscopic vision, as compared to traditional environments with monitors or printouts. The controllers for these devices further allow direct three-dimensional interaction with the virtual environment. In this paper, we make use of these advantages to implement a novel multiple and coordinated view (MCV) system in the form of a vertical stack, showing tilted layers of geospatial data. In a formal study based on a use-case from urbanism that requires cross-referencing four layers of geospatial urban data, we compared it against more conventional systems similarly implemented in VR: a simpler grid of layers, and one map that allows for switching between layers. Performance and oculometric analyses showed a slight advantage of the two spatial-multiplexing methods (the grid or the stack) over the temporal multiplexing in blitting. Subgrouping the participants based on their preferences, characteristics, and behavior allowed a more nuanced analysis, allowing us to establish links between e.g., saccadic information, experience with video games, and preferred system. In conclusion, we found that none of the three systems are optimal and a choice of different MCV systems should be provided in order to optimally engage users.
Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of “poised fragments” with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process.
Stuttgart 21 – eine Rekonstruktion der Proteste : Soziale Bewegungen in Zeiten der Postdemokratie
(2020)
Die Konflikte um das Großprojekt »Stuttgart 21« verdeutlichen exemplarisch, wie Protestbewegungen das postdemokratische Zusammenspiel von Staat und Wirtschaft herausfordern. Bürgerbeteiligung und Kostentransparenz sind seither nahezu obligatorisch, dabei hat die Bewegung gegen »S21« ihr eigentliches Ziel, das Bahn- und Immobilienprojekt zu stoppen, verfehlt, trotz scheinbar positiver Ausgangslage. Anhand von Schlüsselereignissen im Konflikt um das Großprojekt rekonstruiert Julia von Staden die Dynamiken und Diskurse einer sozialen Bewegung, die in ihrer Art eine Neuheit in der Protest- und Bewegungsforschung darstellt und gleichzeitig ein Lehrstück für andere soziale Bewegungen wurde.
Neutron-induced fission cross sections of isotopes involved in the nuclear fuel cycle are vital for the design and safe operation of advanced nuclear systems. Such experimental data can also provide additional constraints for the adjustment of nuclear model parameters used in the evaluation process, resulting in the further development of fission models. In the present work, the 237Np(n,f) cross section was studied at the EAR2 vertical beam-line at CERN's n_TOF facility, over a wide range of neutron energies, from meV to MeV, using the time-of-flight technique and a set-up based on Micromegas detectors, in an attempt to provide accurate experimental data. Preliminary results in the 200 keV – 14 MeV neutron energy range as well as the experimental procedure, including a description of the facility and the data handling and analysis, will be presented.
Under the Kigali Amendment to the Montreal Protocol, new controls are being implemented to reduce emissions of HFC-23 (CHF3), a by-product during the manufacture of HCFC-22 (CHClF2). Starting in 2015, China and India, who dominate global HCFC-22 production (75% in 2017), set out ambitious programs to reduce HFC-23 emissions. Here, we estimate that these measures should have seen global emissions drop by 87% between 2014 and 2017. Instead, atmospheric observations show that emissions have increased and in 2018 were higher than at any point in history (15.9 ± 0.9 Gg yr−1). Given the magnitude of the discrepancy between expected and observation-inferred emissions, it is likely that the reported reductions have not fully materialized or there may be substantial unreported production of HCFC-22, resulting in unaccounted-for HFC-23 by-product emissions. The difference between reported and observation-inferred estimates suggests that an additional ~309 Tg CO2-equivalent emissions were added to the atmosphere between 2015 and 2017.
Recent research has identified significant correlations between traumatic events and depression in refugees. However, few studies have addressed the role of acculturation strategies in this relationship. This study explored the relationship between cultural orientation, traumatic events and depression in female refugees from Syria, Afghanistan, Eritrea, Iran, Iraq, and Somalia living in Germany. We expected acculturation strategies to moderate the effect of traumatic experiences on depression. The sample included 98 female refugees in Germany. The depression scale of the Hopkins Symptom Checklist (HSCL) represented the dependent measure. The trauma checklists derived from the Post-traumatic Diagnostic Scale (PDS) and the Harvard Trauma Questionnaire (HTQ) as well as the Frankfurt Acculturation Scale (FRACC) were used as independent measures for traumatic events and orientation toward the host culture as well as orientation toward the culture of origin, respectively. A moderation analysis was conducted to examine whether the relationship between the number of traumatic events and depression was influenced by the women’s orientation toward the culture of origin and the host culture. We identified a significant model explaining 26.85% of the variance in depressive symptoms (Cohen’s f2 = 0.37). The number of traumatic events and the orientation toward the host culture exerted significant effects on depressive symptoms. The moderating effect was not significant, indicating that the effect of the number of traumatic events was not influenced by cultural orientation. Based on our results, orientation toward the host culture as well as traumatic experiences exert independent effects on depressive symptoms in refugees.
Chronic inflammation is considered to be a cause of the autoimmune diseases such as rheumatoid arthritis, Alzheimer’s disease, multiple sclerosis, etc. The search for effective compounds with anti-inflammatory properties to combat these diseases is still ongoing. Natural compound narciclasine, derived from plants of Narcissus species, demonstrated its anti-inflammatory activity in in vivo arthritis models. Further investigation of narciclasine’s anti-inflammatory activity together with its impact on the interaction between leukocytes and endothelial cells was the main focus of this PhD thesis.
Narciclasine reduced the infiltration of monocytes and neutrophils to the abdomen and the concentration of the pro-inflammatory cytokines TNF, IL-6 and IL-1β. Together with this, it reduced acute visceral pain caused by zymosan injection. Narciclasine interfered with leukocyte-endothelial cell interaction in both in vivo and in vitro models. In vivo microscopy revealed that the compound reduced rolling, adhesion and transmigration of leukocytes in the vessels of an injured murine cremaster muscle. This observation was confirmed in the in vitro models for adhesion and transmigration where narciclasine reduced the level of leukocyte’s interaction with HUVECs. Narciclasine demonstrated profound anti-inflammatory properties based on its interference with leukocyte-endothelium interaction by downregulation of endothelial cell adhesion molecules expression (ICAM-1, VCAM-1, E-selectin, CX3CL1) and shutdown of NF-κB pathway. All these effects were a result of the TNF receptor 1 protein translation blocking by narciclasine.
In this work the ability of the compound to reduce visceral pain, downregulate the expression of the endothelial cell adhesion molecules and to interfere with the interaction between leukocytes and endothelial cells was demonstrated for narciclasine for the first time. Obtained results open a promising insight into the understanding of narciclasine’s anti-inflammatory properties and justify further investigation of its potential for treatment of inflammatory diseases.
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
Die Studie untersucht die Rezeption des Thukydides und deren geschichtspolitische Funktion in Dror Zahavis Biopic Das Geheimnis der Freiheit (2020), das vom Scheitern der 1974 von Berthold Beitz bei Golo Mann in Auftrag gegebenen Biographie über Alfried Krupp v. Bohlen und Halbach erzählt. In dem Film werden – so die These – bundesrepublikanische Kontroversen über Modi des Umgangs mit dem Nationalsozialismus (re-)inszeniert. Dieses Thema besitzt wegen gesellschaftlicher Wandlungsprozesse auch in der Gegenwart, in der sich die Frage nach der Stellung des Nationalsozialismus im Geschichtsbewusstsein neu stellt, eine hohe gesellschaftsdidaktische Relevanz. Als zentrale Argumentationsfigur der Protagonisten im Film dient ein zum Sprichwort mutierter Satz aus dem Epitaphios des Perikles (Thuk. 2,43,4). Die Untersuchung weist nach, wie der Film bei der Nutzung des Zitats in Bezug auf Beitz’ Biographie eine Deutungstradition fortschreibt, die Berthold Beitz selbst begründet hat und die von seinem Biographen Joachim Käppner und Bundespräsident Joachim Gauck in das kulturelle Gedächtnis der Bundesrepublik eingeführt worden ist. Es zeigt sich, dass Das Geheimnis der Freiheit seine geschichtspolitischen Ziele nur durch eine fundamentale Manipulation am Wortlaut des Thukydides erreicht, damit jedoch seine erkenntnistheoretischen Prämissen und sein Plädoyer für Professionalität im Umgang mit der Geschichte konterkariert. Der Name des Thukydides, dessen Autorität der Film als historiographische Instanz in Anspruch nimmt, wird so zu einem Etikett ohne Substanz. Durch die unsachgemäße Berufung auf sein Werk werden überdies effektivere, in der deutschen Geschichtskultur angelegte Zugänge zur Debatte über die künftige Bedeutung der nationalsozialistischen Vergangenheit blockiert. Perspektiven für eine konstruktive Rezeption des Thukydides im gesellschaftlichen Diskurs über die Geschichte sieht der Aufsatz im Verzicht auf das Konzept einer historia magistra vitae, das auf der Einebnung von Alteritäten zwischen Vergangenheit und Gegenwart fußt, sowie in der Nutzung des Reflexionspotentials, das Thukydides’ Darstellung bietet und das auch in seinem „Methodenkapitel“ (1,20-3) eingefordert wird. Zumindest auf diese Weise besitzt Thukydides eine orientierungsstiftende Aktualität für die Bundesrepublik.
Purpose: Perfusion-weighted MRI (PWI) and O-(2-[18F]fluoroethyl-)-l-tyrosine ([18F]FET) PET are both applied to discriminate tumor progression (TP) from treatment-related changes (TRC) in patients with suspected recurrent glioma. While the combination of both methods has been reported to improve the diagnostic accuracy, the performance of a sequential implementation has not been further investigated. Therefore, we retrospectively analyzed the diagnostic value of consecutive PWI and [18F]FET PET.
Methods: We evaluated 104 patients with WHO grade II–IV glioma and suspected TP on conventional MRI using PWI and dynamic [18F]FET PET. Leakage corrected maximum relative cerebral blood volumes (rCBVmax) were obtained from dynamic susceptibility contrast PWI. Furthermore, we calculated static (i.e., maximum tumor to brain ratios; TBRmax) and dynamic [18F]FET PET parameters (i.e., Slope). Definitive diagnoses were based on histopathology (n = 42) or clinico-radiological follow-up (n = 62). The diagnostic performance of PWI and [18F]FET PET parameters to differentiate TP from TRC was evaluated by analyzing receiver operating characteristic and area under the curve (AUC).
Results: Across all patients, the differentiation of TP from TRC using rCBVmax or [18F]FET PET parameters was moderate (AUC = 0.69–0.75; p < 0.01). A rCBVmax cutoff > 2.85 had a positive predictive value for TP of 100%, enabling a correct TP diagnosis in 44 patients. In the remaining 60 patients, combined static and dynamic [18F]FET PET parameters (TBRmax, Slope) correctly discriminated TP and TRC in a significant 78% of patients, increasing the overall accuracy to 87%. A subgroup analysis of isocitrate dehydrogenase (IDH) mutant tumors indicated a superior performance of PWI to [18F]FET PET (AUC = 0.8/< 0.62, p < 0.01/≥ 0.3).
Conclusion: While marked hyperperfusion on PWI indicated TP, [18F]FET PET proved beneficial to discriminate TP from TRC when PWI remained inconclusive. Thus, our results highlight the clinical value of sequential use of PWI and [18F]FET PET, allowing an economical use of diagnostic methods. The impact of an IDH mutation needs further investigation.
Objective: To determine the impact of an exercise-based prehabilitation (EBPrehab) program on preand postoperative exercise capacity, functional capacity (FC) and quality of life (QoL) in patients awaiting elective coronary artery bypass graft surgery (CABG).
Design: A two-group randomized controlled trail.
Setting: Ambulatory prehabilitation.
Subjects: Overall 230 preoperative elective CABG-surgery patients were randomly assigned to an intervention (IG, n=88; n=27 withdrew after randomization) or control group (CG, n=115).
Intervention: IG: two-week EBPrehab including supervised aerobic exercise. CG: usual care.
Main measures: At baseline (T1), one day before surgery (T2), at the beginning (T3) and at the end of cardiac rehabilitation (T4) the following measurements were performed: cardiopulmonary exercise test, six-minute walk test (6MWT), Timed-Up-and-Go Test (TUG) and QoL (MacNew questionnaire).
Results: A total of 171 patients (IG, n=81; CG, n=90) completed the study. During EBPrehab no complications occurred. Preoperatively FC (6MWTIG: 443.0±80.1m to 493.5±75.5m, P=0.003; TUGIG: 6.9±2.0 s to 6.1±1.8 s, P=0.018) and QoL (IG: 5.1±0.9 to 5.4±0.9, P<0.001) improved significantly more in IG compared to CG. Similar effects were observed postoperatively in FC (6MWDIG: Δ-64.7m, pT1–T3=0.013; Δ+47.2m, pT1–T4<0.001; TUGIG: Δ+1.4s, pT1–T3=0.003).
Conclusions: A short-term EBPrehab is effective to improve perioperative FC and preoperative QoL in patients with stable coronary artery disease awaiting CABG-surgery.
In Ludwig Tiecks Die Elfen (1812) und E.T.A. Hoffmanns Das fremde Kind (1817) nehmen Naturräume eine zentrale Position ein. Insbesondere der Wald ist als ein Kindheitsraum besetzt, der ambivalent konnotiert ist. Im Wald können sich die kindlichen Figuren fernab der Eltern autonom bewegen, dennoch geht diese Raumaneignung auch mit bedrohlichen Erfahrungen einher, die die aufstörenden Ablösungsprozesse in der Kindheit verdeutlichen...