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Studies over the past decade have revealed that metabolism profoundly influences immune responses. In particular, metabolism causes epigenetic regulation of gene expression, as a growing number of metabolic intermediates are substrates for histone post-translational modifications altering chromatin structure. One of these substrates is acetyl-coenzyme A (CoA), which donates an acetyl group for histone acetylation. Cytosolic acetyl-CoA is also a critical substrate for de novo synthesis of fatty acids and sterols necessary for rapid cellular growth. One of the main enzymes catalyzing cytosolic acetyl-CoA formation is ATP-citrate lyase (ACLY). In addition to its classical function in the provision of acetyl-CoA for de novo lipogenesis, ACLY contributes to epigenetic regulation through histone acetylation, which is increasingly appreciated. In this review we explore the current knowledge of ACLY and acetyl-CoA in mediating innate and adaptive immune responses. We focus on the role of ACLY in supporting de novo lipogenesis in immune cells as well as on its impact on epigenetic alterations. Moreover, we summarize alternative sources of acetyl-CoA and their contribution to metabolic and epigenetic regulation in cells of the immune system.
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell diseases leading to an insufficient formation of functional blood cells. Disease-immanent factors as insufficient erythropoiesis and treatment-related factors as recurrent treatment with red blood cell transfusions frequently lead to systemic iron overload in MDS and AML patients. In addition, alterations of function and expression of proteins associated with iron metabolism might are increasingly recognized to be pathogenetic factors and potential vulnerabilities of these diseases. Iron is known to be involved in multiple intracellular and extracellular processes. It is essential for cell metabolism as well as for cell proliferation and closely linked to the formation of reactive oxygen species. Therefore, iron can influence the course of clonal myeloid disorders, the leukemic environment and the occurrence as well as the defense of infections. Imbalances of iron homeostasis may induce cell death of normal but also of malignant cells. New potential treatment strategies utilizing the importance of the iron homeostasis include iron chelation, modulation of proteins involved in iron metabolism, induction of leukemic cell death via ferroptosis and exploitation of iron proteins for the delivery of antileukemic drugs.
Here, we provide a summary of some of the latest findings about the function, the prognostic impact and potential treatment strategies of iron in patients with MDS and AML.
Constraining the architecture of complex 3D volcanic plumbing systems within active rifts, and their impact on rift processes, is critical for examining the interplay between faulting, magmatism and magmatic fluids in developing rift segments. The Natron basin of the East African Rift System provides an ideal location to study these processes, owing to its recent magmatic-tectonic activity and ongoing active carbonatite volcanism at Oldoinyo Lengai. Here, we report seismicity and fault plane solutions from a 10-month temporary seismic network spanning Oldoinyo Lengai, Naibor Soito volcanic field and Gelai volcano. We locate 6827 earthquakes with ML -0.85 to 3.6, which are related to previous and ongoing magmatic and volcanic activity in the region, as well as regional tectonic extension. We observe seismicity down to ~17 km depth north and south of Oldoinyo Lengai and shallow seismicity (3 - 10 km) beneath Gelai, including two swarms. The deepest seismicity (~down to 20 km) occurs above a previously imaged magma body below Naibor Soito. These seismicity patterns reveal a detailed image of a complex volcanic plumbing system, supporting potential lateral and vertical connections between shallow- and deep-seated magmas, where fluid and melt transport to the surface is facilitated by intrusion of dikes and sills. Focal mechanisms vary spatially. T-axis trends reveal dominantly WNW-ESE extension near Gelai, while strike-slip mechanisms and a radial trend in P-axes are observed in the vicinity of Oldoinyo Lengai. These data support local variations in the state of stress, resulting from a combination of volcanic edifice loading and magma-driven stress changes imposed on a regional extensional stress field. Our results indicate that the southern Natron basin is a segmented rift system, in which fluids preferentially percolate vertically and laterally in a region where strain transfers from a border fault to a developing magmatic rift segment.
The recently observed disconnect between inflation and economic activity can be explained by the interplay between the zero lower bound (ZLB) and the costs of external financing. In normal times, credit spreads and the nominal interest rate balance out; factor costs dominate firms' marginal costs. When nominal rates are constrained, larger spreads can more than offset the effect of lower factor costs and induce only moderate inflation responses. The Phillips curve is hence flat at the ZLB, but features a positive slope in normal times and thus a hockey stick shape. Via this mechanism, forward guidance may induce deflationary effects.
We conducted a large-scale household survey in November 2020 to study how altering the time frame of a message (temporal framing) regarding an imminent positive income shock affects consumption plans. The income shock derives from the abolishment of the German solidarity surcharge on personal income taxes, effective in January 2021. We randomize across survey participants whether their extra disposable income is presented in Euros per month, Euros per year, or Euros per ten year-period. Our main findings are as follows: In General, we find our respondents’ intended Marginal Propensity to Consume (MPC) is 28.2%. Across all three treatments, the MPC is a positive function of age and being female while it is a negative function of the income increase’s size, self- control, and being unemployed. Temporal framing effects are statistically and economically highly significant as we find the monthly treatment groups’ average MPC 5.6 and 8.7 percentage points higher compared to the yearly and 10-yearly treatment groups. We will be able to analyze the real consumption behavior of households throughout 2021 based on re-surveying the participants as well as by using transaction-based bank data.
Die Lincoln-Siedlung, eine ehemalige Housing Area der US-Army im Süden von Darmstadt, wird seit dem amerikanischen Truppenabzug im Jahr 2008 als autoreduziertes Wohnquartier entwickelt. Der Autobesitz der Bewohner*innen wird über eine zentrale Stellplatzvergabe mit einem Stellplatzschlüssel von 0,65 Parkplätzen pro Wohneinheit reglementiert. Gleichzeitig stehen zahlreiche Alternativen, wie eine verbesserte Fuß- und Radverkehrsinfrastruktur, eine eng getaktete ÖPNV-Verbindung in die Innenstadt, mehrere (teils vergünstigte) Carsharing- und Fahrradverleihangebote sowie eine Mobilitätsberatung zur Verfügung. Die vorliegende Studie stützt sich auf eine quantitative Haushaltsbefragung (N = 166), evaluiert die genannten Elemente alternativer Mobilität aus Bewohner*innensicht und untersucht die umzugsbedingten Veränderungen im Mobilitätsverhalten der Bewohner*innen. Diese befürworten die Maßnahmen grundsätzlich, bezweifeln jedoch teilweise deren Wirksamkeit, etwa hinsichtlich der Minderung von Verkehrsaufkommen und Schadstoffbelastung. Im Hinblick auf das Mobilitätsverhalten zeigen die Daten eine signifikante Verringerung von Besitz und Nutzung privater Pkw im Vergleich zum Zeitraum vor dem Umzug in die Lincoln-Siedlung. Die Nutzung von Carsharing-Angeboten sowie Bus und Bahn ist hingegen signifikant angewachsen. Diese Veränderungen sind hinsichtlich der überwiegend kurzen Wohndauer der befragten Personen sowie der andauernden Quartiersentwicklung bemerkenswert. Als künftige Maßnahmen konnten bessere Informationen über das Gesamtkonzept und die einzelnen Mobilitätsangebote sowie die Kommunikation von Visionen der fertiggestellten Siedlung identifiziert werden.
The complete elastic stiffness tensor of thiourea has been determined from thermal diffuse scattering (TDS) using high-energy photons (100 keV). Comparison with earlier data confirms a very good agreement of the tensor coefficients. In contrast with established methods to obtain elastic stiffness coefficients (e.g. Brillouin spectroscopy, inelastic X-ray or neutron scattering, ultrasound spectroscopy), their determination from TDS is faster, does not require large samples or intricate sample preparation, and is applicable to opaque crystals. Using high-energy photons extends the applicability of the TDS-based approach to organic compounds which would suffer from radiation damage at lower photon energies.
Plastid DNA sequence data have been traditionally widely used in plant phylogenetics because of the high copy number of plastids, their uniparental inheritance, and the blend of coding and non-coding regions with divergent substitution rates that allow the reconstruction of phylogenetic relationships at different taxonomic ranks. In the present study, we evaluate the utility of the plastome for the reconstruction of phylogenetic relationships in the pantropical plant family Ochnaceae (Malpighiales). We used the off-target sequence read fraction of a targeted sequencing study (targeting nuclear loci only) to recover more than 100 kb of the plastid genome from the majority of the more than 200 species of Ochnaceae and all but two genera using de novo and reference-based assembly strategies. Most of the recalcitrant nodes in the family’s backbone were resolved by our plastome-based phylogenetic inference, corroborating the most recent classification system of Ochnaceae and findings from a phylogenomic study based on nuclear loci. Nonetheless, the phylogenetic relationships within the major clades of tribe Ochnineae, which comprise about two thirds of the family’s species diversity, received mostly low support. Generally, the phylogenetic resolution was lowest at the infrageneric level. Overall there was little phylogenetic conflict compared to a recent analysis of nuclear loci. Effects of taxon sampling were invoked as the most likely reason for some of the few well-supported discords. Our study demonstrates the utility of the off-target fraction of a target enrichment study for assembling near-complete plastid genomes for a large proportion of samples.
Human GLUT2 and GLUT3, members of the GLUT / SLC2 gene family, facilitate glucose transport in specific tissues. Their malfunction or misregulation is associated with serious diseases, including diabetes, metabolic syndrome, and cancer. Despite being promising drug targets, GLUTs have only a few specific inhibitors. To identify and characterize potential GLUT2 and GLUT3 ligands, we developed a whole-cell system based on a yeast strain deficient in hexose uptake, whose growth defect on glucose can be rescued by the functional expression of human transporters. The simplicity of handling yeast cells makes this platform convenient for screening potential GLUT2 and GLUT3 inhibitors in a growth-based manner, amenable to high-throughput approaches. Moreover, our expression system is less laborious for detailed kinetic characterization of inhibitors than alternative methods such as the preparation of proteoliposomes or uptake assays in Xenopus oocytes. We show that functional expression of GLUT2 in yeast requires the deletion of the extended extracellular loop connecting transmembrane domains TM1 and TM2, which appears to negatively affect the trafficking of the transporter in the heterologous expression system. Furthermore, single amino acid substitutions at specific positions of the transporter sequence appear to positively affect the functionality of both GLUT2 and GLUT3 in yeast. We show that these variants are sensitive to known inhibitors phloretin and quercetin, demonstrating the potential of our expression systems to significantly accelerate the discovery of compounds that modulate the hexose transport activity of GLUT2 and GLUT3.
During RUN3 (2021-2023) of the Large Hadron Collider, the Time Projection Chamber (TPC) of ALICE will be operated with quadruple stacks of Gas Electron Multipliers (GEMs). This technology will allow to overcome the rate limitation due to the gated operation of the Multi-Wire Proportional Chambers (MWPCs) used in RUN1 (2009-2013) and RUN2 (2015-2018).
As part of the Upgrade project, long-term irradiation tests, so called "ageing tests", have been carried out. A test setup with a detector using a quadruple stack of 10x10cm2 GEMs was built and operated in Ar-CO2 and Ne-CO2-N2 gas mixtures. The detector performance such as gas gain and energy resolution were monitored continuously. In addition, outgassing tests of materials used for the assembly process of the upgraded TPC were performed. To reach the expected dose of the GEM-based TPC, the detector was operated at much higher gains than the TPC. It was found, that the GEMs could keep their performance within the projected lifetime of the TPC. Most of the tested materials showed no negative impact on the detector. For the tested epoxy adhesive no certain conclusion could be drawn.
At much higher doses than expected for the upgraded TPC, a new phenomenon was observed, which changed the hole geometry of the GEMs and led to a degradation of the energy resolution. Even though its occurrence is not expected during the lifetime of the GEM-based TPC, simulations were carried out to study this effect more systematically. The simulations confirmed, that a change of the hole geometries of the GEMs, lead to an increase of the local gain variation, which results in a decrease of the energy resolution.
Furthermore the effect of methane as quench gas on GEMs was studied, even though this gas is not foreseen to be used in the TPC. From ageing tests with single-wire proportional counters it is well known that hydrocarbons are produced in the plasma of the avalanches, which cover the electrodes and lead to a degradation of the detector performance. Even though GEMs have a quite different geometry, the ageing tests showed, that also this technology tends to methane-induced ageing. A loss of gas gain as well as a degradation of the energy resolution due to deposits on the electrodes was monitored. A qualitative and quantitative comparison between ageing in GEMs and proportional counters was performed.
The authors examine the effectiveness of labor cost reductions as a means to stimulate economic activity and assesses the differences which may occur with the prevailing exchange rate regime. They develop a medium-scale three-region DSGE model and show that the impact of a cut in the employers’ social security contributions rate does not vary significantly under different exchange rate regimes. They find that both the interest rate and the exchange rate channel matters. Furthermore, the measure appears to be effective even if it comes along with a consumption tax increase to preserve long-term fiscal sustainability.
Finally, they assess whether obtained theoretical results hold up empirically by applying the local projection method. Regression results suggest that changes in employers’ social security contributions rates have statistically significant real effects – a one percentage point reduction leads to an average cumulative rise in output of around 1.3 percent in the medium term. Moreover, the outcome does not differ significantly across the different exchange rate regimes.
How people form beliefs is crucial for understanding decision-making un- der uncertainty. This is particularly true in a situation such as a pandemic, where beliefs will affect behaviors that impact public health as well as the aggregate economy. We conduct two survey experiments to shed light on potential biases in belief formation, focusing in particular on the tone of information people choose to consume and how they incorporate this information into their beliefs. In the first experiment, people express their preferences over pandemic-related articles with optimistic and pessimistic headlines, and are then randomly shown one of the articles. We find that respondents with more pessimistic prior beliefs about the pandemic are substantially more likely to prefer pessimistic articles, which we interpret as evidence of confirmation bias. In line with this, respondents assigned to the less preferred article rate it as less reliable and informative (relative to those who prefer it); they also discount information from the article when it is less preferred. We further find that these motivated beliefs end up impacting incentivized behavior. In a second experiment, we study how partisan views interact with information selection and processing. We find strong evidence of source dependence: revealing the news source further distorts information acquisition and processing, eliminating the role of prior beliefs in article choice.
We assess the effect and the timing of the corporate arm of the ECB quantitative easing (CSPP) on corporate bond issuance. Because of several contemporaneous measures, to isolate the programme effects we rely on one key eligibility feature: the euro denomination of newly issued bonds. We find that the significant increase in bonds issuance by eligible firms is due to the CSPP and that this effect took at least six months to unfold. This result holds even when comparing firms with similar ratings, thus providing evidence that unconventional monetary policy can foster a financing diversification regardless of firms’ risk profile. We also highlight the impact of the programme on the real economic activity. The evidence suggests that while all firms increased investment in capital expenditures and intangible assets, the CSPP induced eligible firms to invest in marketable and equity securities, to repurchase their own stocks, to hold cash and to carry out short-term investment.
By focusing on the cost conditions at issuance, I find that not only the Covid-19 pandemic effects were different across bonds and firms at different stages, but also that the market composition was significantly affected, collapsing on investment- grade bonds, a segment in which the share of bonds eligible to the ECB corporate programmes strikingly increased from 15% to 40%. At the same time the high-yield segment shrunk to almost disappear at 4%. In addition to a market segmentation along the bond grade and the eligibility to the ECB programmes, another source of risk detected in the pricing mechanism is the weak resilience to pandemic: the premium requested is around 30 basis points and started to be priced only after the early containment actions taken by the national authorities. On the contrary, I do not find evidence supporting an increased risk for corporations headquartered in countries with a reduced fiscal space, nor the existence of a premium in favour of green bonds, which should be the backbone of a possible “green recovery”.
Relying on a perspective borrowed from monetary policy announcements and introducing an econometric twist in the traditional event study analysis, we document the existence of an .event risk transfer., namely a significant credit risk transmission from the sovereign to the corporate sector after a sovereign rating downgrade. We find that after the delivery of the downgrade, corporate CDS spreads rise by 36% per annum and there is a widespread contagion across countries, in particular among those which were most exposed to the sovereign debt crisis. This effect exists on top of the standard relation between sovereign and corporate credit risk.
Freier Zugang: befristet
(2021)
Die diesjährige Inhaberin der Alfred-Grosser-Gastprofessur des Fachbereichs Gesellschaftswissenschaften, eine Kooperation mit der Stiftung Polytechnische Gesellschaft Frankfurt am Main, ist Prof. Dr. Astrid von Busekist, seit 2001 Professorin für Politische Theorie an der Sciences Po in Paris. Ihr stadtöffentlicher Vortrag mit dem Titel »Träume von Räumen. Exkurs über die Grenze« findet digital am Dienstag, 23. Februar 2021, um 19.00 Uhr c.t. statt.
Neuer Band der Reihe Frankfurter Beiträge zur Erziehungswissenschaft nimmt Adornos berühmten Radioessay als Ausgangs- und Bezugspunkt für vielfältige Interpretationen und Gegenwartsanalysen.
Rezension zu: Sabine Andresen, Dieter Nittel, Christiane Thompson (Hg.) Erziehung nach Auschwitz bis heute. Aufklärungsanspruch und Gesellschaftsanalyse. Frankfurter Beiträge zur Erziehungswissenschaft, Band 22, Goethe-Universität, FB 04, 2019
Neugründung: Buber-Rosenzweig-Institut als zentrale Forschungsstätte zum Judentum der Moderne
(2021)
Beobachten, untersuchen, experimentieren: Wie soll das gehen unter Pandemiebedingungen? Wenn auch die Chancen der digitalen Medien nun gezwungenermaßen zusehends sichtbar wurden, so sind gerade für angehende Biologielehrkräfte Primärerfahrungen mit originalen Organismen und das Einüben naturwissenschaftlicher Arbeitsmethoden sehr wichtig...
Einst war eine Filmvorführung ein flüchtiges Ereignis, das außer schönen Erinnerungen im Gedächtnis des Publikums keine Spuren hinterließ. Heute, im Zeitalter des Streaming, setzt jeder Film einen digitalen Fußabdruck im Reich der Daten. Und nicht nur das: Der Film selbst hat sich mit der digitalen Transformation grundlegend verändert und neue Formen und Formate entwickelt. Diese Umbrüche stellen das kleine Fach Filmwissenschaft vor große Herausforderungen – und bieten zugleich neue Chancen für Forschung und Lehre. In den kommenden fünf Jahren wird ein Team aus Filmwissenschaftlerinnen und Filmwissenschaftlern der Universitäten Marburg, Mainz und Frankfurt im »Digital Cinema-Hub« (DiCi-Hub) erforschen, wie diesen Herausforderungen und Chancen begegnet werden kann. Das Projekt wird von der VolkswagenStiftung im Rahmen der Förderlinie »Weltwissen – Strukturelle Stärkung Kleiner Fächer« mit 1 Million Euro gefördert.
DiCi-Hub stellt drei Schlüsselbereiche der Filmkultur ins Zentrum – nämlich Netzwerke (Philipps-Universität Marburg), Formate (Johannes Gutenberg-Universität Mainz) und Märkte (Goethe-Universität Frankfurt).
Der UniReport hatte die Gelegenheit, dem Filmwissenschaftler Prof. Vinzenz Hediger, der an der Goethe-Universität den Schlüsselbereich »Märkte« verantworten wird, einige Fragen zu stellen.
[Nachruf] Klaus Weltner
(2021)
[Nachruf] Julia Zernack
(2021)
Hocherfreut zeigten sich die US-amerikanischen Wissenschaftler Prof. Michael R. Silverman Ph.D. (77) und Prof. Bonnie L. Bassler Ph.D. (58), als der Vorsitzende des Stiftungsrats Prof. Thomas Boehm sie informierte: Sie erhalten den Paul Ehrlich- und Ludwig Darmstaedter-Preis 2021 für ihre Entdeckungen zur bakteriellen Kommunikation. Die feierliche Würdigung der Preisträger in der Paulskirche – auch der mit dem Nachwuchspreis ausgezeichneten Prof. Dr. Elvira Mass (34) – wird allerdings wegen der Corona-Pandemie erst im nächsten Jahr stattfinden können.
The function of the cerebral cortex essentially depends on the ability to form functional assemblies across different cortical areas serving different functions. Here we investigated how developmental hearing experience affects functional and effective interareal connectivity in the auditory cortex in an animal model with years-long and complete auditory deprivation (deafness) from birth, the congenitally deaf cat (CDC). Using intracortical multielectrode arrays, neuronal activity of adult hearing controls and CDCs was registered in the primary auditory cortex and the secondary posterior auditory field (PAF). Ongoing activity as well as responses to acoustic stimulation (in adult hearing controls) and electric stimulation applied via cochlear implants (in adult hearing controls and CDCs) were analyzed. As functional connectivity measures pairwise phase consistency and Granger causality were used. While the number of coupled sites was nearly identical between controls and CDCs, a reduced coupling strength between the primary and the higher order field was found in CDCs under auditory stimulation. Such stimulus-related decoupling was particularly pronounced in the alpha band and in top–down direction. Ongoing connectivity did not show such a decoupling. These findings suggest that developmental experience is essential for functional interareal interactions during sensory processing. The outcomes demonstrate that corticocortical couplings, particularly top-down connectivity, are compromised following congenital sensory deprivation.
leporello #7
(2021)
This paper studies the behavior of competing firms in a duopoly with rational inattentive consumers. Firms play a sequential game in which they decide to obfuscate their individual prices before competing on price. Probabilistic demand functions are endogenously determined by the consumers’ optimal information strategy, which depends on the firms’ obfuscation choice and the consumers’ unrestricted prior beliefs. We show that the game may result in an obfuscation equilibrium with high prices where both firms obfuscate and a transparency equilibrium with low prices and no obfuscation, providing an argument for market regulation. Lower information costs and asymmetric prior beliefs about prices reduce the probability of an obfuscation equilibrium. Using data on Sweden, we document a decrease in price complexity and corresponding prices in the market for mobile phone subscriptions in the last two decades. Our model rationalizes these changes and explains why complexity and high prices persist in some but not all digitalized markets.
The disposition effect is implicitly assumed to be constant over time. However, drivers of the disposition effect (preferences and beliefs) are rather countercyclical. We use individual investor trading data covering several boom and bust periods (2001-2015). We show that the disposition effect is countercyclical, i.e. is higher in bust than in boom periods. Our findings are driven by individuals being 25% more likely to realize gains in bust than in boom periods. These changes in investors’ selling behavior can be linked to changes in investors’ risk aversion and in their beliefs across financial market cycles.
The centrality of the United States in the global financial system is taken for granted, but its response to recent political and epidemiological events has suggested that China now holds a comparable position. Using minute-by-minute data from 2012 to 2020 on the financial performance of twelve country-specific exchange-traded funds, we construct daily snapshots of the global financial network and analyze them for the centrality and connectedness of each country in our sample. We find evidence that the U.S. was central to the global financial system into 2018, but that the U.S.-China trade war of 2018–2019 diminished its centrality, and the Covid-19 outbreak of 2019–2020 increased the centrality of China. These indicators may be the first signals that the global financial system is moving from a unipolar to a bipolar world.
Smart(phone) investing? A within investor-time analysis of new technologies and trading behavior
(2021)
Using transaction-level data from two German banks, we study the effects of smartphones on investor behavior. Comparing trades by the same investor in the same month across different platforms, we find that smartphones increase purchasing of riskier and lottery-type assets and chasing past returns. After the adoption of smartphones, investors do not substitute trades across platforms and buy also riskier, lottery-type, and hot investments on other platforms. Using smartphones to trade specific assets or during specific hours contributes to explain our results. Digital nudges and the device screen size do not mechanically drive our results. Smartphone effects are not transitory.
The FOMC risk shift
(2021)
We identify a component of monetary policy news that is extracted from high-frequency changes in risky asset prices. These surprises, which we call “risk shifts”, are uncorrelated, and therefore complementary, to risk-free rate surprises. We show that (i) risk shifts capture the lion’s share of stock price movements around FOMC announcements; (ii) that they are accompanied by significant investor fund flows, suggesting that investors react heterogeneously to monetary policy news; and (iii) that price pressure amplifies the stock market response to monetary policy news. Our results imply that central bank information effects are overshadowed by short-term dynamics stemming from investor rebalancing activities and are likely to be more difficult to identify than previously thought.
Broad, long-term financial and economic datasets are a scarce resource, in particular in the European context. In this paper, we present an approach for an extensible, i.e. adaptable to future changes in technologies and sources, data model that may constitute a basis for digitized and structured long- term, historical datasets. The data model covers specific peculiarities of historical financial and economic data and is flexible enough to reach out for data of different types (quantitative as well as qualitative) from different historical sources, hence achieving extensibility. Furthermore, based on historical German company and stock market data, we discuss a relational implementation of this approach.
The so-called Troika, consisting of the EU-Commission, the European Central Bank (ECB) and the International Monetary Fund (IMF), was supposed to support the member states of the euro area which had been hit hard by a sovereign debt crisis. For that purpose, economic adjustment programs were drafted and monitored in order to prevent the break-up of the euro area and sovereign defaults. The cooperation of these institutions, which was born out of necessity, has been partly successful, but has also created persistent problems. With the further increase of public debt, especially in France and Italy, the danger of a renewed crisis in the euro area was growing. The European Stability Mechanism (ESM) together with the European Commission will replace the Troika in the future, following decisions of the EU Summit of December 2018. It shall play the role of a European Monetary Fund in the event of a crisis. The IMF, on the other side, will no longer play an active role in solving sovereign debt crises in the euro area. The current course is, however, inadequate to tackle the core problems of the euro zone and to avoid future crises, which are mainly structural in nature and due to escalating public debt and lack of international competitiveness of some member countries. The current Corona crisis will aggravate the institutional problems. It has led to a common European fiscal response ("Next Generation EU"). This rescue and recovery program will not be financed by ESM resources and will not be monitored by the ESM. One important novelty of this package is that it involves the issuance of substantial common European debt.
Der Einsatz von Künstliche Intelligenz (KI) – Technologien eröffnet viele Chancen, birgt aber auch viele Risiken – insbesondere in der Finanzbranche. Dieses Whitepaper gibt einen Überblick über den aktuellen Stand der Anwendung und Regulierung von KI-Technologien in der Finanzbranche, und diskutiert Chancen und Risiken von KI. KI findet in der Finanzbranche zahlreiche Anwendungsgebiete. Dazu gehören Chatbots, intelligente Assistenten für Kunden, automatischer Hochfrequenzhandel, automatisierte Betrugserkennung, Überwachung der Compliance, Gesichtserkennungssoftware zur Kundenidentifikation u. v. m. Auch Finanzaufsichtsbehörden setzen zunehmend KI-Anwendungen ein, um große und komplexe Datenmengen (Big Data) automatisiert und skalierbar auf Muster zu untersuchen und ihren Aufsichtspflichten nachzukommen.
Die Regulierung von KI in der Finanzbranche ist ein Balanceakt. Auf der einen Seite gibt es eine Notwendigkeit Flexibilität zu gewährleisten, um Innovationen nicht einzudämmen und im internationalen Wettbewerb nicht abgehängt zu werden. Strenge Auflagen können in diesem Zusammenhang als Barriere für die erfolgreiche Weiter-)Entwicklung von KI-Applikationen in der Finanzbranche wirken. Auf der anderen Seite müssen Persönlichkeitsrechte geschützt und Entscheidungsprozesse nachvollziehbar bleiben. Die fehlende Erklärbarkeit und Interpretierbarkeit von KI-Modellen entsteht in erster Linie durch Intransparenz bei einem Großteil heutiger KI-Anwendungen, bei welchen zwar die Natur der Ein- und Ausgaben beobachtbar und verständlich ist, nicht jedoch die genauen Verarbeitungsschritte dazwischen (Blackbox Prinzip).
Dieses Spannungsfeld zeigt sich auch im aktuellen regulatorischen Ansatz verschiedener Behörden. So werden einerseits die positiven Seiten von KI betont, wie Effizienz- und Effektivitätsgewinne sowie Rentabilitäts- und Qualitätssteigerungen (Bundesregierung, 2019) oder neue Methoden der Gefahrenanalyse in der Finanzmarktregulierung (BaFin, 2018a). Andererseits, wird darauf verwiesen, dass durch KI getroffene Entscheidungen immer von Menschen verantwortet werden müssen (EU Art. 22 DSGVO) und demokratische Rahmenbedingungen des Rechtsstaats zu wahren seien (FinTechRat, 2017).
Für die Zukunft sehen wir die Notwendigkeit internationale Regularien prinzipienbasiert, vereinheitlicht und technologieneutral weiterzuentwickeln, ohne dabei die Entwicklung neuer KIbasierter Geschäftsmodelle zu bremsen. Im globalen Wettstreit sollte Europa bei der Regulierung des KI-Einsatzes eine Vorreiterrolle einnehmen und damit seine demokratischen Werte der digitalen Freiheit, Selbstbestimmung und das Recht auf Information weltweit exportieren. Förderprogramme sollten einen stärkeren Fokus auf die Entwicklung nachhaltiger und verantwortungsvoller KI in Banken legen. Dazu zählt insbesondere die (Weiter-)Entwicklung breit einsetzbarer Methoden, die es erlauben, menschen-interpretierbare Erklärungen für erzeugte Ausgaben bereitzustellen und Problemen wie dem Blackbox Prinzip entgegenzuwirken.
Aus Sicht der Unternehmen in der Finanzbranche könnte eine Kooperation mit BigTech-Unternehmen sinnvoll sein, um gemeinsam das Potential der Technologie bestmöglich ausschöpfen zu können. Nützlich wäre auch ein gemeinsames semantisches Metadatenmodell zur Beschreibung der in der Finanzbranche anfallenden Daten. In Zukunft könnten künstliche Intelligenzen Daten aus sozialen Netzwerken berücksichtigen oder Smart Contracts aushandeln. Eine der größten Herausforderungen der Zukunft wird das Anwerben geeigneten Personals darstellen.
In the past decades, the use and production of chemicals has been on the rise globally due to increasing industrialization and intensive agriculture; resulting in the occurrence and ecotoxicological risks of chemicals of emerging concern (CECs) in the aquatic compartments. Risks include changes in community structure resulting in the dominance of one species and ecosystem imbalance. When dominant disease-causing organisms are in the environment, the disease transmission is increased. For example, host snails for the schistosomiasis, a human trematode disease, are known to be tolerant to pesticide
exposure compared to the predators. This would therefore result in an increased abundance of snails which consequently increase the disease transmission in the human population.
Kenya, being a low income country faces a lot of challenges with provision of clean water, diseases and sanitation facilities, and increasing population which results in intensive agriculture coupled with pesticide use. Although a lot of research has been carried out on the environmental occurrence and risk of CECs (Chapter 1), most of these studies have been done in developed countries with limited information from Africa. Additionally, research in Africa focused on urban areas with limited number of compounds analyzed and mostly in the water phase, and inadequate information on the effects of CECs on the aquatic organisms. In order to reduce this knowledge gap, this dissertation focused on identification and quantification of CECs present in water, sediment and snails from western Kenya, and the contribution of pesticides to the transmission of schistosomiasis.
Chapter 2 gives a summary of the results and discussion of the dissertation. In Chapter 3, a comprehensive chemical analysis was carried out on 48 water samples to identify compounds, spatial patterns and associated risks for fish, crustacean and algae using toxic unit (TU) approach. A total of 78 compounds were detected with pesticides and biocides being the compounds most frequently detected. Spatial pattern analysis revealed limited compound grouping based on land use. Acute risk for crustaceans and algae were driven by one to three individual compounds. These compounds responsible for toxicity were prioritized as candidate compounds for monitoring and regulation in Kenya.
In Chapter 4, an extension of Chapter 3 was done to cover the CECs present in snails and sediment from the 48 sites. A total of 30 compounds were found in snails and 78 in sediments with 68 additional compounds being found which were not previously detected in water. Higher contaminant concentrations were found in agricultural sites than in areas without anthropogenic activities. The highest acute toxicity (TU 0.99) was determined for crustaceans based on compounds in sediment samples. The risk was driven by diazinon and pirimiphos-methyl. Acute and chronic risks to algae were driven by diuron whereas fish were found to be at low to no acute risk.
In Chapter 5, the effect of pesticide contamination on schistosomiasis transmission was evaluated by applying complimentary laboratory and field studies. In the field studies, the ecological mechanisms through which pesticides and physical chemical parameters affect host snails, predators and competitors were investigated. Pesticide data was obtained from the results in chapter 3. The overall distribution of grazers and predators was not affected by pesticide pollution. However, within the grazers, pesticide pollution increased dominance of host snails. On the contrary, the host-snail competitors were highly sensitive to pesticide exposure. For the laboratory studies, macroinvertebrates including Schistosoma-host snails, competitors and predators were exposed to 6 concentrations levels of imidacloprid and diazinon. Snails showed higher insecticide tolerance compared to competitors and predators. Finally, Chapter 6 summarizes the conclusions of this dissertation, placing it in a broader
context. In this dissertation, a comprehensive chemical characterization and risk assessment of CECs has been carried out in freshwater systems; together with the effects of pesticides on schistosomiasis transmission in rural western Kenya. Results of this dissertation showed that rural areas are contaminated posing a risk to aquatic organisms which contribute to schistosomiasis transmission. This shows the need for regular monitoring and policy formulation to reduce pollutant emissions which contributes negatively to both ecological and human health effects.
Background: Extracorporeal life support (ECLS) has become an integral part of modern intensive therapy. The choice of support mode depends largely on the indication. Patients with respiratory failure are predominantly treated with a venovenous (VV) approach. We hypothesized that mortality in Germany in ECLS therapy did not differ from previously reported literature
Methods: Inpatient data from Germany from 2007 to 2018 provided by the Federal Statistical Office of Germany were analysed. The international statistical classification of diseases and related health problems codes (ICD) and process keys (OPS) for extracorporeal membrane oxygenation (ECMO) types, acute respiratory distress syndrome (ARDS) and hospital mortality were used.
Results: In total, 45,647 hospitalized patients treated with ECLS were analysed. In Germany, 231 hospitals provided ECLS therapy, with a median of 4 VV-ECMO and 9 VA-ECMO in 2018. Overall hospital mortality remained higher than predicted in comparison to the values reported in the literature. The number of VV-ECMO cases increased by 236% from 825 in 2007 to 2768 in 2018. ARDS was the main indication for VV-ECMO in only 33% of the patients in the past, but that proportion increased to 60% in 2018. VA-ECMO support is of minor importance in the treatment of ARDS in Germany. The age distribution of patients undergoing ECLS has shifted towards an older population. In 2018, the hospital mortality decreased in VV-ECMO patients and VV-ECMO patients with ARDS to 53.9% (n = 1493) and 54.4% (n = 926), respectively.
Conclusions: ARDS is a severe disease with a high mortality rate despite ECLS therapy. Although endpoints and timing of the evaluations differed from those of the CESAR and EOLIA studies and the Extracorporeal Life Support Organization (ELSO) Registry, the reported mortality in these studies was lower than in the present analysis. Further prospective analyses are necessary to evaluate outcomes in ECMO therapy at the centre volume level.
Objective: The COVID-19 pandemic made it necessary to convert a course on history taking, in theory and practice, to an online format over a very short time. A key question was whether, and if so to what extent, basic theory and, in particular, the practical skills required to conduct medical interviews can be learned online.
Methodology/project description: The teaching program in basic theory was didactically redesigned and asynchronously placed on a learning platform, while the practical program, which consisted of training in conducting history-taking interviews, took place with the help of video conferencing software during synchronous sessions. For the practical sessions, the lecturers received organizational and technical support.
Results: Based on initial evaluation results, a positive picture of the conversion has emerged since the course was completed. The need to restructure the course and use new teaching methods because of the COVID-19 pandemic was well accepted by lecturers and students, and the course content was successfully adapted to an online format.
Conclusion: Overall, the online format enabled the learning objectives of the course to be successfully achieved. For topics such as non-verbal communication, the evaluation results indicated that a classroom format is preferable. Asynchronous theory teaching was generally very well received. Blended learning formats thus represent an appropriate means of teaching how to conduct medical interviews. Overall, online courses on conducting medical interviews provide students with the opportunity to become acquainted with the use of digital formats to conduct doctor-patient interviews, and to develop the relevant skills.
In this talk we presented a novel technique, based on Deep Learning, to determine the impact parameter of nuclear collisions at the CBM experiment. PointNet based Deep Learning models are trained on UrQMD followed by CBMRoot simulations of Au+Au collisions at 10 AGeV to reconstruct the impact parameter of collisions from raw experimental data such as hits of the particles in the detector planes, tracks reconstructed from the hits or their combinations. The PointNet models can perform fast, accurate, event-by-event impact parameter determination in heavy ion collision experiments. They are shown to outperform a simple model which maps the track multiplicity to the impact parameter. While conventional methods for centrality classification merely provide an expected impact parameter distribution for a given centrality class, the PointNet models predict the impact parameter from 2–14 fm on an event-by-event basis with a mean error of −0.33 to 0.22 fm.
Objective: Due to the prohibition of face-to-face courses during the Corona pandemic, the seminar "Written Examinations" of the Frankfurter Arbeitsstelle für Medizindidaktik (FAM) was converted into an asynchronous online seminar. This pilot project investigated how such a format is accepted and evaluated by the participants. Methodology: A forum-based online format with group and individual tasks was chosen, which was didactically designed according to the problem-oriented design by Reinmann and Mandl. Results: The seminar was attended by 14 people, 13 of whom took part in the evaluation. The overall evaluation was, with one exception, a grade of 2 (and better). The three items "practical relevance", "subjective learning success" and the question of recommendation also received very high approval ratings. The weekly workload reported by the participants was very heterogeneous (mean=2.4 hours; SD=1.1). For some participants, the use of the learning platform was not intuitive and group collaboration was somewhat faltering.Conclusion: The experiences made show that courses on medical didactics can be implemented online and are gladly accepted by the participants. Based on the experience gained, online seminars or blended learning formats will certainly continue to be part of the FAM course program in the future.
Scanning Hall probe microscopy is attractive for minimally invasive characterization of magnetic thin films and nanostructures by measurement of the emanating magnetic stray field. Established sensor probes operating at room temperature employ highly miniaturized spin-valve elements or semimetals, such as Bi. As the sensor layer structures are fabricated by patterning of planar thin films, their adaption to custom-made sensor probe geometries is highly challenging or impossible. Here we show how nanogranular ferromagnetic Hall devices fabricated by the direct-write method of focused electron beam induced deposition (FEBID) can be tailor-made for any given probe geometry. Furthermore, we demonstrate how the magnetic stray field sensitivity can be optimized in situ directly after direct-write nanofabrication of the sensor element. First proof-of-principle results on the use of this novel scanning Hall sensor are shown.
Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network.
During dynamic ultrasound assessments, unintended transducer movement over the skin needs to be prevented as it may bias the results. The present study investigated the validity of two methods quantifying transducer motion. An ultrasound transducer was moved on a pre-specified 3 cm distance over the semitendinosus muscle of eleven adults (35.8 ± 9.8 years), stopping briefly at intervals of 0.5 cm. Transducer motion was quantified (1) measuring the 2-D displacement of the shadow produced by reflective tape (RT) attached to the skin and (2) using a marker-based, three-dimensional movement analysis system (MAS). Differences between methods were detected with Wilcoxon tests; associations were checked by means of intraclass correlation coefficients (ICC 3.1) and Bland–Altman plots. Values for RT (r = 0.57, p < 0.001) and MAS (r = 0.19, p = 0.002) were significantly higher than true distances (TD). Strong correlations were found between RT and TD (ICC: 0.98, p < 0.001), MAS and TD (ICC: 0.95, p < 0.001), and MAS and RT (ICC: 0.97, p < 0.001). Bland–Altman plots showed narrow limits of agreement for both RT (−0.49 to 0.13 cm) and MAS (−0.49 to 0.34 cm) versus TD. RT and MAS are valid methods to quantify US transducer movement. In view of its low costs and complexity, RT can particularly be recommended for application in research and clinical practice. View Full-Text
Keywords: ultrasound; reflective tape; transducer movement
The ability to learn sequential contingencies of actions for predicting future outcomes is indispensable for flexible behavior in many daily decision-making contexts. It remains open whether such ability may be enhanced by transcranial direct current stimulation (tDCS). The present study combined tDCS with functional near-infrared spectroscopy (fNIRS) to investigate potential tDCS-induced effects on sequential decision-making and the neural mechanisms underlying such modulations. Offline tDCS and sham stimulation were applied over the left and right dorsolateral prefrontal cortex (dlPFC) in young male adults (N = 29, mean age = 23.4 years, SD = 3.2) in a double-blind between-subject design using a three-state Markov decision task. The results showed (i) an enhanced dlPFC hemodynamic response during the acquisition of sequential state transitions that is consistent with the findings from a previous functional magnetic resonance imaging (fMRI) study; (ii) a tDCS-induced increase of the hemodynamic response in the dlPFC, but without accompanying performance-enhancing effects at the behavioral level; and (iii) a greater tDCS-induced upregulation of hemodynamic responses in the delayed reward condition that seems to be associated with faster decision speed. Taken together, these findings provide empirical evidence for fNIRS as a suitable method for investigating hemodynamic correlates of sequential decision-making as well as functional brain correlates underlying tDCS-induced modulation. Future research with larger sample sizes for carrying out subgroup analysis is necessary in order to decipher interindividual differences in tDCS-induced effects on sequential decision-making process at the behavioral and brain levels.
Aufbau: Acoustic Radiation Force Impulse (ARFI)- Bildgebung ist eine auf der konventionellen Ultraschall- Bildgebung basierende Elastographie- Methode, die die quantitative Messung der Festigkeit und Elastizität von Gewebe ermöglicht. Das Ziel der vorliegenden Studie war es, ARFI- Bildgebung für die Differenzierung von Schilddrüsenknoten zu evaluieren und mit der bereits gut erprobten qualitativen Messmethode der Real-Time Elastographie (RTE) zu vergleichen.
Material und Methoden: ARFI- Bildgebung basiert auf der Aussendung von akustischen Impulsen in Gewebe, wodurch lokale Gewebeverschiebungen hervorgerufen werden. Die dabei entstehenden Transversalwellen wiederum werden über auf Korrelation basierende Methoden mittels Ultraschallwellen detektiert und in m/s angegeben. Einschlusskriterien der Studie waren: Knoten ≥ 5 mm sowie eine zytologische/histologische Aufarbeitung. Alle Patienten erhielten eine konventionelle Ultraschall- Untersuchung, eine Real-Time Elastographie sowie eine ARFI- Bildgebung.
Ergebnisse: Es standen 158 Knoten aus 138 Patienten zur Analyse zur Verfügung. 137 Knoten erbrachten bei der zytologischen/histologischen Aufarbeitung ein benignes Ergebnis, 21 Knoten hingegen wurden als maligne eingestuft. Die mittlere Geschwindigkeit der Messungen der ARFI- Bildgebung in gesundem Schilddrüsengewebe betrug 1,76 m/s, in benignen Knoten 1,90 m/s und in malignen Knoten 2,69 m/s. Es konnte kein signifikanter Unterschied der mittleren Geschwindigkeit zwischen gesundem Schilddrüsengewebe und benignen Knoten ermitteltet werden, wohingegen ein signifikanter Unterschied zwischen malignen Knoten und gesundem Schilddrüsengewebe (p= 0,0019) einerseits und benignen Schilddrüsenknoten (p=0,0039) andererseits bestand. Für die diagnostische Genauigkeit bei der Diagnose von malignen Schilddrüsenknoten konnte kein signifikanter Unterschied zwischen RTE und ARFI- Bildgebung festgestellt werden (0,74 vs. 0,69, p=0,54). Die Kombination von RTE und ARFI- Bildgebung erhöhte die Spezifität bei der Diagnose von malignen Schilddrüsenknoten von 72% (nur RTE) auf 92% (kombiniert).
Schlussfolgerungen: ARFI- Bildgebung kann als zusätzliche Methode bei der diagnostischen Aufarbeitung von Schilddrüsenknoten genutzt werden und liefert dabei einen hohen negativen prädiktiven Wert sowie vergleichbare Ergebnisse wie die RTE.
Despite the increasing use of cashless payment instruments, the notion that cash loses importance over time can be unambiguously refuted. In contrast, the authors show that cash demand increased steeply over the past 30 years. This is not only true on a global scale, but also for the most important currencies in advanced countries (USD, EUR, CHF, GBP and JPY). In this paper, they focus especially on the role of different crises (technological crises, financial market crises, natural disasters) and analyse the demand for small and large banknote denominations since the 1990s in an international perspective. It is evident that cash demand always increases in times of crises, independent of the nature of the crisis itself. However, largely unaffected from crises we observe a trend increase in global cash aligned with a shift from transaction balances towards more hoarding, especially in the form of large denomination banknotes.
Uni-Highlights Februar 2021 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2021)
Tuberöse Sklerose („tuberous sclerosis complex“ [TSC]) ist eine seltene genetische Erkrankung, die neben kutanen und viszeralen Organmanifestationen typischerweise bereits in einem sehr frühen Erkrankungsstadium mit einer schweren, meist therapierefraktären Epilepsie einhergeht. Aufgrund seiner direkten Wirkung am durch TSC dysregulierten mTOR-Signalweg sowie der synergistischen Effekte auf andere Organmanifestationen kommt das Rapamycin-Derivat Everolimus (EVE) zunehmend zur Anwendung. Ziel dieses systematischen Reviews ist, die Wirksamkeit, Sicherheit und Verträglichkeit von EVE bei Patienten mit TSC-assoziierter, therapierefraktärer Epilepsie aufzuarbeiten.
Drug resistance is a commonly unavoidable consequence of cancer treatment that results in therapy failure and disease relapse. Intrinsic (pre-existing) or acquired resistance mechanisms can be drug-specific or be applicable to multiple drugs, resulting in multidrug resistance. The presence of drug resistance is, however, tightly coupled to changes in cellular homeostasis, which can lead to resistance-coupled vulnerabilities. Unbiased gene perturbations through RNAi and CRISPR technologies are invaluable tools to establish genotype-to-phenotype relationships at the genome scale. Moreover, their application to cancer cell lines can uncover new vulnerabilities that are associated with resistance mechanisms. Here, we discuss targeted and unbiased RNAi and CRISPR efforts in the discovery of drug resistance mechanisms by focusing on first-in-line chemotherapy and their enforced vulnerabilities, and we present a view forward on which measures should be taken to accelerate their clinical translation.
Background: To test the effect of variant histology relative to urothelial histology on stage at presentation, cancer specific mortality (CSM) and overall mortality (OM) after chemotherapy use, in urethral cancer.
Materials and Methods: Within the Surveillance, Epidemiology and End Results (2004–2016) database, we identified 1,907 primary variant histology urethral cancer patients. Kaplan-Meier plots, Cox regression analyses, cumulative incidence-plots, multivariable competing-risks regression models and propensity score matching for patient and tumor characteristics were used.
Results:Of 1,907 eligible urethral cancer patients, urothelial histology affected 1,009 (52.9%) vs. squamous cell carcinoma (SCC) 455 (23.6%) vs. adenocarcinoma 278 (14.6%) vs. other histology 165 (8.7%) patients. Urothelial histological patients exhibited lower stages at presentation than SCC, adenocarcinoma or other histology patients. In urothelial histology patients, five-year CSM was 23.5% vs. 34.4% in SCC (Hazard Ratio (HR) 1.57) vs. 40.7% in adenocarcinoma (HR 1.69) vs. 43.4% in other histology (HR 1.99, p<0.001). After matching in multivariate competing-risks regression models, variant histology exhibited 1.35-fold higher CSM than urothelial. Finally, in metastatic urethral cancer, lower OM was recorded after chemotherapy in general, including metastatic adenocarcinoma and other variant histology subtypes, except metastatic SCC.
Conclusion: Adenocarcinoma, SCC and other histology subtypes affect fewer patients than urothelial histology. Presence of variant histology results in higher CSM. Finally, chemotherapy for metastatic urethral cancer improves survival in adenocarcinoma and other variant histology subtypes, but not in SCC.
The Global South is facing severe challenges in ensuring livelihood security due to climate change impacts, environmental degradation and population growth as well as changing lifestyles. These complex problems cannot be solely solved by single scientific disciplines – they require transdisciplinary research (TDR). Stakeholders from civil society, the corporate sector, government and science need to pool their knowledge to find solutions for sustainable transformations. In Namibia, we have been involved in TDR projects on water supply, and sanitation services as well as livestock management in rangeland systems. In this paper, we review two TDR projects that differ in multiple ways and hence allow us to carve out structural differences and critically discuss research outcomes, lessons learned and the challenge of North–South collaborations. Our review builds upon published and unpublished project documents as well as expert interviews with Namibian and German researchers who were involved in the projects. Our results show that TDR can be put into practice in different ways, depending on the research focus and the period available. The TDR phases of problem framing, inter- and transdisciplinary integration were implemented with different tools and foci points. We discuss the role of project length and funding conditions for project success and outcome generation. In addition, we critically consider the role of Namibian and German researchers in these international collaborations. The conclusions we draw touch upon the points of preparatory research funding, the equal acknowledgement of Global South contributions to joint research projects and the explicit handling of TDR components in project work. Significance: • The current social-ecological challenges are complex and require TDR as a mode of knowledge coproduction, particularly in a development context. • Inter- and transdisciplinary integration are critical processes for a project to be successful and require the allocation of adequate time and monetary resources. • Longer-term projects with a funded preparatory research phase constitute a structural model for TDR as project outcomes can evolve over time. • Global South researchers carry a hidden burden in international collaborations that has to be adequately acknowledged upfront in project planning and final products.
Abstract In the middle of the twentieth century, the from North America sooty bark disease (SBD) of maples was first discovered in England and has spread in the last decades in Central Europe, in particular. The trigger of SBD is the mould fungus Cryptostroma (C.) corticale. The most common infested maple is the sycamore, Acer pseudoplatanus, a common tree in woods and parks. The disease is characterised by peeling of the outer layer of the bark and brownish-black spores under the peeled off bark. These spores can cause maple bark disease (MBD) in humans, a hypersensitivity pneumonitis (HP) with similar symptoms like COPD, allergic asthma, influenza or flu-like infections and interstitial pneumonia. Persons who have intensive respectively occupational contact with infested trees or wood, e.g., woodman, foresters, sawyers or paper mill workers, are at risk in particular. Since C. corticale favours hot summers and host trees weakened by drought, SBD will increasingly spread in the future due to ongoing climate change. Consequently, the risk of developing MBD will increase, too. As with all HPs, e.g., farmer’s lung and pigeon breeder’s disease, the diagnosis of MBD is intricate because it has no clear distinguishing characteristics compared to other interstitial lung diseases. Therefore, the establishment of consistent diagnosis guidelines is required. For correct diagnosis and successful therapy, multidisciplinary expertise including pulmonologists, radiologists, pathologists and occupational physicians is recommended. If MBD is diagnosed in time, the removal of the triggering fungus or the infested maple wood leads to complete recovery in most cases. Chronic HP can lead to lung fibrosis and a total loss of lung function culminating in death. HP and, thus, MBD, is a disease with a very high occupational amount. To avoid contact with spores of C. corticale, persons working on infested wood or trees have to wear personal protective equipment. To protect the public, areas with infested maples have to be cordoned off, and the trees should be removed. This is also for impeding further spreading of the spores.
Background: Cumulative anticholinergic exposure, also known as anticholinergic burden, is associated with a variety of adverse outcomes. However, studies show that anticholinergic effects tend to be underestimated by prescribers, and anticholinergics are the most frequently prescribed potentially inappropriate medication in older patients. The grading systems and drugs included in existing scales to quantify anticholinergic burden differ considerably and do not adequately account for patients’ susceptibility to medications. Furthermore, their ability to link anticholinergic burden with adverse outcomes such as falls is unclear. This study aims to develop a prognostic model that predicts falls in older general practice patients, to assess the performance of several anticholinergic burden scales, and to quantify the added predictive value of anticholinergic symptoms in this context.
Methods: Data from two cluster-randomized controlled trials investigating medication optimization in older general practice patients in Germany will be used. One trial (RIME, n = 1,197) will be used for the model development and the other trial (PRIMUM, n = 502) will be used to externally validate the model. A priori, candidate predictors will be selected based on a literature search, predictor availability, and clinical reasoning. Candidate predictors will include socio-demographics (e.g. age, sex), morbidity (e.g. single conditions), medication (e.g. polypharmacy, anticholinergic burden as defined by scales), and well-being (e.g. quality of life, physical function). A prognostic model including sociodemographic and lifestyle-related factors, as well as variables on morbidity, medication, health status, and well-being, will be developed, whereby the prognostic value of extending the model to include additional patient-reported symptoms will be also assessed. Logistic regression will be used for the binary outcome, which will be defined as “no falls” vs. “≥1 fall” within six months of baseline, as reported in patient interviews. Discussion: As the ability of different anticholinergic burden scales to predict falls in older patients is unclear, this study may provide insights into their relative importance as well as into the overall contribution of anticholinergic symptoms and other patient characteristics. The results may support general practitioners in their clinical decision-making and in prescribing fewer medications with anticholinergic properties.
Simple Summary
Seizures are among the most common symptoms of meningioma patients even after surgery. This study sought to identify risk factors for early and late seizures in meningioma patients and to evaluate a modified version of a score to predict postoperative seizures on an independent cohort. The data underline that there are distinct factors identifying patients with a high risk of postoperative seizures following meningioma surgery which has been already shown before. We could further show that the high proportion of 43% of postoperative seizures occur as late seizures which are more dangerous because they may happen out of hospital. The modified STAMPE2 score could predict postoperative seizures when reaching very high scores but was not generally transferable to our independent cohort.
Abstract
Seizures are among the most common symptoms of meningioma. This retrospective study sought to identify risk factors for early and late seizures in meningioma patients and to evaluate a modified STAMPE2 score. In 556 patients who underwent meningioma surgery, we correlated different risk factors with the occurrence of postoperative seizures. A modified STAMPE2 score was applied. Risk factors for preoperative seizures were edema (p = 0.039) and temporal location (p = 0.038). For postoperative seizures preoperative tumor size (p < 0.001), sensomotory deficit (p = 0.004) and sphenoid wing location (p = 0.032) were independent risk factors. In terms of postoperative status epilepticus; sphenoid wing location (p = 0.022), tumor volume (p = 0.045) and preoperative seizures (p < 0.001) were independent risk factors. Postoperative seizures lead to a KPS deterioration and thus an impaired quality of life (p < 0.001). Late seizures occurred in 43% of patients with postoperative seizures. The small sub-cohort of patients (2.7%) with a STAMPE2 score of more than six points had a significantly increased risk for seizures (p < 0.001, total risk 70%). We concluded that besides distinct risk factors, high scores of the modified STAMPE2 score could estimate the risk of postoperative seizures. However, it seems not transferable to our cohort
Innovative ideas are essential to sustainable development. Students’ innovative potential in higher education for sustainable development (HESD) has so far been neglected. Innovation is often associated with an interdisciplinary approach. However, the results of research on diversity and its role in innovation are inconsistent. The present study takes a longitudinal approach to investigating student teams in project-based learning courses in HESD in Germany. This study examines how innovation develops in interdisciplinary student teams in contrast to monodisciplinary student teams. The results of the latent change approach from a sample of 69 student teams indicate significant changes in students’ innovation over time. Monodisciplinary student teams outperform interdisciplinary student teams in idea promotion (convincing potential allies) at the beginning, whereas interdisciplinary student teams outperform monodisciplinary student teams in idea generation (production of novel and useful ideas) in the midterm. There is no difference in the long term. The results indicate that interdisciplinary student teams have an advantage in the generation of novel ideas but need time to leverage their access to different discipline-based knowledge. We discuss practical implications for the design of interdisciplinary learning with strategies to support students in the formation phase in project-based learning in HESD.
In times of global warming caused by the extensive use of fossil fuels, the need to capture gaseous carbon compounds is growing bigger. Several groups of microorganisms can fix the greenhouse gas CO2. Out of these, acetogenic bacteria are role models in their ability to reduce CO2 with hydrogen to acetate, which makes acetogens prime candidates for genetic modification towards biotechnological production of value-added compounds from CO2, such as biofuels. However, growth of acetogens on gaseous substrates is strongly energy-limited, and successful metabolic engineering requires a detailed knowledge of the bioenergetics. In 1939, Clostridium aceticum was the first acetogen to be described. A recent genomic study revealed that this organism contains cytochromes and therefore may use a proton gradient in its respiratory chain. We have followed up these studies and will present data that C. aceticum does not use a H+ but a Na+ gradient for ATP synthesis, established by a Na+-Rnf. Experimental data and in silico analyses enabled us to propose the biochemistry and bioenergetics of acetogenesis from H2 + CO2 in C. aceticum.
Mesial temporal lobe epilepsy (mTLE) is a common form of epilepsy and is characterized by recurrent spontaneous seizures originating from the temporal lobe. The majority of mTLE patients develop pharmacoresistance to available anti-epileptic drugs (AEDs) while exhibiting severe pathological changes that can include hippocampal atrophy, neuronal death, gliosis and chronic seizures. The molecular mechanisms leading to mTLE remain incompletely understood, but are known to include defects in post-transcriptional gene expression regulation, including in non-coding RNAs (ncRNAs). Circular RNAs (circRNAs) are a class of recently rediscovered ncRNAs with high levels of expression in the brain and proposed roles in diverse neuronal processes. To explore a potential role for circRNAs in epilepsy, RNA-sequencing (RNA-seq) was performed on hippocampal tissue from a rat perforant pathway stimulation (PPS) model of TLE at different post-stimulation time points. This analysis revealed 218 differentially expressed (DE) circRNAs. Remarkably, the majority of these circRNAs were changed at the time of the occurrence of the first spontaneous seizure (DOFS). The expression pattern of two circRNAs, circ_Arhgap4 and circ_Nav3, was further validated and linked to miR-6328 and miR-10b-3p target regulation, respectively. This is the first study to examine the regulation of circRNAs during the development of epilepsy. It reveals an intriguing link between circRNA deregulation and the transition of brain networks into the state of spontaneous seizure activity. Together, our results provide a molecular framework for further understanding the role and mechanism-of-action of circRNAs in TLE.
Human societies are characterized by three constituent features, besides others. (A) Options, as for jobs and societal positions, differ with respect to their associated monetary and non-monetary payoffs. (B) Competition leads to reduced payoffs when individuals compete for the same option as others. (C) People care about how they are doing relatively to others. The latter trait –the propensity to compare one’s own success with that of others– expresses itself as envy. It is shown that the combination of (A)–(C) leads to spontaneous class stratification. Societies of agents split endogenously into two social classes, an upper and a lower class, when envy becomes relevant. A comprehensive analysis of the Nash equilibria characterizing a basic reference game is presented. Class separation is due to the condensation of the strategies of lower-class agents, which play an identical mixed strategy. Upper-class agents do not condense, following individualist pure strategies. The model and results are size-consistent, holding for arbitrary large numbers of agents and options. Analytic results are confirmed by extensive numerical simulations. An analogy to interacting confined classical particles is discussed.
The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.
In patients with von Willebrand disease (vWD) the interest in age-related comorbidities has grown, because the life expectancy of these patients has increased. The research question of this study was whether patients with vWD show a different endothelial function compared to the general population. A total of 37 patients with type 1 (n = 23), type 2 (n = 10) and type 3 (n = 4) vWD, 14 controls and 38 patients with coronary artery disease (CAD) were included in this study. Five markers of endothelial dysfunction (MOED) were determined. Moreover, the endothelial function was examined using the Itamar Endo-PAT. The reactive hyperemia index (RHI) was calculated from the results. The markers soluble intercellular adhesion molecule-1 (p = 0.171), P-Selectin (p = 0.512), interleukin-6 (p = 0.734) and monocyte chemoattractant protein-1 (p = 0.761) showed higher levels in patients with vWD, but were not significantly different compared to the control group. RHI was impaired in CAD-patients (1.855), whereas vWD patients had mean results of 1.870 and controls 2.112 (p = 0.367). In this study, the endothelial function measurements of patients with von Willebrand disease were not significantly different compared to healthy controls.
Interleukin-7 (IL-7) is an important cytokine with pivotal pro-survival functions in the adaptive immune system. However, the role of IL-7 in innate immunity is not fully understood. In the present study, the impact of hepatic IL-7 on innate immune cells was assessed by functional experiments as well as in patients with different stages of liver cirrhosis or acute-on-chronic liver failure (ACLF). Human hepatocytes and liver sinusoidal endothelial cells secreted IL-7 in response to stimulation with interferons (IFNs) of type I and II, yet not type III. De novo translation of interferon-response factor-1 (IRF-1) restricted IL-7 production to stimulation with type I and II IFNs. LPS-primed human macrophages were identified as innate immune target cells responding to IL-7 signaling by inactivation of Glycogen synthase kinase-3 (GSK3). IL-7-mediated GSK3 inactivation augmented LPS-induced secretion of pro-inflammatory cytokines and blunted LPS tolerance of macrophages. The IFN-IRF-1-IL-7 axis was present in liver cirrhosis patients. However, liver cirrhosis patients with or without ACLF had significantly lower concentrations of IL-7 in serum compared to healthy controls, which might contribute to LPS-tolerance in these patients. In conclusion, we propose the presence of an inflammatory cascade where IFNs of type I/II induce hepatocellular IL-7 in an IRF-1-restriced way. Beyond its role in adaptive immune responses, IL-7 appears to augment the response of macrophages to LPS and to ameliorate LPS tolerance, which may improve innate immune responses against invading pathogens.
Einleitung: Der Typ 1 Diabetes (T1D) ist eine Autoimmunendokrinopathie, die mit zahlreichen Langzeitkomplikationen assoziiert ist. Kardiovaskuläre Erkrankungen (CVD) stellen hierbei den zentralen Grund für Morbidität und Mortalität dar. Ihre Pathogenese wird zunehmend im Kontext autoimmunologischer Prozesse diskutiert. Wir konnten bereits zeigen, dass Vitamin D (VD) sowohl immunmodulatorische als auch gefäßprotektive Effekte vermittelt. Daher untersuchten wir, ob durch VD die inflammatorische Aktivität CD8+ zytotoxischer T-Zellen (CTL) von Patienten mit T1D ohne und mit kardiovaskulärer Komplikation beeinflusst werden kann.
Methoden: Primär isolierte CTLs von sowohl Patienten mit T1D ohne (T1D Ø CVD, n = 20) und mit CVD (T1D + CVD, n = 20) als auch von gesunden Kontrollprobanden (HCs , n = 20) wurden über 72 h in An- bzw. Abwesenheit (+/-VD) von VD (1,25(OH)2D3) kultiviert. Die relative mRNA-Transkriptmenge der Zytokine IL-2, TNF-α, IFN-γ, IL-4, IL-6 und IL-10 sowie der Zelloberflächen- und Seneszenzmarker CD28, CD57 und CD95 wurde mittels RTqPCR analysiert. Zudem wurde die Proteinkonzentration der sezernierten Zytokine mittels CBA quantifiziert.
Ergebnisse: Die VD-Behandlung in vitro reduzierte die relative mRNA-Transkriptmenge von IL-2 (p = 0.01 und p = 0.02 resp.) und IFN-γ (p = 2x10-6 resp.) in CTLs von Patienten und HCs während die Genexpression von IL-4 (p = 2x10-6 und p = 2x10-3 resp.) und IL-6 (p = 2x10-6 und p = 4x10-6 resp.) erhöht wurde. Überdies war der VD-Effekt (ΔVDbehandelt-unbehandelt) auf die IL-4 Genexpression bei T1D + CVD stärker ausgeprägt als in der Kontrollgruppe (1.7 vs. 1.1; p = 0.03). Subgruppenanalysen zeigten zudem eine reduzierte IL-2 Genexpression durch die Behandlung mit VD in vitro bei T1D + CVD bei manifester diabetischer Nephropathie (142 vs. 97; p = 0.04) wohingegen dies bei erhaltener Nierenfunktion nicht beobachtet werden konnte (62 vs. 56; p = 0.31).
Schlussfolgerung: Die breite Modifikation der Genexpressionslevel untersuchter Zytokine bestätigt den immunmodulatorischen Effekt von VD bei Patienten mit T1D und kardiovaskulärer Komplikation. Die stark reduzierte Genexpression des pro-inflammatorischen IFN-γ legt hierbei einen potenziellen Effekt von VD in der Prävention chronisch-inflammatorischer Prozesse nahe. Die gruppenübergreifend unterschiedlich ausgeprägten VD-Effekte auf die Genexpression von IL-4 sowie die Subgruppenanalysen deuten jedoch auf eine relevante Heterogenität der immunmodulatorischen VD-Effekte hin: sowohl der individuelle klinische Zustand unter Einbeziehung assoziierter Komorbiditäten wie der diabetischen Nephropathie als auch die genetischen Variationen des VD-Systems müssen in groß angelegten Follow-up-Studien weiter untersucht werden, um optimale VD-Dosis-Effekte für klinisch relevante Subgruppen zu identifizieren.
In dieser Arbeit werden die Ergebnisse quantenchemischer Untersuchungen von verschiedenen Siliciumverbindungsklassen vorgestellt, die in weiten Teilen als Begleitung zu experimentellen Arbeiten durchgeführt wurden. Das erste Hauptkapitel befasst sich mit den Chloridkomplexen von Perchlorsilanen, zu denen die inversen Sandwichkomplexe und die Silafullerane mit endohedralem Gast gehören. Der Fokus liegt dabei auf den Bindungseigenschaften zwischen Ligand und Silan. Weiterhin werden thermodynamische Untersuchungen zu Aufbaureaktionen und Eigenschaften der Verbindungen vorgestellt. Mit den durchgeführten Rechnungen kann gezeigt werden, dass durch Wahl geeigneter Substituenten am Siliciumatom ein Wechsel in den Chloridkomplexen von einem hyperkoordinierten Siliciumatom hin zu einem Siliciumatom mit ausgebildeter Tetrelbindung erreicht werden kann. Bei den inversen Sandwichkomplexen sind beide Bindungsmodi möglich, von denen die Tetrelbindung die stärkere darstellt. Neben Chloridionen können hier auch Nitrile und Chlorsubstituenten am eigenen Silangerüst als Liganden fungieren. Die stärksten Tetrelbindungen können bei den endohedral funktionalisierten Silafullerankomplexen gefunden werden. Hier stellt das experimentell isolierte Strukturmotiv mit zwölf äußeren Trichlorsilylsubstituenten das thermodynamisch stabilste Substitutionsmuster dar. Im folgenden Kapitel werden die generellen physikalischen Ursachen für die beobachteten thermodynamischen Trends zwischen Perchlorsilanisomeren sowie Disproportionierungsreaktionen behandelt und ein direkter Vergleich mit Alkanhomologen angestellt. Bei den Perchlorsilanen und den meisten Homologen ist bei den untersuchten Systemen eine energetische Präferenz von verzweigteren Strukturen zu erkennen. Die Ursache hierfür liegt hauptsächlich bei stärkeren attraktiven Wechselwirkungen durch Korrelationseffekte, Hyperkonjugation sowie elektrostatische Effekte, welche stärkere repulsive Wechselwirkungen wie die Pauli-Repulsion überkompensieren. Im letzten Kapitel kommen zu den bisher behandelten Reaktionen unter Si-Cl- und Si-Si-Bindungsbeteiligung noch Reaktionen unter Si-C-Bindungsbeteiligungen hinzu. Dort werden die auch wegen ihrer Elektronentransporteigenschaften interessanten Silacyclopentadiene (Silole) hinsichtlich ihrer Isomerisierung, Dimerisierung und weiteren pericyclischen Reaktivität untersucht. Gegenüber dem verwandten Cyclopentadien zeigen diese eine deutlich erhöhte Reaktivität, was zu verschiedenen Dimerisierungsreaktionen führt, solange keine Abfangreagenzien im Überschuss zugegen sind.
Although the elderly are more vulnerable to COVID-19, the empirical evidence suggests that they do not behave more cautiously in the pandemic than younger individuals. This theoretical model argues that some individuals might not comply with the COVID-19 measures to reassure themselves that they are not vulnerable, and that the incentives for such self-signaling can be stronger for the elderly. The results suggest that communication strategies emphasizing the dangers of COVID-19 could backfire and reduce compliance among the elderly.
We study risk taking in a panel of subjects in Wuhan, China - before, during the COVID-19 crisis, and after the country reopened. Subjects in our sample traveled for semester break in January, generating variation in exposure to the virus and quarantine in Wuhan. Higher exposure leads subjects to reduce planned risk taking, risky investments, and optimism. Our findings help unify existing studies by showing that aggregate shocks affect general preferences for risk and economic expectations, while heterogeneity in experience further affect risk taking through beliefs about individuals’ own outcomes such as luck and sense of control.
JEL Classification: G50, G51, G11, D14, G41
Alman Anayasası velilere, öğrencilere ve dinî cemaatlere eğitim alanında haklar ve yetkiler tanımaktadır. Buna göre veliler ve öğrenciler doğrudan hak sahibi iken dinî cemaatler bu hakkın devletle birlikte taşıyıcısı ve uygulayıcısıdır. Anayasa; devletin, din dersi verme sorumluluğunu dinî cemaatlerle paylaşması gerektiğini ve din derslerini, dinî cemaatlerle uyum, anlaşma ve iş birliği içerisinde vermek zorunda olduğunu hükme bağlamıştır. Bu bağlamda din derslerinin, Devlet’in şekline ve Anayasa’sına halel getirmeden kiliselerin veya dinî cemaatlerin tasavvuru çerçevesinde verilmesi ve organize edilmesi öngörülmüştür. Bu makalede Devlet tarafından teminat altına alınan bu hak ve özgürlüklerin Alman okullarında uygulanabilmesi için söz konusu mevzuatın incelenerek okula, aileye ve ilgili cemaatlere düşen görev ve sorumlulukların belirlenmesi amaçlanmaktadır. Makalede anayasal çerçevesi ve hukuki statüsü incelenecek olan din dersleri meselesi, okullarda verilecek İslam din öğretimini yakından ilgilendirmektedir. Bu anlamda öncelikle Almanya’da din öğretiminin yasal dayanakları ile dinî cemaatlerin hukuki statüleri ortaya konulmuş, sonra da Almanya’da zorunlu temel öğretim kademelerinde okuyan Müslüman öğrencilere yönelik düzenlenen İslam din derslerine yer verilmiştir