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Distributed ledger technology especially in the form of publicly coordinated validation networks such as Ethereum and Bitcoin with their own monetary circles provide for a revealing litmus test for current financial regulatory schemes. The paper highlights the interrelation between distributed coordination and the emission of virtual currency to make sense of the function of the new monetary phenomenon. It then argues for the regulation of financial services on the ground of the technology to ensure integrity standards. In this respect, it is useful to gear the development of a regulatory scheme towards the existing financial regulatory principles. However, future measures of the regulators must take the distributed nature of the platforms into account by relying on a “regulated self-regulation” of the community. Finally, the article focuses on the shortcomings of the current EU regulatory regimes, especially the regulation frameworks regarding financial services, payment services and electronic money.
Recently, Fuest and Sinn (2018) have demanded a change of rules for the Eurozone’s Target 2 payment system, claiming it would violate the Statutes of the European System of Central Banks and of the European Central Bank. The authors present a stylized model based on a set of macro-economic assumptions, and show that Target 2 may lead to loss sharing among national central banks (NCBs), thus violating the no risk-sharing requirement laid out by the Eurosystem Statutes.
In this note, I present an augmented model that incorporates essential features of the micro- and macroprudential regulatory and supervisory regime that today is hard-wired into Europe’s banking system. The model shows that the original no-risk-sharing principle is not necessarily violated during a financial crisis of a member state. Moreover, it shows that under a banking union regime, financial crisis asset value losses at or below the 99.9th percentile are borne by private investors, not by taxpayers, and particularly not by central banks.
Therefore, policy conclusions from the micro-founded model differ significantly from those suggested by Fuest and Sinn (2018).
n der Literatur wird oftmals angeführt, dass die Grunderwerbsteuer weder aus Sicht des Äquivalenzprinzips noch aus Sicht des Leistungsfähigkeitsprinzips zu rechtfertigen ist und daher in einem modernen Steuersystem nichts verloren hätte. Das vorliegende Papier weist darauf hin, dass die Grunderwerbsteuer Parallelen zur Grundsteuer aufweist und sich, zumindest aus ökonomischer Sicht, in eine Grundsteuer umbauen ließe. Dies könnte insbesondere dann interessant sein, wenn die derzeitige deutsche Grundsteuer in eine reine Flächensteuer umgebaut wird, die den Wert der Bebauung unbesteuert lässt. Ein Umbau der Grunderwerbsteuer, bei der der Kaufpreis dynamisiert wird und dann einer jährlichen Steuer unterworfen wird, hat einige Vorteile. Diese resultieren daraus, dass der negative Effekt auf die Zahl der Immobilientransaktionen (Lock-in-Effekt) abgemildert würde. Könnte die Dynamisierung treffsicher an die regionale Immobilienpreisentwicklung angepasst werden, entfällt der Lock-in-Effekt für Immobilien, die bereits einmal der dynamisierten Grunderwerbsteuer unterworfen waren, sogar komplett. Dies hat nicht nur positive Effekte auf das Funktionieren des Wohnungs- und Arbeitsmarktes, sondern kann auch dem Problem der Share Deals entgegen wirken.
We report on the observation of coherent terahertz (THz) emission from the quasi-one-dimensional charge-density wave (CDW) system, blue bronze (K0.3MoO3), upon photo-excitation with ultrashort near-infrared optical pulses. The emission contains a broadband, low-frequency component due to the photo-Dember effect, which is present over the whole temperature range studied (30–300 K), as well as a narrow-band doublet centered at 1.5 THz, which is only observed in the CDW state and results from the generation of coherent transverse-optical phonons polarized perpendicular to the incommensurate CDW b-axis. As K0.3MoO3 is centrosymmetric, the lowest-order generation mechanism which can account for the polarization dependence of the phonon emission involves either a static surface field or quadrupolar terms due to the optical field gradients at the surface. This phonon signature is also present in the ground-state conductivity, and decays in strength with increasing temperature to vanish above $T\sim 100\,{\rm{K}}$, i.e. significantly below the CDW transition temperature. The temporal behavior of the phonon emission can be well described by a simple model with two coupled modes, which initially oscillate with opposite polarity.
Spheroids resemble features of tissues and serve as model systems to study cell–cell and cell–ECM interactions in non-adhesive three-dimensional environments. Although it is generally accepted that mature spheroids resemble tissue properties very well, no studies relate different phases in the spheroid formation processes that contribute to tissue integrity. Tissue integrity involves the cellular processes adhesion formation, adhesion reinforcement, rearrangement as well as proliferation. They maintain the structure and function of tissues and, upon dysregulation, contribute to malignancy. We investigated spheroid formation dynamics in cell lines of different metastatic potential. We dissected spheroid formation into phases of aggregation, compaction and growth to identify the respective contributions of E-cadherin, actin, microtubules and FAK. E-cadherin, actin and microtubules drive the first two phases. Microtubules and FAK are involved in the proliferation phase. FAK activity correlates with the metastatic potential of the cells. A robust computational model based on a very large number of experiments reveals the temporal resolution of cell adhesion. Our results provide novel hypotheses to unveil the general mechanisms that contribute to tissue integrity.
Meinungsbeitrag vor dem Hintergrund der Veröffentlichungen The German White Paper 2016 and the Challenge of Crafting Security Strategies, Frankfurt und Berlin: Goethe Universität und Aspen Institute Germany (2019) und Das Weißbuch 2016 und die Herausforderungen von Strategiebildung (ZfAS Sonderheft 2019), Wiesbaden: Springer VS Verlag für Sozialwissenschaften (2019)
Background: Pulmonary nocardiosis (PN) is an uncommon but potentially life-threatening infection. Most of our knowledge is derived from case reports or smaller case series. Recently, increasing PN incidence rates have been reported. We aim to describe the clinical course of and risk factors for PN in four Western European countries and to estimate population-based annual hospitalization rates.
Methods: Retrospective evaluation (1995 to 2011) of the clinical course of and risk factors for PN in patients from 11 hospitals in four European countries (Germany, Austria, Switzerland and The Netherlands). Calculation of population-based estimates of hospitalization rates of PN in Germany (2005 to 2011) using official German nationwide diagnosis-related groups (DRG) hospital statistics.
Results: Forty-three patients fulfilled stringent criteria for proven (n = 8) and probable (n = 35) PN; seven with extrapulmonary dissemination. Within the 43 patients, major PN risk factors were immunocompromising (83.7%) and/or pulmonary (58.1%; in 27.9% as only comorbidity) comorbidities. Median duration of PN targeted therapy was 12 weeks. Distinguished patterns of resistance were observed (imipenem susceptibility: N. farcinica 33.3%; N. asteroides 66.7%). Overall mortality rate was 18.9%; in disseminated PN 50%. Over time, annual PN hospitalization rates remained unchanged at around 0.04/100′000 with the highest rate among men aged 75–84 years (0.24/100′000).
Conclusion: PN is rare, but potentially life-threatening, and mainly affects immunocompromised elder males. Overall annual hospitalization rates remained stable between 2005 and 2011.
Heat stress transcription factors (HSFs) regulate transcriptional response to a large number of environmental influences, such as temperature fluctuations and chemical compound applications. Plant HSFs represent a large and diverse gene family. The HSF members vary substantially both in gene expression patterns and molecular functions. HEATSTER is a web resource for mining, annotating, and analyzing members of the different classes of HSFs in plants. A web-interface allows the identification and class assignment of HSFs, intuitive searches in the database and visualization of conserved motifs, and domains to classify novel HSFs.
Objective: Inhaled particulate matter (PM) in secondhand smoke (SHS) is deleterious for smokers and non-smokers. Different additives in cigarettes might effect the amount of PM. This study aimed to assess the influence of additives on the PM emissions from different cigarette types in SHS.
Design: An experimental study of PM measuring in SHS of cigarettes without exposition of any person.
Method: The concentrations of PM (PM10, PM2.5 and PM1) in SHS of four different types of cigarettes of the brand Lucky Strike, two types with additives (Original Red, Original Blue) and two types without additives (Straight Red, Straight Blue), in comparison to the reference cigarette 3R4F were analysed. An automatic environmental tobacco smoke emitter generated SHS in an enclosed space with a volume of 2.88 m3. PM was measured with a laser aerosol spectrometer (Grimm model 1.109). Afterwards, the measuring values of the four Lucky Strike brands and the reference cigarette were statistically evaluated and visualised.
Results: Lucky Strike Straight Blue, a cigarette type without additives and lower tar amount, showed 10% to 25% lower PM mean values compared with the other tested Lucky Strike products, but 21% (PM1) respectively 27% (PM2.5,PM10) higher mean values than the reference cigarette. The PM mean of all measured smoke-free baseline values (clean air) was 1.6 µg/m³. It increased up to about 1800 µg/m³ for the reference cigarette and up to about 3070 µg/m³ for the Lucky Strike Original Blue.
Conclusions: The findings of this study show the massive increase of PM amount by smoking cigarettes in enclosed spaces and suggest that additives in tobacco products increase the PM amount in SHS. For validation, further comparative studies are necessary focusing on the comparison of the PM concentration of cigarettes with and without additives.
Implications: Due to the exposure to SHS, 890 000 people die each year worldwide. PM in SHS endangers the health of both non-smokers and smokers. This study considers the effect of additives like aromatics and humectant agents in cigarettes on PM in SHS. Do additives in tobacco products increase the amount of PM?
By running a temperature series of molecular dynamics (MD) simulations starting from the known low-temperature phase, the experimentally observed phase transition in a `jumping crystal' was captured, thereby providing a prediction of the unknown crystal structure of the high-temperature phase and clarifying the phase-transition mechanism. The phase transition is accompanied by a discontinuity in two of the unit-cell parameters. The structure of the high-temperature phase is very similar to that of the low-temperature phase. The anisotropic displacement parameters calculated from the MD simulations readily identified libration as the driving force behind the phase transition. Both the predicted crystal structure and the phase-transition mechanism were verified experimentally using TLS (translation, libration, screw) refinement against X-ray powder diffraction data.
We propose a shrinkage and selection methodology specifically designed for network inference using high dimensional data through a regularised linear regression model with Spike-and-Slab prior on the parameters. The approach extends the case where the error terms are heteroscedastic, by adding an ARCH-type equation through an approximate Expectation-Maximisation algorithm. The proposed model accounts for two sets of covariates. The first set contains predetermined variables which are not penalised in the model (i.e., the autoregressive component and common factors) while the second set of variables contains all the (lagged) financial institutions in the system, included with a given probability. The financial linkages are expressed in terms of inclusion probabilities resulting in a weighted directed network where the adjacency matrix is built “row by row". In the empirical application, we estimate the network over time using a rolling window approach on 1248 world financial firms (banks, insurances, brokers and other financial services) both active and dead from 29 December 2000 to 6 October 2017 at a weekly frequency. Findings show that over time the shape of the out degree distribution exhibits the typical behavior of financial stress indicators and represents a significant predictor of market returns at the first lag (one week) and the fourth lag (one month).
Extending the data set used in Beyer (2009) to 2017, we estimate I(1) and I(2) money demand models for euro area M3. After including two broken trends and a few dummies to account for shifts in the variables following the global financial crisis and the ECB's non-standard monetary policy measures, we find that the money demand and the real wealth relations identified in Beyer (2009) have remained remarkably stable throughout the extended sample period. Testing for price homogeneity in the I(2) model we find that the nominal-to-real transformation is not rejected for the money relation whereas the wealth relation cannot be expressed in real terms.
Feathers are arranged in a precise pattern in avian skin. They first arise during development in a row along the dorsal midline, with rows of new feather buds added sequentially in a spreading wave. We show that the patterning of feathers relies on coupled fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) signalling together with mesenchymal cell movement, acting in a coordinated reaction-diffusion-taxis system. This periodic patterning system is partly mechanochemical, with mechanical-chemical integration occurring through a positive feedback loop centred on FGF20, which induces cell aggregation, mechanically compressing the epidermis to rapidly intensify FGF20 expression. The travelling wave of feather formation is imposed by expanding expression of Ectodysplasin A (EDA), which initiates the expression of FGF20. The EDA wave spreads across a mesenchymal cell density gradient, triggering pattern formation by lowering the threshold of mesenchymal cells required to begin to form a feather bud. These waves, and the precise arrangement of feather primordia, are lost in the flightless emu and ostrich, though via different developmental routes. The ostrich retains the tract arrangement characteristic of birds in general but lays down feather primordia without a wave, akin to the process of hair follicle formation in mammalian embryos. The embryonic emu skin lacks sufficient cells to enact feather formation, causing failure of tract formation, and instead the entire skin gains feather primordia through a later process. This work shows that a reaction-diffusion-taxis system, integrated with mechanical processes, generates the feather array. In flighted birds, the key role of the EDA/Ectodysplasin A receptor (EDAR) pathway in vertebrate skin patterning has been recast to activate this process in a quasi-1-dimensional manner, imposing highly ordered pattern formation.
Dieses Dokument beschreibt Use Cases und daraus resultierende Anforderungen für Forschungsdatenrepositorien im Rahmen des HeFDI-Projektes. Es baut auf die von der Unterarbeitsgruppe Repositorien erarbeiteten Ergebnisse auf, die im Dokument Anforderungsspezifikation V3 der Unterarbeitsgruppe spezifiziert wurden. Das vorliegende Dokument ist ein aktives Dokument, das während der Laufzeit des HeFDI-Projektes geändert werden kann.
Gegenstand der vorliegenden Arbeit ist die postulierte operationale Komplementarität von Selbstkonstruktion und Selbstorganisation. Den Ausgangspunkt der Überlegungen hierzu bilden die sich mehrenden Hinweise seitens der Neuro- und Kognitionswissenschaften, die auf die Wichtigkeit sozialer und kultureller Realitäten für die wissenschaftliche Auseinandersetzung mit Bewusstsein und speziell Selbstbewusstsein im Sinne von Metakognition deuten. Das zentrale Erkenntnisinteresse dieser Arbeit gilt dabei der Frage nach der Viabilität des Selbst. Theoriegrundlage ist damit das radikal-konstruktivistische Viabilitätskonzept, welches als instrumentale Perspektive die Gangbarkeit oder Funktionalität von Wirklichkeitskonstruktionen adressiert. Entscheidend ist damit nicht die Klärung des ontologischen Status des Selbst, nicht die Frage, was das Selbst ist, sondern wann oder wozu es ist. Selbstkonstruktion, so wird in dieser Arbeit grundlegend vorausgesetzt, vollzieht sich prinzipiell in Abhängigkeit der Konstruktion aller anderen Lebenszustände des Menschen. Verbunden damit ist die Grundannahme, dass Selbstkonstruktion aufgrund der operationalen Komplementarität zur Selbstorganisation nicht nur eine alleinige Angelegenheit des isolierten Individuums ist, sondern synchron in Mikro- und Makroebenen aller menschlichen Lebenszusammenhänge fließt. Entwicklungsgeschichtlich finden diese Zusammenhänge ihren Widerhall in Zwecksetzung und Antizipation und resultieren in der Erschließung neuer Existenzbereiche. „Selbstorganisation“ als kreative, selbstreferentielle Wahrnehmungstätigkeit äußert sich dabei in dem menschlichen Hinzufügen oder Verwerfen von Bedeutungszusammenhängen und der Konstruktion von Selektivität. Das „Verhältnis“ zwischen Selbstkonstruktion und Selbstorganisation definiert sich über koevolutionäre Entwicklungsprozesse und ist damit eine Dimension struktureller Kopplungen. Vor dem fachlichen Hintergrund der Kulturanthropologie versteht sich die vorliegende Arbeit als Beitrag zur holistischen Untersuchung von Veränderungsdynamiken menschlicher Selbstorganisation und den daran geknüpften Bedeutungskonstruktionen.
Warum versucht sich ein zu diesem Zeitpunkt berühmter Gelehrter wie Georg Simmel, der ja 1900 "Philosophie des Geldes" publiziert, in der Dichtung? Ganz unabhängig von seinem Scheitern in diesem Fach möchte ich im Folgenden diese Frage ausweiten und in den Kontext einer umfassenderen Beobachtung stellen. Nämlich der, dass sich im Laufe der langen Jahrhundertwende Texte herausbilden, die in ihrer Form einmalig oder zumindest besonders sind und zu denen auch viele Arbeiten von Georg Simmel gehören – nicht nur die, die er als Momentbilder publiziert. In einem ersten Schritt werde ich diese neuen Texte der langen Jahrhundertwende beschreiben, um im Anschluss Überlegungen dazu anzustellen, welche Bedingungen diese Formen begünstigt haben. Abschließend wende ich mich kurz einem Vergleich von Simmel und Benjamin zu, um auf diese Weise aufzuzeigen, dass für diese Texte die Formation mehr ist als nur Grundlage für die Vermittlung von Konzepten und selbst eine konzeptuelle Funktion übernehmen soll. Daher ist es hilfreich, die jeweils formalen Strukturen und Modi genauer unter die Lupe zu nehmen. Ich werde mich Simmel also nicht aus der Perspektive der Soziologie oder Kunstphilosophie nähern, sondern aus der einer kulturwissenschaftlichen Literaturwissenschaft.
Increasing atmospheric CO2 stimulates photosynthesis which can increase net primary production (NPP), but at longer timescales may not necessarily increase plant biomass. Here we analyse the four decade-long CO2-enrichment experiments in woody ecosystems that measured total NPP and biomass. CO2 enrichment increased biomass increment by 1.05 ± 0.26 kg C m−2 over a full decade, a 29.1 ± 11.7% stimulation of biomass gain in these early-secondary-succession temperate ecosystems. This response is predictable by combining the CO2 response of NPP (0.16 ± 0.03 kg C m−2 y−1) and the CO2-independent, linear slope between biomass increment and cumulative NPP (0.55 ± 0.17). An ensemble of terrestrial ecosystem models fail to predict both terms correctly. Allocation to wood was a driver of across-site, and across-model, response variability and together with CO2-independence of biomass retention highlights the value of understanding drivers of wood allocation under ambient conditions to correctly interpret and predict CO2 responses.
Golgi phosphoprotein 3 (GOLPH3) is a conserved protein of the Golgi apparatus that in humans has been implicated in tumorigenesis. However, the precise function of GOLPH3 in malignant transformation is still unknown. Nevertheless, clinicopathological data shows that in more than a dozen kinds of cancer, including gliomas, GOLPH3 could be found overexpressed, which correlates with poor prognosis. Experimental data shows that overexpression of GOLPH3 leads to transformation of primary cells and to tumor growth enhancement. Conversely, the knocking down of GOLPH3 in GOLPH3-overexpressing tumor cells reduces tumorigenic features, such as cell proliferation and cell migration and invasion. The cumulative evidence indicate that GOLPH3 is an oncoprotein that promotes tumorigenicity by a mechanism that impact at different levels in different types of cells, including the sorting of Golgi glycosyltransferases, signaling pathways, and the actin cytoskeleton. How GOLPH3 connects mechanistically these processes has not been determined yet. Further studies are important to have a more complete understanding of the role of GOLPH3 as oncoprotein. Given the genetic diversity in cancer, a still outstanding aspect is how in this inherent heterogeneity GOLPH3 could possibly exert its oncogenic function. We have aimed to evaluate the contribution of GOLPH3 overexpression in the malignant phenotype of different types of tumor cells. Here, we analyzed the effect on cell migration that resulted from stable, RNAi-mediated knocking down of GOLPH3 in T98G cells of glioblastoma multiforme, a human glioma cell line with unique features. We found that the reduction of GOLPH3 levels produced dramatic changes in cell morphology, involving rearrangements of the actin cytoskeleton and reduction in the number and dynamics of focal adhesions. These effects correlated with decreased cell migration and invasion due to affected persistence and directionality of cell motility. Moreover, the knocking down of GOLPH3 also caused a reduction in autoactivation of focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase that regulates focal adhesions. Our data support a model in which GOLPH3 in T98G cells promotes cell migration by stimulating the activity of FAK.
The trade in bear parts for medicine and for status is a conservation challenge throughout Asia. The Asiatic black bear (Ursus thibetanus) and the sun bear (Helarctos malayanus) are endemic to this region, and populations are estimated to have declined throughout their ranges due to widespread illegal killing of bears and trade in parts, combined with loss of habitat. Previous studies have indicated that legislation alone is insufficient to prevent illegal hunting and trade, indicating instead a need to address demand for bear parts and products. We conducted mixed-method surveys in Cambodia to understand the key motivators for individuals to consume bear parts, and to understand whether specialised questioning techniques are applicable in this context. Bear part use is illegal in Cambodia and may therefore be considered a sensitive behaviour, in that individuals may be reluctant to admit to it. To counteract possible biases, four specialised questioning techniques were used in this study: randomised response technique (RRT), unmatched count technique (UCT), nominative technique (NT), and false consensus bias (FCB). All four methods serve to shield a respondent’s admittance of a sensitive behaviour from the interviewer. The results presented here show that great variability exists in anonymous methods’ efficacy in certain contexts. However, the results overall indicate that individuals in Cambodia are under-reporting their consumption of bear parts when directly asked, and that the prevalence of bear part use in Cambodia may be as high as 15% of the population, representing a significant conservation challenge.
The hepatitis C virus (HCV) RNA replication cycle is a dynamic intracellular process occurring in three-dimensional space (3D), which is difficult both to capture experimentally and to visualize conceptually. HCV-generated replication factories are housed within virus-induced intracellular structures termed membranous webs (MW), which are derived from the Endoplasmatic Reticulum (ER). Recently, we published 3D spatiotemporal resolved diffusion–reaction models of the HCV RNA replication cycle by means of surface partial differential equation (sPDE) descriptions. We distinguished between the basic components of the HCV RNA replication cycle, namely HCV RNA, non-structural viral proteins (NSPs), and a host factor. In particular, we evaluated the sPDE models upon realistic reconstructed intracellular compartments (ER/MW). In this paper, we propose a significant extension of the model based upon two additional parameters: different aggregate states of HCV RNA and NSPs, and population dynamics inspired diffusion and reaction coefficients instead of multilinear ones. The combination of both aspects enables realistic modeling of viral replication at all scales. Specifically, we describe a replication complex state consisting of HCV RNA together with a defined amount of NSPs. As a result of the combination of spatial resolution and different aggregate states, the new model mimics a cis requirement for HCV RNA replication. We used heuristic parameters for our simulations, which were run only on a subsection of the ER. Nevertheless, this was sufficient to allow the fitting of core aspects of virus reproduction, at least qualitatively. Our findings should help stimulate new model approaches and experimental directions for virology.
Mitochondrial ATP synthases form dimers, which assemble into long ribbons at the rims of the inner membrane cristae. We reconstituted detergent-purified mitochondrial ATP synthase dimers from the green algae Polytomella sp. and the yeast Yarrowia lipolytica into liposomes and examined them by electron cryotomography. Tomographic volumes revealed that ATP synthase dimers from both species self-assemble into rows and bend the lipid bilayer locally. The dimer rows and the induced degree of membrane curvature closely resemble those in the inner membrane cristae. Monomers of mitochondrial ATP synthase reconstituted into liposomes do not bend membrane visibly and do not form rows. No specific lipids or proteins other than ATP synthase dimers are required for row formation and membrane remodelling. Long rows of ATP synthase dimers are a conserved feature of mitochondrial inner membranes. They are required for cristae formation and a main factor in mitochondrial morphogenesis.
Precise slow oscillation-spindle coupling promotes memory consolidation in younger and older adults
(2019)
Memory consolidation during sleep relies on the precisely timed interaction of rhythmic neural events. Here, we investigate differences in slow oscillations (SO; 0.5–1 Hz), sleep spindles (SP), and their coupling across the adult human lifespan and ask whether observed alterations relate to the ability to retain associative memories across sleep. We demonstrate that older adults do not show the fine-tuned coupling of fast SPs (12.5–16 Hz) to the SO peak present in younger adults but, instead, are characterized most by a slow SP power increase (9–12.5 Hz) at the end of the SO up-state. This slow SP power increase, typical for older adults, coincides with worse memory consolidation in young age already, whereas the tight precision of SO–fast SP coupling promotes memory consolidation across younger and older adults. Crucially, brain integrity in source regions of SO and SP generation, including the medial prefrontal cortex, thalamus, hippocampus and entorhinal cortex, reinforces this beneficial SO–SP coupling in old age. Our results reveal that cognitive functioning is not only determined by maintaining structural brain integrity across the adult lifespan, but also by the preservation of precisely timed neural interactions during sleep that enable the consolidation of declarative memories.
Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato (s.l.) complex differ in their ability to establish infection and to survive in diverse vertebrate hosts. Association with and adaption to various hosts most likely correlates with the spirochetes' ability to acquire complement regulator factor H (FH) to overcome the host's innate immune response. Here we assessed binding of serum FH from human and various animals including bovine, cat, chicken, dog, horse, mouse, rabbit, and rat to viable B. burgdorferi sensu stricto (s.s.), B. afzelii, B. garinii, B. spielmanii, B. valaisiana, and B. lusitaniae. Spirochetes ectopically producing CspA orthologs of B. burgdorferi s.s., B. afzelii, and B. spielmanii, CspZ, ErpC, and ErpP, respectively, were also investigated. Our comparative analysis using viable bacterial cells revealed a striking heterogeneity among Lyme disease spirochetes regarding their FH-binding patterns that almost mirrors the serum susceptibility of the respective borrelial genospecies. Moreover, native CspA from B. burgdorferi s.s., B. afzelii, and B. spielmanii as well as CspZ were identified as key ligands of FH from human, horse, and rat origin while ErpP appears to bind dog and mouse FH and to a lesser extent human FH. By contrast, ErpC did not bind FH from human as well as from animal origin. These findings indicate a strong restriction of distinct borrelial proteins toward binding of polymorphic FH of various vertebrate hosts.
Introduction: Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration.
Methods: MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with (n = 22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS).
Results: Median age at diagnosis was 74 (range, 42–100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8, 58.6, and 47.1%, respectively. A positive MCPyV status was associated with female gender (p = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (p = 0.011) and combined CD8/PD-L1 expression (p = 0.038). Overall CD8+ infiltration was inversely associated with N-stage (p = 0.048). Stromal TILs correlated significantly with both PD-L1 expression (p = 0.010) and N-stage (p = 0.037). A high viral load (>median) was significantly associated with worse OS (p = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (p = 0.045).
Conclusion: These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches.
The optimal treatment strategy for secondary prevention in patients with cryptogenic stroke and patent foramen ovale (PFO) has been a matter of controversy for decades. After three randomized trials failed to show a benefit of closure with an excess of complications in the interventional arm, two large recent trials suggest a benefit with regard of preventing further ischemic strokes. With this discrepancy in results it is important to discuss recent trials in detail and evolve an informed clinical approach for daily practice.
Background: Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy.
Methods: The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9–10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5–9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect.
Discussion: The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery.
Trial registration: ClinicalTrials.gov (identifier: NCT03369210).
Komparatistik online 2019: Berühren. Relationen des Taktilen in Literatur, Philosophie und Theater
(2019)
Körper und ihre Sinneswahrnehmung gehören zu den Voraussetzungen von Literatur und, Philosophie; die Bestimmung ihrer Funktion zählt zugleich zu einer der schwierigsten und umstrittensten Aufgaben dieser Künste und Disziplinen. Der Komplex um das Berühren, zu dem Haptik, Taktilität und Gefühl, Motorik, Sensorik und Affektivität gleichermaßen gehören, ist in der Körper- und Sinnesgeschichte notorisch von Vernachlässigung bedroht, hat in den Kultur- und Medienwissenschaften aber zuletzt neue Aufmerksamkeit erfahren. Philologische Ansätze befinden sich derzeit noch am Rand dieser Debatten, obwohl ihre Begriffe und Verfahren sogar als besonders 'berührungsaffin' gelten können. Genaue philologische Lektüren bieten die Möglichkeit, das je singuläre Verhältnis von Affektion und Sinnlichkeit und die Bedeutung des Tastsinns im Zusammenspiel mit anderen Sinnen zu erfassen. Philologische Verfahren können das metaphorische Potenzial des Berührens ebenso ausloten wie sein Verhältnis zum 'Realen'. Die Beiträge dieses Bandes zur europäischen Literatur, aber auch zur Philosophie von der Antike bis ins späte 20. Jahrhundert untersuchen das Berühren als relationale Figur, in der poetische Gestaltung und Materialität, Bildlichkeit und Buchstäblichkeit, Begreifen und Ergreifen, Anschauung und Affizierung in Beziehung treten. Im Zentrum stehen Fragen nach dem Verhältnis von Gemeinschaft und Individualität, von Literatur und Philosophie sowie nach der Funktion von Ansteckungs- und Distanzierungsverfahren in diesen Zusammenhängen. Dabei geraten gerade auch Wahrnehmungsräume in den Blick, die zumeist unter dem Primat des Visuellen verhandelt wurden. In Re- und Gegenlektüren schlagen die Beiträge eine Ausweitung der Sinnesbezüge vor.
On the one side there is book culture, centered on the printed book as a material object; on the other digital culture, centered on what is displayed on a screen, by now more often than not that of a mobile phone. In the cultural imaginary, the two practices are separated by far more than just media technology. The girl in Delevingne's picture, in choosing to read a book rather than participate in the social media arena, opts (as the black-and-white blocking of the caption neatly reflects) for a commendable type of media use: She sharpens her intellect and exercises her imagination, she digs deep rather than staying on the surface, and she engages – in a seemingly disinterested manner – with valuable content rather than obsessing over how to present herself in the best light. Her absorption is a badge of honor, much different from the 'bad' absorption of digital media users, a recurring trope that is artistically represented, for example, in the much-acclaimed surrealist photo series "SURFAKE" by the French photographer Antoine Geiger, which represents mobile phone users whose faces are sucked into their devices.
The adaptation of disaster: representations of environmental crises in climate change fiction
(2019)
In light of climate change, the attempt to overcome the gap between the 'Two Cultures' appears more urgent than ever. With climate change being only one of the environmental crises marking the so-called Anthropocene, knowledge production and representations are constantly challenged. The very reason that led to the idea of proclaiming a new geological epoch can be taken as evidence for the collapse of the Cartesian dichotomy between nature and culture. The Anthropocene marks an epoch in Earth's history in which the human species has become a geological force. That is, the effects of industrialized civilization are now forming geological strata that irreversibly change the face of the planet and its future. However, if nature and culture cannot be meaningfully distinguished anymore, how, one might ask, is a divide within academia still of concern? Would it not naturally perish with the insight that what has been regarded as nature has now been thoroughly pervaded by remnants of human actions? To the contrary, the persistence of the gap between the sciences and the humanities is one of the main reasons that complicates the representation and, ultimately, hinders the understanding of the problems which characterize the new epoch. Inability or unwillingness to change behavior on a collective level will most probably lead to environmental, political and social disaster on an unprecedented scale.
In this article, I will argue for a different notion of adaptation as a form of appropriation that allows a more productive analysis of the literary works of German author Rainald Goetz. Therefore I will draw on a specific understanding of pop music, which derives from Diedrich Diederichsen 'Über Pop-Musik' (On pop music). According to Diederichsen, pop-music is not limited to certain kinds of music, but moreover to the practices pop-music entails.
In the early 21st century, scientists once more declared God a delusion and announced the end of faith, boosting the current critique of religious belief known as 'New Atheism'. Yet the contemporary British and Irish novel engage with religion in various forms, and religion has indeed "returned", Andrew Tate argues, "to the study of literature". The Bible in particular proves a rich source for novelists as different as Colm Tóibín, Zadie Smith, and Philip Pullman among others. Where Colm Tóibín's 'The Testament of Mary' (2012) offers a fictional memoir by the mother of God, depicting the Virgin Mary as "a powerful, unsparing figure" ('Guardian'), Zadie Smith's 'NW' (2012) describes the lives of its two female protagonists against the backdrop of the stories of Mary and Elizabeth in the Gospel of Luke. And Philip Pullman's bestselling trilogy 'His Dark Materials' (1995- 2000) is a re-writing of Milton's 'Paradise Lost' (1667) that "only really makes sense" according to Tate "if the reader has a detailed knowledge of the biblical scriptures against which it writes". Despite being written from a very critical, ironic or atheist stance, all these novels rely on the Bible as an intertext in crucial ways. The Bible, in other words, is once more living up to its ancient reputation as "the Book of Books", "the Urtext of Western literature".
The discipline of adaptation studies has come a long way from its academic inception in novel-to-film studies. Since George Bluestone's seminal 1957 study Novels into Film, often regarded as the starting point of modern day Anglo-American adaptation studies, the discipline has seen a continual widening of its methodology as well as of the material scholars are willing to regard as adaptations. Particularly since the turn of the 21st century and the increasing institutionalization of the discipline as distinct from literary or film studies, adaptation scholars have widened the scope to include a broad range of media, encompassing not only the traditional adaptations from novels and drama into film, but also novelizations of various other media, video game and comic adaptations, TV series, opera, theme parks and tie in vacations, and many more. Others have included the study of media franchises as dependent on adaptation. As part of this redefinition of the discipline, scholars have also widened their discussion to bring to the centre aspects that were not originally the main focus of adaptation researchers' comparative textual analyses, including industrial structures, legal frameworks, and, most frequently and emphatically, questions of intertextuality and the cultural and ideological embeddedness of adapted texts.
Informationen zu Bildern des Afghanistankriegs werden im Internet auf den Seiten, auf denen sie veröffentlicht werden, ausschließlich durch die das Bild ergänzende Bildunterschrift geliefert. Im Internet gelten spezifische Regeln der Publikation von Bildern, die Einfluss auf Bildmotive und deren Reichweite nehmen. Es existiert eine Informationslücke hinsichtlich der Bildquelle, der innewohnenden Deutungen sowie der Bedingungen ihrer Entstehung und Verbreitung im Internet. Die eigens für Bilder im Internet entwickelte Methode des verfeinerten Netzscans legt die Regularien der Bildveröffentlichungen und Bildproduktionen frei, welche durch den eingebetteten Journalismus, neue netzinhärente Gatekeeping-Prozesse sowie die Suchmaschine Google bestimmt werden und schafft Zugangsweisen der Decodierung von Bildern und deren Quellen.
The discipline of adaptation studies has come a long way from its academic inception in novel-to-film studies. Since George Bluestone's seminal 1957 study Novels into Film, often regarded as the starting point of modern day Anglo-American adaptation studies, the discipline has seen a continual widening of its methodology as well as of the material scholars are willing to regard as adaptations. Particularly since the turn of the 21st century and the increasing institutionalization of the discipline as distinct from literary or film studies, adaptation scholars have widened the scope to include a broad range of media, encompassing not only the traditional adaptations from novels and drama into film, but also novelizations of various other media, video game and comic adaptations, TV series, opera, theme parks and tie in vacations, and many more. Others have included the study of media franchises as dependent on adaptation. As part of this redefinition of the discipline, scholars have also widened their discussion to bring to the centre aspects that were not originally the main focus of adaptation researchers' comparative textual analyses, including industrial structures, legal frameworks, and, most frequently and emphatically, questions of intertextuality and the cultural and ideological embeddedness of adapted texts.
Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.
The IPS e.max system by Ivoclar Vivadent, offering a variety of products and indications, is widely used for all-ceramic restorations. We analyzed the clinical track record of these products in daily clinical practice, associating their restorative survival rate with various parameters to define recommendations for long-term stability. A total of 1058 full-coverage crowns and fixed partial dentures (FPDs) were evaluated retrospectively over up to 66.48 (37.05 ± 18.4) months. All were made of IPS e.max Press, IPS e.max CAD, IPS e.max Ceram or IPS e.max ZirPress and had been delivered by a private dental practice within three years. Uses not recommended by the manufacturer were also deliberately included. The five-year cumulative survival was 94.22% (i.e., 94.69% or 90.58% for glass-ceramic crowns or FDPs and 100% or 90.06% for zirconia-based crowns or FDPs). Significantly superior outcomes emerged for conventional vs. adhesive cementation and for vital vs. non-vital abutment teeth, but not for recommended vs. non-recommended uses. Caution is required in restoring non-vital teeth, but the spectrum of recommended uses should generally be reconsidered and expanded, given our finding of high survival and success rates for IPS e.max ceramics, even for uses not currently recommended by the manufacturer.
A novel osteotomy preparation technique to preserve implant site viability and enhance osteogenesis
(2019)
The preservation of bone viability at an osteotomy site is a critical variable for subsequent implant osseointegration. Recent biomechanical studies evaluating the consequences of site preparation led us to rethink the design of bone-cutting drills, especially those intended for implant site preparation. We present here a novel drill design that is designed to efficiently cut bone at a very low rotational velocity, obviating the need for irrigation as a coolant. The low-speed cutting produces little heat and, consequently, osteocyte viability is maintained. The lack of irrigation, coupled with the unique design of the cutting flutes, channels into the osteotomy autologous bone chips and osseous coagulum that have inherent osteogenic potential. Collectively, these features result in robust, new bone formation at rates significantly faster than those observed with conventional drilling protocols. These preclinical data have practical implications for the clinical preparation of osteotomies and alveolar bone reconstructive surgeries.
Diverse epidermal appendages including grouped filaments closely resembling primitive feathers in non-avian theropods, are associated with skeletal elements in the primitive ornithischian dinosaur Kulindadromeus zabaikalicus from the Kulinda locality in south-eastern Siberia. This discovery suggests that “feather-like” structures did not evolve exclusively in theropod dinosaurs, but were instead potentially widespread in the whole dinosaur clade. The dating of the Kulinda locality is therefore particularly important for reconstructing the evolution of “feather-like” structures in dinosaurs within a chronostratigraphic framework. Here we present the first dating of the Kulinda locality, combining U-Pb analyses (LA-ICP-MS) on detrital zircons and monazites from sedimentary rocks of volcaniclastic origin and palynological observations. Concordia ages constrain the maximum age of the volcaniclastic deposits at 172.8 ± 1.6 Ma, corresponding to the Aalenian (Middle Jurassic). The palynological assemblage includes taxa that are correlated to Bathonian palynozones from western Siberia, and therefore constrains the minimum age of the deposits. The new U-Pb ages, together with the palynological data, provide evidence of a Bathonian age—between 168.3 ± 1.3 Ma and 166.1 ± 1.2 Ma—for Kulindadromeus. This is older than the previous Late Jurassic to Early Cretaceous ages tentatively based on local stratigraphic correlations. A Bathonian age is highly consistent with the phylogenetic position of Kulindadromeus at the base of the neornithischian clade and suggests that cerapodan dinosaurs originated in Asia during the Middle Jurassic, from a common ancestor that closely looked like Kulindadromeus. Our results consequently show that Kulindadromeus is the oldest known dinosaur with “feather-like” structures discovered so far.
Background: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses.
Methods: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after ≥4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after ≥4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after ≥3 and ≤ 6 months EGFR-tyrosine kinase inhibitor (TKI) treatment [n = 2]). Patients received intradermal BI1361849, local radiation (4 × 5 Gy), then BI1361849 until disease progression. Strata 1 and 3 also had maintenance pemetrexed or continued EGFR-TKI therapy, respectively. The primary endpoint was evaluation of safety; secondary objectives included assessment of clinical efficacy (every 6 weeks during treatment) and of immune response (on Days 1 [baseline], 19 and 61).
Results: Study treatment was well tolerated; injection site reactions and flu-like symptoms were the most common BI1361849-related adverse events. Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia). In comparison to baseline, immunomonitoring revealed increased BI1361849 antigen-specific immune responses in the majority of patients (84%), whereby antigen-specific antibody levels were increased in 80% and functional T cells in 40% of patients, and involvement of multiple antigen specificities was evident in 52% of patients. One patient had a partial response in combination with pemetrexed maintenance, and 46.2% achieved stable disease as best overall response. Best overall response was SD in 57.7% for target lesions.
Conclusion: The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors.
Trial registration: ClinicalTrials.gov identifier: NCT01915524.
Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.
Background: With the recent introduction of novel treatment options, real-world data from patients with metastatic castration-resistant prostate cancer (mCRPC) are required to better understand the impact on routine clinical practice. This study primarily aimed to describe the time to treatment failure (TTF) of mCRPC patients treated with abiraterone acetate plus prednisone or the corticosteroid of choice (AAP) in the pre-chemotherapy setting. Other relevant outcomes, clinical and treatment characteristics of these patients were also evaluated.
Methods: This retrospective, observational study collected data from chemotherapy-naïve mCRPC patients treated with AAP from four European countries. Kaplan-Meier curves were used to estimate TTF, progression-free survival (PFS), and time to first skeletal-related event. The impact of baseline characteristics on TTF and PFS was explored using univariate and multivariate Cox proportional hazard models. Log-rank test was used to assess the potential role of duration of response to ADT in predicting response to AAP treatment.
Results: Data from 481 eligible patients (Belgium: 68; France: 61; Germany: 150; UK: 202) were analysed. At AAP initiation, the median age of patients was 75.0 years (interquartile range [IQR]: 69.0–81.0), and the median PSA was 56.2 ng/mL (IQR: 22.2–133.1), with over 50% of patients presenting an ECOG score of 0 or 1. Visceral metastases were present in 7.5% of patients; an exclusion criterion in the COU-AA-302 clinical trial. The median TTF with AAP was 10.0 months (95%CI: 9.2–11.1) and the median PFS was 10.8 months (95%CI: 9.6–11.8). Shorter TTF was significantly associated with higher ALP (> 119 units/L), higher PSA (> 56.2 ng/mL), or poorer ECOG PS scores at AAP initiation (p < 0.05). Patients with longer duration of response to ADT (≥12 months) presented longer TTF and longer time to progression (p < 0.0001).
Conclusions: This European real-world study provides valuable insights into the characteristics, treatment, and outcomes of chemotherapy-naïve patients with mCRPC who received AAP in routine clinical practice. Treatment effectiveness of AAP in the real-world is maintained despite patients having poorer clinical features at initiation than those observed in the COU-AA-302 trial population.
The capability of directing gaze to relevant parts in the environment is crucial for our survival. Computational models have proposed quantitative accounts of human gaze selection in a range of visual search tasks. Initially, models suggested that gaze is directed to the locations in a visual scene at which some criterion such as the probability of target location, the reduction of uncertainty or the maximization of reward appear to be maximal. But subsequent studies established, that in some tasks humans instead direct their gaze to locations, such that after the single next look the criterion is expected to become maximal. However, in tasks going beyond a single action, the entire action sequence may determine future rewards thereby necessitating planning beyond a single next gaze shift. While previous empirical studies have suggested that human gaze sequences are planned, quantitative evidence for whether the human visual system is capable of finding optimal eye movement sequences according to probabilistic planning is missing. Here we employ a series of computational models to investigate whether humans are capable of looking ahead more than the next single eye movement. We found clear evidence that subjects’ behavior was better explained by the model of a planning observer compared to a myopic, greedy observer, which selects only a single saccade at a time. In particular, the location of our subjects’ first fixation differed depending on the stimulus and the time available for the search, which was well predicted quantitatively by a probabilistic planning model. Overall, our results are the first evidence that the human visual system’s gaze selection agrees with optimal planning under uncertainty.
In psychotherapy, movement synchrony seems to be associated with higher patient satisfaction and treatment outcome. However, it remains unclear whether movement synchrony rated by humans and movement synchrony identified by automated methods reflect the same construct. To address this issue, video sequences showing movement synchrony of patients and therapists (N = 10) or not (N = 10), were analyzed using motion energy analysis. Three different synchrony conditions with varying levels of complexity (naturally embedded, naturally isolated, and artificial) were generated for time series analysis with windowed cross-lagged correlation/ -regression (WCLC, WCLR). The concordance of ratings (human rating vs. automatic assessment) was computed for 600 different parameter configurations of the WCLC/WCLR to identify the parameter settings that measure movement synchrony best. A parameter configuration was rated as having a good identification rate if it yields high concordance with human-rated intervals (Cohen’s kappa) and a low amount of over-identified data points. Results indicate that 76 configurations had a good identification rate (IR) in the least complex condition (artificial). Two had an acceptable IR with regard to the naturally isolated condition. Concordance was low with regard to the most complex (naturally embedded) condition. A valid identification of movement synchrony strongly depends on parameter configuration and goes beyond the identification of synchrony by human raters. Differences between human-rated synchrony and nonverbal synchrony measured by algorithms are discussed.
Background: To evaluate optimal therapy and potential risk factors.
Methods: Data of DSRCT patients <40 years treated in prospective CWS trials 1997‐2015 were analyzed.
Results: Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high‐dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three‐year event‐free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra‐abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse.
Conclusion: Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.