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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.
Switching between reading tasks leads to phase-transitions in reading times in L1 and L2 readers
(2019)
Reading research uses different tasks to investigate different levels of the reading process, such as word recognition, syntactic parsing, or semantic integration. It seems to be tacitly assumed that the underlying cognitive process that constitute reading are stable across those tasks. However, nothing is known about what happens when readers switch from one reading task to another. The stability assumptions of the reading process suggest that the cognitive system resolves this switching between two tasks quickly. Here, we present an alternative language-game hypothesis (LGH) of reading that begins by treating reading as a softly-assembled process and that assumes, instead of stability, context-sensitive flexibility of the reading process. LGH predicts that switching between two reading tasks leads to longer lasting phase-transition like patterns in the reading process. Using the nonlinear-dynamical tool of recurrence quantification analysis, we test these predictions by examining series of individual word reading times in self-paced reading tasks where native (L1) and second language readers (L2) transition between random word and ordered text reading tasks. We find consistent evidence for phase-transitions in the reading times when readers switch from ordered text to random-word reading, but we find mixed evidence when readers transition from random-word to ordered-text reading. In the latter case, L2 readers show moderately stronger signs for phase-transitions compared to L1 readers, suggesting that familiarity with a language influences whether and how such transitions occur. The results provide evidence for LGH and suggest that the cognitive processes underlying reading are not fully stable across tasks but exhibit soft-assembly in the interaction between task and reader characteristics.
Cette communication a pour but de révéler l'implication du personnage dans des discours hégémoniques qui mettent en scène une société de la diversité par une apparente absence de la ligne de couleur. Deux générations seront confrontées existentiellement- et ontologiquement avec des imaginaires interchangeables autour de la notion de « Noir de France ». Les deux romans Blues pour Élise (2010) et Ces âmes chagrines (2011) offrent un parallélisme dans leur description similaire, tant sur le plan diachronique que dans la variation des significations des points de vue.
L'auteur sénégalaise Ken Bugul focalise dans son oeuvre surtout des destins féminins. Dans le cas du roman La Folie et la Mort les mouvements des héroïnes se réalisent dans un paysage urbain et rural centralisé par le pouvoir d'un parti unique. En subissant constamment la violence, les deux femmes se métamorphosent. À travers leurs changements intérieurs et extérieurs le récit réalise la mise en scène d'une dictature qui ne laisse guère une lueur d'espoir. Cette conversation propose une lecture qui perçoit l'ouverture d'un discours critique par un tiers espace littéraire, voyant la métamorphose autant comme destruction que comme point de départ.
This paper examines how networks of professional contacts contribute to the development of the careers of executives of North American and European companies. We build a dynamic model of career progression in which career moves may both depend upon existing networks and contribute to the development of future networks. We test the theory on an original dataset of nearly 73 000 executives in over 10 000 _rms. In principle professional networks could be relevant both because they are rewarded by the employer and because they facilitate job mobility. Our econometric analysis suggests that, although there is a substantial positive correlation between network size and executive compensation, with an elasticity of around 20%, almost all of this is due to unobserved individual characteristics. The true causal impact of networks on compensation is closer to an elasticity of 1 or 2% on average, all of this due to enhanced probability of moving to a higher-paid job. And there appear to be strongly diminishing returns to network size.
Using a unique confidential contract level dataset merged with firm-level asset price data, we find robust evidence that firms' stock market valuations and employment levels respond more to monetary policy announcements the higher the degree of wage rigidity. Data on the renegotiations of collective bargaining agreements allow us to construct an exogenous measure of wage rigidity. We also find that the amplification induced by wage rigidity is stronger for firms with high labor intensity and low profitability, providing evidence of distributional consequences of monetary policy. We rationalize the evidence through a model in which firms in different sectors feature different degrees of wage rigidity due to staggered renegotiations vis-a-vis unions.
This paper analyzes the effect of financial constraints on firms' corporate social responsibility. Exploiting heterogeneity in firms' exposure to a monetary policy shock in the U.S., which reduced financial constraints for some firms, I find that firms increase their environmental responsibility. I use facility-level data to account for unobservable time-varying influences on pollution and find that toxic emissions decrease when parent companies are more exposed to the monetary policy shock. I further find that these facilities are also more likely to implement pollution abatement activities. Examining within-parent company heterogeneity I find that pollution abatement investments center on facilities at greater risk of facing additional costs due to environmental regulation. The findings are consistent with the idea that a reduction in financial constraints reduces pollution as it allows firms to implement pollution abatement measures.
Households buy life insurance as part of their liquidity management. The option to surrender such a policy can serve as a buffer when a household faces a liquidity need. In this study, we investigate empirically which individual and household specific sociodemographic factors influence the surrender behavior of life insurance policyholders. Based on the Socio-Economic Panel (SOEP), an ongoing wide-ranging representative longitudinal study of around 11,000 private households in Germany, we construct a proxy to identify life insurance surrender in the data. We use this proxy to conduct fixed effect regressions and support the results with survival analyses. We find that life events that possibly impose a liquidity shock to the household, such as birth of a child and divorce increase the likelihood to surrender an existing life insurance policy for an average household in the panel. The acquisition of a dwelling and unemployment are further aspects that can foster life insurance surrender. Our results are robust with respect to different models and hold conditioning on region specific trends; they vary however for different age groups. Our analyses contribute to the existing literature supporting the emergency fund hypothesis. The findings obtained in this study can help life insurers and regulators to detect and understand industry specific challenges of the demographic change.
Background: Liver cirrhosis is associated with profound immunodysfunction, i.e. a parallel presence of chronic systemic inflammation and immunosuppression, which can result in acute-on-chronic liver failure (ACLF). Omega-3 fatty acids are precursors of pro-resolving mediators and support the resolution of inflammation.
Objective: The aim of this study was to determine plasma levels of omega-3 fatty acids in patients with liver cirrhosis and ACLF.
Methods: Patients with liver cirrhosis with and without ACLF were enrolled in a prospective cohort study and analyzed post-hoc for the present sub-study. Clinical data and biomaterials were collected at baseline and at day 7, 28 and after 3 months of follow-up. Plasma concentrations of arachidonic acid (ARA) and docosahexaenoic acid (DHA), which represent key omega-6 and -3 fatty acids, respectively, were quantified and associated with markers of systemic inflammation and severity of liver cirrhosis.
Results: A total of 117 patients were included in the present analyses. Of those, 26 (22.2%), 51 (43.6%) and 40 (34.2%) patients had compensated or decompensated liver cirrhosis, and ACLF. Plasma levels of ARA and DHA were similar in patients with compensated cirrhosis, decompensated cirrhosis, and ACLF. Furthermore, no significant association between plasma ARA or DHA and C-reactive protein or peripheral blood leukocytes were observed (P>0.05).
Conclusion: In our study plasma levels of key omega-3 and omega-6 fatty acid are neither associated with the severity of liver cirrhosis nor with liver-cirrhosis-associated systemic inflammation.
In many countries a majority of cancer patients are not treated at Comprehensive Cancer Centers (CCCs). Even for those that are, parts of the treatment or follow‐up may be carried out in local community hospitals or in private practices. How to assure quality in cancer care and create innovation? How to integrate decentralized versus centralized patient care, education, and cancer research? Outlined here is a 360° view of outreach to include all stake holders – most importantly patients and their families, patient advocacy groups, health care providers, health insurers, and policy makers.
Das Wirken des dänischen Bildhauers Niels Hansen Jacobsen (1861-1941) fällt in eine Zeit politischer Wirrungen infolge der Deutsch-Dänischen Kriege 1848-1850 und 1864. Dänemark unterliegt 1864 im Zweiten Deutsch-Dänischen Krieg, welcher im Namen des Deutschen Bundes gemeinsam von Preußen und Österreich gegen Dänemark geführt wird. Die Niederlage bedeutet das Ende des dänischen Gesamtstaats und Dänemark muss die Herzogtümer Schleswig, Holstein und Lauenburg an Deutschland abtreten. Im nördlichen Schleswig gerät die dänisch sprachige Bevölkerung dadurch unter preußische Herrschaft. Hat man hier zuvor bereitwillig geistesgeschichtliche und künstlerische deutsche Strömungen adaptiert, tritt nun eine politisch motivierte Abgrenzung von Deutschland auf.
Die Spannungen zwischen Dänemark und Deutschland äußern sich auch in den Kunstwerken Hansen Jacobsens. Zu seinem künstlerischen Gesamtwerk zählen unter anderem Großplastiken, von denen eine Auswahl in der vorliegenden Arbeit vorgestellt wird, um sein OEuvre zu charakterisieren und in den kulturellen und politischen Kontext seiner Zeit zu setzen. Stilistisch und thematisch unterscheiden sich diese Werke von dem Gros der dänischen Bildhauerei um die Jahrhundertwende: Hansen Jacobsen orientiert sich nicht an der kanonisierten klassizistischen Formensprache des einflussreichen dänischen Bildhauers Bertel Thorvaldsen (1770-1844), sondern entwickelt seinen eigenen Stil. Er wendet sich stilistisch gegen die klassizistische Tradition, um sich von Deutschland abzugrenzen und sich gegen die Verschiebung der Landesgrenze auszusprechen. Mit demselben Ziel wählt er oftmals die nordische Mythologie als Themengrundlage und intendiert eine Einflussnahme auf das politische Zeitgeschehen anhand seiner Kunstwerke. Dabei richtet er seine expressive Formensprache nach den zu vermittelnden Inhalten aus. Der kompromisslose Stil und die Sujets werden in den Kunstwerken Hansen Jacobsens zu Werkzeugen politischer Kritik.
Dieses Working Paper zeigt Wege auf, wie völkerrechtlich verbindliche Regeln im Bereich der Cyber-Sicherheit entwickelt werden können. Wichtige Wegmarken können dabei nichtbindende Normen darstellen; auch aus Völkergewohnheitsrecht – besonders dem Kooperationsgebot – lassen sich präventive Schutzpflichten für Staaten (‚due diligence’) ableiten. Diesen präventiven Schutzpflichten müssen Staaten mit gemeinsamem Handeln zur Hebung von Cyber-Sicherheit gerecht werden. Um langfristig Rechts-sicherheit zu schaffen und Cyber-Sicherheit ganzheitlich zu fördern, führt aber kein Weg am Abschluss eines verbindlichen Übereinkommens über Cyber-Sicherheit vorbei.
Die Fähigkeit, negative und belastende Ereignisse in Worte zu fassen und sich mit den damit verbundenen Emotionen und Gedanken auseinanderzusetzen, ist eine wichtige Entwicklungsaufgabe des Kindesalters, die entscheidend von den Eltern geprägt wird (Nelson & Fivush, 2004). Mit Hilfe von Emotionsworten, mentalen Verben (kognitiv, perzeptiv und volitional) und globalen Evaluationen, zusammengefasst unter dem Begriff internal state language (ISL), kann das innere Befinden während eines Ereignisses ausgedrückt werden. Neben der Verwendung von ISL wird auch die Entwicklung der Emotionsregulation im Kindesalter insbesondere durch die Eltern geprägt (Morris, Silk, Steinberg, Myers & Robinson, 2007). Während sowohl die Verwendung von ISL als auch die die mütterliche Unterstützung bei der Emotionsregulation im Kindesalter bislang vielfach untersucht wurde, fehlen mitunter Studien im Jugendalter. Dabei ist diese Entwicklungsphase von besonderer Bedeutung, da hier u.a. kognitive sowie Emotionsregulationsfähigkeiten ausreifen, ebenso wie die Geschlechtsidentität (z.B. Hill & Lynch, 1983; Powers & Casey, 2015).
Die vorliegende kumulative Dissertation beschäftigte sich daher zum einen mit der Frage, ob das Alter und Geschlecht der Jugendlichen einen Einfluss darauf haben, wie sie und ihre Mütter von emotionalen Erlebnissen erzählen. Zum anderen wurde untersucht, wie Mütter ihre jugendlichen Kinder bei der Verarbeitung dieser Erlebnisse unterstützen. Zur Beantwortung dieser Frage wurden 60 Mutter-Kind Paare im Jugendalter von 12, 15 und 18 Jahren (gleichverteilt über Geschlecht und Alter) gebeten, sowohl allein als auch gemeinsam von drei emotionalen Ereignissen (Traurigkeit, Ärger, Glück) zu erzählen.
Das erste Manuskript untersuchte die Verwendung von ISL in allein erzählten Emotionserzählungen der Jugendlichen und konnte zeigen, dass ältere Jugendliche weniger Emotionsworte und mehr mentale Verben verwenden als jüngere. Während die selbstempfundene Emotionsintensität über alle Altersgruppen hinweg gleich blieb, wirkten Trauer- und Ärgererzählungen von älteren Jugendlichen auf unabhängige Beurteiler emotionaler als von jüngeren. Die Verwendung von ISL korrelierte nicht mit der selbstempfundenen Emotionsintensität, die Verwendung von kognitiven Verben allerdings mit der von Beurteilern eingeschätzten Emotionalität. Die Ergebnisse deuten darauf hin, dass im Verlauf des Jugendalters zunehmend kognitive Verben die Aufgabe übernehmen, Emotionalität zu vermitteln.
Das zweite Manuskript untersuchte die Verwendung von ISL in allein erzählten Emotionserzählungen der Jugendlichen sowie in gemeinsamen Mutter-Kind Erzählungen. Entgegen der Erwartung verwendeten Mütter Emotionsworte und globale Evaluationen gleich häufig mit Töchtern und Söhnen, jedoch mehr mentale Verben mit Jungen als mit Mädchen. Zudem benannten sie Traurigkeit gleich häufig über beide Geschlechter, Ärger aber häufiger mit Töchtern als mit Söhnen. Ebenfalls entgegen der Erwartung verwendeten weibliche und männliche Jugendliche Emotionsworte und mentale Verben gleich häufig. Lediglich globale Evaluationen wurden von Mädchen häufiger verwendet als von Jungen, jedoch nur in den allein erzählten Emotionserzählungen. Traurigkeit und Ärger wurden von beiden Geschlechtern gleich häufig benannt. Die Ergebnisse deuten an, dass sich die Geschlechtsunterschiede des Kindesalters im Jugendalter aufzulösen scheinen.
Das dritte Manuskript untersuchte, wie Mütter ihre jugendlichen Kinder bei der narrativen Emotionsregulation unterstützen. Anhand der Trauererzählung einer 12- und eines 18-Jährigen konnte exemplarisch gezeigt werden, dass Mütter die narrative Emotionsregulation durch die Identifizierung und Rechtfertigung von Emotionen, als auch durch die Neubewertung der Ereignisse unterstützen. Die Ergebnisse verdeutlichen, dass Mütter auch im Jugendalter einen wichtigen Beitrag zur Emotionsregulation ihrer Kinder leisten.
Insgesamt tragen die Ergebnisse wesentlich zum Verständnis dessen bei, wie Jugendliche emotionale Erlebnisse sprachlich verarbeiten und wie Mütter sie bei der Verarbeitung dieser Erlebnisse unterstützen.
Endothelial to mesenchymal transition in cardiovascular disease : JACC state-of-the-art review
(2019)
Endothelial to mesenchymal transition (EndMT) is a process whereby an endothelial cell undergoes a series of molecular events that lead to a change in phenotype toward a mesenchymal cell (e.g., myofibroblast, smooth muscle cell). EndMT plays a fundamental role during development, and mounting evidence indicates that EndMT is involved in adult cardiovascular diseases (CVDs), including atherosclerosis, pulmonary hypertension, valvular disease, and fibroelastosis. Therefore, the targeting of EndMT may hold therapeutic promise for treating CVD. However, the field faces a number of challenges, including the lack of a precise functional and molecular definition, a lack of understanding of the causative pathological role of EndMT in CVDs (versus being a “bystander-phenomenon”), and a lack of robust human data corroborating the extent and causality of EndMT in adult CVDs. Here, we review this emerging but exciting field, and propose a framework for its systematic advancement at the molecular and translational levels.
Sepsis is characterized by dysregulated gene expression, provoking a hyper-inflammatory response occurring in parallel to a hypo-inflammatory reaction. This is often associated with multi-organ failure, leading to the patient’s death. Therefore, reprogramming of these pro- and anti-inflammatory, as well as immune-response genes which are involved in acute systemic inflammation, is a therapy approach to prevent organ failure and to improve sepsis outcomes. Considering epigenetic, i.e., reversible, modifications of chromatin, not altering the DNA sequence as one tool to adapt the expression profile, inhibition of factors mediating these changes is important. Acetylation of histones by histone acetyltransferases (HATs) and initiating an open-chromatin structure leading to its active transcription is counteracted by histone deacetylases (HDACs). Histone deacetylation triggers a compact nucleosome structure preventing active transcription. Hence, inhibiting the activity of HDACs by specific inhibitors can be used to restore the expression profile of the cells. It can be assumed that HDAC inhibitors will reduce the expression of pro-, as well as anti-inflammatory mediators, which blocks sepsis progression. However, decreased cytokine expression might also be unfavorable, because it can be associated with decreased bacterial clearance.
Big data, data mining, machine learning und predictive analytics – ein konzeptioneller Überblick
(2019)
Mit der fortschreitenden Digitalisierung von Wirtschaft und Gesellschaft wächst die Bedeutung von Big Data Analytics, maschinellem Lernen und Künstlicher Intelligenz für die Analyse und Pognose ökonomischer Trends. Allerdings werden in wirtschaftspolitischen Diskussionen diese Begriffe häufig verwendet, ohne dass jeweils klar zwischen den einzelnen Methoden und Disziplinen differenziert würde. Daher soll nachfolgend ein konzeptioneller Überblick über die Gemeinsamkeiten, Unterschiede und Interdependenzen der vielfältigen Begrifflichkeiten im Bereich Data Science gegeben werden. Denn gerade für Entscheidungsträger aus Wirtschaft und Politik kann eine grundlegende Einordnung der Konzepte eine sachgerechte Diskussion über politische Weichenstellungen erleichtern.
The attention control video has been frequently applied to test the ego depletion effect. However, its validity has never been tested, a shortcoming we address in this preregistered study. In the first task, self-control strength was temporarily depleted in the depletion condition (n = 56) but remained intact in the control condition (n = 56). The attention control video served as the secondary task, and we assumed that the depletion condition would perform significantly worse compared to the control condition. Attention regulation was measured with an eye-tracking device. The results revealed that the gaze behavior in the two conditions differed statistically significantly; however, the actual difference was small, indicating that the attention control video may not be an optimal measure of self-control.
Introduction: The global spread of multidrug-resistant organisms (MDRO) complicates treatment and isolation measures in hospitals and has shown to increase mortality. Patients with disease- or therapy-related immunodeficiency are especially at risk for fatal infections caused by MDRO. The impact of MDRO colonization on the clinical course of AML patients undergoing intensive induction chemotherapy—a potentially curative but highly toxic treatment option—has not been systematically studied.
Materials & methods: 312 AML patients undergoing intensive induction chemotherapy between 2007 and 2015 were examined for MDRO colonization. Patients with evidence for MDRO before or during the hospital stay of induction chemotherapy were defined as colonized, patients who never had a positive swab for MDRO were defined as noncolonized.
Results: Of 312 AML patients 90 were colonized and 130 were noncolonized. Colonized patients suffered from significantly more days with fever, spent more days on the intensive care unit and had a higher median C-reactive protein value during the hospital stay. These findings did not result in a prolonged length of hospital stay or an increased mortality rate for colonized patients. However, in a subgroup analysis, patients colonized with carbapenem-resistant enterobacteriaceae (CRE) had a significantly reduced 60- and 90-day, as well as 1- and 2-year survival rates when compared to noncolonized patients.
Conclusion: Our analysis highlights the importance of intensive MDRO screening especially in patients with febrile neutropenia since persisting fever can be a sign of MDRO-colonization. CRE-colonized patients require special surveillance, since they seem to be at risk for death.