TY - JOUR A1 - Jozi Najafabadi, Azam A1 - Haberland, Christian A1 - Ryberg, Trond A1 - Verwater, Vincent F. A1 - Breton, Eline le A1 - Handy, Mark R. A1 - Weber, Michael T1 - Relocation of earthquakes in the southern and eastern Alps (Austria, Italy) recorded by the dense, temporary SWATH-D network using a Markov chain Monte Carlo inversion JF - Solid earth : SE ; an interaktive open access journal of the European Geosciences Union N2 - In this study, we analyzed a large seismological dataset from temporary and permanent networks in the southern and eastern Alps to establish high-precision hypocenters and 1-D V-P and V-P/V-S models. The waveform data of a subset of local earthquakes with magnitudes in the range of 1-4.2 M-L were recorded by the dense, temporary SWATH-D network and selected stations of the AlpArray network between September 2017 and the end of 2018. The first arrival times of P and S waves of earthquakes are determined by a semi-automatic procedure. We applied a Markov chain Monte Carlo inversion method to simultaneously calculate robust hypocenters, a 1-D velocity model, and station corrections without prior assumptions, such as initial velocity models or earthquake locations. A further advantage of this method is the derivation of the model parameter uncertainties and noise levels of the data. The precision estimates of the localization procedure is checked by inverting a synthetic travel time dataset from a complex 3-D velocity model and by using the real stations and earthquakes geometry. The location accuracy is further investigated by a quarry blast test. The average uncertainties of the locations of the earthquakes are below 500m in their epicenter and similar to 1.7 km in depth. The earthquake distribution reveals seismicity in the upper crust (0-20 km), which is characterized by pronounced clusters along the Alpine frontal thrust, e.g., the Friuli-Venetia (FV) region, the Giudicarie-Lessini (GL) and Schio-Vicenza domains, the Austroalpine nappes, and the Inntal area. Some seismicity also occurs along the Periadriatic Fault. The general pattern of seismicity reflects head-on convergence of the Adriatic indenter with the Alpine orogenic crust. The seismicity in the FV and GL regions is deeper than the modeled frontal thrusts, which we interpret as indication for southward propagation of the southern Alpine deformation front (blind thrusts). Y1 - 2021 U6 - https://doi.org/10.5194/se-12-1087-2021 SN - 1869-9529 SN - 1869-9510 VL - 12 IS - 5 SP - 1087 EP - 1109 PB - Copernicus CY - Göttingen ER - TY - BOOK A1 - Schenck, Marcia C. T1 - Remembering African Labor Migration to the Second World BT - Socialist Mobilities between Angola, Mozambique, and East Germany. T3 - Palgrave Macmillan Transnational History Series N2 - This open access book is about Mozambicans and Angolans who migrated in state-sponsored schemes to East Germany in the late 1970s and throughout the 1980s. They went to work and to be trained as a vanguard labor force for the intended African industrial revolutions. While they were there, they contributed their labor power to the East German economy.  This book draws on more than 260 life history interviews and uncovers complex and contradictory experiences and transnational encounters. What emerges is a series of dualities that exist side by side in the memories of the former migrants: the state and the individual, work and consumption, integration and exclusion, loss and gain, and the past in the past and the past in the present and future. By uncovering these dualities, the book explores the lives of African migrants moving between the Third and Second worlds.  Devoted to the memories of worker-trainees, this transnational study comes at a time when historians are uncovering the many varied, complicated, and important connections within the global socialist world. KW - Open access KW - Third World KW - Second World KW - East Germany KW - Angola KW - Mozambique KW - Socialism KW - Labor Migration Y1 - 2022 SN - 978-3-031-06775-4 SN - 978-3-031-06778-5 SN - 978-3-031-06776-1 U6 - https://doi.org/10.1007/978-3-031-06776-1 SN - 2634-6273 SN - 2634-6281 PB - Palgrave Macmillan CY - Cham ER - TY - GEN A1 - Hänel, Hilkje C. T1 - The intricacies of ideology and ignorance BT - a reply to Mason T2 - Social epistemology review & reply collective : SERRC Y1 - 2021 UR - https://wp.me/p1Bfg0-62M SN - 2471-9560 VL - 10 IS - 7 SP - 58 EP - 62 PB - Social epistemology review & reply collective CY - [Erscheinungsort nicht ermittelbar] ER - TY - JOUR A1 - Perottoni, Hélio D. A1 - Limberg, Guilherme A1 - Amarante, João A. S. A1 - Rossi, Silvia A1 - Queiroz, Anna B. A. A1 - Santucci, Rafael M. A1 - Pérez-Villegas, Angeles A1 - Chiappini, Cristina T1 - The unmixed debris of Gaia-Sausage/Enceladus in the form of a pair of halo stellar overdensities JF - Astrophysical journal letters N2 - In the first billion years after its formation, the galaxy underwent several mergers with dwarf satellites of various masses. The debris of Gaia-Sausage/Enceladus (GSE), the galaxy responsible for the last significant merger of the Milky Way, dominates the inner halo and has been suggested to be the progenitor of both the Hercules-Aquila Cloud (HAC) and Virgo Overdensity (VOD). We combine SEGUE, APOGEE, Gaia, and StarHorse distances to characterize the chemodynamical properties and verify the link between HAC, VOD, and GSE. We find that the orbital eccentricity distributions of the stellar overdensities and GSE are comparable. We also find that they have similar, strongly peaked, metallicity distribution functions, reinforcing the hypothesis of common origin. Furthermore, we show that HAC and VOD are indistinguishable from the prototypical GSE population within all chemical-abundance spaces analyzed. All these evidences combined provide a clear demonstration that the GSE merger is the main progenitor of the stellar populations found within these halo overdensities. Y1 - 2022 U6 - https://doi.org/10.3847/2041-8213/ac88d6 SN - 2041-8213 VL - 936 IS - 1 PB - IOP Publishing CY - Bristol ER - TY - JOUR A1 - Klaus, Benita A1 - Müller, Patrick A1 - van Wickeren, Nora A1 - Dordevic, Milos A1 - Schmicker, Marlen A1 - Zdunczyk, Yael A1 - Brigadski, Tanja A1 - Lessmann, Volkmar A1 - Vielhaber, Stefan A1 - Schreiber, Stefanie A1 - Müller, Notger Germar T1 - Structural and functional brain alterations in patients with myasthenia gravis JF - Brain communications N2 - Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 +/- 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 +/- 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T-1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200). Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail. Klaus et al. compared myasthenia gravis patients to matched healthy control subjects and identified functional alterations in memory functions as well as structural alterations in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. KW - myasthenia gravis KW - neuroplasticity KW - VBM KW - neuropsychological testing KW - BDNF Y1 - 2022 U6 - https://doi.org/10.1093/braincomms/fcac018 SN - 2632-1297 VL - 4 IS - 1 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Menze, Inga A1 - Müller, Notger Germar A1 - Zähle, Tino A1 - Schmicker, Marlen T1 - Individual response to transcranial direct current stimulation as a function of working memory capacity and electrode montage JF - Frontiers in human neuroscience N2 - Introduction Attempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method's susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks. Methods We investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling. Results The interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity. Discussion Our results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation. KW - tDCS KW - electrode montage KW - individual differences KW - working memory KW - capacity KW - distractor inhibition KW - frontoparietal network Y1 - 2023 U6 - https://doi.org/10.3389/fnhum.2023.1134632 SN - 1662-5161 VL - 17 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Menze, Inga A1 - Müller, Patrick A1 - Müller, Notger Germar A1 - Schmicker, Marlen T1 - Age-related cognitive effects of the COVID-19 pandemic restrictions and associated mental health changes in Germans JF - Scientific reports N2 - Restrictive means to reduce the spread of the COVID-19 pandemic have not only imposed broad challenges on mental health but might also affect cognitive health. Here we asked how restriction-related changes influence cognitive performance and how age, perceived loneliness, depressiveness and affectedness by restrictions contribute to these effects. 51 Germans completed three assessments of an online based study during the first lockdown in Germany (April 2020), a month later, and during the beginning of the second lockdown (November 2020). Participants completed nine online cognitive tasks of the MyBrainTraining and online questionnaires about their perceived strain and impact on lifestyle factors by the situation (affectedness), perceived loneliness, depressiveness as well as subjective cognitive performance. The results suggested a possible negative impact of depressiveness and affectedness on objective cognitive performance within the course of the lockdown. The younger the participants, the more pronounced these effects were. Loneliness and depressiveness moreover contributed to a worse evaluation of subjective cognition. In addition, especially younger individuals reported increased distress. As important educational and social input has partly been scarce during this pandemic and mental health problems have increased, future research should also assess cognitive long-term consequences. Y1 - 2022 U6 - https://doi.org/10.1038/s41598-022-11283-9 SN - 2045-2322 VL - 12 IS - 1 PB - Nature portfolio CY - Berlin ER - TY - JOUR A1 - Zielhofer, Christoph A1 - Schmidt, Johannes A1 - Reiche, Niklas A1 - Tautenhahn, Marie A1 - Ballasus, Helen A1 - Burkart, Michael A1 - Linstädter, Anja A1 - Dietze, Elisabeth A1 - Kaiser, Knut A1 - Mehler, Natascha T1 - The lower Havel River Region (Brandenburg, Germany) BT - a 230-Year-Long historical map record indicates a decrease in surface water areas and groundwater levels JF - Water N2 - Instrumental data show that the groundwater and lake levels in Northeast Germany have decreased over the past decades, and this process has accelerated over the past few years. In addition to global warming, the direct influence of humans on the local water balance is suspected to be the cause. Since the instrumental data usually go back only a few decades, little is known about the multidecadal to centennial-scale trend, which also takes long-term climate variation and the long-term influence by humans on the water balance into account. This study aims to quantitatively reconstruct the surface water areas in the Lower Havel Inner Delta and of adjacent Lake Gulpe in Brandenburg. The analysis includes the calculation of surface water areas from historical and modern maps from 1797 to 2020. The major finding is that surface water areas have decreased by approximately 30% since the pre-industrial period, with the decline being continuous. Our data show that the comprehensive measures in Lower Havel hydro-engineering correspond with groundwater lowering that started before recent global warming. Further, large-scale melioration measures with increasing water demands in the upstream wetlands beginning from the 1960s to the 1980s may have amplified the decline in downstream surface water areas. KW - long-term hydrological changes KW - historical maps KW - review of written KW - sources KW - preindustrial to industrial period KW - hydro-engineering history; KW - effects of global warming KW - drying trend KW - wetlands KW - drainage works to KW - create cropland KW - Lower Havel River Region KW - Brandenburg KW - Germany Y1 - 2022 U6 - https://doi.org/10.3390/w14030480 SN - 2073-4441 VL - 14 IS - 3 PB - MDPI CY - Basel ER - TY - JOUR A1 - Ring, Raphaela M. A1 - Eisenmann, Clemens A1 - Kandil, Farid A1 - Steckhan, Nico A1 - Demmrich, Sarah A1 - Klatte, Caroline A1 - Kessler, Christian S. A1 - Jeitler, Michael A1 - Boschmann, Michael A1 - Michalsen, Andreas A1 - Blakeslee, Sarah B. A1 - Stöckigt, Barbara A1 - Stritter, Wiebke A1 - Koppold-Liebscher, Daniela A. T1 - Mental and behavioural responses to Bahá’í fasting: Looking behind the scenes of a religiously motivated intermittent fast using a mixed methods approach JF - Nutrients N2 - Background/Objective: Historically, fasting has been practiced not only for medical but also for religious reasons. Baha'is follow an annual religious intermittent dry fast of 19 days. We inquired into motivation behind and subjective health impacts of Baha'i fasting. Methods: A convergent parallel mixed methods design was embedded in a clinical single arm observational study. Semi-structured individual interviews were conducted before (n = 7), during (n = 8), and after fasting (n = 8). Three months after the fasting period, two focus group interviews were conducted (n = 5/n = 3). A total of 146 Baha'i volunteers answered an online survey at five time points before, during, and after fasting. Results: Fasting was found to play a central role for the religiosity of interviewees, implying changes in daily structures, spending time alone, engaging in religious practices, and experiencing social belonging. Results show an increase in mindfulness and well-being, which were accompanied by behavioural changes and experiences of self-efficacy and inner freedom. Survey scores point to an increase in mindfulness and well-being during fasting, while stress, anxiety, and fatigue decreased. Mindfulness remained elevated even three months after the fast. Conclusion: Baha'i fasting seems to enhance participants' mindfulness and well-being, lowering stress levels and reducing fatigue. Some of these effects lasted more than three months after fasting. KW - intermittent food restriction KW - mindfulness KW - self-efficacy KW - well-being KW - mixed methods KW - health behaviour KW - coping ability KW - religiously motivated KW - dry fasting Y1 - 2022 U6 - https://doi.org/10.3390/nu14051038 SN - 2072-6643 VL - 14 IS - 5 PB - MDPI CY - Basel ER - TY - BOOK A1 - Meinel, Christoph A1 - Döllner, Jürgen Roland Friedrich A1 - Weske, Mathias A1 - Polze, Andreas A1 - Hirschfeld, Robert A1 - Naumann, Felix A1 - Giese, Holger A1 - Baudisch, Patrick A1 - Friedrich, Tobias A1 - Böttinger, Erwin A1 - Lippert, Christoph A1 - Dörr, Christian A1 - Lehmann, Anja A1 - Renard, Bernhard A1 - Rabl, Tilmann A1 - Uebernickel, Falk A1 - Arnrich, Bert A1 - Hölzle, Katharina T1 - Proceedings of the HPI Research School on Service-oriented Systems Engineering 2020 Fall Retreat N2 - Design and Implementation of service-oriented architectures imposes a huge number of research questions from the fields of software engineering, system analysis and modeling, adaptability, and application integration. Component orientation and web services are two approaches for design and realization of complex web-based system. Both approaches allow for dynamic application adaptation as well as integration of enterprise application. Service-Oriented Systems Engineering represents a symbiosis of best practices in object-orientation, component-based development, distributed computing, and business process management. It provides integration of business and IT concerns. The annual Ph.D. Retreat of the Research School provides each member the opportunity to present his/her current state of their research and to give an outline of a prospective Ph.D. thesis. Due to the interdisciplinary structure of the research school, this technical report covers a wide range of topics. These include but are not limited to: Human Computer Interaction and Computer Vision as Service; Service-oriented Geovisualization Systems; Algorithm Engineering for Service-oriented Systems; Modeling and Verification of Self-adaptive Service-oriented Systems; Tools and Methods for Software Engineering in Service-oriented Systems; Security Engineering of Service-based IT Systems; Service-oriented Information Systems; Evolutionary Transition of Enterprise Applications to Service Orientation; Operating System Abstractions for Service-oriented Computing; and Services Specification, Composition, and Enactment. N2 - Der Entwurf und die Realisierung dienstbasierender Architekturen wirft eine Vielzahl von Forschungsfragestellungen aus den Gebieten der Softwaretechnik, der Systemmodellierung und -analyse, sowie der Adaptierbarkeit und Integration von Applikationen auf. Komponentenorientierung und WebServices sind zwei Ansätze für den effizienten Entwurf und die Realisierung komplexer Web-basierender Systeme. Sie ermöglichen die Reaktion auf wechselnde Anforderungen ebenso, wie die Integration großer komplexer Softwaresysteme. "Service-Oriented Systems Engineering" repräsentiert die Symbiose bewährter Praktiken aus den Gebieten der Objektorientierung, der Komponentenprogrammierung, des verteilten Rechnen sowie der Geschäftsprozesse und berücksichtigt auch die Integration von Geschäftsanliegen und Informationstechnologien. Die Klausurtagung des Forschungskollegs "Service-oriented Systems Engineering" findet einmal jährlich statt und bietet allen Kollegiaten die Möglichkeit den Stand ihrer aktuellen Forschung darzulegen. Bedingt durch die Querschnittstruktur des Kollegs deckt dieser Bericht ein weites Spektrum aktueller Forschungsthemen ab. Dazu zählen unter anderem Human Computer Interaction and Computer Vision as Service; Service-oriented Geovisualization Systems; Algorithm Engineering for Service-oriented Systems; Modeling and Verification of Self-adaptive Service-oriented Systems; Tools and Methods for Software Engineering in Service-oriented Systems; Security Engineering of Service-based IT Systems; Service-oriented Information Systems; Evolutionary Transition of Enterprise Applications to Service Orientation; Operating System Abstractions for Service-oriented Computing; sowie Services Specification, Composition, and Enactment. T3 - Technische Berichte des Hasso-Plattner-Instituts für Digital Engineering an der Universität Potsdam - 138 KW - Hasso Plattner Institute KW - research school KW - Ph.D. retreat KW - service-oriented systems engineering KW - Hasso-Plattner-Institut KW - Forschungskolleg KW - Klausurtagung KW - Service-oriented Systems Engineering Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-504132 SN - 978-3-86956-513-2 SN - 1613-5652 SN - 2191-1665 IS - 138 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - De Freitas, Jessica K. A1 - Johnson, Kipp W. A1 - Golden, Eddye A1 - Nadkarni, Girish N. A1 - Dudley, Joel T. A1 - Böttinger, Erwin A1 - Glicksberg, Benjamin S. A1 - Miotto, Riccardo T1 - Phe2vec BT - Automated disease phenotyping based on unsupervised embeddings from electronic health records JF - Patterns N2 - Robust phenotyping of patients from electronic health records (EHRs) at scale is a challenge in clinical informatics. Here, we introduce Phe2vec, an automated framework for disease phenotyping from EHRs based on unsupervised learning and assess its effectiveness against standard rule-based algorithms from Phenotype KnowledgeBase (PheKB). Phe2vec is based on pre-computing embeddings of medical concepts and patients' clinical history. Disease phenotypes are then derived from a seed concept and its neighbors in the embedding space. Patients are linked to a disease if their embedded representation is close to the disease phenotype. Comparing Phe2vec and PheKB cohorts head-to-head using chart review, Phe2vec performed on par or better in nine out of ten diseases. Differently from other approaches, it can scale to any condition and was validated against widely adopted expert-based standards. Phe2vec aims to optimize clinical informatics research by augmenting current frameworks to characterize patients by condition and derive reliable disease cohorts. Y1 - 2021 U6 - https://doi.org/10.1016/j.patter.2021.100337 SN - 2666-3899 VL - 2 IS - 9 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Klippert, Monika A1 - Stolpmann, Robert A1 - Grum, Marcus A1 - Thim, Christof A1 - Gronau, Norbert A1 - Albers, Albert T1 - Knowledge transfer quality improvement BT - the quality enhancement of knowledge transfers in product engineering T2 - Procedia CIRP N2 - Developing a new product generation requires the transfer of knowledge among various knowledge carriers. Several factors influence knowledge transfer, e.g., the complexity of engineering tasks or the competence of employees, which can decrease the efficiency and effectiveness of knowledge transfers in product engineering. Hence, improving those knowledge transfers obtains great potential, especially against the backdrop of experienced employees leaving the company due to retirement, so far, research results show, that the knowledge transfer velocity can be raised by following the Knowledge Transfer Velocity Model and implementing so-called interventions in a product engineering context. In most cases, the implemented interventions have a positive effect on knowledge transfer speed improvement. In addition to that, initial theoretical findings describe factors influencing the quality of knowledge transfers and outline a setting to empirically investigate how the quality can be improved by introducing a general description of knowledge transfer reference situations and principles to measure the quality of knowledge artifacts. To assess the quality of knowledge transfers in a product engineering context, the Knowledge Transfer Quality Model (KTQM) is created, which serves as a basis to develop and implement quality-dependent interventions for different knowledge transfer situations. As a result, this paper introduces the specifications of eight situation-adequate interventions to improve the quality of knowledge transfers in product engineering following an intervention template. Those interventions are intended to be implemented in an industrial setting to measure the quality of knowledge transfers and validate their effect. KW - knowledge transfer KW - product generation engineering KW - improvement KW - quality KW - intervention Y1 - 2023 U6 - https://doi.org/10.1016/j.procir.2023.02.171 SN - 2212-8271 VL - 119 SP - 919 EP - 925 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Panzer, Marcel A1 - Gronau, Norbert T1 - Enhancing economic efficiency in modular production systems through deep reinforcement learning T2 - Procedia CIRP N2 - In times of increasingly complex production processes and volatile customer demands, the production adaptability is crucial for a company's profitability and competitiveness. The ability to cope with rapidly changing customer requirements and unexpected internal and external events guarantees robust and efficient production processes, requiring a dedicated control concept at the shop floor level. Yet in today's practice, conventional control approaches remain in use, which may not keep up with the dynamic behaviour due to their scenario-specific and rigid properties. To address this challenge, deep learning methods were increasingly deployed due to their optimization and scalability properties. However, these approaches were often tested in specific operational applications and focused on technical performance indicators such as order tardiness or total throughput. In this paper, we propose a deep reinforcement learning based production control to optimize combined techno-financial performance measures. Based on pre-defined manufacturing modules that are supplied and operated by multiple agents, positive effects were observed in terms of increased revenue and reduced penalties due to lower throughput times and fewer delayed products. The combined modular and multi-staged approach as well as the distributed decision-making further leverage scalability and transferability to other scenarios. KW - modular production KW - production control KW - multi-agent system KW - deep reinforcement learning KW - discrete event simulation Y1 - 2024 U6 - https://doi.org/10.1016/j.procir.2023.09.229 SN - 2212-8271 VL - 121 SP - 55 EP - 60 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Grdseloff, Nastasja A1 - Boulday, Gwenola A1 - Roedel, Claudia J. A1 - Otten, Cecile A1 - Vannier, Daphne Raphaelle A1 - Cardoso, Cecile A1 - Faurobert, Eva A1 - Dogra, Deepika A1 - Tournier-Lasserve, Elisabeth A1 - Abdelilah-Seyfried, Salim T1 - Impaired retinoic acid signaling in cerebral cavernous malformations JF - Scientific reports N2 - The capillary-venous pathology cerebral cavernous malformation (CCM) is caused by loss of CCM1/Krev interaction trapped protein 1 (KRIT1), CCM2/MGC4607, or CCM3/PDCD10 in some endothelial cells. Mutations of CCM genes within the brain vasculature can lead to recurrent cerebral hemorrhages. Pharmacological treatment options are urgently needed when lesions are located in deeply-seated and in-operable regions of the central nervous system. Previous pharmacological suppression screens in disease models of CCM led to the discovery that treatment with retinoic acid improved CCM phenotypes. This finding raised a need to investigate the involvement of retinoic acid in CCM and test whether it has a curative effect in preclinical mouse models. Here, we show that components of the retinoic acid synthesis and degradation pathway are transcriptionally misregulated across disease models of CCM. We complemented this analysis by pharmacologically modifying retinoic acid levels in zebrafish and human endothelial cell models of CCM, and in acute and chronic mouse models of CCM. Our pharmacological intervention studies in CCM2-depleted human umbilical vein endothelial cells (HUVECs) and krit1 mutant zebrafish showed positive effects when retinoic acid levels were increased. However, therapeutic approaches to prevent the development of vascular lesions in adult chronic murine models of CCM were drug regiment-sensitive, possibly due to adverse developmental effects of this hormone. A treatment with high doses of retinoic acid even worsened CCM lesions in an adult chronic murine model of CCM. This study provides evidence that retinoic acid signaling is impaired in the CCM pathophysiology and suggests that modification of retinoic acid levels can alleviate CCM phenotypes. KW - Developmental biology KW - Molecular medicine Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-31905-0 SN - 2045-2322 VL - 13 IS - 1 PB - Nature Portfolio CY - Berlin ER - TY - JOUR A1 - Lewkowicz, Daniel A1 - Wohlbrandt, Attila A1 - Böttinger, Erwin T1 - Economic impact of clinical decision support interventions based on electronic health records JF - BMC Health Services Research N2 - Background Unnecessary healthcare utilization, non-adherence to current clinical guidelines, or insufficient personalized care are perpetual challenges and remain potential major cost-drivers for healthcare systems around the world. Implementing decision support systems into clinical care is promised to improve quality of care and thereby yield substantial effects on reducing healthcare expenditure. In this article, we evaluate the economic impact of clinical decision support (CDS) interventions based on electronic health records (EHR). Methods We searched for studies published after 2014 using MEDLINE, CENTRAL, WEB OF SCIENCE, EBSCO, and TUFTS CEA registry databases that encompass an economic evaluation or consider cost outcome measures of EHR based CDS interventions. Thereupon, we identified best practice application areas and categorized the investigated interventions according to an existing taxonomy of front-end CDS tools. Results and discussion Twenty-seven studies are investigated in this review. Of those, twenty-two studies indicate a reduction of healthcare expenditure after implementing an EHR based CDS system, especially towards prevalent application areas, such as unnecessary laboratory testing, duplicate order entry, efficient transfusion practice, or reduction of antibiotic prescriptions. On the contrary, order facilitators and undiscovered malfunctions revealed to be threats and could lead to new cost drivers in healthcare. While high upfront and maintenance costs of CDS systems are a worldwide implementation barrier, most studies do not consider implementation cost. Finally, four included economic evaluation studies report mixed monetary outcome results and thus highlight the importance of further high-quality economic evaluations for these CDS systems. Conclusion Current research studies lack consideration of comparative cost-outcome metrics as well as detailed cost components in their analyses. Nonetheless, the positive economic impact of EHR based CDS interventions is highly promising, especially with regard to reducing waste in healthcare. KW - Economic evaluation KW - Electronic health record KW - Clinical decision support KW - Behavioral economics Y1 - 2020 U6 - https://doi.org/10.1186/s12913-020-05688-3 SN - 1472-6963 VL - 20 PB - BioMed Central CY - London ER - TY - JOUR A1 - Wachs, Sebastian A1 - Wettstein, Alexander A1 - Bilz, Ludwig A1 - Gamez-Guadix, Manuel T1 - Motivos del discurso de odio en la adolescencia y su relación con las normas sociales BT - Adolescents' motivations to perpetrate hate speech and links with social norms JF - Comunicar : revista científica de comunicación y educación N2 - Hate speech has become a widespread phenomenon, however, it remains largely unclear why adolescents engage in it and which factors are associated with their motivations for perpetrating hate speech. To this end, we developed the multidimensional "Motivations for Hate Speech Perpetration Scale" (MHATE) and evaluated the psychometric properties. We also explored the associations between social norms and adolescents' motivations for hate speech perpetration. The sample consisted of 346 adolescents from Switzerland (54.6% boys; Mage=14; SD=0.96) who reported engagement in hate speech as perpetrators. The analyses revealed good psychometric properties for the MHATE, including good internal consistency. The most frequently endorsed subscale was revenge, followed by ideology, group conformity, status enhancement, exhilaration, and power. The results also showed that descriptive norms and peer pressure were related to a wide range of different motivations for perpetrating hate speech. Injunctive norms, however, were only associated with power. In conclusion, findings indicate that hate speech fulfills various functions. We argue that knowing the specific motivations that underlie hate speech could help us derive individually tailored prevention strategies (e.g., anger management, promoting an inclusive classroom climate). Furthermore, we suggest that practitioners working in the field of hate speech prevention give special attention to social norms surrounding adolescents. KW - Hate speech KW - cyberhate KW - motives KW - social norms KW - injunctive norms KW - peer KW - pressure Y1 - 2022 U6 - https://doi.org/10.3916/C71-2022-01 SN - 1134-3478 SN - 1988-3293 VL - 30 IS - 71 SP - 9 EP - 20 PB - Grupo Comunicar CY - Huelva ER - TY - JOUR A1 - Smith, Taylor A1 - Boers, Niklas T1 - Global vegetation resilience linked to water availability and variability JF - Nature Communications N2 - Quantifying the resilience of vegetated ecosystems is key to constraining both present-day and future global impacts of anthropogenic climate change. Here we apply both empirical and theoretical resilience metrics to remotely-sensed vegetation data in order to examine the role of water availability and variability in controlling vegetation resilience at the global scale. We find a concise global relationship where vegetation resilience is greater in regions with higher water availability. We also reveal that resilience is lower in regions with more pronounced inter-annual precipitation variability, but find less concise relationships between vegetation resilience and intra-annual precipitation variability. Our results thus imply that the resilience of vegetation responds differently to water deficits at varying time scales. In view of projected increases in precipitation variability, our findings highlight the risk of ecosystem degradation under ongoing climate change. Vegetation dynamics depend on both the amount of precipitation and its variability over time. Here, the authors show that vegetation resilience is greater where water availability is higher and where precipitation is more stable from year to year. Y1 - 2023 U6 - https://doi.org/10.1038/s41467-023-36207-7 SN - 2041-1723 VL - 14 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Falkenhagen, Undine A1 - Knöchel, Jane A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models BT - an application to warfarin JF - CPT: Pharmacometrics & Systems Pharmacology N2 - Quantitative systems pharmacology (QSP) models integrate comprehensive qualitative and quantitative knowledge about pharmacologically relevant processes. We previously proposed a first approach to leverage the knowledge in QSP models to derive simpler, mechanism-based pharmacodynamic (PD) models. Their complexity, however, is typically still too large to be used in the population analysis of clinical data. Here, we extend the approach beyond state reduction to also include the simplification of reaction rates, elimination of reactions, and analytic solutions. We additionally ensure that the reduced model maintains a prespecified approximation quality not only for a reference individual but also for a diverse virtual population. We illustrate the extended approach for the warfarin effect on blood coagulation. Using the model-reduction approach, we derive a novel small-scale warfarin/international normalized ratio model and demonstrate its suitability for biomarker identification. Due to the systematic nature of the approach in comparison with empirical model building, the proposed model-reduction algorithm provides an improved rationale to build PD models also from QSP models in other applications. Y1 - 2023 U6 - https://doi.org/10.1002/psp4.12903 SN - 2163-8306 VL - 12 IS - 4 SP - 432 EP - 443 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Moreno-Romero, Jordi A1 - Probst, Aline V. A1 - Trindade, Inês A1 - Kalyanikrishna, A1 - Engelhorn, Julia A1 - Farrona, Sara T1 - Looking At the Past and Heading to the Future BT - Meeting Summary of the 6th European Workshop on Plant Chromatin 2019 in Cologne, Germany JF - Frontiers in Plant Science N2 - In June 2019, more than a hundred plant researchers met in Cologne, Germany, for the 6th European Workshop on Plant Chromatin (EWPC). This conference brought together a highly dynamic community of researchers with the common aim to understand how chromatin organization controls gene expression, development, and plant responses to the environment. New evidence showing how epigenetic states are set, perpetuated, and inherited were presented, and novel data related to the three-dimensional organization of chromatin within the nucleus were discussed. At the level of the nucleosome, its composition by different histone variants and their specialized histone deposition complexes were addressed as well as the mechanisms involved in histone post-translational modifications and their role in gene expression. The keynote lecture on plant DNA methylation by Julie Law (SALK Institute) and the tribute session to Lars Hennig, honoring the memory of one of the founders of the EWPC who contributed to promote the plant chromatin and epigenetic field in Europe, added a very special note to this gathering. In this perspective article we summarize some of the most outstanding data and advances on plant chromatin research presented at this workshop. KW - EWPC2019 KW - chromatin KW - epigenetics KW - transcription KW - nucleus Y1 - 2020 U6 - https://doi.org/10.3389/fpls.2019.01795 SN - 1664-462X VL - 10 IS - 1795 SP - 1 EP - 12 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Dellepiane, Sergio A1 - Vaid, Akhil A1 - Jaladanki, Suraj K. A1 - Coca, Steven A1 - Fayad, Zahi A. A1 - Charney, Alexander W. A1 - Böttinger, Erwin A1 - He, John Cijiang A1 - Glicksberg, Benjamin S. A1 - Chan, Lili A1 - Nadkarni, Girish T1 - Acute kidney injury in patients hospitalized with COVID-19 in New York City BT - Temporal Trends From March 2020 to April 2021 JF - Kidney medicine Y1 - 2021 U6 - https://doi.org/10.1016/j.xkme.2021.06.008 SN - 2590-0595 VL - 3 IS - 5 SP - 877 EP - 879 PB - Elsevier CY - Amsterdam ER -