63 research outputs found

    Analyse der morphininduzierten Genexpression in Zellmodellen primär-sensorischer Neurone

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    Analyse der morphininduzierten Genexpression in Zellmodellen primär-sensorischer Neurone

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    Violent Climate Imaginaries: Science-Fiction-Politics

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    There are many ways in which climate futures can be envisioned, such as global and regional climate models, scenarios of future emission trajectories, or pathways and visions of societal transformation. All these anticipatory practices aim to make the climatic future knowable in the present. In so doing, they quite often envision a climatic future that is inherently violent: a future marked by disasters, wars, mass migration, turmoil, and terror. This working paper seeks to explain the popularity and tenacity of such violent imaginaries of (future) climate change in scientific research, popular culture, and political discourse. For this, it asks two interrelated questions: First, how do violent imaginaries of future climate change come about? Second, why and how do these imaginaries circulate and proliferate? To answer these questions, the paper provides a discussion of the concept of “violence” and elaborates how different forms of it are featured in imaginaries of future climate change. On this basis, the paper then traces three different modes of future-making that together produce and reproduce violent climate imaginaries: modeling the future, writing the future, and visualizing the future. Finally, the paper proposes and discusses several factors that could help explaining the circulation of violent climate imaginaries between the fields of science, fiction, and politics. These factors include the existence of an interdiscourse that bridges different specialized discourses, the broader political economy of imaginaries, interpersonal relations between actors in different fields, and the coproduction of dominant imaginaries with broader technological developments

    Violent Climate Imaginaries: Science-Fiction-Politics

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    There are many ways in which climate futures can be envisioned, such as global and regional climate models, scenarios of future emission trajectories, or pathways and visions of societal transformation. All these anticipatory practices aim to make the climatic future knowable in the present. In so doing, they quite often envision a climatic future that is inherently violent: a future marked by disasters, wars, mass migration, turmoil, and terror. This working paper seeks to explain the popularity and tenacity of such violent imaginaries of (future) climate change in scientific research, popular culture, and political discourse. For this, it asks two interrelated questions: First, how do violent imaginaries of future climate change come about? Second, why and how do these imaginaries circulate and proliferate? To answer these questions, the paper provides a discussion of the concept of “violence” and elaborates how different forms of it are featured in imaginaries of future climate change. On this basis, the paper then traces three different modes of future-making that together produce and reproduce violent climate imaginaries: modeling the future, writing the future, and visualizing the future. Finally, the paper proposes and discusses several factors that could help explaining the circulation of violent climate imaginaries between the fields of science, fiction, and politics. These factors include the existence of an interdiscourse that bridges different specialized discourses, the broader political economy of imaginaries, interpersonal relations between actors in different fields, and the coproduction of dominant imaginaries with broader technological developments

    Strategies for increasing diagnostic yield of community-onset bacteraemia within the emergency department: A retrospective study

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    Bloodstream infections (BSI) are associated with high mortality. Therefore, reliable methods of detection are of paramount importance. Efficient strategies to improve diagnostic yield of bacteraemia within the emergency department (ED) are needed. We conducted a retrospective analysis of all ED encounters in a high-volume, city-centre university hospital within Germany during a five-year study period from October 2013 to September 2018. A time-series analysis was conducted for all ED encounters in which blood cultures (BCs) were collected. BC detection rates and diagnostic yield of community-onset bacteraemia were compared during the study period (which included 45 months prior to the start of a new diagnostic Antibiotic Stewardship (ABS) bundle and 15 months following its implementation). BCs were obtained from 5,191 out of 66,879 ED admissions (7.8%). Bacteraemia was detected in 1,013 encounters (19.5% of encounters where BCs were obtained). The overall yield of true bacteraemia (defined as yielding clinically relevant pathogens) was 14.4%. The new ABS-related diagnostic protocol resulted in an increased number of hospitalised patients with BCs collected in the ED (18% compared to 12.3%) and a significant increase in patients with two or more BC sets taken (59% compared to 25.4%), which resulted in an improved detection rate of true bacteraemia (2.5% versus 1.8% of hospital admissions) without any decrease in diagnostic yield. This simultaneous increase in BC rates without degradation of yield was a valuable finding that indicated success of this strategy. Thus, implementation of the new diagnostic ABS bundle within the ED, which included the presence of a skilled infectious disease (ID) team focused on obtaining BCs, appeared to be a valuable tool for the accurate and timely detection of community-onset bacteraemia

    A diagnostic algorithm for detection of urinary tract infections in hospitalized patients with bacteriuria: The "Triple F" approach supported by Procalcitonin and paired blood and urine cultures

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    For acute medicine physicians, distinguishing between asymptomatic bacteriuria (ABU) and clinically relevant urinary tract infections (UTI) is challenging, resulting in overtreatment of ABU and under-recognition of urinary-source bacteraemia without genitourinary symptoms (USB). We conducted a retrospective analysis of ED encounters in a university hospital between October 2013 and September 2018 who met the following inclusion criteria: Suspected UTI with simultaneous collection of paired urinary cultures and blood cultures (PUB) and determination of Procalcitonin (PCT). We sought to develop a simple algorithm based on clinical signs and PCT for the management of suspected UTI. Individual patient presentations were retrospectively evaluated by a clinical "triple F" algorithm (F1 ="fever", F2 ="failure", F3 ="focus") supported by PCT and PUB. We identified 183 ED patients meeting the inclusion criteria. We introduced the term UTI with systemic involvement (SUTI) with three degrees of diagnostic certainty: bacteremic UTI (24.0%;44/183), probable SUTI (14.2%;26/183) and possible SUTI (27.9%;51/183). In bacteremic UTI, half of patients (54.5%;24/44) presented without genitourinary symptoms. Discordant bacteraemia was diagnosed in 16 patients (24.6% of all bacteremic patients). An alternative focus was identified in 67 patients, five patients presented withS.aureusbacteremia. 62 patients were diagnosed with possible UTI (n = 20) or ABU (n = 42). Using the proposed "triple F" algorithm, dichotomised PCT of < 0.25 pg/ml had a negative predictive value of 88.7% and 96.2% for bacteraemia und accordant bacteraemia respectively. The application of the algorithm to our cohort could have resulted in 33.3% reduction of BCs. Using the diagnostic categories "possible" or "probable" SUTI as a trigger for initiation of antimicrobial treatment would have reduced or streamlined antimicrobial use in 30.6% and 58.5% of cases, respectively. In conclusion, the "3F" algorithm supported by PCT and PUB is a promising diagnostic and antimicrobial stewardship tool

    Come, tell me how you live: Habitat suitability analysis for Ostrea edulis restoration

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    Against the background of the UN decade on ecosystem restoration and the new EU Biodiversity Strategy for 2030, and in the context of marine spatial planning and complex maritime user conflicts, reliable information on habitat suitability for large-scale restoration is an important prerequisite for implementing conservation management and for supporting successful, sustainable, and ecologically efficient restoration measures. In this study, habitat suitability was assessed using multicriteria decision analysis (MCDA) for the restoration of the European oyster, Ostrea edulis, in marine protected areas (MPAs) of the German Bight in the North Sea: Borkum Reef Ground (Borkum Riffgrund, BRG) and Sylt Outer Reef – Eastern German Bight (Sylter Außenriff, SAR). Based on site selection criteria, exclusion and suitability factors for the MCDA were defined. Results were integrated with the available geodata to produce habitat suitability maps for oyster restoration in the area of interest. Suitable as well as unsuitable habitats have been successfully identified for both MPAs: several hundred square kilometres (≥97.2% of BRG) or several thousand square kilometres (≥74.5% of SAR) were classified as ecologically and logistically suitable for oyster restoration measures in the respective MPAs. As oyster restoration is significantly limited by human activities (e.g. bottom trawl fisheries), the management of fisheries is an important prerequisite for successful oyster restoration in both MPAs. Results show that designated fishery management measures will increase the possibilities for oyster restoration. In BRG, our results correspond to the known historical distribution. In SAR, our results significantly exceed the historically known distribution. The habitat suitability analysis will facilitate decision-making regarding ocean use, and will reduce restoration costs through targeted management activities in areas of high suitability and expand species recovery by improving the survival of reintroduced individuals. The habitat suitability analysis procedure is easily adaptable for application to other areas, other species, or other habitat restoration projects, or to other conservation management settings. The software applied is open source and the suitability calculation is described in detail to inform wider applications

    Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

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    Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

    CRISPR/Cas9 Immunoengineering of Hoxb8-Immortalized Progenitor Cells for Revealing CCR7-Mediated Dendritic Cell Signaling and Migration Mechanisms in vivo

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    To present antigens to cognate T cells, dendritic cells (DCs) exploit the chemokine receptor CCR7 to travel from peripheral tissue via afferent lymphatic vessels to directly enter draining lymph nodes through the floor of the subcapsular sinus. Here, we combined unlimited proliferative capacity of conditionally Hoxb8-immortalized hematopoietic progenitor cells with CRISPR/Cas9 technology to create a powerful experimental system to investigate DC migration and function. Hematopoietic progenitor cells from the bone marrow of Cas9-transgenic mice were conditionally immortalized by lentiviral transduction introducing a doxycycline-regulated form of the transcription factor Hoxb8 (Cas9-Hoxb8 cells). These cells could be stably cultured for weeks in the presence of doxycycline and puromycin, allowing us to introduce additional genetic modifications applying CRISPR/Cas9 technology. Importantly, modified Cas9-Hoxb8 cells retained their potential to differentiate in vitro into myeloid cells, and GM-CSF-differentiated Cas9-Hoxb8 cells showed the classical phenotype of GM-CSF-differentiated bone marrow-derived dendritic cells. Following intralymphatic delivery Cas9-Hoxb8 DCs entered the lymph node in a CCR7-dependent manner. Finally, we used two-photon microscopy and imaged Cas9-Hoxb8 DCs that expressed the genetic Ca2+ sensor GCaMP6S to visualize in real-time chemokine-induced Ca2+ signaling of lymph-derived DCs entering the LN parenchyma. Altogether, our study not only allows mechanistic insights in DC migration in vivo, but also provides a platform for the immunoengineering of DCs that, in combination with two-photon imaging, can be exploited to further dissect DC dynamics in vivo
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