| 1. |
- Halbgebauer, Rebecca, et al.
(author)
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Thirty-Eight-Negative Kinase 1 Is a Mediator of Acute Kidney Injury in Experimental and Clinical Traumatic Hemorrhagic Shock
- 2020
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 11, s. 1-12
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Journal article (peer-reviewed)abstract
- Trauma represents a major socioeconomic burden worldwide. After a severe injury, hemorrhagic shock (HS) as a frequent concomitant aspect is a central driver of systemic inflammation and organ damage. The kidney is often strongly affected by traumatic-HS, and acute kidney injury (AKI) poses the patient at great risk for adverse outcome. Recently, thirty-eight-negative kinase 1 (TNK1) was proposed to play a detrimental role in organ damage after trauma/HS. Therefore, we aimed to assess the role of TNK1 in HS-induced kidney injury in a murine and apost hocanalysis of a non-human primate model of HS comparable to the clinical situation. Mice and non-human primates underwent resuscitated HS at 30 mmHg for 60 min. 5 h after the induction of shock, animals were assessed for systemic inflammation and TNK1 expression in the kidney.In vitro, murine distal convoluted tubule cells were stimulated with inflammatory mediators to gain mechanistic insights into the role of TNK1 in kidney dysfunction. In a translational approach, we investigated blood drawn from either healthy volunteers or severely injured patients at different time points after trauma (from arrival at the emergency room and at fixed time intervals until 10 days post injury; identifier: NCT02682550,). A pronounced inflammatory response, as seen by increased IL-6 plasma levels as well as early signs of AKI, were observed in mice, non-human primates, and humans after trauma/HS. TNK1 was found in the plasma early after trauma-HS in trauma patients. Renal TNK1 expression was significantly increased in mice and non-human primates after HS, and these effects with concomitant induction of apoptosis were blocked by therapeutic inhibition of complement C3 activation in non-human primates. Mechanistically,in vitrodata suggested that IL-6 rather than C3 cleavage products induced upregulation of TNK1 and impaired barrier function in renal epithelial cells. In conclusion, these data indicate that C3 inhibitionin vivomay inhibit an excessive inflammatory response and mediator release, thereby indirectly neutralizing TNK1 as a potent driver of organ damage. In future studies, we will address the therapeutic potential of direct TNK1 inhibition in the context of severe tissue trauma with different degrees of additional HS.
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| 2. |
- Hamperl, Jonas, et al.
(author)
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High Energy Parametric Laser Source and Frequency-Comb-Based Wavelength Reference for CO2 and Water Vapor DIAL in the 2 mu m Region : Design and Pre-Development Experimentations
- 2021
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In: Atmosphere. - : MDPI AG. - 2073-4433. ; 12:3
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Journal article (peer-reviewed)abstract
- We present a differential absorption lidar (DIAL) laser transmitter concept designed around a Nested Cavity Optical Parametric Oscillator (NesCOPO) based Master Oscillator Power Amplifier (MOPA). The spectral bands are located around 2051 nm for CO2 probing and 1982 nm for (H2O)-O-16 and (HDO)-O-16 water vapor isotopes. This laser is aimed at being integrated into an airborne lidar, intended to demonstrate future spaceborne instrument characteristics: high-energy (several tens of mJ nanosecond pulses) and high optical frequency stability (less than a few hundreds of kHz long term drift). For integration and efficiency purposes, the proposed design is oriented toward the use of state-of-the-art high aperture periodically poled nonlinear materials. This approach is supported by numerical calculations and preliminary experimental validations, showing that it is possible to achieve energies in the 40-50 mJ range, reaching the requirement levels for spaceborne Integrated Path Differential Absorption (IPDA) measurements. We also propose a frequency referencing technique based on beat note measurement of the laser signal with a self-stabilized optical frequency comb, which is expected to enable frequency measurement precisions better than a few 100 kHz over tens of seconds integration time, and will then be used to feed the cavity locking of the NesCOPO.
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| 3. |
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| 4. |
- Marto, João Pedro, et al.
(author)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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In: Neurology. - 1526-632X. ; 100:7
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Journal article (peer-reviewed)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 5. |
- Schipper, C. Ian, et al.
(author)
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Silicic conduits as supersized tuffisites : Clastogenic influences on shifting eruption styles at Cordon Caulle volcano (Chile)
- 2021
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In: Bulletin of Volcanology. - : Springer Nature. - 0258-8900 .- 1432-0819. ; 83:2
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Journal article (peer-reviewed)abstract
- Understanding the processes that drive explosive-effusive transitions during large silicic eruptions is crucial to hazard mitigation. Conduit models usually treat magma ascent and degassing as a gradual, unidirectional progression from bubble nucleation through magmatic fragmentation. However, there is growing evidence for the importance of bi-directional clastogenic processes that sinter fragmented materials into coherent clastogenic magmas. Bombs that were ejected immediately before the first emergence of lava in the 2011-2012 eruption at Cordon Caulle volcano (Chile) are texturally heterogeneous composite assemblages of welded pyroclastic material. Although diverse in density and appearance, SEM and X-ray tomographic analysis show them all to have been formed by multi-generational viscous sintering of fine ash. Sintering created discrete clasts ranging from obsidian to pumice and formed a pervasive clast-supporting matrix that assembled these clasts into a conduit-sealing plug. An evaluation of sintering timescales reveals texturally disparate bomb components to represent only minutes of difference in residence time within the conduit. Permeability modelling indicates that the plug was an effective conduit seal, with outgassing potential-even from high-porosity regions-being limited by the inability of gas to flow across tendrils of densely sintered inter-clast matrix. Contrary to traditional perspectives, declining expressions of explosivity at the surface need not be preceded or accompanied by a decline in fragmentation efficiency. Instead, they result from tips in balance between the opposing processes of fragmentation and sintering that occur in countless cycles within volcanic conduits. These processes may be particularly enhanced at silicic fissure volcanoes, which have laterally extensive subsurface plumbing systems that require complex magma ascent pathways. The textures investigated here reveal the processes occurring within silicic fissures to be phenomenologically identical to those that have been inferred to occur in tuffisite veins: silicic conduits are essentially supersized examples of edifice-penetrating tuffisites.
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| 6. |
- Soliveres, Santiago, et al.
(author)
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Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7617, s. 456-459
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Journal article (peer-reviewed)abstract
- Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend. However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa and that the functional effects of any trophic group may depend on the abundance and diversity of others. Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above- and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.
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| 7. |
- Soliveres, Santiago, et al.
(author)
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Locally rare species influence grassland ecosystem multifunctionality
- 2016
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In: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1694
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Journal article (peer-reviewed)abstract
- Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above-and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.
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