| 1. |
- Carraminana, Albert, et al.
(author)
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Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
- 2019
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In: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
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Journal article (peer-reviewed)abstract
- Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
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| 2. |
- Ebersole, Charles R., et al.
(author)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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In: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Journal article (peer-reviewed)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 3. |
- Fevola, Giovanni, et al.
(author)
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A Monte Carlo ray-tracing simulation of coherent X-ray diffractive imaging
- 2020
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In: Journal of Synchrotron Radiation. - 0909-0495. ; 27, s. 134-145
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Journal article (peer-reviewed)abstract
- Coherent diffractive imaging (CDI) experiments are adequately simulated assuming the thin sample approximation and using a Fresnel or Fraunhofer wavefront propagator to obtain the diffraction pattern. Although this method is used in wave-based or hybrid X-ray simulators, here the applicability and effectiveness of an alternative approach that is based solely on ray tracing of Huygens wavelets are investigated. It is shown that diffraction fringes of a grating-like source are accurately predicted and that diffraction patterns of a ptychography dataset from an experiment with realistic parameters can be sampled well enough to be retrieved by a standard phase-retrieval algorithm. Potentials and limits of this approach are highlighted. It is suggested that it could be applied to study imperfect or non-standard CDI configurations lacking a satisfactory theoretical formulation. The considerable computational effort required by this method is justified by the great flexibility provided for easy simulation of a large-parameter space.
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| 4. |
- Gustafsson, Gabriel
(author)
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Alpha-Synuclein Oligomers : Cellular Mechanisms and Aspects of Antibody Treatment
- 2017
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Doctoral thesis (other academic/artistic)abstract
- In Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), aggregated α-synuclein deposit inside cells within the brain. Smaller soluble α-synuclein aggregates, oligomers, are present both intra- and extracellularly. The α-synuclein oligomers are known to be particularly harmful, although the underlying neurotoxic mechanisms are not fully understood. The aim of this thesis was to investigate the pathogenic roles of α-synuclein oligomers and the possibility to target such species with antibody treatment.Passive immunotherapy with α-synuclein antibodies can lead to reduced pathology and ameliorated symptoms in transgenic mice. However, it remains unknown whether the antibodies are taken up by cells or whether they act extracellularly. In Paper I, we assessed cellular internalization of various α-synuclein monoclonal antibodies. The oligomer selective mAb47 displayed the highest uptake, which was promoted by the extracellular presence of α-synuclein.Alpha-synuclein aggregates can be found in both neurons and glial cells, but the pathogenic role of glial deposits has only been sparsely investigated. In Paper II, co-cultures of neurons and glia were exposed to α-synuclein oligomers. The astrocytes in the cultures rapidly accumulated oligomers, which were only partially degraded by lysosomes. The sustained intracellular α-synuclein deposits were associated with mitochondrial stress reactions in the astrocytes. In Paper III, we sought to explore whether the astrocytic pathology induced by α-synuclein oligomers could be ameliorated by antibody treatment. Pre-incubation of oligomers with mAb47 promoted α-synuclein clearance, reduced astrocytic accumulation and rescued cells from mitochondrial stress. We could demonstrate that binding of the antibody to its antigen in the extracellular space was crucial for these effects to occur.The progressive pathology in PD is believed to be driven by cell-to-cell spreading of α-synuclein aggregates, potentially via exosomes and other extracellular vesicles (EVs). In Paper IV, we found that either fusing α-synuclein to a non-physiological protein tag or introducing the PD-causing A53T mutation directed α-synuclein towards EV secretion. Also, EV-associated α-synuclein was particularly prone to induce toxicity in recipient cells.In conclusion, this thesis sheds new light on the cellular dysfunction related to α-synuclein pathology and on how the underlying pathogenic processes may be targeted by antibody treatment.
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| 5. |
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| 6. |
- Lotze, Heike K., et al.
(author)
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Global ensemble projections reveal trophic amplification of ocean biomass declines with climate change
- 2019
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:26, s. 12907-12912
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Journal article (peer-reviewed)abstract
- While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (+/- 4% SD) under low emissions and 17% (+/- 11% SD) under high emissions by 2100, with an average 5% decline for every 1 degrees C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends.
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| 7. |
- Pereira, Francielly Dias, et al.
(author)
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Oxidative stress and antioxidant defense in the heart, liver, and kidney of bat species with different feeding habits
- 2023
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In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:22
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Journal article (peer-reviewed)abstract
- The aim of this study was to compare the oxidative metabolism of four neotropical bat species with different feeding habits and investigate the relationship between their feeding habits and oxidative status. In terms of oxidative damage, our findings revealed major differences among the four bat species. In particular, hematophagous bats had lower levels of oxidative damage in the heart but higher levels in the liver. Nectarivorous bats had lower levels of carbonyl groups in the kidneys compared to insectivorous and hematophagous bats. The activity of various antioxidant and non-antioxidant enzymes in the heart, liver, and kidney also showed significant differences among the bat species. H2O2 consumption was lower in the heart of hematophagous bats, while insectivorous bats exhibited the highest enzymatic activity in the kidney. SOD activity was lower in the heart of hematophagous bats and lower in nectarivorous bats in the liver. Fumarase activity was higher in the heart of frugivorous/insectivorous and lower in nectarivorous/hematophagous bats. GPx activity was higher in the heart of nectarivorous/insectivorous and higher in the kidney of insectivorous bats. GST activity was higher in the heart of nectarivorous and lower in hematophagous bats. The correlation analysis between oxidative markers and enzymatic/non-enzymatic antioxidants in the heart, liver, and kidney exhibited distinct patterns of correlations due to variations in antioxidant defense mechanisms and oxidative stress responses in different organs. The observed differences in oxidative damage, antioxidant enzyme activities, and correlations between oxidative markers and antioxidants highlight the adaptability and complexity of the antioxidant defense systems in these bats. Each organ appears to have specific demands and adaptations to cope with oxidative stress based on its physiological functions and exposure to dietary components. Our results have major significance for the conservation and management of bats, which are threatened species despite being crucial components of ecosystems. Our study's implications go beyond bat biology and offer valuable insights into comparative oxidative physiology.
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| 8. |
- Pocas, Juliana, et al.
(author)
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Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
- 2023
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:20
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Journal article (peer-reviewed)abstract
- Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane pro-teoglycan, is highly expressed in intestinal subtype gastric tumors and that this sig -nature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.
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| 9. |
- Saadaldin, Abdellatif, et al.
(author)
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Multi-modal characterization of kesterite thin-film solar cells : experimental results and numerical interpretation
- 2022
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In: Faraday Discussions. - : Royal Society of Chemistry (RSC). - 1359-6640 .- 1364-5498. ; 239, s. 160-179
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Journal article (peer-reviewed)abstract
- We report a multi-modal study of the electrical, chemical and structural properties of a kesterite thin-film solar cell by combining the spatially-resolved X-ray beam induced current and fluorescence imaging techniques for the evaluation of a fully functional device on a cross-section. The data allowed the correlation of the chemical composition, defects at interfaces and inhomogeneous deposition of the layers with the local charge-collection efficiency of the device. We support our observations with Monte Carlo simulations of high-energy X-ray interactions with the semiconductor device, and finite-volume modeling of the charge-collection efficiency.
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| 10. |
- Tittensor, Derek P., et al.
(author)
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A protocol for the intercomparison of marine fishery and ecosystem models : Fish-MIP v1.0
- 2018
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In: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 11:4, s. 1421-1442
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Journal article (peer-reviewed)abstract
- Model intercomparison studies in the climate and Earth sciences communities have been crucial to building credibility and coherence for future projections. They have quantified variability among models, spurred model development, contrasted within- and among-model uncertainty, assessed model fits to historical data, and provided ensemble projections of future change under specified scenarios. Given the speed and magnitude of anthropogenic change in the marine environment and the consequent effects on food security, biodiversity, marine industries, and society, the time is ripe for similar comparisons among models of fisheries and marine ecosystems. Here, we describe the Fisheries and Marine Ecosystem Model Intercomparison Project protocol version 1.0 (Fish-MIP v1.0), part of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP), which is a cross-sectoral network of climate impact modellers. Given the complexity of the marine ecosystem, this class of models has substantial heterogeneity of purpose, scope, theoretical underpinning, processes considered, parameterizations, resolution (grain size), and spatial extent. This heterogeneity reflects the lack of a unified understanding of the marine ecosystem and implies that the assemblage of all models is more likely to include a greater number of relevant processes than any single model. The current Fish-MIP protocol is designed to allow these heterogeneous models to be forced with common Earth System Model (ESM) Coupled Model Intercomparison Project Phase 5 (CMIP5) outputs under prescribed scenarios for historic (from the 1950s) and future (to 2100) time periods; it will be adapted to CMIP phase 6 (CMIP6) in future iterations. It also describes a standardized set of outputs for each participating Fish-MIP model to produce. This enables the broad characterization of differences between and uncertainties within models and projections when assessing climate and fisheries impacts on marine ecosystems and the services they provide. The systematic generation, collation, and comparison of results from Fish-MIP will inform an understanding of the range of plausible changes in marine ecosystems and improve our capacity to define and convey the strengths and weaknesses of model-based advice on future states of marine ecosystems and fisheries. Ultimately, Fish-MIP represents a step towards bringing together the marine ecosystem modelling community to produce consistent ensemble medium- and long-term projections of marine ecosystems.
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