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Sökning: WFRF:(Whitehouse Marc)

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1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2.
  • Bellucci, Jeremy, et al. (författare)
  • Terrestrial-like zircon in an Apollo 14 breccia.
  • 2019
  • Ingår i: Earth and Planetary Science Letters. - Netherlands : Elsevier. - 0012-821X .- 1385-013X. ; 510, s. 173-185
  • Tidskriftsartikel (refereegranskat)
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3.
  • El Albani, Abderrazak, et al. (författare)
  • The 2.1 Ga old Francevillian biota: biogenicity, taphonomy and biodiversity.
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6:e99438, s. 1-18
  • Tidskriftsartikel (refereegranskat)abstract
    • The Paleoproterozoic Era witnessed crucial steps in the evolution of Earth’s surface environments following the first appreciable rise of free atmospheric oxygen concentrations ~2.3 to 2.1 Ga ago, and concomitant shallow ocean oxygenation. While most sedimentary successions deposited during this time interval have experienced thermal overprinting from burial diagenesis and metamorphism, the ca. 2.1 Ga black shales of the Francevillian B Formation (FB2) cropping out in southeastern Gabon have not. The Francevillian Formation contains centimeter-sized structures interpreted as organized and spatially discrete populations of colonial organisms living in an oxygenated marine ecosystem. Here, new material from the FB2 black shales is presented and analyzed to further explore its biogenicity and taphonomy. Our extended record comprises variably sized, shaped, and structured pyritized macrofossils of lobate, elongated, and rodshaped morphologies as well as abundant non-pyritized disk-shaped macrofossils and organic-walled acritarchs. Combined microtomography, geochemistry, and sedimentary analysis suggest a biota fossilized during early diagenesis. The emergence of this biota follows a rise in atmospheric oxygen, which is consistent with the idea that surface oxygenation allowed the evolution and ecological expansion of complex megascopic life.
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4.
  • Grooten, Liset, et al. (författare)
  • A scaling-up strategy supporting the expansion of integrated care : a study protocol
  • 2019
  • Ingår i: Journal of Integrated Care. - : Emerald Group Publishing Limited. - 1476-9018. ; 27:3, s. 215-231
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeTo ensure that more people will benefit from integrated care initiatives, scaling-up of successful initiatives is the way forward. However, new challenges present themselves as knowledge on how to achieve successful large-scale implementation is scarce. The EU-funded project SCIROCCO uses a step-based scaling-up strategy to explore what to scale-up, and how to scale-up integrated care initiatives by matching the complementary strengths and weaknesses of five European regions involved in integrated care. The purpose of this paper is to describe a multi-method evaluation protocol designed to understand what factors influence the implementation of the SCIROCCO strategy to support the scaling-up of integrated care.Design/methodology/approachThe first part of the protocol focuses on the assessment of the implementation fidelity of the SCIROCCO step-based strategy. The objective is to gain insight in whether the step-based strategy is implemented as it was designed to explore what works and does not work when implementing the scaling-up strategy. The second part concerns a realist evaluation to examine what it is about the SCIROCCO’s strategy that works for whom, why, how and in which circumstances when scaling-up integrated care.FindingsThe intended study will provide valuable information on the implementation of the scaling-up strategy which will help to explain for what specific reasons the implementation succeeds and will facilitate further improvement of project outcomes.Originality/valueThe expected insights could be useful to guide the development, implementation and evaluation of future scaling-up strategies to advance the change towards more sustainable health and care systems.
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5.
  • Harrison, Sandy P., et al. (författare)
  • Development and testing scenarios for implementing land use and land cover changes during the Holocene in Earth system model experiments
  • 2020
  • Ingår i: Geoscientific Model Development. - : Copernicus Gesellschaft MBH. - 1991-959X .- 1991-9603. ; 13:2, s. 805-824
  • Tidskriftsartikel (refereegranskat)abstract
    • Anthropogenic changes in land use and land cover (LULC) during the pre-industrial Holocene could have affected regional and global climate. Existing scenarios of LULC changes during the Holocene are based on relatively simple assumptions and highly uncertain estimates of population changes through time. Archaeological and palaeoenvironmental reconstructions have the potential to refine these assumptions and estimates. The Past Global Changes (PAGES) LandCover6k initiative is working towards improved reconstructions of LULC globally. In this paper, we document the types of archaeological data that are being collated and how they will be used to improve LULC reconstructions. Given the large methodological uncertainties involved, both in reconstructing LULC from the archaeological data and in implementing these reconstructions into global scenarios of LULC, we propose a protocol to evaluate the revised scenarios using independent pollen-based reconstructions of land cover and climate. Further evaluation of the revised scenarios involves carbon cycle model simulations to determine whether the LULC reconstructions are consistent with constraints provided by ice core records of CO2 evolution and modern-day LULC. Finally, the protocol outlines how the improved LULC reconstructions will be used in palaeoclimate simulations in the Palaeoclimate Modelling Intercomparison Project to quantify the magnitude of anthropogenic impacts on climate through time and ultimately to improve the realism of Holocene climate simulations.
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7.
  • Long, Tao, et al. (författare)
  • Constraining the formation and transport of lunar impact glasses using the ages and chemical compositions of Chang’e-5 glass beads
  • 2022
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:39
  • Tidskriftsartikel (refereegranskat)abstract
    • Impact glasses found in lunar soils provide a possible window into the impact history of the inner solar system. However, their use for precise reconstruction of this history is limited by an incomplete understanding of the physical mechanisms responsible for their origin and distribution and possible relationships to local and regional geology. Here, we report U-Pb isotopic dates and chemical compositions of impact glasses from the Chang’e-5 soil and quantitative models of impact melt formation and ejection that account for the compositions of these glasses. The predominantly local provenance indicated by their compositions, which constrains transport distances to <~150 kilometers, and the age-frequency distribution are consistent with formation mainly in impact craters 1 to 5 kilometers in diameter. Based on geological mapping and impact cratering theory, we tentatively identify specific craters on the basaltic unit sampled by Chang’e-5 that may have produced these glasses and compare their ages with the impact record of the asteroid belt.
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8.
  • Mathieu, François, et al. (författare)
  • Impact of Antithrombotic Agents on Radiological Lesion Progression in Acute Traumatic Brain Injury : A CENTER-TBI Propensity-Matched Cohort Analysis
  • 2020
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:19, s. 2069-2080
  • Tidskriftsartikel (refereegranskat)abstract
    • An increasing number of elderly patients are being affected by traumatic brain injury (TBI) and a significant proportion are on pre-hospital antithrombotic therapy for cardio- or cerebrovascular indications. We have quantified the impact of antiplatelet/anticoagulant (APAC) agents on radiological lesion progression in acute TBI, using a novel, semi-automated approach to volumetric lesion measurement, and explored the impact of use on clinical outcomes in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We used a 1:1 propensity-matched cohort design, matching controls to APAC users based on demographics, baseline clinical status, pre-injury comorbidities, and injury severity. Subjects were selected from a pool of patients enrolled in CENTER-TBI with computed tomography (CT) scan at admission and repeated within 7 days of injury. We calculated absolute changes in volume of intraparenchymal, extra-axial, intraventricular, and total intracranial hemorrhage (ICH) between scans, and compared volume of hemorrhagic progression, proportion of patients with significant degree of progression (>25% of initial volume), proportion with new ICH on follow-up CT, as well as clinical course and outcomes. A total of 316 patients were included (158 APAC users; 158 controls). The mean volume of progression was significantly higher in the APAC group for extra-axial (3.1 vs. 1.3 mL, p = 0.01), but not intraparenchymal (3.8 vs. 4.6 mL, p = 0.65), intraventricular (0.2 vs. 0.0 mL, p = 0.79), or total intracranial hemorrhage (ICH; 7.0 vs. 6.0 mL, p = 0.08). More patients had significant hemorrhage growth (54.1 vs. 37.0%, p = 0.003) and delayed ICH (4 of 18 vs. none; p = 0.04) in the APAC group compared with controls, but this was not associated with differences in length of stay (LOS), rates of neurosurgical intervention, mortality or Glasgow Outcome Scale Extended (GOS-E) score at 6 months. Pre-injury use of antithrombotic agents was associated with greater expansion of extra-axial lesions, higher rates of significant hemorrhagic progression, and higher risk of delayed traumatic ICH, but this was not associated with worse clinical course or functional outcomes.
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9.
  • Morrison, Kathleen D., et al. (författare)
  • Mapping past human land use using archaeological data : A new classification for global land use synthesis and data harmonization
  • 2021
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:4
  • Tidskriftsartikel (refereegranskat)abstract
    • In the 12,000 years preceding the Industrial Revolution, human activities led to significant changes in land cover, plant and animal distributions, surface hydrology, and biochemical cycles. Earth system models suggest that this anthropogenic land cover change influenced regional and global climate. However, the representation of past land use in earth system models is currently oversimplified. As a result, there are large uncertainties in the current understanding of the past and current state of the earth system. In order to improve representation of the variety and scale of impacts that past land use had on the earth system, a global effort is underway to aggregate and synthesize archaeological and historical evidence of land use systems. Here we present a simple, hierarchical classification of land use systems designed to be used with archaeological and historical data at a global scale and a schema of codes that identify land use practices common to a range of systems, both implemented in a geospatial database. The classification scheme and database resulted from an extensive process of consultation with researchers worldwide. Our scheme is designed to deliver consistent, empirically robust data for the improvement of land use models, while simultaneously allowing for a comparative, detailed mapping of land use relevant to the needs of historical scholars. To illustrate the benefits of the classification scheme and methods for mapping historical land use, we apply it to Mesopotamia and Arabia at 6 kya (c. 4000 BCE). The scheme will be used to describe land use by the Past Global Changes (PAGES) LandCover6k working group, an international project comprised of archaeologists, historians, geographers, paleoecologists, and modelers. Beyond this, the scheme has a wide utility for creating a common language between research and policy communities, linking archaeologists with climate modelers, biodiversity conservation workers and initiatives.
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