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Sökning: WFRF:(Cecconi M)

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1.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • 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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  • Zouganelis, I., et al. (författare)
  • The Solar Orbiter Science Activity Plan : Translating solar and heliospheric physics questions into action
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642
  • Tidskriftsartikel (refereegranskat)abstract
    • Solar Orbiter is the first space mission observing the solar plasma both in situ and remotely, from a close distance, in and out of the ecliptic. The ultimate goal is to understand how the Sun produces and controls the heliosphere, filling the Solar System and driving the planetary environments. With six remote-sensing and four in-situ instrument suites, the coordination and planning of the operations are essential to address the following four top-level science questions: (1) What drives the solar wind and where does the coronal magnetic field originate?; (2) How do solar transients drive heliospheric variability?; (3) How do solar eruptions produce energetic particle radiation that fills the heliosphere?; (4) How does the solar dynamo work and drive connections between the Sun and the heliosphere? Maximising the mission's science return requires considering the characteristics of each orbit, including the relative position of the spacecraft to Earth (affecting downlink rates), trajectory events (such as gravitational assist manoeuvres), and the phase of the solar activity cycle. Furthermore, since each orbit's science telemetry will be downloaded over the course of the following orbit, science operations must be planned at mission level, rather than at the level of individual orbits. It is important to explore the way in which those science questions are translated into an actual plan of observations that fits into the mission, thus ensuring that no opportunities are missed. First, the overarching goals are broken down into specific, answerable questions along with the required observations and the so-called Science Activity Plan (SAP) is developed to achieve this. The SAP groups objectives that require similar observations into Solar Orbiter Observing Plans, resulting in a strategic, top-level view of the optimal opportunities for science observations during the mission lifetime. This allows for all four mission goals to be addressed. In this paper, we introduce Solar Orbiter's SAP through a series of examples and the strategy being followed.
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  • Maksimovic, M., et al. (författare)
  • The Solar Orbiter Radio and Plasma Waves (RPW) instrument
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642
  • Tidskriftsartikel (refereegranskat)abstract
    • The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is described in this paper. This instrument is designed to measure in-situ magnetic and electric fields and waves from the continuous to a few hundreds of kHz. RPW will also observe solar radio emissions up to 16 MHz. The RPW instrument is of primary importance to the Solar Orbiter mission and science requirements since it is essential to answer three of the four mission overarching science objectives. In addition RPW will exchange on-board data with the other in-situ instruments in order to process algorithms for interplanetary shocks and type III langmuir waves detections.
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  • Maksimovic, M., et al. (författare)
  • First observations and performance of the RPW instrument on board the Solar Orbiter mission
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
  • Tidskriftsartikel (refereegranskat)abstract
    • The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is designed to measure in situ magnetic and electric fields and waves from the continuum up to several hundred kHz. The RPW also observes solar and heliospheric radio emissions up to 16 MHz. It was switched on and its antennae were successfully deployed two days after the launch of Solar Orbiter on February 10, 2020. Since then, the instrument has acquired enough data to make it possible to assess its performance and the electromagnetic disturbances it experiences. In this article, we assess its scientific performance and present the first RPW observations. In particular, we focus on a statistical analysis of the first observations of interplanetary dust by the instrument's Thermal Noise Receiver. We also review the electro-magnetic disturbances that RPW suffers, especially those which potential users of the instrument data should be aware of before starting their research work.
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16.
  • Berthomier, M., et al. (författare)
  • Alfven : magnetosphere-ionosphere connection explorers
  • 2012
  • Ingår i: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
  • Tidskriftsartikel (refereegranskat)abstract
    • The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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17.
  • Bilous, A. V., et al. (författare)
  • Dual-frequency single-pulse study of PSR B0950+08
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
  • Tidskriftsartikel (refereegranskat)abstract
    • PSR B0950+08 is a bright nonrecycled pulsar whose single-pulse fluence variability is reportedly large. Based on observations at two widely separated frequencies, 55 MHz (NenuFAR) and 1.4 GHz (Westerbork Synthesis Radio Telescope), we review the properties of these single pulses. We conclude that they are more similar to ordinary pulses of radio emission than to a special kind of short and bright giant pulses, observed from only a handful of pulsars. We argue that a temporal variation of the properties of the interstellar medium along the line of sight to this nearby pulsar, namely the fluctuating size of the decorrelation bandwidth of diffractive scintillation makes an important contribution to the observed single-pulse fluence variability. We further present interesting structures in the low-frequency single-pulse spectra that resemble the "sad trombones"seen in fast radio bursts (FRBs); although for PSR B0950+08 the upward frequency drift is also routinely present. We explain these spectral features with radius-to-frequency mapping, similar to the model developed by Wang et al. (2019, ApJ, 876, L15) for FRBs. Finally, we speculate that μs-scale fluence variability of the general pulsar population remains poorly known, and that its further study may bring important clues about the nature of FRBs.
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18.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
  • 2008
  • Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
  • Forskningsöversikt (refereegranskat)abstract
    • Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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  • Wernly, B, et al. (författare)
  • Sex-specific outcome disparities in very old patients admitted to intensive care medicine: a propensity matched analysis
  • 2020
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 18671-
  • Tidskriftsartikel (refereegranskat)abstract
    • Female and male very elderly intensive patients (VIPs) might differ in characteristics and outcomes. We aimed to compare female versus male VIPs in a large, multinational collective of VIPs with regards to outcome and predictors of mortality. In total, 7555 patients were included in this analysis, 3973 (53%) male and 3582 (47%) female patients. The primary endpoint was 30-day-mortality. Baseline characteristics, data on management and geriatric scores including frailty assessed by Clinical Frailty Scale (CFS) were documented. Two propensity scores (for being male) were obtained for consecutive matching, score 1 for baseline characteristics and score 2 for baseline characteristics and ICU management. Male VIPs were younger (83 ± 5 vs. 84 ± 5; p < 0.001), less often frail (CFS > 4; 38% versus 49%; p < 0.001) but evidenced higher SOFA (7 ± 6 versus 6 ± 6 points; p < 0.001) scores. After propensity score matching, no differences in baseline characteristics could be observed. In the paired analysis, the mortality in male VIPs was higher (mean difference 3.34% 95%CI 0.92–5.76%; p = 0.007) compared to females. In both multivariable logistic regression models correcting for propensity score 1 (aOR 1.15 95%CI 1.03–1.27; p = 0.007) and propensity score 2 (aOR 1.15 95%CI 1.04–1.27; p = 0.007) male sex was independently associated with higher odds for 30-day-mortality. Of note, male gender was not associated with ICU mortality (OR 1.08 95%CI 0.98–1.19; p = 0.14). Outcomes of elderly intensive care patients evidenced independent sex differences. Male sex was associated with adverse 30-day-mortality but not ICU-mortality. Further research to identify potential sex-specific risk factors after ICU discharge is warranted.Trial registration: NCT03134807 and NCT03370692; Registered on May 1, 2017 https://clinicaltrials.gov/ct2/show/NCT03370692.
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24.
  • Azoulay, E., et al. (författare)
  • International variation in the management of severe COVID-19 patients
  • 2020
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1466-609X .- 1364-8535. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background There is little evidence to support the management of severe COVID-19 patients. Methods To document this variation in practices, we performed an online survey (April 30-May 25, 2020) on behalf of the European Society of Intensive Care Medicine (ESICM). A case vignette was sent to ESICM members. Questions investigated practices for a previously healthy 39-year-old patient presenting with severe hypoxemia from COVID-19 infection. Results A total of 1132 ICU specialists (response rate 20%) from 85 countries (12 regions) responded to the survey. The survey provides information on the heterogeneity in patient's management, more particularly regarding the timing of ICU admission, the first line oxygenation strategy, optimization of management, and ventilatory settings in case of refractory hypoxemia. Practices related to antibacterial, antiviral, and anti-inflammatory therapies are also investigated. Conclusions There are important practice variations in the management of severe COVID-19 patients, including differences at regional and individual levels. Large outcome studies based on multinational registries are warranted.
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  • Azoulay, E., et al. (författare)
  • Symptoms of burnout in intensive care unit specialists facing the COVID-19 outbreak
  • 2020
  • Ingår i: Annals of Intensive Care. - : Springer Science and Business Media LLC. - 2110-5820. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The COVID-19 pandemic has resulted in an unprecedented healthcare crisis with a high prevalence of psychological distress in healthcare providers. We sought to document the prevalence of burnout syndrome amongst intensivists facing the COVID-19 outbreak. Methods Cross-sectional survey among intensivists part of the European Society of Intensive Care Medicine. Symptoms of severe burnout, anxiety and depression were collected. Factors independently associated with severe burnout were assessed using Cox model. Results Response rate was 20% (1001 completed questionnaires were returned, 45 years [39-53], 34% women, from 85 countries, 12 regions, 50% university-affiliated hospitals). The prevalence of symptoms of anxiety and depression or severe burnout was 46.5%, 30.2%, and 51%, respectively, and varied significantly across regions. Rating of the relationship between intensivists and other ICU stakeholders differed significantly according to the presence of anxiety, depression, or burnout. Similar figures were reported for their rating of the ethical climate or the quality of the decision-making. Factors independently associated with anxiety were female gender (HR 1.85 [1.33-2.55]), working in a university-affiliated hospital (HR 0.58 [0.42-0.80]), living in a city of > 1 million inhabitants (HR 1.40 [1.01-1.94]), and clinician's rating of the ethical climate (HR 0.83 [0.77-0.90]). Independent determinants of depression included female gender (HR 1.63 [1.15-2.31]) and clinician's rating of the ethical climate (HR 0.84 [0.78-0.92]). Factors independently associated with symptoms of severe burnout included age (HR 0.98/year [0.97-0.99]) and clinician's rating of the ethical climate (HR 0.76 [0.69-0.82]). Conclusions The COVID-19 pandemic has had an overwhelming psychological impact on intensivists. Follow-up, and management are warranted to assess long-term psychological outcomes and alleviate the psychological burden of the pandemic on frontline personnel.
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