| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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. |
- Aktas, A., et al.
(författare)
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Measurement and QCD analysis of the diffractive deep-inelastic scattering cross section at HERA
- 2006
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 48:3, s. 715-748
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Forskningsöversikt (refereegranskat)abstract
- A detailed analysis is presented of the diffractive deep-inelastic scattering process ep -> eXY, where Y is a proton or a low mass proton excitation carrying a fraction 1 - x(IP) > 0.95 of the incident proton longitudinal momentum and the squared four-momentum transfer at the proton vertex satisfies |t| < 1 GeV2. Using data taken by the H1 experiment, the cross section is measured for photon virtualities in the range 3.5 <= Q(2) <= 1600 GeV2, triple differentially in x(IP), Q(2) and beta = x/x(P), where x is the Bjorken scaling variable. At low x(IP), the data are consistent with a factorisable x(IP) dependence, which can be described by the exchange of an effective pomeron trajectory with intercept alpha(IP)(0) = 1.118 +/- 0.008(exp.)(-0.010)(+0.029)(model). Diffractive parton distribution functions and their uncertainties are determined from a next-to-leading order DGLAP QCD analysis of the Q(2)and beta dependences of the cross section. The resulting gluon distribution carries an integrated fraction of around 70% of the exchanged momentum in the Q(2) range studied. Total and differential cross sections are also measured for the diffractive charged current process e(+) p -> (v) over bar eXY and are found to be well described by predictions based on the diffractive parton distributions. The ratio of the diffractive to the inclusive neutral current ep cross sections is studied. Over most of the kinematic range, this ratio shows no significant dependence on Q(2) at fixed x(P) and x or on x at fixed Q(2) and beta.
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| 3. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 4. |
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| 5. |
- Nowak-Sliwinska, Patrycja, et al.
(författare)
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Consensus guidelines for the use and interpretation of angiogenesis assays
- 2018
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Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
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Forskningsöversikt (refereegranskat)abstract
- The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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| 6. |
- Torbert, R. B., et al.
(författare)
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The FIELDS Instrument Suite on MMS : Scientific Objectives, Measurements, and Data Products
- 2016
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Ingår i: Space Science Reviews. - : Springer Science+Business Media B.V.. - 0038-6308 .- 1572-9672. ; 199:1-4, s. 105-135
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Forskningsöversikt (refereegranskat)abstract
- The FIELDS instrumentation suite on the Magnetospheric Multiscale (MMS) mission provides comprehensive measurements of the full vector magnetic and electric fields in the reconnection regions investigated by MMS, including the dayside magnetopause and the night-side magnetotail acceleration regions out to 25 Re. Six sensors on each of the four MMS spacecraft provide overlapping measurements of these fields with sensitive cross-calibrations both before and after launch. The FIELDS magnetic sensors consist of redundant flux-gate magnetometers (AFG and DFG) over the frequency range from DC to 64 Hz, a search coil magnetometer (SCM) providing AC measurements over the full whistler mode spectrum expected to be seen on MMS, and an Electron Drift Instrument (EDI) that calibrates offsets for the magnetometers. The FIELDS three-axis electric field measurements are provided by two sets of biased double-probe sensors (SDP and ADP) operating in a highly symmetric spacecraft environment to reduce significantly electrostatic errors. These sensors are complemented with the EDI electric measurements that are free from all local spacecraft perturbations. Cross-calibrated vector electric field measurements are thus produced from DC to 100 kHz, well beyond the upper hybrid resonance whose frequency provides an accurate determination of the local electron density. Due to its very large geometric factor, EDI also provides very high time resolution (similar to 1 ms) ambient electron flux measurements at a few selected energies near 1 keV. This paper provides an overview of the FIELDS suite, its science objectives and measurement requirements, and its performance as verified in calibration and cross-calibration procedures that result in anticipated errors less than 0.1 nT in B and 0.5 mV/m in E. Summaries of data products that result from FIELDS are also described, as well as algorithms for cross-calibration. Details of the design and performance characteristics of AFG/DFG, SCM, ADP, SDP, and EDI are provided in five companion papers.
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| 7. |
- Ariens, Robert, et al.
(författare)
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Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress
- 2020
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Ingår i: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS. - : Wiley. - 2475-0379. ; 4:5, s. 680-713
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Forskningsöversikt (refereegranskat)abstract
- The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education.
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| 8. |
- Biermann, F., et al.
(författare)
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The Earth System Governance Project as a network organization : a critical assessment after ten years
- 2019
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 39, s. 17-23
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Forskningsöversikt (refereegranskat)abstract
- The social sciences have engaged since the late 1980s in international collaborative programmes to study questions of sustainability and global change. This article offers an in-depth analysis of the largest long-standing social-science network in this field: the Earth System Governance Project. Originating as a core project of the former International Human Dimensions Programme on Global Environmental Change, the Earth System Governance Project has matured into a global, self-sustaining research network, with annual conferences, numerous taskforces, research centers, regional research fellow meetings, three book series, an open access flagship journal, and a lively presence in social media. The article critically reviews the experiences of the Earth System Governance network and its integration and interactions with other programmes over the last decade.
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| 9. |
- Breimer, Lars H., et al.
(författare)
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Immune checkpoint inhibitors of the PD-1/PD-L1-axis in non-small cell lung cancer : promise, controversies and ambiguities in the novel treatment paradigm
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 80:5, s. 360-369
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Forskningsöversikt (refereegranskat)abstract
- Immune checkpoint inhibitors (ICIs) have received much attention not least for melanoma since the award of the Nobel prize in 2018. Here, we review the current state of knowledge about the use of these monoclonal antibodies (mAbs) in non-small cell lung cancer (NSCLC). These drugs have generally been conditionally approved on limited early data and there are few long-term follow-up data from randomized clinical trials. The effect observed for NSCLC thus far is, on average, moderately better than that obtained with chemotherapy. Severe side-effects are more common than might have been expected. The drugs themselves are expensive and are associated with time-consuming histopathologic testing even though the predictive value of these tests can be discussed. In addition, monitoring for side-effects involves increased workload and budgetary expense for clinical chemistry laboratories. Here, we review and summarize the current knowledge, controversies and ambiguities of ICIs for the treatment of NSCLC.
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| 10. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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