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1.
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2.
  • 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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3.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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4.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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5.
  • Brütt, Katharina, et al. (författare)
  • Competition and moral behavior: A meta-analysis of forty-five crowd-sourced experimental designs
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences - PNAS. - : National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 120:23
  • Tidskriftsartikel (refereegranskat)abstract
    • Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity-variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity-estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs-indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.
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6.
  • Abbasi, Rasha, et al. (författare)
  • IceCube search for neutrinos from GRB 221009A
  • 2023
  • Ingår i: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
  • Konferensbidrag (refereegranskat)abstract
    •  GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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7.
  • Bhatt, Deepak L., et al. (författare)
  • Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
  • 2019
  • Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
  • Tidskriftsartikel (refereegranskat)abstract
    • In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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8.
  • Carleo, Ilaria, et al. (författare)
  • The Multiplanet System TOI-421*
  • 2020
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
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10.
  • Krauss, Tobias, et al. (författare)
  • Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors
  • 2018
  • Ingår i: Endocrine-Related Cancer. - : BIOSCIENTIFICA LTD. - 1351-0088 .- 1479-6821. ; 25:9, s. 783-793
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were >= 2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off >= 2.8 cm, 44% and 91% for TVDT cut-off of <= 24 months). In 117 of 273 patients, PanNETs > 1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs < 2.8 cm vs >= 2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.
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11.
  • Murari, A., et al. (författare)
  • A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
  • 2024
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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13.
  • Schael, S, et al. (författare)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Forskningsöversikt (refereegranskat)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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15.
  • Albers, Roland, et al. (författare)
  • Magnetospheric Venus Space Explorers (MVSE) mission : a proposal for understanding the dynamics of induced magnetospheres
  • 2024
  • Ingår i: Acta Astronautica. - : Elsevier. - 0094-5765 .- 1879-2030. ; 221, s. 194-205
  • Tidskriftsartikel (refereegranskat)abstract
    • Induced magnetospheres form around planetary bodies with atmospheres through the interaction of the solar wind with their ionosphere. Induced magnetospheres are highly dependent on the solar wind conditions and have only been studied with single spacecraft missions in the past. Without simultaneous measurements of solar wind variations and phenomena in the magnetosphere, establishing a link between both can only be done indirectly, using statistics over a large set of measurements. This gap in knowledge could be addressed by a multi-spacecraft plasma mission, optimized for studying global spatial and temporal variations in the magnetospheric system around Venus, which hosts the most prominent example of an induced magnetosphere in our solar system. The MVSE mission comprises four satellites, of which three are identical scientific spacecraft, carrying the same suite of instruments probing different regions of the induced magnetosphere and the solar wind simultaneously. The fourth spacecraft is the transfer vehicle which acts as a relay satellite for communications at Venus. In this way, changes in the solar wind conditions and extreme solar events can be observed, and their effects can be quantified as they propagate through the Venusian induced magnetosphere. Additionally, energy transfer in the Venusian induced magnetosphere can be investigated. The scientific payload includes instrumentation to measure the magnetic field, electric field, and ion–electron velocity distributions. This study presents the scientific motivation for the mission as well as requirements and the resulting mission design. Concretely, a mission timeline along with a complete spacecraft design, including mass, power, communication, propulsion and thermal budgets are given. This mission was initially conceived at the Alpbach Summer School 2022 and refined during a week-long study at ESA's Concurrent Design Facility in Redu, Belgium.
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16.
  • Alfonso, Fernando, et al. (författare)
  • Authorship : from credit to accountability. Reflections from the Editors' Network.
  • 2019
  • Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 108:7, s. 723-729
  • Tidskriftsartikel (refereegranskat)abstract
    • The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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17.
  • Alfonso, Fernando, et al. (författare)
  • Authorship : From credit to accountability - Reflections from the Editors' network.
  • 2019
  • Ingår i: Archivos de cardiologia de Mexico. - 1665-1731. ; 89:1, s. 93-99
  • Tidskriftsartikel (refereegranskat)abstract
    • The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new -(fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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18.
  • Alfonso, Fernando, et al. (författare)
  • Authorship : From credit to accountability. Reflections from the Editors' Network.
  • 2019
  • Ingår i: Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology. - : Elsevier BV. - 2174-2030. ; 38:7, s. 519-525
  • Tidskriftsartikel (refereegranskat)abstract
    • The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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19.
  • Alfonso, Fernando, et al. (författare)
  • Authorship : From credit to accountability - Reflections from the Editors' network.
  • 2019
  • Ingår i: Archivos de cardiologia de Mexico. - 1665-1731. ; 89:2, s. 105-111
  • Tidskriftsartikel (refereegranskat)abstract
    • The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new -(fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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20.
  • Alfonso, Fernando, et al. (författare)
  • Authorship : from credit to accountability. Reflections from the Editors' Network.
  • 2019
  • Ingår i: Basic Research in Cardiology. - : Springer Science and Business Media LLC. - 0300-8428 .- 1435-1803. ; 114:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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21.
  • Alfonso, Fernando, et al. (författare)
  • Authorship : From Credit to Accountability Reflections From the Editors´ Network.
  • 2019
  • Ingår i: Anatolian journal of cardiology. - 2149-2263 .- 2149-2271. ; 21:5, s. 281-286
  • Tidskriftsartikel (refereegranskat)abstract
    • The Editors´ Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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22.
  • Bartsch, Yannic C, et al. (författare)
  • IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants
  • 2020
  • Ingår i: The Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 146:3, s. 652-666
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Effector functions of IgG antibodies (Abs) are regulated by their Fc N-glycosylation pattern. IgG Fc glycans that lack galactose and terminal sialic acid residues correlate with the severity of inflammatory (auto)immune disorders and have also been linked to the protection against viral infection and discussed in the context of vaccine-induced protection. In contrast, sialylated IgG Abs have shown immunosuppressive effects.OBJECTIVE: We sought to investigate IgG glycosylation programming during the germinal center (GC) reaction upon immunization of mice with a foreign protein antigen and different adjuvants.METHODS: Mice were analyzed for GC T, B cell and plasma cell responses as well as antigen-specific serum IgG subclass titers and Fc glycosylation patterns.RESULTS: Different adjuvants induce distinct IgG+ GC B cell responses with specific transcriptomes and expression levels of the α2,6-sialyltransferase responsible for IgG sialylation that correspond to distinct serum IgG Fc glycosylation patterns. Low IgG Fc sialylation programming in GC B cells was overall highly dependent on the T follicular helper (TFH) cell-inducing cytokine IL-6, especially induced by water-in-oil adjuvants and Mycobacterium tuberculosis (Mtb). Furthermore, low IgG Fc sialylation programming was dependent on adjuvants that induced IL-27R-dependent IFNγ+ TFH1 cells, IL-6/IL-23-dependent IL-17A+ TFH17 cells and high TFH/T follicular regulatory (TFR) cell ratios. The two latter were here dependent on Mtb and its cord factor.CONCLUSION: These findings on adjuvant-dependent GC responses and IgG glycosylation programming may aid the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns.
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23.
  • Batrancea, Larissa, et al. (författare)
  • Trust and power as determinants of tax compliance across 44 nations
  • 2019
  • Ingår i: Journal of Economic Psychology. - : Elsevier BV. - 0167-4870 .- 1872-7719. ; 74
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019 The slippery slope framework of tax compliance emphasizes the importance of trust in authorities as a substantial determinant of tax compliance alongside traditional enforcement tools like audits and fines. Using data from an experimental scenario study in 44 nations from five continents (N = 14,509), we find that trust in authorities and power of authorities, as defined in the slippery slope framework, increase tax compliance intentions and mitigate intended tax evasion across societies that differ in economic, sociodemographic, political, and cultural backgrounds. We also show that trust and power foster compliance through different channels: trusted authorities (those perceived as benevolent and enhancing the common good) register the highest voluntary compliance, while powerful authorities (those perceived as effectively controlling evasion) register the highest enforced compliance. In contrast to some previous studies, the results suggest that trust and power are not fully complementary, as indicated by a negative interaction effect. Despite some between-country variations, trust and power are identified as important determinants of tax compliance across all nations. These findings have clear implications for authorities across the globe that need to choose best practices for tax collection.
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24.
  • Carneiro, Ana P. B., et al. (författare)
  • A framework for mapping the distribution of seabirds by integrating tracking, demography and phenology
  • 2020
  • Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 57:3, s. 514-525
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of geographic areas where the densities of animals are highest across their annual cycles is a crucial step in conservation planning. In marine environments, however, it can be particularly difficult to map the distribution of species, and the methods used are usually biased towards adults, neglecting the distribution of other life-history stages even though they can represent a substantial proportion of the total population. Here we develop a methodological framework for estimating population-level density distributions of seabirds, integrating tracking data across the main life-history stages (adult breeders and non-breeders, juveniles and immatures). We incorporate demographic information (adult and juvenile/immature survival, breeding frequency and success, age at first breeding) and phenological data (average timing of breeding and migration) to weight distribution maps according to the proportion of the population represented by each life-history stage. We demonstrate the utility of this framework by applying it to 22 species of albatrosses and petrels that are of conservation concern due to interactions with fisheries. Because juveniles, immatures and non-breeding adults account for 47%-81% of all individuals of the populations analysed, ignoring the distributions of birds in these stages leads to biased estimates of overlap with threats, and may misdirect management and conservation efforts. Population-level distribution maps using only adult distributions underestimated exposure to longline fishing effort by 18%-42%, compared with overlap scores based on data from all life-history stages. Synthesis and applications. Our framework synthesizes and improves on previous approaches to estimate seabird densities at sea, is applicable for data-poor situations, and provides a standard and repeatable method that can be easily updated as new tracking and demographic data become available. We provide scripts in the R language and a Shiny app to facilitate future applications of our approach. We recommend that where sufficient tracking data are available, this framework be used to assess overlap of seabirds with at-sea threats such as overharvesting, fisheries bycatch, shipping, offshore industry and pollutants. Based on such an analysis, conservation interventions could be directed towards areas where they have the greatest impact on populations.
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25.
  • Charles, Dolley, et al. (författare)
  • Longitudinal changes in concentrations of persistent organic pollutants (1986–2016) and their associations with type 2 diabetes mellitus
  • 2022
  • Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 204
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Positive associations have been reported between persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM); however, causality has not been established. Over the last decades, environmental exposure to legacy POPs has decreased, complicating epidemiological studies. In addition, physiological risk factors for T2DM may also influence POP concentrations, contributing to a complex network of factors that could impact associations with T2DM. Longitudinal studies on this topic are lacking, and few have assessed prospective and cross-sectional associations between repeated POP measurements and T2DM in the same individuals, which may shed light on causality.Objectives: To compare longitudinal trends in concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in T2DM cases and controls, and to examine prospective and cross-sectional associations between PCBs, OCPs and T2DM at different time-points before and after T2DM diagnosis in cases.Methods: We conducted a longitudinal, nested case-control study (1986–2016) of 116 T2DM cases and 139 controls from the Tromsø Study. All participants had three blood samples collected before T2DM diagnosis in cases, and up to two samples thereafter. We used linear mixed-effect models to assess temporal changes of POPs within and between T2DM cases and controls, and logistic regression models to investigate the associations between different POPs and T2DM at different time-points.Results: PCBs, trans-nonachlor, cis-nonachlor, oxychlordane, cis-heptachlor epoxide, p,p’-DDE, and p,p’-DDT declined more slowly in cases than controls, whereas β-HCH and HCB declined similarly in both groups. Most POPs showed positive associations between both pre- and post-diagnostic concentrations and T2DM, though effect estimates were imprecise. These associations were most consistent for cis-heptachlor epoxide.Discussion: The observed positive associations between certain POPs and T2DM may be because of higher POP concentrations within prospective T2DM cases, due to slower temporal declines as compared to controls.
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26.
  • Charles, Dolley, et al. (författare)
  • Polybrominated diphenyl ethers in type 2 diabetes mellitus cases and controls : Repeated measurements prior to and after diagnosis
  • 2023
  • Ingår i: International journal of hygiene and environmental health. - : Elsevier. - 1438-4639 .- 1618-131X. ; 249
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous studies have reported associations between certain persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM). Polybrominated diphenyl ethers (PBDEs) are a class of POPs that are found in increasing concentrations in humans. Although obesity is a known risk factor for T2DM and PBDEs are fat-soluble, very few studies have investigated associations between PBDEs and T2DM. No longitudinal studies have assessed associations between repeated measurements of PBDE and T2DM in the same individuals and compared time trends of PBDEs in T2DM cases and controls.Objectives: To investigate associations between pre- and post-diagnostic measurements of PBDEs and T2DM and to compare time trends of PBDEs in T2DM cases and controls.Methods: Questionnaire data and serum samples from participants in the Tromsø Study were used to conduct a longitudinal nested case-control study among 116 T2DM cases and 139 controls. All included study participants had three pre-diagnostic blood samples (collected before T2DM diagnosis in cases), and up to two post-diagnostic samples after T2DM diagnosis. We used logistic regression models to investigate pre- and post-diagnostic associations between PBDEs and T2DM, and linear mixed-effect models to assess time trends of PBDEs in T2DM cases and controls.Results: We observed no substantial pre- or post-diagnostic associations between any of the PBDEs and T2DM, except for BDE-154 at one of the post-diagnostic time-points (OR = 1.65, 95% CI: 1.00, 2.71). The overall time trends of PBDE concentrations were similar for cases and controls.Discussion: The study did not support PBDEs increasing the odds of T2DM, prior to or after T2DM diagnosis. T2DM status did not influence the time trends of PBDE concentrations.
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27.
  • Chen, Gongbo, et al. (författare)
  • Mortality risk attributable to wildfire-related PM2·5 pollution : a global time series study in 749 locations
  • 2021
  • Ingår i: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 5:9, s. e579-e587
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world.METHODS: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated.FINDINGS: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period.INTERPRETATION: Short-term exposure to wildfire-related PM2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.
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28.
  • Chen, Yin Huai, et al. (författare)
  • Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome
  • 2020
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann-like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. We identified essential loss-of-function variants in IL6ST (a homozygous nonsense variant and a homozygous intronic splice variant with exon skipping). Functional tests showed absent cellular responses to GP130-dependent cytokines including IL-6, IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF). Genetic reconstitution of GP130 by lentiviral transduction in patient-derived cells reversed the signaling defect. This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development.
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29.
  • Connolly, Stuart J., et al. (författare)
  • The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study
  • 2013
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:3, s. 237-243
  • Tidskriftsartikel (refereegranskat)abstract
    • Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death. 
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30.
  •  
31.
  • Eikelboom, John W., et al. (författare)
  • Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation An Analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Trial
  • 2011
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 123:21, s. 2363-2372
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial. Methods and Results-The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated with a lower risk of major bleeding (2.87% versus 3.57%; P=0.002), whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P=0.32). There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged = 75 years (4.43% versus 4.37%; P=0.89; P for interaction = 75 years (5.10% versus 4.37%; P=0.07; P for interaction = 75 years, intracranial bleeding risk is lower but extracranial bleeding risk is similar or higher with both doses of dabigatran compared with warfarin.
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32.
  • Gasparrini, Antonio, et al. (författare)
  • Projections of temperature-related excess mortality under climate change scenarios
  • 2017
  • Ingår i: The Lancet Planetary Health. - 2542-5196. ; 1:9, s. e360-e367
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Climate change can directly affect human health by varying exposure to non-optimal outdoor temperature. However, evidence on this direct impact at a global scale is limited, mainly due to issues in modelling and projecting complex and highly heterogeneous epidemiological relationships across different populations and climates.Methods: We collected observed daily time series of mean temperature and mortality counts for all causes or non-external causes only, in periods ranging from Jan 1, 1984, to Dec 31, 2015, from various locations across the globe through the Multi-Country Multi-City Collaborative Research Network. We estimated temperature-mortality relationships through a two-stage time series design. We generated current and future daily mean temperature series under four scenarios of climate change, determined by varying trajectories of greenhouse gas emissions, using five general circulation models. We projected excess mortality for cold and heat and their net change in 1990-2099 under each scenario of climate change, assuming no adaptation or population changes.Findings: Our dataset comprised 451 locations in 23 countries across nine regions of the world, including 85 879 895 deaths. Results indicate, on average, a net increase in temperature-related excess mortality under high-emission scenarios, although with important geographical differences. In temperate areas such as northern Europe, east Asia, and Australia, the less intense warming and large decrease in cold-related excess would induce a null or marginally negative net effect, with the net change in 2090-99 compared with 2010-19 ranging from -1·2% (empirical 95% CI -3·6 to 1·4) in Australia to -0·1% (-2·1 to 1·6) in east Asia under the highest emission scenario, although the decreasing trends would reverse during the course of the century. Conversely, warmer regions, such as the central and southern parts of America or Europe, and especially southeast Asia, would experience a sharp surge in heat-related impacts and extremely large net increases, with the net change at the end of the century ranging from 3·0% (-3·0 to 9·3) in Central America to 12·7% (-4·7 to 28·1) in southeast Asia under the highest emission scenario. Most of the health effects directly due to temperature increase could be avoided under scenarios involving mitigation strategies to limit emissions and further warming of the planet.Interpretation: This study shows the negative health impacts of climate change that, under high-emission scenarios, would disproportionately affect warmer and poorer regions of the world. Comparison with lower emission scenarios emphasises the importance of mitigation policies for limiting global warming and reducing the associated health risks.
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33.
  • Grünig, Marc, et al. (författare)
  • A harmonized database of European forest simulations under climate change
  • 2024
  • Ingår i: Data in Brief. - 2352-3409. ; 54
  • Tidskriftsartikel (refereegranskat)abstract
    • Process-based forest models combine biological, physical, and chemical process understanding to simulate forest dynamics as an emergent property of the system. As such, they are valuable tools to investigate the effects of climate change on forest ecosystems. Specifically, they allow testing of hypotheses regarding long-term ecosystem dynamics and provide means to assess the impacts of climate scenarios on future forest development. As a consequence, numerous local-scale simulation studies have been conducted over the past decades to assess the impacts of climate change on forests. These studies apply the best available models tailored to local conditions, parameterized and evaluated by local experts. However, this treasure trove of knowledge on climate change responses remains underexplored to date, as a consistent and harmonized dataset of local model simulations is missing. Here, our objectives were (i) to compile existing local simulations on forest development under climate change in Europe in a common database, (ii) to harmonize them to a common suite of output variables, and (iii) to provide a standardized vector of auxiliary environmental variables for each simulated location to aid subsequent investigations. Our dataset of European stand- and landscape-level forest simulations contains over 1.1 million simulation runs representing 135 million simulation years for more than 13,000 unique locations spread across Europe. The data were harmonized to consistently describe forest development in terms of stand structure (dominant height), composition (dominant species, admixed species), and functioning (leaf area index). Auxiliary variables provided include consistent daily climate information (temperature, precipitation, radiation, vapor pressure deficit) as well as information on local site conditions (soil depth, soil physical properties, soil water holding capacity, plant-available nitrogen). The present dataset facilitates analyses across models and locations, with the aim to better harness the valuable information contained in local simulations for large-scale policy support, and for fostering a deeper understanding of the effects of climate change on forest ecosystems in Europe.
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34.
  • Grötsch, Marie Therese, et al. (författare)
  • A Modified Progressive Supranuclear Palsy Rating Scale
  • 2021
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:5, s. 1203-1215
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status. Objective: The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones. Methods: Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy. Results: The modified scale retained 14 items (yielding 0–2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months). Conclusions: The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine.
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35.
  • Handl, Verena, et al. (författare)
  • Continuous iontronic chemotherapy reduces brain tumor growth in embryonic avian in vivo models
  • 2024
  • Ingår i: Journal of Controlled Release. - : ELSEVIER. - 0168-3659 .- 1873-4995. ; 369, s. 668-683
  • Tidskriftsartikel (refereegranskat)abstract
    • Local and long-lasting administration of potent chemotherapeutics is a promising therapeutic intervention to increase the efficiency of chemotherapy of hard-to-treat tumors such as the most lethal brain tumors, glioblastomas (GBM). However, despite high toxicity for GBM cells, potent chemotherapeutics such as gemcitabine (Gem) cannot be widely implemented as they do not efficiently cross the blood brain barrier (BBB). As an alternative method for continuous administration of Gem, we here operate freestanding iontronic pumps - "GemIPs" - equipped with a custom-synthesized ion exchange membrane (IEM) to treat a GBM tumor in an avian embryonic in vivo system. We compare GemIP treatment effects with a topical metronomic treatment and observe that a remarkable growth inhibition was only achieved with steady dosing via GemIPs. Daily topical drug administration (at the maximum dosage that was not lethal for the embryonic host organism) did not decrease tumor sizes, while both treatment regimes caused S-phase cell cycle arrest and apoptosis. We hypothesize that the pharmacodynamic effects generate different intratumoral drug concentration profiles for each technique, which causes this difference in outcome. We created a digital model of the experiment, which proposes a fast decay in the local drug concentration for the topical daily treatment, but a long-lasting high local concentration of Gem close to the tumor area with GemIPs. Continuous chemotherapy with iontronic devices opens new possibilities in cancer treatment: the long-lasting and highly local dosing of clinically available, potent chemotherapeutics to greatly enhance treatment efficiency without systemic side-effects. Significance statement: Iontronic pumps (GemIPs) provide continuous and localized administration of the chemotherapeutic gemcitabine (Gem) for treating glioblastoma in vivo. By generating high and constant drug concentrations near the vascularized growing tumor, GemIPs offer an efficient and less harmful alternative to systemic administration. Continuous GemIP dosing resulted in remarkable growth inhibition, superior to daily topical Gem application at higher doses. Our digital modelling shows the advantages of iontronic chemotherapy in overcoming limitations of burst release and transient concentration profiles, and providing precise control over dosing profiles and local distribution. This technology holds promise for future implants, could revolutionize treatment strategies, and offers a new platform for studying the influence of timing and dosing dependencies of already -established drugs in the fight against hard -to -treat tumors.
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36.
  • Hellström, Matti, et al. (författare)
  • An SCC-DFTB Repulsive Potential for Various ZnO Polymorphs and the ZnO-Water System
  • 2013
  • Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 117:33, s. 17004-17015
  • Tidskriftsartikel (refereegranskat)abstract
    • We have developed an efficient scheme for the generation of accurate repulsive potentials for self-consistent charge density-functional-based tight-binding calculations, which involves energy-volume scans of bulk polymorphs with different coordination numbers. The scheme was used to generate an optimized parameter set for various ZnO polymorphs. The new potential was subsequently tested for ZnO bulk, surface, and nanowire systems as well as for water adsorption on the low-index wurtzite (10 (1) over bar0) and (11 (2) over bar0) surfaces. By comparison to results obtained at the density functional level of theory, we show that the newly generated repulsive potential is highly transferable and capable of capturing most of the relevant chemistry of ZnO and the ZnO/water interface.
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37.
  • Huber, Amelie, et al. (författare)
  • Beyond “Socially Constructed” Disasters : Re-politicizing the Debate on Large Dams through a Political Ecology of Risk
  • 2016
  • Ingår i: Capitalism, Nature, Socialism. - HUDDINGE : Informa UK Limited. - 1045-5752 .- 1548-3290. ; , s. 1-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Questions of dam safety and hazard potential most often do not take center-stage in contestations and articulations concerning large dams. Through a comparative study of two of Europe’s most emblematic dam disasters – Vajont (Italy) and Ribadelago (Spain) – and the ongoing conflict over the safety of the Lower Subansiri Hydroelectric Project in Northeast India, this article argues that the damage caused by dam disasters is often not unavoidable or unforeseen but instead allowed to happen. Our cases show that power relations, economic pressures and profit influence “risky” dam management decisions, often disregarding the vernacular knowledge of concerned communities and silencing critical voices that do not fit dominant narratives of modernization and progress. We posit that an essential requirement for re-politicizing the question of dam safety is to unpack the apolitical notion of “socially constructed disasters,” thinking instead about “capital-driven destructions.” By emphasizing resistance against dam projects and against dominant risk discourses across space and time, this article seeks to underline the legitimacy of past and ongoing struggles surrounding the construction of large dams.
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38.
  • Huber, Malin, et al. (författare)
  • "From hell to healed" - A qualitative study on women's experience of recovery, relationships and sexuality after severe obstetric perineal injury
  • 2022
  • Ingår i: Sexual & Reproductive HealthCare. - : Elsevier. - 1877-5756 .- 1877-5764. ; 33
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Few studies have investigated women's experiences of daily life after childbirth complicated by obstetric anal sphincter injury (OASI). The aim of the present study was to explore experiences related to recovery, sexual function, relationships and coping strategies among women affected by OASI.METHODS: In-depth interviews were conducted using a purposive sample of 11 women affected by OASI. Women were interviewed 1-2 years after their first childbirth. Inductive qualitative content analysis was applied.RESULTS: The theme "From hell to healed" illustrates women's experiences of recovery, relationships and sexual function after OASI. Three categories addressing women's perceptions emerged: "Challenged to the core", "At the mercy of the care provider" and "For better or for worse". Support from partners and family and comprehensive care were important elements for the experiences of coping and healing from OASI. Elements that negatively influenced women's experiences were the pain and physical symptoms of pelvic floor dysfunction, normalization of symptoms by heath care providers, and unrealistic expectations about how this period in life should be experienced.CONCLUSION: OASI greatly affects women's experiences of their first years with their newborn child, relationships, social context and sexuality. For some women, OASI negatively affects everyday life for a long period after childbirth. However, others heal and cope quite quickly. Health care professionals need to identify and pay attention to women with persisting problems after OASI so that they can be directed to the right level of care.
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39.
  • Huber, Maria, et al. (författare)
  • Metabolic correlates of dopaminergic loss in dementia with lewy bodies
  • 2020
  • Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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40.
  • Huber, Malin, 1979- (författare)
  • To tear and to heal : pelvic floor dysfunction and childbirth
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Up to 80% of women are affected by a perineal laceration after their first vaginal birth. An estimated 40–50% of lacerations involve the perineal muscles, and up to 7% are obstetric anal sphincter injuries (OASI). There is a lack of knowledge about the extent of short-term complications such as pelvic floor dysfunction (PFD) following spontaneous or iatrogenic pelvic floor trauma. Women’s experiences of daily life after childbirth complicated by OASI is poorly understood. Three-dimensional endoanal ultrasonography (3D-EAUS) is a welldocumented method for evaluating damage to the anal sphincter in other contexts. Adding ultrasonography to standard clinical examination has revealed injuries previously missed, and research evaluating diagnostic methods for the routine screening of OASI has been called for.Aim: This thesis aims to evaluate the diagnostics of OASI, determine if the degree of perineal injury or anal sphincter defects after childbirth are associated with pelvic dysfunction, and explore women’s experiences of OASI.Methods Studies I and IV were prospective cohort-studies to evaluate any association between perineal tear or sphincter defect to PFD. Study II was an interview study addressing women’s experiences of OASI by qualitative content analysis. Study III was a cross-sectional study designed to examine the utility of endoanal ultrasound to detect OASI. Participants were clinically examined after birth and 3D-EAUS was performed immediately after giving birth and 3 months postpartum. PFD was evaluated using a web-based questionnaire one year after delivery.Results: A total of 511 women completed the one-year questionnaire (Study I) and a purposive sample of 11 women were invited to take part in Study II. In Study III, 680 women underwent a clinical examination and 3D-EAUS recording immediately after birth. In Study IV, 239 women who attended all follow-ups were included. PFD was experienced by women with a perineal laceration of any grade, but also those with an intact perineum. Dyspareunia and urinary incontinence were the most common problems. Women with OASI had a higher risk for developing vi symptoms of prolapse, urinary urge incontinence, dyspareunia, and pain as well as experiencing a negative impact on their daily life. Elements that negatively influenced women’s experiences of OASI were pain and symptoms of PFD, normalisation of symptoms by healthcare providers, and unrealistic expectations about this period in life. 3D-EAUS immediately after delivery had poor sensitivity and specificity in detecting clinically diagnosed OASI. Postpartum anal sphincter defects were associated with genital pain and dyspareunia.Conclusions: OASI is an evident risk factor for pelvic floor dysfunction after childbirth, but symptoms of pelvic floor disorder were found to be common, even in women with mild to moderate perineal laceration. OASI has a negative impact on how a woman experiences relationships, social contact, and sexuality. Using 3D-EAUS in a maternity ward to diagnose OASI is demanding. Staff generally have little experience in 3D-EAUS. There are also difficulties in obtaining good image quality, due to local oedema, bleeding, positioning of the woman, and unintentional movements. These factors all complicate the interpretation of images.
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41.
  • Jimenez Berrocoso, Alvaro, et al. (författare)
  • The Lindi Formation (upper Albian-Coniacian) and Tanzania Drilling Project Sites 36-40 (Lower Cretaceous to Paleogene) : Lithostratigraphy, biostratigraphy and chemostratigraphy
  • 2015
  • Ingår i: Journal of African earth sciences. - : Elsevier BV. - 1464-343X. ; 101, s. 282-308
  • Tidskriftsartikel (refereegranskat)abstract
    • The 2009 Tanzania Drilling Project (TDP) expedition to southeastern Tanzania cored a total of 572.3 m of sediments at six new mid-Cretaceous to mid-Paleocene boreholes (TDP Sites 36, 37, 38, 39, 40A, 40B). Added to the sites drilled in 2007 and 2008, the new boreholes confirm the common excellent preservation of planktonic and benthic foraminifera and calcareous nannofossils from core samples that will be used for biostratigraphy, evolutionary studies, paleoceanography and climatic reconstructions from the Tanzanian margin, with implications elsewhere. The new sites verify the presence of a relatively expanded Upper Cretaceous succession in the region that has allowed a new stratigraphic unit, named here as the Lindi Formation (Fm), to be formally defined. The Lindi Fm (upper Albian to Coniacian), extending similar to 120 km between Kilwa and Lindi, comprises a 335-m-thick, outer-shelf to upper-slope unit, consisting of dark gray claystone and siltstone interbeds, common finely-laminated intervals, minor cm-thick sandstones and up to 2.6% organic carbon in the Turonian. A subsurface, composite stratotype section is proposed for the Lindi Fm, with a gradational top boundary with the overlying Nangurukuru Fm (Santonian to Maastrichtian) and a sharp bottom contact with underlying upper Albian sandstones. The section cored at TDP Sites 36 and 38 belongs to the Lindi Fm and are of lower to middle Turonian age (planktonic foraminifera Whiteinella archaeocretacea to Helvetoglobotruncana helvetica Zones and nannofossils subzones UC6b +/- UC7). The lower portion of TDP Site 39 (uppermost part of the Lindi Fm) is assigned to the lower to upper Coniacian (planktonic foraminifera Dicarinella concavata Zone and nannofossils zone UC 10), while the remaining part of this site is attributed to the Coniacian-Santonian transition and younger Santonian (planktonic foraminifera D. asymetrica Zone and upper part of nannofossils zone UC10). TDP Site 37 recovered relatively expanded (150 m thick), monotonous calcareous claystones from the lower to upper Maastrichtian (planktonic foraminifera Pseudoguembelina palpebra to Abathomphalus mayaroensis Zones and nannofossils zones UC19 to UC20a(TP)) that were separated by a hiatus and/or a faulted contact from overlying brecciated carbonates of the Selandian (middle Paleocene: PF Zone P3 and nannofossil zone NP5). The lower portion of TDP Sites 40A and 40B recovered sandstones and conglomerates barren of microfossils. Their overlying parts were assigned to incomplete sections of the nannofossil zones NC6A to NC8 (uppermost Barremian to lower Albian). Benthic foraminiferal assemblages allowed the Barremian to lower Aptian to be identified in TDP Sites 40A and 40B, while the upper Aptian to middle Albian (Hedbergella trocoidea to Ticinella primula Zones) were assigned using planktonic foraminifera. Cores recovered at TDP 39 (Coniacian-Santonian) and at TDP Sites 40A and 40B (Barremian-middle Albian) represent the first time that these two intervals have been continuously cored and publicly documented in Tanzania. Bulk sediment isotope records generated for the new sites show lower delta O-18(carb) values in the Turonian and Santonian (similar to-3.5 parts per thousand to -5 parts per thousand) than in the Maastrichtian (similar to-3 parts per thousand), a situation consistent with extreme global warmth in the older intervals and cooling toward the end of the Cretaceous. Also, similar to Turonian sites from previous TDP expeditions, a negative delta C-13(org) excursion was detected across the W. archaeocretacea-H. helvetica boundary of TDP Site 36 (close to, but above, the Cenomanian-Turonian boundary). This excursion probably responded to local processes in the region, but it is unknown whether they were related to the recovery phase from Ocean Anoxic Event 2.
  •  
42.
  • Larsson, Maria, et al. (författare)
  • Procedural texturing of solid wood with knots
  • 2022
  • Ingår i: ACM Transactions on Graphics. - : Association for Computing Machinery. - 0730-0301 .- 1557-7368. ; 41:4
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a procedural framework for modeling the annual ring pattern of solid wood with knots. Although wood texturing is a well-studied topic, there have been few previous attempts at modeling knots inside the wood texture. Our method takes the skeletal structure of a tree log as input and produces a three-dimensional scalar field representing the time of added growth, which defines the volumetric annual ring pattern. First, separate fields are computed around each strand of the skeleton, i.e., the stem and each knot. The strands are then merged into a single field using smooth minimums. We further suggest techniques for controlling the smooth minimum to adjust the balance of smoothness and reproduce the distortion effects observed around dead knots. Our method is implemented as a shader program running on a GPU with computation times of approximately 0.5 s per image and an input data size of 600 KB. We present rendered images of solid wood from pine and spruce as well as plywood and cross-laminated timber (CLT). Our results were evaluated by wood experts, who confirmed the plausibility of the rendered annual ring patterns.
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43.
  • Mannes, Marco, et al. (författare)
  • Complement and platelets : prothrombotic cell activation requires membrane attack complex-induced release of danger signals
  • 2023
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:20, s. 6367-6380
  • Tidskriftsartikel (refereegranskat)abstract
    • Complement activation in the diseases paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) results in cytolysis and fatal thrombotic events, which are largely refractory to anticoagulation and/or antiplatelet therapy. Anticomplement therapy, however, efficiently prevents thrombotic events in PNH and aHUS, but the underlying mechanisms remain unresolved. We show that complement-mediated hemolysis in whole blood induces platelet activation similarly to activation by adenosine 5 '-diphosphate (ADP). Blockage of C3 or C5 abolished platelet activation. We found that human platelets failed to respond functionally to the anaphylatoxins C3a and C5a. Instead, complement activation did lead to prothrombotic cell activation in the whole blood when membrane attack complex (MAC)-mediated cytolysis occurred. Consequently, we demonstrate that ADP receptor antagonists efficiently inhibited platelet activation, although full complement activation, which causes hemolysis, occurred. By using an established model of mismatched erythrocyte transfusions in rats, we crossvalidated these findings in vivo using the complement inhibitor OmCI and cobra venom factor. Consumptive complement activation in this animal model only led to a thrombotic phenotype when MAC-mediated cytolysis occurred. In conclusion, complement activation only induces substantial prothrombotic cell activation if terminal pathway activation culminates in MAC-mediated release of intracellular ADP. These results explain why anticomplement therapy efficiently prevents thromboembolisms without interfering negatively with hemostasis.
  •  
44.
  • Mastellos, Dimitrios C., et al. (författare)
  • Complement C3 vs C5 inhibition in severe COVID-19 : Early clinical findings reveal differential biological efficacy
  • 2020
  • Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 220
  • Tidskriftsartikel (refereegranskat)abstract
    • Growing clinical evidence has implicated complement as a pivotal driver of COVID-19 immunopathology. Deregulated complement activation may fuel cytokine-driven hyper-inflammation, thrombotic microangiopathy and NET-driven immunothrombosis, thereby leading to multi-organ failure. Complement therapeutics have gained traction as candidate drugs for countering the detrimental consequences of SARS-CoV-2 infection. Whether blockade of terminal complement effectors (C5, C5a, or C5aR1) may elicit similar outcomes to upstream intervention at the level of C3 remains debated. Here we compare the efficacy of the C5-targeting monoclonal antibody eculizumab with that of the compstatin-based C3-targeted drug candidate AMY-101 in small independent cohorts of severe COVID-19 patients. Our exploratory study indicates that therapeutic complement inhibition abrogates COVID-19 hyper-inflammation. Both C3 and C5 inhibitors elicit a robust anti-inflammatory response, reflected by a steep decline in C-reactive protein and IL-6 levels, marked lung function improvement, and resolution of SARS-CoV-2-associated acute respiratory distress syndrome (ARDS). C3 inhibition afforded broader therapeutic control in COVID-19 patients by attenuating both C3a and sC5b-9 generation and preventing FB consumption. This broader inhibitory profile was associated with a more robust decline of neutrophil counts, attenuated neutrophil extracellular trap (NET) release, faster serum LDH decline, and more prominent lymphocyte recovery. These early clinical results offer important insights into the differential mechanistic basis and underlying biology of C3 and C5 inhibition in COVID-19 and point to a broader pathogenic involvement of C3-mediated pathways in thromboinflammation. They also support the evaluation of these complement-targeting agents as COVID-19 therapeutics in large prospective trials.
  •  
45.
  • Meng, Xia, et al. (författare)
  • Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality : multilocation analysis in 398 cities.
  • 2021
  • Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 372
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate the short term associations between nitrogen dioxide (NO2) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol.DESIGN: Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis.SETTING: 398 cities in 22 low to high income countries/regions.MAIN OUTCOME MEASURES: Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018.RESULTS: On average, a 10 μg/m3 increase in NO2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM10 and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities.CONCLUSIONS: This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO2.
  •  
46.
  • Owenius, Rikard, et al. (författare)
  • Influence of solvent polarity and hydrogen bonding on the EPR parameters of a nitroxide spin label studied by 9-GHz and 95-GHz EPR spectroscopy and DFT calculations
  • 2001
  • Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 105:49, s. 10967-10977
  • Tidskriftsartikel (refereegranskat)abstract
    • The isotropic and anisotropic hyperfine coupling constants and g-values of the nitroxide spin label (1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl)methanethiosulfonate (MTSSL) were determined from 9-GHz and 95-GHz electron paramagnetic resonance (EPR) measurements in various solvents with a large distribution in polarity and proticity. The parameters Aiso, giso, Azz, and gxx of MTSSL were found to be sensitive to changes in solvent properties, where A-values increased and g-values decreased due to increased solvent polarity or proticity. A linear correlation was found for the isotropic (giso, Aiso) and anisotropic (gxx, Azz) parameters, respectively. Furthermore, density functional theory (DFT) calculations of the same parameters were performed for a model spin label with the possibility to vary the dielectric constant (e) of the medium and the number of hydrogen bonds formed with the nitroxide oxygen. From a qualitative analysis of experimental and calculated results, it was possible to specify the causes of the parameter shifts in more detail. In the "apolar region" (e < 25), the sensitivity of Aiso and Azz to e is large. However, in the "polar region" (e > 25), the sensitivity to epsi, is small, and the shifts in Aiso and Azz are mainly determined by the proticity of the solvent. Methanol was found to form ~1 and water ~2 hydrogen bonds to the nitroxide on average. The DFT method determined the shifts in giso and gxx due to hydrogen bonding more accurately compared with the restricted open-shell Hartree-Fock method. The anisotropic spin label-solvent data can be used in the interpretation of rigid-limit data from spin-labeled proteins to gain further insight in local environmental properties.
  •  
47.
  • Regenspurg, Simona, et al. (författare)
  • Removal of uranium(VI) from the aqueous phase by iron(II) minerals in presence of bicarbonate
  • 2009
  • Ingår i: Applied Geochemistry. - : Elsevier BV. - 0883-2927 .- 1872-9134. ; 24:9, s. 1617-1625
  • Tidskriftsartikel (refereegranskat)abstract
    • Uranium(VI) mobility in groundwater is strongly affected by sorption of mobile U(VI) species (e.g. uranyl, UO22+) to mineral surfaces, precipitation of U(VI) compounds, such as schoepite (UO2)(4)O(OH)(6)center dot 6H(2)O), and by reduction to U(IV), forming sparingly soluble phases (uraninite; UO2). The latter pathway, in particular, would be very efficient for long-term immobilization of U. In nature, Fe(II) is an important reducing agent for U(VI) because it frequently occurs either dissolved in natural waters, sorbed to matrix minerals, or structurally bound in many minerals. Redox reactions between U(VI) and Fe(II) depend not only on the availability of Fe(II) in the environment, but also on the chemical conditions in the aqueous solution. Under natural groundwater condition U(VI) forms complexes with many anionic ligands, which strongly affect its speciation. Carbonate, in particular, is known to form stable complexes with U, raising the question, if U(VI), when complexed by carbonate, can be reduced to UO2. The goal of this study was to find out if Fe(II) when structurally bound in a mineral (as magnetite, Fe3O4) or sorbed to a mineral surface (as corundum, Al2O3) can reduce U(VI) to U(IV) in the presence of HCO3-. Batch experiments were conducted under anaerobic conditions to observe U removal from the aqueous phase by the two minerals depending on HCO3- addition (1 mM), U concentration (0.01-30 mu M) and pH value (6-10). Immediately after the experiments, the mineral surfaces were analyzed by X-ray photoelectron spectroscopy (XPS) to obtain information on the redox state of U bound to the solid surfaces. XPS results gave evidence that U(VI) can be reduced both by magnetite and by corundum amended with Fe(II). In the presence of HCO3 the amount of reduced U on the mineral surfaces increased compared to carbonate-free solutions. This can be explained by the formation of Fe(II) carbonates on the mineral surfaces which represent an easily available Fe(II) pool for the U(VI) reduction. A facilitated U(VI) reduction is also considered possible when U is present as a carbonate complex compared to non-complexed U (e.g. uranyl).
  •  
48.
  • Schiele, Francois, et al. (författare)
  • Quality indicators for acute myocardial infarction : A position paper of the Acute Cardiovascular Care Association.
  • 2017
  • Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 6:1, s. 34-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Evaluation of quality of care is an integral part of modern healthcare, and has become an indispensable tool for health authorities, the public, the press and patients. However, measuring quality of care is difficult, because it is a multifactorial and multidimensional concept that cannot be estimated solely on the basis of patients' clinical outcomes. Thus, measuring the process of care through quality indicators (QIs) has become a widely used practice in this context. Other professional societies have published QIs for the evaluation of quality of care in the context of acute myocardial infarction (AMI), but no such indicators exist in Europe. In this context, the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) has reflected on the measurement of quality of care in the context of AMI (ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI)) and created a set of QIs, with a view to developing programmes to improve quality of care for the management of AMI across Europe. We present here the list of QIs defined by the ACCA, with explanations of the methodology used, scientific justification and reasons for the choice for each measure.
  •  
49.
  • Skendros, Panagiotis, et al. (författare)
  • Complement C3 inhibition in severe COVID-19 using compstatin AMY-101
  • 2022
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:33
  • Tidskriftsartikel (refereegranskat)abstract
    • Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 <= 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.
  •  
50.
  • Solmi, Marco, et al. (författare)
  • Physical and mental health impact of COVID-19 on children, adolescents, and their families :
  • 2022
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 367-376
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www. coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via nonprobability/snowball and representative sampling and assessed via self-rating and parental rating. Nonmodifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COHFIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on childrens, adolescents and families, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
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