| 1. |
- Bortz, Robert H., et al.
(author)
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Single-Dilution COVID-19 Antibody Test with Qualitative and Quantitative Readouts
- 2021
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In: mSphere. - : American Society for Microbiology. - 2379-5042. ; 6:2
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Journal article (peer-reviewed)abstract
- The coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to place an immense burden on societies and health care systems. A key component of COVID-19 control efforts is serological testing to determine the community prevalence of SARS-CoV-2 exposure and quantify individual immune responses to prior SARS-CoV-2 infection or vaccination. Here, we describe a laboratory-developed antibody test that uses readily available research-grade reagents to detect SARS-CoV-2 exposure in patient blood samples with high sensitivity and specificity. We further show that this sensitive test affords the estimation of viral spike-specific IgG titers from a single sample measurement, thereby providing a simple and scalable method to measure the strength of an individual's immune response. The accuracy, adaptability, and cost-effectiveness of this test make it an excellent option for clinical deployment in the ongoing COVID-19 pandemic.IMPORTANCE Serological surveillance has become an important public health tool during the COVID-19 pandemic. Detection of protective antibodies and seroconversion after SARS-CoV-2 infection or vaccination can help guide patient care plans and public health policies. Serology tests can detect antibodies against past infections; consequently, they can help overcome the shortcomings of molecular tests, which can detect only active infections. This is important, especially when considering that many COVID-19 patients are asymptomatic. In this study, we describe an enzyme-linked immunosorbent assay (ELISA)-based qualitative and quantitative serology test developed to measure IgG and IgA antibodies against the SARS-CoV-2 spike glycoprotein. The test can be deployed using commonly available laboratory reagents and equipment and displays high specificity and sensitivity. Furthermore, we demonstrate that IgG titers in patient samples can be estimated from a single measurement, enabling the assay's use in high-throughput clinical environments.
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| 2. |
- Gnann, J. W., et al.
(author)
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Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy
- 2015
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 61:5, s. 683-691
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Journal article (peer-reviewed)abstract
- Background. Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. Methods. Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. Results. The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. Conclusions. Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.
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| 3. |
- Mittler, Eva, et al.
(author)
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Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody
- 2023
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 15:700
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Journal article (peer-reviewed)abstract
- Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
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| 4. |
- Modini, R. L., et al.
(author)
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Primary marine aerosol-cloud interactions off the coast of California
- 2015
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In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 120:9, s. 4282-4303
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Journal article (peer-reviewed)abstract
- Primary marine aerosol (PMA)-cloud interactions off the coast of California were investigated using observations of marine aerosol, cloud condensation nuclei (CCN), and stratocumulus clouds during the Eastern Pacific Emitted Aerosol Cloud Experiment (E-PEACE) and the Stratocumulus Observations of Los-Angeles Emissions Derived Aerosol-Droplets (SOLEDAD) studies. Based on recently reported measurements of PMA size distributions, a constrained lognormal-mode-fitting procedure was devised to isolate PMA number size distributions from total aerosol size distributions and applied to E-PEACE measurements. During the 12 day E-PEACE cruise on the R/V Point Sur, PMA typically contributed less than 15% of total particle concentrations. PMA number concentrations averaged 12 cm(-3) during a relatively calmer period (average wind speed 12m/s(1)) lasting 8 days, and 71cm(-3) during a period of higher wind speeds (average 16m/s(1)) lasting 5 days. On average, PMA contributed less than 10% of total CCN at supersaturations up to 0.9% during the calmer period; however, during the higher wind speed period, PMA comprised 5-63% of CCN (average 16-28%) at supersaturations less than 0.3%. Sea salt was measured directly in the dried residuals of cloud droplets during the SOLEDAD study. The mass fractions of sea salt in the residuals averaged 12 to 24% during three cloud events. Comparing the marine stratocumulus clouds sampled in the two campaigns, measured peak supersaturations were 0.20.04% during E-PEACE and 0.05-0.1% during SOLEDAD. The available measurements show that cloud droplet number concentrations increased with >100 nm particles in E-PEACE but decreased in the three SOLEDAD cloud events.
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| 5. |
- Sanchez, K. J., et al.
(author)
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Meteorological and aerosol effects on marine cloud microphysical properties
- 2016
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In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 121:8, s. 4142-4161
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Journal article (peer-reviewed)abstract
- Meteorology and microphysics affect cloud formation, cloud droplet distributions, and shortwave reflectance. The Eastern Pacific Emitted Aerosol Cloud Experiment and the Stratocumulus Observations of Los-Angeles Emissions Derived Aerosol-Droplets studies provided measurements in six case studies of cloud thermodynamic properties, initial particle number distribution and composition, and cloud drop distribution. In this study, we use simulations from a chemical and microphysical aerosol-cloud parcel (ACP) model with explicit kinetic drop activation to reproduce observed cloud droplet distributions of the case studies. Four cases had subadiabatic lapse rates, resulting in fewer activated droplets, lower liquid water content, and higher cloud base height than an adiabatic lapse rate. A weighted ensemble of simulations that reflect measured variation in updraft velocity and cloud base height was used to reproduce observed droplet distributions. Simulations show that organic hygroscopicity in internally mixed cases causes small effects on cloud reflectivity (CR) (<0.01), except for cargo ship and smoke plumes, which increased CR by 0.02 and 0.07, respectively, owing to their high organic mass fraction. Organic hygroscopicity had larger effects on droplet concentrations for cases with higher aerosol concentrations near the critical diameter (namely, polluted cases with a modal peak near 0.1 mu m). Differences in simulated droplet spectral widths (k) caused larger differences in CR than organic hygroscopicity in cases with organic mass fractions of 60% or less for the cases shown. Finally, simulations from a numerical parameterization of cloud droplet activation suitable for general circulation models compared well with the ACP model, except under high organic mass fraction.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Kim, J., et al.
(author)
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Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments
- 2016
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:1, s. 293-304
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Journal article (peer-reviewed)abstract
- Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study,we focus on a challenging size range, i.e., particles that have grown to diameters of 10 and 15 nm following nucleation, and measure their water uptake. Water uptake is useful information for indirectly obtaining chemical composition of aerosol particles. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at sub-saturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) campaign performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from alpha-pinene oxidation. The hygroscopicity parameter kappa decreased with increasing particle size, indicating decreasing acidity of particles. No clear effect of the sulfuric acid concentration on the hygroscopicity of 10 nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15 nm particles sharply decreased with decreasing sulfuric acid concentrations. In particular, when the concentration of sulfuric acid was 5.1 x 10(6) molecules cm(-3) in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured kappa of 15 nm particles was 0.31 +/- 0.01: close to the value reported for dimethylaminium sulfate (DMAS) (kappa(DMAS) similar to 0.28). Furthermore, the difference in kappa between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The kappa values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from alpha-pinene ozonolysis play a significant role in particle growth even at 10 nm sizes.
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| 10. |
- Mittler, Eva, et al.
(author)
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Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
- 2022
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In: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:636
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Journal article (peer-reviewed)abstract
- The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.
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| 11. |
- Tröstl, Jasmin, et al.
(author)
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The role of low-volatility organic compounds in initial particle growth in the atmosphere
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533:7604, s. 527-531
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Journal article (peer-reviewed)abstract
- About half of present-day cloud condensation nuclei originate from atmospheric nucleation, frequently appearing as a burst of new particles near midday(1). Atmospheric observations show that the growth rate of new particles often accelerates when the diameter of the particles is between one and ten nanometres(2,3). In this critical size range, new particles are most likely to be lost by coagulation with pre-existing particles(4), thereby failing to form new cloud condensation nuclei that are typically 50 to 100 nanometres across. Sulfuric acid vapour is often involved in nucleation but is too scarce to explain most subsequent growth(5,6), leaving organic vapours as the most plausible alternative, at least in the planetary boundary layer(7-10). Although recent studies(11-13) predict that low-volatility organic vapours contribute during initial growth, direct evidence has been lacking. The accelerating growth may result from increased photolytic production of condensable organic species in the afternoon(2), and the presence of a possible Kelvin (curvature) effect, which inhibits organic vapour condensation on the smallest particles (the nano-Kohler theory)(2,14), has so far remained ambiguous. Here we present experiments performed in a large chamber under atmospheric conditions that investigate the role of organic vapours in the initial growth of nucleated organic particles in the absence of inorganic acids and bases such as sulfuric acid or ammonia and amines, respectively. Using data from the same set of experiments, it has been shown(15) that organic vapours alone can drive nucleation. We focus on the growth of nucleated particles and find that the organic vapours that drive initial growth have extremely low volatilities (saturation concentration less than 10(-4.5) micrograms per cubic metre). As the particles increase in size and the Kelvin barrier falls, subsequent growth is primarily due to more abundant organic vapours of slightly higher volatility (saturation concentrations of 10(-4.5) to 10(-0.5) micrograms per cubic metre). We present a particle growth model that quantitatively reproduces our measurements. Furthermore, we implement a parameterization of the first steps of growth in a global aerosol model and find that concentrations of atmospheric cloud concentration nuclei can change substantially in response, that is, by up to 50 per cent in comparison with previously assumed growth rate parameterizations.
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| 12. |
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| 13. |
- Ahlm, Lars, et al.
(author)
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Particle number concentrations over Europe in 2030 : the role of emissions and new particle formation
- 2013
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In: Atmospheric Chemistry and Physics Discussions. - : Copernicus GmbH. - 1680-7367 .- 1680-7375 .- 1680-7324. ; 13:20, s. 10271-10283
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Journal article (peer-reviewed)abstract
- The aerosol particle number concentration is a key parameter when estimating impacts of aerosol particles on climate and human health. We use a three-dimensional chemical transport model with detailed microphysics, PMCAMx-UF, to simulate particle number concentrations over Europe in the year 2030, by applying emission scenarios for trace gases and primary aerosols. The scenarios are based on expected changes in anthropogenic emissions of sulfur dioxide, ammonia, nitrogen oxides, and primary aerosol particles with a diameter less than 2.5 mu m (PM2.5) focusing on a photochemically active period, and the implications for other seasons are discussed. For the baseline scenario, which represents a best estimate of the evolution of anthropogenic emissions in Europe, PMCAMx-UF predicts that the total particle number concentration (N-tot) will decrease by 30-70% between 2008 and 2030. The number concentration of particles larger than 100 nm (N-100), a proxy for cloud condensation nuclei (CCN) concentration, is predicted to decrease by 40-70% during the same period. The predicted decrease in N-tot is mainly a result of reduced new particle formation due to the expected reduction in SO2 emissions, whereas the predicted decrease in N-100 is a result of both decreasing condensational growth and reduced primary aerosol emissions. For larger emission reductions, PMCAMx-UF predicts reductions of 60-80% in both N-tot and N-100 over Europe. Sensitivity tests reveal that a reduction in SO2 emissions is far more efficient than any other emission reduction investigated, in reducing N-tot. For N-100, emission reductions of both SO2 and PM2.5 contribute significantly to the reduced concentration, even though SO2 plays the dominant role once more. The impact of SO2 for both new particle formation and growth over Europe may be expected to be somewhat higher during the simulated period with high photochemical activity than during times of the year with less incoming solar radiation. The predicted reductions in both N-tot and N-100 between 2008 and 2030 in this study will likely reduce both the aerosol direct and indirect effects, and limit the damaging effects of aerosol particles on human health in Europe
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| 14. |
- Bergman, Lina, 1982, et al.
(author)
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Cognitive impairment in preeclampsia complicated by eclampsia and pulmonary edema after delivery
- 2021
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In: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:7, s. 1280-1287
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Journal article (peer-reviewed)abstract
- Introduction We aimed to assess cognitive function in women with preeclampsia stratified by severity, before and after onset of disease. Material and methods Prospective study performed at a referral hospital in Cape Town, South Africa. Pregnant women between 20 and 42 weeks of gestation with eclampsia, pulmonary edema and preeclampsia without severe features, and a normotensive pregnancy were approached. Women were included at diagnosis of preeclampsia or at admission for delivery (women with normotensive pregnancies). Two cognitive assessments, the Cognitive Failure Questionnaire to assess the cognitive function subjectively before inclusion in the study, and Montreal Cognitive Assessment to assess the current cognitive function objectively before discharge from the hospital after delivery, were performed. Results We included 61 women with eclampsia, 28 with preeclampsia complicated by pulmonary edema, 38 with preeclampsia without severe features, and 26 with normotensive pregnancies. There was no difference in cognitive function from early pregnancy between groups. Women with eclampsia and preeclampsia complicated by pulmonary edema scored lower on the Montreal Cognitive Assessment at time of discharge compared with women with normotensive pregnancies. The results were attenuated in pulmonary edema after adjustment for confounders. Conclusions Women with preeclampsia complicated by pulmonary edema and in particular eclampsia had impaired cognitive function after onset of disease compared with women with normotensive pregnancies. The impairment did not seem to be present before onset of disease. Women with preeclampsia without severe features did not have impaired cognitive function.
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| 15. |
- Byström, JW, et al.
(author)
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Serological assessment of SARS-CoV-2 exposure in northern Sweden by the use of at-home sampling to meet geographical challenges in rural regions
- 2022
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Journal article (other academic/artistic)abstract
- The current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture is usually performed by trained staff at health care centers. Long travel distances may introduce a bias of testing towards relatively large communities with close access to health care centers. Rural regions may thus be overlooked. Here, we demonstrate a sensitive method to measure antibodies to the S-protein of SARS-CoV-2. We adapted and optimized this assay for clinical use together with capillary blood sampling to meet the geographical challenges of serosurveillance. Finally, we tested remote at-home capillary blood sampling together with centralized assessment of S-specific IgG in a rural region of northern Scandinavia that encompasses 55,185 sq kilometers. We conclude that serological assessment from capillary blood sampling gives comparable results as analysis of venous blood. Importantly, at-home sampling enabled citizens living in remote rural areas access to centralized and sensitive laboratory antibody tests.
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| 16. |
- Cagigi, Alberto, et al.
(author)
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Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
- 2021
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In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:22
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Journal article (peer-reviewed)abstract
- Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.
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| 17. |
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| 18. |
- Engström, Gunnar, et al.
(author)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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In: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Journal article (peer-reviewed)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Klingstrom, J., et al.
(author)
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Innate and adaptive immune responses against human Puumala virus infection : immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus-associated syndromes
- 2019
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In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 285:5, s. 510-523
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Journal article (peer-reviewed)abstract
- Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%-40% for HPS. Puumala virus (PUUV) is the most common HFRS-causing hantavirus in Europe. Here, we describe recent insights into the generation of innate and adaptive cell-mediated immune responses following clinical infection with PUUV. First described are studies demonstrating a marked redistribution of peripheral blood mononuclear phagocytes (MNP) to the airways, a process that may underlie local immune activation at the site of primary infection. We then describe observations of an excessive natural killer (NK) cell activation and the persistence of highly elevated numbers of NK cells in peripheral blood following PUUV infection. A similar vigorous CD8 Tcell response is also described, though Tcell responses decline with viraemia. Like MNPs, many NK cells and CD8 T cells also localize to the lung upon acute PUUV infection. Following this, findings demonstrating the ability of hantaviruses, including PUUV, to cause apoptosis resistance in infected target cells, are described. These observations, and associated inflammatory cytokine responses, may provide new insights into HFRS and HPS disease pathogenesis. Based on similarities between inflammatory responses in severe hantavirus infections and other hyperinflammatory disease syndromes, we speculate whether some therapeutic interventions that have been successful in the latter conditions may also be applicable in severe hantavirus infections.
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| 23. |
- Lehtipalo, Katrianne, et al.
(author)
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The effect of acid-base clustering and ions on the growth of atmospheric nano-particles
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere.
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| 24. |
- Palmcrantz, Johan, et al.
(author)
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Pelvic fractures at a new level 1 trauma centre: who dies from pelvic trauma? : The Inkosi Albert Luthuli Central Hospital Experience
- 2012
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In: Orthopaedic surgery. - : Tianjin Hospital and Wiley Publishing Asia Pty Ltd. - 1757-7861 .- 1757-7853. ; 4:4, s. 216-221
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Journal article (peer-reviewed)abstract
- Objective: To identify the incidence of pelvic trauma, causes of death and factors predicting death with pelvic fractures.Methods: All pelvic fractures were retrospectively identified from a registry spanning from March 2007 to August 2009. Data was captured on a proforma. Data for survivors, non-survivors and a subgroup with pelvic injury as the underlying cause of death were compared.Results: Pelvic fracture incidence was 16% of major trauma cases. Patient with pelvic fractures had 31% mortality and 9% pelvic fracture-induced mortality. Motor vehicle collisions were the commonest external cause of pelvic fractures (59%); however, the highest mortality was from falls >6 m. The Injury Severity Score (ISS) was 29 in survivors, 36 in non-survivors, and 54 in the pelvic death subgroup. Type C fracture was a predictor of mortality (P = 0.135). 53% of the cases required transfusion in the first 24 hours. The pelvic death subgroup received a mean of 10.7 units of blood, versus 4 units for survivors and 3.7 units for non-survivors (P = 0.259).Conclusion: The overall incidence of pelvic fracture and associated mortality were higher than previously reported. Fracture severity and falls from heights are associated with additional injuries (higher ISS) and mortality. More severe fractures cause deaths directly attributable to the pelvic injury. The requirement for major blood transfusions for pelvic fracture hemorrhage was related to mortality. Female patients appeared to fare worse than males.
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| 25. |
- Palo, Thomas, et al.
(author)
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Site and density dependent factors related to hantavirus prevalence among bank voles in forest areas afflicted with human disease
-
Other publication (pop. science, debate, etc.)abstract
- The bank vole (Clethrionomys glareolus) is the natural host of the Puumala virus (PUUV), an hantavirus endemic in Central and Northern Europe that cause a mild haemorrhagic fever with renal syndrome in humans. We studied the bank vole populations during five years at forest sites near households with confirmed repeated human infections and at forest areas chosen at random some distance away from the settlement. We found that voles where more abundant at the site near the human settlement compared to randomly chosen forest areas. We also found that voles with large body mass were more likely to have PUUV antibody reaction than smaller individuals irrespective of site and year of collection. We found that gut concentrations of nitrogen (N) of voles varied between sites but that N concentration of PUUV seropositive animals did not differ from the seronegative ones. Nitrogen concentration in the gut content did not vary between the sexes nor with body mass of animals. Age of animals were not important in relation to diet quality. A weak positive but statistically non-significant relationship between N in gut content and vole density was observed. The vole populations at the two areas showed direct density dependence and similar dynamic. On the other hand the seropositive cohort did not show a significant density regulation. One conclusion is that human disturbance of the environment near settlement may facilitate higher population densities of voles than at more undisturbed forest sites. It seems also that large animals living near human settlements are more likely candidates for transfer of the hantavirus within the vole population and to man.
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| 26. |
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| 27. |
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| 28. |
- Sironen, Tarja, et al.
(author)
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Fatal Puumala Hantavirus Disease : Involvement of Complement Activation and Vascular Leakage in the Pathobiology
- 2017
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In: Open Forum Infectious Diseases. - : Oxford University Press. - 2328-8957. ; 4:4
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Journal article (peer-reviewed)abstract
- The case-fatality rate of hantavirus disease depends strongly on the causative hantavirus, ranging from 0.1% to 40%. However, the pathogenesis is not fully understood, and at present no licensed therapies exist. We describe fatal cases caused by Puumala hantavirus indicating involvement of complement activation and vascular leakage.
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| 29. |
- Stjern, Camilla W., et al.
(author)
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Response to marine cloud brightening in a multi-model ensemble
- 2018
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:2, s. 621-634
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Journal article (peer-reviewed)abstract
- Here we show results from Earth system model simulations from the marine cloud brightening experiment G4cdnc of the Geoengineering Model Intercomparison Project (GeoMIP). The nine contributing models prescribe a 50% increase in the cloud droplet number concentration (CDNC) of low clouds over the global oceans in an experiment dubbed G4cdnc, with the purpose of counteracting the radiative forcing due to anthropogenic greenhouse gases under the RCP4.5 scenario. The model ensemble median effective radiative forcing (ERF) amounts to -1.9W m(-2), with a substantial inter-model spread of -0.6 to -2.5W m(-2). The large spread is partly related to the considerable differences in clouds and their representation between the models, with an underestimation of low clouds in several of the models. All models predict a statistically significant temperature decrease with a median of (for years 2020-2069) 0.96 [-0.17 to -1.21] K relative to the RCP4.5 scenario, with particularly strong cooling over low-latitude continents. Globally aver-aged there is a weak but significant precipitation decrease of -2.35 [-0.57 to -2.96]% due to a colder climate, but at low latitudes there is a 1.19% increase over land. This increase is part of a circulation change where a strong negative top-of-atmosphere (TOA) shortwave forcing over subtropical oceans, caused by increased albedo associated with the increasing CDNC, is compensated for by rising motion and positive TOA longwave signals over adjacent land regions.
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| 31. |
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| 32. |
- Welén, Karin, 1970, et al.
(author)
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A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
- 2022
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:3, s. 285-293
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Journal article (peer-reviewed)abstract
- Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
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- Welen, Karin, et al.
(author)
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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Journal article (peer-reviewed)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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