| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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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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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 8. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 9. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 10. |
- Spina, L., et al.
(författare)
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The GALAH survey : tracing the Galactic disc with open clusters
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 503:3, s. 3279-3296
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Tidskriftsartikel (refereegranskat)abstract
- Open clusters are unique tracers of the history of our own Galaxy's disc. According to our membership analysis based on Gala astrometry, out of the 226 potential clusters falling in the footprint of the GALactic Archaeology with HERMES (GALAH) survey or the Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey, we find that 205 have secure members that were observed by at least one of the surveys. Furthermore, members of 134 clusters have high-quality spectroscopic data that we use to determine their chemical composition. We leverage this information to study the chemical distribution throughout the Galactic disc of 21 elements, from C to Eu. The radial metallicity gradient obtained from our analysis is -0.076 +/- 0.009 dex kpc(-1), which is in agreement with previous works based on smaller samples. Furthermore, the gradient in the (Fe/Hi-guiding radius (r(guid)) plane is -0.073 +/- 0.008 dex kpc(-1). We show consistently that open clusters trace the distribution of chemical elements throughout the Galactic disc differently than field stars. In particular, at the given radius, open clusters show an age-metallicity relation that has less scatter than field stars. As such scatter is often interpreted as an effect of radial migration, we suggest that these differences are due to the physical selection effect imposed by our Galaxy: clusters that would have migrated significantly also had higher chances to get destroyed. Finally, our results reveal trends in the [X/Fe]-r(guid)-age space, which are important to understand production rates of different elements as a function of space and time.
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| 11. |
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| 12. |
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| 13. |
- Becker, Joel, et al.
(författare)
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Resource profile and user guide of the Polygenic Index Repository
- 2021
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Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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| 14. |
- Coscieme, Luca, et al.
(författare)
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Multiple conceptualizations of nature are key to inclusivity and legitimacy in global environmental governance
- 2020
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011 .- 1873-6416. ; 104, s. 36-42
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Tidskriftsartikel (refereegranskat)abstract
- Despite increasing scientific understanding of the global environmental crisis, we struggle to adopt the policies science suggests would be effective. One of the reasons for that is the lack of inclusive engagement and dialogue among a wide range of different actors. Furthermore, there is a lack of consideration of differences between languages, worldviews and cultures. In this paper, we propose that engagement across the science-policy interface can be strengthened by being mindful of the breadth and depth of the diverse human-nature relations found around the globe. By examining diverse conceptualizations of nature in more than 60 languages, we identify three clusters: inclusive conceptualizations where humans are viewed as an integral component of nature; non-inclusive conceptualizations where humans are separate from nature; and deifying conceptualizations where nature is understood and experienced within a spiritual dimension. Considering and respecting this rich repertoire of ways of describing, thinking about and relating to nature can help us communicate in ways that resonate across cultures and worldviews. This repertoire also provides a resource we can draw on when defining policies and sustainability scenarios for the future, offering opportunities for finding solutions to global environmental challenges.
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| 15. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 16. |
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| 17. |
- Kuhrmann, Marco, et al.
(författare)
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What Makes Agile Software Development Agile
- 2022
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Ingår i: IEEE Transactions on Software Engineering. - 0098-5589 .- 1939-3520. ; 48:9, s. 3523-3539
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Tidskriftsartikel (refereegranskat)abstract
- Together with many success stories, promises such as the increase in production speed and the improvement in stakeholders' collaboration have contributed to making agile a transformation in the software industry in which many companies want to take part. However, driven either by a natural and expected evolution or by contextual factors that challenge the adoption of agile methods as prescribed by their creator(s), software processes in practice mutate into hybrids over time. Are these still agile In this article, we investigate the question: what makes a software development method agile We present an empirical study grounded in a large-scale international survey that aims to identify software development methods and practices that improve or tame agility. Based on 556 data points, we analyze the perceived degree of agility in the implementation of standard project disciplines and its relation to used development methods and practices. Our findings suggest that only a small number of participants operate their projects in a purely traditional or agile manner (under 15%). That said, most project disciplines and most practices show a clear trend towards increasing degrees of agility. Compared to the methods used to develop software, the selection of practices has a stronger effect on the degree of agility of a given discipline. Finally, there are no methods or practices that explicitly guarantee or prevent agility. We conclude that agility cannot be defined solely at the process level. Additional factors need to be taken into account when trying to implement or improve agility in a software company. Finally, we discuss the field of software process-related research in the light of our findings and present a roadmap for future research.
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| 18. |
- Song, Jiao-Jiao, et al.
(författare)
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Relocalization of uranium 5f electrons in the antiferromagnetic heavy-fermion superconductor UPd2Al3 : Insights from angle-resolved photoemission spectroscopy
- 2024
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Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 109:20
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the antiferromagnetic heavy fermion superconductor UPd2Al3, employing angle-resolved photoemission spectroscopy to unravel the complex electronic structure of its U 5? electrons. We observe unexpected characteristics that challenge the conventional temperature-dependent behavior of heavy fermion systems, revealing unexpected characteristics. At temperatures above the anticipated coherence temperature (?*), we observe itinerant U 5? electrons at temperatures higher than previously postulated. Additionally, a previously unidentified dispersionless band emerges around 600 meV below the Fermi energy, potentially linked to spin-orbit splitting within the U 5? states. Hybridization between the 5? electrons and conduction band was observed with an energy dispersion of 10 meV at low temperatures, suggesting that U 5? electrons near and at the Fermi surface have an itinerant nature. Temperature-dependent 5?−5? resonance spectra reveal that the 5? electron spectrum weight increases with lowering temperature and begins to decrease at temperatures significantly higher than the Néel temperature (??). We further show that the competition between the Kondo effect and Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions may be responsible for the relocalization of 5? electrons, making relocalization a precursor to the establishment of magnetic order at lower temperatures. Our experiments also provide evidence that 5? electrons with the same orbital are involved in both the Kondo effect and RKKY interactions, suggesting that the two coexist at lower temperatures.
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| 19. |
- Tahmasian, Masoud, et al.
(författare)
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ENIGMA-Sleep : Challenges, opportunities, and the road map
- 2021
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:6
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Forskningsöversikt (refereegranskat)abstract
- Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
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| 20. |
- Visser-Vandewalle, Veerle, et al.
(författare)
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Deep brain stimulation for obsessive-compulsive disorder : a crisis of access
- 2022
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Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 28:8, s. 1529-1532
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation is an effective treatment for obsessive–compulsive disorder but is rarely used. Action is needed by psychologists, psychiatrists and insurers so that patients with otherwise intractable cases can receive this therapy to improve their mental health.
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| 21. |
- An, Kevin R, et al.
(författare)
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Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.
- 2024
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - 1873-734X.
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Tidskriftsartikel (refereegranskat)abstract
- The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated.We pooled individual patient data from randomized clinical trials with systematic post-operative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed.Six trials comprising 3,928 patients and 12,048 grafts were included. The median time to imaging was 1.03 (IQR, 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1,668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9), and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure (adjusted odds ratio [aOR] 0.98 [95% CI, 0.97-0.99]) at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight (aOR 0.79 [95% CI, 0.64-0.96]), obesity class 1 (aOR 0.81 [95% CI, 0.64-1.01]), and obesity class 2 (aOR 0.61 [95% CI, 0.45-0.83]) patients, but not different compared to obesity class 3 (aOR 0.94 [95% CI, 0.62-1.42]) patients. Findings were similar, but did not reach significance, at the patient level.In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at one year after coronary artery bypass grafting.
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| 22. |
- Denfeld, Quin E., et al.
(författare)
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Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement
- 2024
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier. - 1053-2498 .- 1557-3117. ; 43:1
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Tidskriftsartikel (refereegranskat)abstract
- Frailty is increasingly recognized as a salient condition in patients with heart failure (HF) as previous studies have determined that frailty is highly prevalent and prognostically significant, particularly in those with advanced HF. Definitions of frailty have included a variety of domains, including physical performance, sarcopenia, disability, comorbidity, and cognitive and psychological impairments, many of which are common in advanced HF. Multiple groups have recently recommended incorporating frailty assessments into clinical practice and research studies, indicating the need to standardize the definition and measurement of frailty in advanced HF. Therefore, the purpose of this consensus statement is to provide an integrated perspective on the definition of frailty in advanced HF and to generate a consensus on how to assess and manage frailty. We convened a group of HF clinicians and researchers who have expertise in frailty and related geriatric conditions in HF, and we focused on the patient with advanced HF. Herein, we provide an overview of frailty and how it has been applied in advanced HF (including potential mechanisms), present a definition of frailty, generate suggested assessments of frailty, provide guidance to differentiate frailty and related terms, and describe the assessment and management in advanced HF, including with surgical and nonsurgical interventions. We conclude by outlining critical evidence gaps, areas for future research, and clinical implementation. J Heart Lung Transplant 2024;43:1-27 (c) 2023 International Society for Heart and Lung Transplantation. All rights reserved.
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| 23. |
- Hossain, Shakhawath, et al.
(författare)
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Influence of Bile Composition on Membrane Incorporation of Transient Permeability Enhancers
- 2020
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8392 .- 1543-8384. ; 17:11, s. 4226-4240
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Tidskriftsartikel (refereegranskat)abstract
- Transient permeability enhancers (PEs), such as caprylate, caprate, and salcaprozate sodium (SNAC), improve the bioavailability of poorly permeable macromolecular drugs. However, the effects are variable across individuals and classes of macromolecular drugs and biologics. Here, we examined the influence of bile compositions on the ability of membrane incorporation of three transient PEs-caprylate, caprate, and SNAC-using coarse-grained molecular dynamics (CG-MD). The availability of free PE monomers, which are important near the absorption site, to become incorporated into the membrane was higher in fasted-state fluids than that in fed-state fluids. The simulations also showed that transmembrane perturbation, i.e., insertion of PEs into the membrane, is a key mechanism by which caprylate and caprate increase permeability. In contrast, SNAC was mainly adsorbed onto the membrane surface, indicating a different mode of action. Membrane incorporation of caprylate and caprate was also influenced by bile composition, with more incorporation into fasted- than fed-state fluids. The simulations of transient PE interaction with membranes were further evaluated using two experimental techniques: the quartz crystal microbalance with dissipation technique and total internal reflection fluorescence microscopy. The experimental results were in good agreement with the computational simulations. Finally, the kinetics of membrane insertion was studied with CG-MD. Variation in micelle composition affected the insertion rates of caprate monomer insertion and expulsion from the micelle surface. In conclusion, this study suggests that the bile composition and the luminal composition of the intestinal fluid are important factors contributing to the interindividual variability in the absorption of macromolecular drugs administered with transient PEs.
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| 24. |
- Jhun, Mina-A, et al.
(författare)
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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups. Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.
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| 25. |
- Johnson, Kara A., et al.
(författare)
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Basal Ganglia Pathways Associated With Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome
- 2021
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Ingår i: Biological Psychiatry. - : Elsevier. - 2451-9022. ; 6:10, s. 961-972
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) can improve tics and comorbid obsessive-compulsive behavior (OCB) in patients with treatment-refractory Tourette syndrome (TS). However, some patients’ symptoms remain unresponsive, the stimulation applied across patients is variable, and the mechanisms underlying improvement are unclear. Identifying the fiber pathways surrounding the GPi that are associated with improvement could provide mechanistic insight and refine targeting strategies to improve outcomes.Methods: Retrospective data were collected for 35 patients who underwent bilateral GPi DBS for TS. Computational models of fiber tract activation were constructed using patient-specific lead locations and stimulation settings to evaluate the effects of DBS on basal ganglia pathways and the internal capsule. We first evaluated the relationship between activation of individual pathways and symptom improvement. Next, linear mixed-effects models with combinations of pathways and clinical variables were compared in order to identify the best-fit predictive models of tic and OCB improvement.Results: The best-fit model of tic improvement included baseline severity and the associative pallido-subthalamic pathway. The best-fit model of OCB improvement included baseline severity and the sensorimotor pallido-subthalamic pathway, with substantial evidence also supporting the involvement of the prefrontal, motor, and premotor internal capsule pathways. The best-fit models of tic and OCB improvement predicted outcomes across the cohort and in cross-validation.Conclusions: Differences in fiber pathway activation likely contribute to variable outcomes of DBS for TS. Computational models of pathway activation could be used to develop novel approaches for preoperative targeting and selecting stimulation parameters to improve patient outcomes.
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| 26. |
- Joyce, Jack B., et al.
(författare)
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Should we share qualitative data? Epistemological and practical insights from conversation analysis
- 2022
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Ingår i: International Journal of Social Research Methodology. - : Routledge; Taylor & Francis. - 1364-5579 .- 1464-5300.
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Tidskriftsartikel (refereegranskat)abstract
- Over the last 30 years, there has been substantial debate about the practical, ethical and epistemological issues uniquely associated with qualitative data sharing. In this paper, we contribute to these debates by examining established data sharing practices in Conversation Analysis (CA). CA is an approach to the analysis of social interaction that relies on audio/video recordings of naturally occurring human interactions and moreover works at a level of detail that presents challenges for assumptions about participant anonymity. Nonetheless, data sharing occupies a central position in both the methodology and the wider academic culture of CA as a discipline and a community. Despite this, CA has largely been ignored in qualitative data sharing debates and discussions. We argue that the methodological traditions of CA present a strong case for the value of qualitative data sharing and offer open data sharing practices that might be usefully adopted in other qualitative approaches.
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| 27. |
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| 28. |
- Monk, Bradley J., et al.
(författare)
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A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45)
- 2022
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Ingår i: Journal of Clinical Oncology. - : Lippincott, Williams & Wilkins. - 0732-183X .- 1527-7755. ; 40:34, s. 3952-3964
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEATHENA (ClinicalTrials.gov identifier: ) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo.METHODSPatients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population.RESULTSAs of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade & GE; 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%).CONCLUSIONRucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.
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| 29. |
- O'Brien, K. M., et al.
(författare)
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Resilience of cardiac performance in Antarctic notothenioid fishes in a warming climate
- 2021
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 224:10
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Tidskriftsartikel (refereegranskat)abstract
- Warming in the region of the Western Antarctic Peninsula is occurring at an unprecedented rate, which may threaten the survival of Antarctic notothenioid fishes. Herein, we review studies characterizing thermal tolerance and cardiac performance in notothenioids - a group that includes both red-blooded species and the white-blooded, haemoglobinless icefishes - as well as the relevant biochemistry associated with cardiac failure during an acute temperature ramp. Because icefishes do not feed in captivity, making long-term acclimation studies unfeasible, we focus only on the responses of red-blooded notothenioids to warm acclimation. With acute warming, hearts of the white-blooded icefish Chaenocephalus aceratus display persistent arrhythmia at a lower temperature (8 degrees C) compared with those of the red-blooded Notothenia coriiceps (14 degrees C). When compared with the icefish, the enhanced cardiac performance of N. coriiceps during warming is associated with greater aerobic capacity, higher ATP levels, less oxidative damage and enhanced membrane integrity. Cardiac performance can be improved in N. coriiceps with warm acclimation to 5 degrees C for 6-9 weeks, accompanied by an increase in the temperature at which cardiac failure occurs. Also, both cardiac mitochondrial and microsomal membranes are remodelled in response to warm acclimation in N. coriiceps, displaying homeoviscous adaptation. Overall, cardiac performance in N. coriiceps is malleable and resilient to warming, yet thermal tolerance and plasticity vary among different species of notothenioid fishes; disruptions to the Antarctic ecosystem driven by climate warming and other anthropogenic activities endanger the survival of notothenioids, warranting greater protection afforded by an expansion of marine protected areas.
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| 30. |
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| 31. |
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| 32. |
- Sauvage, Justine, et al.
(författare)
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Bacterial exudates as growth-promoting agents for the cultivation of commercially relevant marine microalgal strains
- 2022
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Ingår i: Journal of the World Aquaculture Society. - : Wiley. - 0893-8849 .- 1749-7345. ; 53:6, s. 1101-1119
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Tidskriftsartikel (refereegranskat)abstract
- In laboratory and industrial cultivation of marine microalgae, it is customary to enrich cultures with macronutrients (N, P), chelated trace metals, and vitamins at similar to 10(4) x concentrations found in nature to obtain high culture densities. Other naturally occurring growth-promoting compounds found in local seawater are not enriched and remain at environmental concentrations. Microalgae may thus be deprived of the mutualistic contributions of co-occurring microorganisms with which they have evolved complex chemical relationships. In the present study, we assess the direct (mixed bacteria-microalgae cultivation) and indirect (exposure to exudates only, without physical contact) effects of 10 bacterial strains on the growth of five marine microalgal strains used as feeds in marine aquaculture hatcheries. Bacterial strains were selected based upon previously reported growth-promoting characteristics in plants or microalgae, or known release of probiotics. Our experiments demonstrate superior stimulation of microalgal growth by bacterial exudates, and without the presence of the bacteria that produced these exudates. However, response to bacterial exudate enrichment was dependent upon the microalgae strain and bacterial pairing. Exudates from Bacillus, Mesorhizobium, arid Phaeobacter strains were most effective, with 22%-69% increases in microalgal specific growth rate. Such findings indicate that bacterial exudates accelerate rate-limiting processes governing nutrient acquisition, assimilation, or anabolism, and possibly algal release of exopolymeric substances. Maximal cell density, however, remained constrained by macronutrient limitation. Scaledup trials in an oyster hatchery confirmed the practical benefit of bacterial exudate culture medium enrichment and demonstrated the suitability of exudate-enriched microalgae to feed hatchery-reared bay scallops. This work presents a promising strategy to improve microalgal culture media formulations using bacterial exudate components as growth promoters, and is the first such study to identify specific pairings with relevance for aquaculture production.
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| 33. |
- Sauvage, Justine, et al.
(författare)
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Biodegradable, metal-chelating compounds as alternatives to EDTA for cultivation of marine microalgae
- 2021
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Ingår i: Journal of Applied Phycology. - : Springer Science and Business Media LLC. - 0921-8971 .- 1573-5176. ; 33, s. 3519-3537
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Tidskriftsartikel (refereegranskat)abstract
- Iron (Fe) is an essential nutrient for microalgal metabolism. The low solubility of Fe in oxic aquatic environments can be a growth-limiting factor for phytoplankton. Synthetic chelating agents, such as ethylenediaminetetraacetic acid (EDTA), are used widely to maintain Fe in solution for microalgal cultivation. The non-biodegradable nature of EDTA, combined with sub-optimal bioavailability of Fe-EDTA complexes to microalgae, indicates opportunity to improve microalgal cultivation practices that amplify production efficiency and environmental compatibility. In the present study, the effects of four organic chelating ligands known to form readily bioavailable organic complexes with Fe in natural aquatic environments were investigated in relation to growth and biochemical composition of two marine microalgae grown as live feeds in shellfish hatcheries (Chaetoceros calcitrans and Tisochrysis lutea). Three saccharides, alginic acid (ALG), glucuronic acid (GLU), and dextran (DEX), as well as the siderophore desferrioxamine B (DFB), were compared to EDTA. Organic ligands characterized by weaker binding capacity for cationic metals (i.e., ALG, GLU, DEX) significantly improved microalgal growth and yields in laboratory-scale static batch cultures or bubbled photobioreactors. Maximal microalgal growth enhancement relative to the control (e.g., EDTA) was recorded for GLU, followed by ALG, with 20-35% increase in specific growth rate in the early stages of culture development of C. calcitrans and T. lutea. Substitution of EDTA with GLU resulted in a 27% increase in cellular omega 3-polyunsaturetd fatty acid content of C. calcitrans and doubled final cell yields. Enhanced microalgal culture performance is likely associated with increased intracellular Fe uptake efficiency combined with heterotrophic growth stimulated by the organic ligands. Based upon these results, we propose that replacement of EDTA with one of these organic metal-chelating ligands is an effective and easily implementable strategy to enhance the environmental compatibility of microalgal cultivation practices while also maximizing algal growth and enhancing the nutritional quality of marine microalgal species commonly cultured for live-feed applications in aquaculture.
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| 34. |
- Schindler, Suzanne E, et al.
(författare)
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Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light.
- 2022
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Ingår i: Neurology. - 1526-632X. ; 99:3
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231) and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age, APOE ε4 carrier status and cognitive status. Each participant underwent blood and cerebrospinal fluid (CSF) collection, and amyloid PET was performed in 103 participants (68%). Plasma Aβ42/Aβ40 was measured by a high-performance immunoprecipitation-mass spectrometry assay. Plasma p-tau181, p-tau231, and NfL were measured by Simoa immunoassays. CSF Aβ42/Aβ40 and amyloid PET status were used as primary and secondary reference standards of brain amyloidosis, respectively.There were 76 matched pairs of AA and NHW participants (n=152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were APOE ε4 carriers and 91% were cognitively normal. AA were less likely than NHW to have brain amyloidosis by CSF Aβ42/Aβ40 (22% versus 43% positive, p = 0.003). The Receiver Operating Characteristic Area Under the Curve (ROC AUC) of CSF Aβ42/Aβ40 status with the plasma biomarkers was as follows: Aβ42/Aβ40, 0.86 (95% confidence intervals [CI] 0.79-0.92); p-tau181, 0.76 (0.68-0.84); p-tau231, 0.69 (0.60-0.78); and NfL, 0.64 (0.55-0.73). In models predicting CSF Aβ42/Aβ40 status with plasma Aβ42/Aβ40 that included covariates (age, sex, APOE ε4 carrier status, race, and cognitive status), race did not affect the probability of CSF Aβ42/Aβ40 positivity. In similar models based on plasma p-tau181, p-tau231 or Nfl, AA had a lower probability of CSF Aβ42/Aβ40 positivity (Odds Ratio [OR] 0.31 [95% CI 0.13-0.73], OR 0.30 [0.13-0.71]) and OR 0.27 [0.12-0.64], respectively. Models of amyloid PET status yielded similar findings.Models predicting brain amyloidosis using a high performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA.
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| 35. |
- Szkudlarek, Betina, et al.
(författare)
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Communication and culture in international business : Moving the field forward
- 2020
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Ingår i: Journal of world business (Print). - : Elsevier BV. - 1090-9516 .- 1878-5573. ; 55:6
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Tidskriftsartikel (refereegranskat)abstract
- The centrality of communication in international business (IB) is undeniable; yet our understanding of the phenomenon is partially constrained by a cross-cultural comparative focus as opposed to intercultural, process-oriented research designs that capture the dynamic nature of communicative interactions. Our brief review of studies at the intersection of culture and communication in the context of global work interactions reveals the dominant research trends that guided IB scholarship to date in this domain. We propose eight shifts in perspective to advance the field's theorizing and create avenues for further research.
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| 36. |
- Van De Munckhof, Anita, et al.
(författare)
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Outcomes of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after the acute phase
- 2022
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization.Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization).Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed).Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
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| 37. |
- Vogeler, Susanne, et al.
(författare)
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Phylogenetic analysis of the caspase family in bivalves: implications for programmed cell death, immune response and development
- 2021
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Apoptosis is an important process for an organism’s innate immune system to respond to pathogens, while also allowing for cell differentiation and other essential life functions. Caspases are one of the key protease enzymes involved in the apoptotic process, however there is currently a very limited understanding of bivalve caspase diversity and function. Results In this work, we investigated the presence of caspase homologues using a combination of bioinformatics and phylogenetic analyses. We blasted the Crassostrea gigas genome for caspase homologues and identified 35 potential homologues in the addition to the already cloned 23 bivalve caspases. As such, we present information about the phylogenetic relationship of all identified bivalve caspases in relation to their homology to well-established vertebrate and invertebrate caspases. Our results reveal unexpected novelty and complexity in the bivalve caspase family. Notably, we were unable to identify direct homologues to the initiator caspase-9, a key-caspase in the vertebrate apoptotic pathway, inflammatory caspases (caspase-1, −4 or−5) or executioner caspases-3, −6, −7. We also explored the fact that bivalves appear to possess several unique homologues to the initiator caspase groups −2 and−8. Large expansions of caspase-3 like homologues (caspase-3A-C), caspase-3/7 group and caspase-3/7-like homologues were also identified, suggesting unusual roles of caspases with direct implications for our understanding of immune response in relation to common bivalve diseases. Furthermore, we assessed the gene expression of two initiator (Cg2A, Cg8B) and four executioner caspases (Cg3A, Cg3B, Cg3C, Cg3/7) in C. gigas late-larval development and during metamorphosis, indicating that caspase expression varies across the different developmental stages. Conclusion Our analysis provides the first overview of caspases across different bivalve species with essential new insights into caspase diversity, knowledge that can be used for further investigations into immune response to pathogens or regulation of developmental processes.
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| 38. |
- Welch, Brian, et al.
(författare)
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JWST Imaging of Earendel, the Extremely Magnified Star at Redshift z=6.2
- 2022
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205 .- 2041-8213. ; 940
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Tidskriftsartikel (refereegranskat)abstract
- The gravitationally lensed star WHL 0137-LS, nicknamed Earendel, was identified with a photometric redshift z (phot) = 6.2 +/- 0.1 based on images taken with the Hubble Space Telescope. Here we present James Webb Space Telescope (JWST) Near Infrared Camera images of Earendel in eight filters spanning 0.8-5.0 mu m. In these higher-resolution images, Earendel remains a single unresolved point source on the lensing critical curve, increasing the lower limit on the lensing magnification to mu > 4000 and restricting the source plane radius further to r < 0.02 pc, or similar to 4000 au. These new observations strengthen the conclusion that Earendel is best explained by an individual star or multiple star system and support the previous photometric redshift estimate. Fitting grids of stellar spectra to our photometry yields a stellar temperature of T (eff) similar to 13,000-16,000 K, assuming the light is dominated by a single star. The delensed bolometric luminosity in this case ranges from log(L)=5.8 L-theta, which is in the range where one expects luminous blue variable stars. Follow-up observations, including JWST NIRSpec scheduled for late 2022, are needed to further unravel the nature of this object, which presents a unique opportunity to study massive stars in the first billion years of the universe.
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| 39. |
- Williams, S., et al.
(författare)
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The water-energy-food nexus : an ecosystems and anthropocentric perspective
- 2022
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Ingår i: Water - Energy - Food Nexus Narratives and Resource Securities. - : Elsevier BV. ; , s. 257-277
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- As the consequences of climate change continue to unfold globally, effective adaptation strategies are critical. There are many uncertainties inherent in climate change adaptation. Thus a holistic approach must be undertaken to ensure all affected environmental resource sectors are accounted for. Adaptation strategies must involve consideration for water, energy, and food systems, and these sectors' impact on one another. This chapter examines the water-energy-food (WEF) nexus as a tool to provide stakeholders with possible future intersectoral adaptation strategies. This chapter uses two case study regions, the Middle East and North Africa (MENA) and Latin America (LA), to illustrate the benefits of the WEF nexus approach for creating robust, intersectoral adaptation approaches for regional stakeholders.
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| 40. |
- Wright, Leah, et al.
(författare)
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A comparison of chitosan, mesoporous silica and poly(lactic-co-glycolic) acid nanocarriers for optimising intestinal uptake of oral protein therapeutics
- 2021
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 217-227
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Tidskriftsartikel (refereegranskat)abstract
- Efficacious oral delivery of therapeutic proteins remains challenging and nanoparticulate approaches are gaining interest for enhancing their permeability. In this study, we explore the ability for three comparably sized nanocarriers, with diverse physicochemical properties (i.e., chitosan (CSNP), mesoporous silica nanoparticles (MSNP) and poly(lactic-co-glycolic) acid (PLGA-NP)), to successfully facilitate epithelial uptake of a model protein, ovalbumin (OVA). We report the effect of nanoparticle surface chemistry and nanostructure on protein release, cell toxicity and the uptake mechanism in a Madin Darby Canine Kidney (MDCK) cell model of the intestinal epithelium. All nanocarriers exhibited bi-phasic OVA release kinetics with sustained and incomplete release after 4 days, and more pronounced release from MSNP than either polymeric nanocarriers. CSNP and MSNP displayed the highest cellular uptake, however CSNP was prone to significant dose-dependent toxicity attributed to the cationic surface charge. Approximately 25% of MSNP uptake was governed by a clathrin-independent endocytic mechanism, while CSNP and PLGA-NP uptake was not controlled via any endocytic mechanisms investigated herein. Furthermore, endosomal localisation was observed for CSNP and MSNP, but not for PLGA-NP's. These findings may assist in the optimal choice and engineering of nanocarriers for specific intestinal permeation enhancement for oral protein delivery.
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| 41. |
- Zhou, Junhua, et al.
(författare)
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Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1360-1372
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Tidskriftsartikel (refereegranskat)abstract
- Sequence analysis identifies gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. Most patients with these mutations presented during puberty, pregnancy or menopause, with elevated LHCGR expression. Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.
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