| 1. |
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| 2. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 6. |
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| 7. |
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| 8. |
- Chapple, C. R., et al.
(författare)
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Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 72:3, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- Context: Surgical nonautologous meshes have been used for several decades to repair abdominal wall herniae. Implantable materials have been adopted for the treatment of female and male stress urinary incontinence (SUI) and female pelvic organ prolapse (POP). Objective: A consensus review of existing data based on published meta-analyses and reviews. Evidence acquisition: This document summarises the deliberations of a consensus group meeting convened by the European Association of Urology (EAU) and the European Urogynecological Association, to explore the current evidence relating to the use of polypropylene (PP) materials used for the treatment of SUI and POP, with reference to the 2016 EAU guidelines (European Association of Urology 2016), the European Commission's SCENIHR report on the use of surgical meshes (SCENIHR 2015), other available high-quality evidence, guidelines, and national recommendations. Evidence synthesis: Current data suggest that the use of nonautologous durable materials in surgery has well-established benefits but significant risks, which are specific to the condition and location they are used for. Various graft-related complications have been described-such as infection, chronic pain including dyspareunia, exposure in the vagina, shrinkage, erosion into other organs of xenografts, synthetic PP tapes (used in SUI), and meshes (used in POP)-which differ from the complications seen with abdominal herniae. Conclusions: When considering surgery for SUI, it is essential to evaluate the available options, which may include synthetic midurethral slings (MUSs) using PP tapes, bulking agents, colposuspension, and autologous sling surgery. The use of synthetic MUSs for surgical treatment of SUI in both male and female patients has good efficacy and acceptable morbidity. Synthetic mesh for POP should be used only in complex cases with recurrent prolapse in the same compartment and restricted to those surgeons with appropriate training who are working in multidisciplinary referral centres. Patient summary: Synthetic slings can be safely used in the surgical treatment of stress incontinence in both male and female patients. Patients need to be aware of the alternative therapy and potential risks and complications of this therapy. Synthetic mesh for treating prolapse should be used only in complex cases with recurrent prolapse in specialist referral centres.
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| 9. |
- Ratcliffe, S., et al.
(författare)
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Biodiversity and ecosystem functioning relations in European forests depend on environmental context
- 2017
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:11, s. 1414-1426
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Tidskriftsartikel (refereegranskat)abstract
- The importance of biodiversity in supporting ecosystem functioning is generally well accepted. However, most evidence comes from small-scale studies, and scaling-up patterns of biodiversity-ecosystem functioning (B-EF) remains challenging, in part because the importance of environmental factors in shaping B-EF relations is poorly understood. Using a forest research platform in which 26 ecosystem functions were measured along gradients of tree species richness in six regions across Europe, we investigated the extent and the potential drivers of context dependency of B-EF relations. Despite considerable variation in species richness effects across the continent, we found a tendency for stronger B-EF relations in drier climates as well as in areas with longer growing seasons and more functionally diverse tree species. The importance of water availability in driving context dependency suggests that as water limitation increases under climate change, biodiversity may become even more important to support high levels of functioning in European forests.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Paschke, K. D., et al.
(författare)
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Experimental determination of the complete spin structure for (p)over-barp ->(Lambda)over-bar Lambda at p((p)over-bar)=1.637 GeV/c
- 2006
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 74:1, s. 015206-
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Tidskriftsartikel (refereegranskat)abstract
- The reaction (p) over barp -> (Lambda) over bar Lambda -> (p) over bar pi(+)p pi(-) has been measured with high statistics at a beam momentum of p((p) over bar)=1.637GeV/c. The use of a transversely polarized frozen-spin target combined with the self-analyzing property of Lambda/(Lambda) over bar decay allows access to unprecedented information on the spin structure of the interaction. The most general spin-scattering matrix can be written in terms of 11 real parameters for each bin of scattering angle; each of these parameters is determined with reasonable precision. From these results, all conceivable spin correlations are determined with inherent self-consistency. Good agreement is found with the few previously existing measurements of spin observables in (p) over barp ->(Lambda) over bar Lambda near this energy. Existing theoretical models do not give good predictions for those spin observables that had not been previously measured.
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| 14. |
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| 15. |
- Gilbert, M. R., et al.
(författare)
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Perspectives on multiscale modelling and experiments to accelerate materials development for fusion
- 2021
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 554
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Forskningsöversikt (refereegranskat)abstract
- Prediction of material performance in fusion reactor environments relies on computational modelling, and will continue to do so until the first generation of fusion power plants come on line and allow long-term behaviour to be observed. In the meantime, the modelling is supported by experiments that attempt to replicate some aspects of the eventual operational conditions. In 2019, a group of leading experts met under the umbrella of the IEA to discuss the current position and ongoing challenges in modelling of fusion materials and how advanced experimental characterisation is aiding model improvement. This review draws from the discussions held during that workshop. Topics covering modelling of irradiation-induced defect production and fundamental properties, gas behaviour, clustering and segregation, defect evolution and interactions are discussed, as well as new and novel multiscale simulation approaches, and the latest effort s to link modelling to experiments through advanced observation and characterisation techniques.
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| 16. |
- Van Hoovels, L., et al.
(författare)
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IgA rheumatoid factor in rheumatoid arthritis
- 2022
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 60:10, s. 1617-1626
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Rheumatoid factor (RF) is a well-established marker for the diagnosis and classification of rheumatoid arthritis (RA). Most studies evaluated IgM RF or isotype-nonspecific total RF assays. We evaluated the added value of IgA RF in this context. Methods An international sample cohort consisting of samples from 398 RA patients and 1073 controls was tested for IgA RF with 3 commercial assays. For all RA patients and 100 controls essential clinical and serological data for ACR/EULAR classification were available. Results The sensitivity of IgA RF for diagnosing RA was lower than the sensitivity of IgM RF. Differences in numerical values between IgA RF assays were observed. With all assays, the highest IgA RF values were found in patients with primary Sjogren's syndrome. Double positivity for IgM RF and IgA RF had a higher specificity for RA than either IgM RF or IgA RF. The sensitivity of double positivity was lower than the sensitivity of either IgA RF or IgM RF. Single positivity for IgA RF was at least as prevalent in controls than in RA patients. Adding IgA RF to IgM RF and anti-citrullinated protein antibodies (ACPA) did not affect RA classification. However, combined positivity for IgA RF, IgM RF and IgG ACPA had a higher specificity and lower sensitivity for RA classification than positivity for either of the antibodies. Conclusions IgA RF showed a lower sensitivity than IgM RF. Combining IgA RF with IgM RF and ACPA did not improve sensitivity of RA classification. Combined positivity (IgA-RF/IgM-RF/ACPA) increased specificity.
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| 17. |
- Van Hoovels, L., et al.
(författare)
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Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results
- 2022
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays. MATERIALS AND METHODS: Six total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls. RESULTS: Using cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA. CONCLUSION: Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 18. |
- Van Hoovels, L., et al.
(författare)
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Standardisation of ACPA tests: evaluation of a new candidate reference preparation
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:10, s. 1379-1384
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Commercial assays measuring antibodies to citrullinated protein/peptide (ACPA) show poor quantitative agreement. The diagnostic industry has never adopted the International Union of Immunological Societies-Centers for Disease Control and Prevention (IUIS-CDC) ACPA reference standard. Recently, the National Institute for Biological Standards and Control (NIBSC) prepared a new candidate ACPA standard (18/204). We evaluated both reference materials using different commercially available ACPA assays. Materials and methods This is an international study in which the NIBSC candidate ACPA standard and the IUIS-CDC ACPA reference material were analysed together with 398 diagnostic samples from individuals with rheumatoid arthritis (RA) and in 1073 individuals who did not have RA using nine commercial ACPA assays. Results For both reference materials and samples from individuals with RA and individuals who did not have RA, there were large differences in quantitative ACPA results between assays. For most assays, values for the IUIS-CDC standard were lower than values for NIBSC 18/204 and the IUIS-CDC/NIBSC ratio was comparable for several, but not all assays. When NIBSC 18/204 was used as a calibrator, an improvement in alignment of ACPA results across several of the evaluated assays was obtained. Moreover, NIBSC 18/204 could align clinical interpretation for some but not all assays. Conclusion Adoption of an international standard for ACPA determination is highly desirable. The candidate NIBSC 18/204 standard improved the standardisation and alignment of most ACPA assays and might therefore be recommended to be used as reference in commercial assays.
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| 19. |
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| 20. |
- Caniglia, Guido, et al.
(författare)
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Practical wisdom and virtue ethics for knowledge co-production in sustainability science
- 2023
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 6:5, s. 493-501
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Forskningsöversikt (refereegranskat)abstract
- Since antiquity, philosophers in the Western tradition of virtue ethics have declared practical wisdom to be the central virtue of citizens involved in public and social life. Practical wisdom is of particular importance when values are conflicting, power is unequal and knowledge uncertain. We propose that practical wisdom and virtue ethics can inform the practice of sustainability researchers by strengthening their capacity to engage with the normative complexities of knowledge co-production when aspiring to contribute to transformative change.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Steele, A., et al.
(författare)
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Organic synthesis on Mars by electrochemical reduction of CO2
- 2018
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- The sources and nature of organic carbon on Mars have been a subject of intense research. Steele et al. (2012) showed that 10 martian meteorites contain macromolecular carbon phases contained within pyroxene- and olivine-hosted melt inclusions. Here, we show that martian meteorites Tissint, Nakhla, and NWA 1950 have an inventory of organic carbon species associated with fluid-mineral reactions that are remarkably consistent with those detected by the Mars Science Laboratory (MSL) mission. We advance the hypothesis that interactions among spinel-group minerals, sulfides, and a brine enable the electrochemical reduction of aqueous CO2 to organic molecules. Although documented here in martian samples, a similar process likely occurs wherever igneous rocks containing spinel-group minerals and/or sulfides encounter brines.
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| 25. |
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| 26. |
- Biederstädt, A., et al.
(författare)
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SUMO pathway inhibition targets an aggressive pancreatic cancer subtype
- 2020
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 69, s. 1472-1482
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumour biology. It is clear that hyperactivation of MYC generates dependencies that can be exploited therapeutically. The aim of the study was to find and to target MYC-associated dependencies. Design: We analysed human PDAC gene expression datasets. Results were corroborated by the analysis of the small ubiquitin-like modifier (SUMO) pathway in a large PDAC cohort using immunohistochemistry. A SUMO inhibitor was used and characterised using human and murine two-dimensional, organoid and in vivo models of PDAC. Results: We observed that MYC is connected to the SUMOylation machinery in PDAC. Components of the SUMO pathway characterise a PDAC subtype with a dismal prognosis and we provide evidence that hyperactivation of MYC is connected to an increased sensitivity to pharmacological SUMO inhibition. Conclusion: SUMO inhibitor-based therapies should be further developed for an aggressive PDAC subtype. © 2020 American Medical Association. All rights reserved.
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| 27. |
- Bloecker, K., et al.
(författare)
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Tibial coverage, meniscus position, size and damage in knees discordant for joint space narrowing - data from the Osteoarthritis Initiative
- 2013
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:3, s. 419-427
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Meniscal extrusion is thought to be associated with less meniscus coverage of the tibial surface, but the association of radiographic disease stage with quantitative measures of tibial plateau coverage is unknown. We therefore compared quantitative and semi-quantitative measures of meniscus position and morphology in individuals with bilateral painful knees discordant on medial joint space narrowing (mJSN). Methods: A sample of 60 participants from the first half (2,678 cases) of the Osteoarthritis Initiative cohort fulfilled the inclusion criteria: bilateral frequent pain, Osteoarthritis Research Society International (OARSI) mJSN grades 1-3 in one, no-JSN in the contra-lateral (CL), and no lateral JSN in either knee (43 unilateral mJSN1; 17 mJSN2/3; 22 men, 38 women, body mass index (BMI) 31.3 +/- 3.9 kg/m(2)). Segmentation and three-dimensional quantitative analysis of the tibial plateau and meniscus, and semiquantitative evaluation of meniscus damage (magnetic resonance imaging (MRI) osteoarthritis knee score = MOAKS) was performed using coronal 3T MR images (MPR DESSwe and intermediate-weighted turbo spin echo (IW-TSE) images). CL knees were compared using paired t-tests (between-knee, within-person design). Results: Medial tibial plateau coverage was 36 +/- 9% in mJSN1 vs 45 +/- 8% in CL no-JSN knees, and was 31 +/- 9% in mJSN2/3 vs 46 +/- 6% in no-JSN knees (both P < 0.001). mJSN knees showed greater meniscus extrusion and damage (MOAKS), but no significant difference in meniscus volume. No significant differences in lateral tibial coverage, lateral meniscus morphology or position were observed. Conclusions: Knees with medial JSN showed substantially less medial tibial plateau coverage by the meniscus. We suggest that the less meniscal coverage, i.e., less mechanical protection may be a reason for greater rates of cartilage loss observed in JSN knees. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 28. |
- Carrasco, Marta, et al.
(författare)
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Probing the Azaaurone Scaffold against the Hepatic and Erythrocytic Stages of Malaria Parasites
- 2016
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Ingår i: Chemmedchem. - : Wiley. - 1860-7179. ; 11:19, s. 2194-2204
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Tidskriftsartikel (refereegranskat)abstract
- The potential of azaaurones as dual-stage antimalarial agents was investigated by assessing the effect of a small library of azaaurones on the inhibition of liver and intraerythrocytic lifecycle stages of the malaria parasite. The whole series was screened against the blood stage of a chloroquine-resistant Plasmodium falciparum strain and the liver stage of P.berghei, yielding compounds with dual-stage activity and sub-micromolar potency against erythrocytic parasites. Studies with genetically modified parasites, using a phenotypic assay based on the P.falciparum Dd2-ScDHODH line, which expresses yeast dihydroorotate dehydrogenase (DHODH), showed that one of the azaaurone derivatives has the potential to inhibit the parasite mitochondrial electron-transport chain. The global urgency in finding new therapies for malaria, especially against the underexplored liver stage, associated with chemical tractability of azaaurones, warrants further development of this chemotype. Overall, these results emphasize the azaaurone chemotype as a promising scaffold for dual-stage antimalarials.
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| 29. |
- Cotofana, S., et al.
(författare)
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Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI
- 2013
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:9, s. 1214-1222
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Conflicting associations between imaging biomarkers and pain in knee osteoarthritis (OA) have been reported. A relation between pain and denuded areas of subchondral bone (dABs) has been suggested and this study explores this relationship further by relating the presence, phenotype, location and size of dABs to different measures of knee pain. Methods: 633 right knees from the Osteoarthritis Initiative (OAI) (250 men, age 61.7 +/- 9.6 yrs, BMI 29.4 +/- 4.7 kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe) images. dABs were defined as areas where the subchondral bone was uncovered by cartilage. The following measures of pain were used: weightbearing-, non-weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. Results: Using pain measures from subjects without dABs as a reference, those with at least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to-severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had a 1.53-fold increased prevalence of having weightbearing pain (95% Cl 1.20-1.97), especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95% CI 135-2.42). Individuals with cartilage-loss-type dABs had a slightly higher prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to individuals with intra-chondral-osteophyte-type dABs. Conclusion: This study supports a positive relation between femorotibial dABs and knee pain, especially when the dABs are located centrally (i.e., in weightbearing regions) or when the respective central subregion is moderately denuded. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 30. |
- Evangelista, C, et al.
(författare)
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Measurement of the (p)over-barp->KsKs reaction for 0.6 to 1.9 GeV/c
- 1997
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Ingår i: PHYSICAL REVIEW D. - : AMER INST PHYSICS. - 0556-2821. ; 56:7, s. 3803-3810
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Tidskriftsartikel (refereegranskat)abstract
- The <(p)over bar p> --> KSKS --> 4 pi(+/-) cross section was measured at incident antiproton momenta between 0.6 and 1.9 GeV/c using the CERN Low Energy Antiproton Ring. This investigation was part of a systematic study of in-flight antiproton-proton anni
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| 31. |
- Evangelista, C, et al.
(författare)
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Study of the reaction (p)over-bar-p ->phi phi from 1.1 to 2.0 GeV/c
- 1998
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Ingår i: PHYSICAL REVIEW D. - : AMERICAN PHYSICAL SOC. - 0556-2821. ; 57:9, s. 5370-5381
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Tidskriftsartikel (refereegranskat)abstract
- A study has been performed of the reaction <(p)over bar p>-->4K(+/-) using in-flight antiprotons from 1.1 to 2.0 GeV/c incident momentum interacting with a hydrogen jet target. The reaction is dominated by the production of a pair of phi mesons. The <(p)o
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| 32. |
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| 33. |
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| 34. |
- Herman, Jonathan D., et al.
(författare)
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A genomic and evolutionary approach reveals non-genetic drug resistance in malaria
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:11, s. 511-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. Results: We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid homeostasis in response to halofuginone pressure. We show that this non-genetic adaptation to halofuginone is not likely mediated by differential RNA expression and precedes mutation or amplification of the cPRS gene. By tracking the evolution of the two drug resistance selections with whole genome sequencing, we further demonstrate that the cPRS locus accounts for the majority of genetic adaptation to halofuginone in P. falciparum. We further validate that copy-number variations at the cPRS locus also contribute to halofuginone resistance. Conclusions: We provide a three-step model for multi-locus evolution of halofuginone drug resistance in P. falciparum. Informed by genomic approaches, our results provide the first comprehensive view of the evolutionary trajectory malaria parasites take to achieve drug resistance. Our understanding of the multiple genetic and non-genetic mechanisms of drug resistance informs how we will design and pair future anti-malarials for clinical use.
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| 35. |
- Kogan, PS, et al.
(författare)
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Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing
- 2022
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Ingår i: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 117:1, s. 11-
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Tidskriftsartikel (refereegranskat)abstract
- Cardiosphere-derived cells (CDCs) generated from human cardiac biopsies have been shown to have disease-modifying bioactivity in clinical trials. Paradoxically, CDCs’ cellular origin in the heart remains elusive. We studied the molecular identity of CDCs using single-cell RNA sequencing (sc-RNAseq) in comparison to cardiac non-myocyte and non-hematopoietic cells (cardiac fibroblasts/CFs, smooth muscle cells/SMCs and endothelial cells/ECs). We identified CDCs as a distinct and mitochondria-rich cell type that shared biological similarities with non-myocyte cells but not with cardiac progenitor cells derived from human-induced pluripotent stem cells. CXCL6 emerged as a new specific marker for CDCs. By analysis of sc-RNAseq data from human right atrial biopsies in comparison with CDCs we uncovered transcriptomic similarities between CDCs and CFs. By direct comparison of infant and adult CDC sc-RNAseq data, infant CDCs revealed GO-terms associated with cardiac development. To analyze the beneficial effects of CDCs (pro-angiogenic, anti-fibrotic, anti-apoptotic), we performed functional in vitro assays with CDC-derived extracellular vesicles (EVs). CDC EVs augmented in vitro angiogenesis and did not stimulate scarring. They also reduced the expression of pro-apoptotic Bax in NRCMs. In conclusion, CDCs were disclosed as mitochondria-rich cells with unique properties but also with similarities to right atrial CFs. CDCs displayed highly proliferative, secretory and immunomodulatory properties, characteristics that can also be found in activated or inflammatory cell types. By special culture conditions, CDCs earn some bioactivities, including angiogenic potential, which might modify disease in certain disorders.
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| 36. |
- Konrad-Schmolke, Matthias, 1970, et al.
(författare)
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Mineral dissolution and reprecipitation mediated by an amorphous phase
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Fluid-mediated mineral dissolution and reprecipitation processes are the most common mineral reaction mechanism in the solid Earth and are fundamental for the Earth's internal dynamics. Element exchange during such mineral reactions is commonly thought to occur via aqueous solutions with the mineral solubility in the coexisting fluid being a rate limiting factor. Here we show in high-pressure/low temperature rocks that element transfer during mineral dissolution and reprecipitation can occur in an alkali-Al-Si-rich amorphous material that forms directly by depolymerization of the crystal lattice and is thermodynamically decoupled from aqueous solutions. Depolymerization starts along grain boundaries and crystal lattice defects that serve as element exchange pathways and are sites of porosity formation. The resulting amorphous material occupies large volumes in an interconnected porosity network. Precipitation of product minerals occurs directly by repolymerization of the amorphous material at the product surface. This mechanism allows for significantly higher element transport and mineral reaction rates than aqueous solutions with major implications for the role of mineral reactions in the dynamic Earth.
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| 37. |
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| 38. |
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| 39. |
- Volkert, D, et al.
(författare)
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ESPEN guidelines on nutrition in dementia
- 2015
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Ingår i: Clinical nutrition (Edinburgh, Scotland). - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 34:6, s. 1052-1073
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Tidskriftsartikel (refereegranskat)
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| 41. |
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