| 1. |
|
|
| 2. |
- Manry, Jérémy, et al.
(författare)
-
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
-
Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
|
|
| 3. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 4. |
- Mogilenko, Denis A., et al.
(författare)
-
Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR
- 2019
-
Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 177:5, s. 1201-
-
Tidskriftsartikel (refereegranskat)abstract
- Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DCs) are exacerbated by a high-fatty-acid (FA) metabolic environment. FAs suppress the TLR-induced hexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changes enhance mitochondria! reactive oxygen species (mtROS) production and, in turn, the unfolded protein response (UPR), leading to a distinct transcriptomic signature with IL-23 as hallmark. Interestingly, chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response. Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23 expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innate immunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR.
|
|
| 5. |
- Arnaud, Laurent, et al.
(författare)
-
Effect of Corticosteroids and Cyclophosphamide on Sex Hormone Profiles in Male Patients With Systemic Lupus Erythematosus or Systemic Sclerosis
- 2017
-
Ingår i: Arthritis & Rheumatology. - : WILEY. - 2326-5191 .- 2326-5205. ; 69:6, s. 1272-1279
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are autoimmune diseases that predominantly affect female patients, and therefore fewer investigations have been conducted in men. The aim of this study was to analyze sex hormone levels in male patients with SLE and those with SSc, compared to matched controls, in relation to the use of corticosteroids and cyclophosphamide (CYC).Methods: Sex hormone levels were measured in fasting blood samples from male patients with SLE (n=71) and those with SSc (n=29) and compared to population-based, age-matched male controls. Relevant hormone profiles were identified using cluster analysis.Results: Male SLE patients had higher levels of luteinizing hormone (LH) (P<0.0001) and more frequent bioactive testosterone deficiency (P=0.02) than their matched controls. The current dosage of prednisolone correlated inversely with the levels of bioactive testosterone (r=-0.36, P=0.03). Cluster analysis identified a subset of SLE patients with increased levels of follicle-stimulating hormone, LH, and prolactin as well as lower levels of bioactive testosterone (P<0.0001) in relation to higher daily doses of prednisolone. In male SSc patients, levels of testosterone (P=0.03) and bioactive testosterone (P=0.02) were significantly lower than those in matched controls. Use of CYC during the previous year was associated with lower bioactive testosterone levels in both SLE patients (P=0.02) and SSc patients (P=0.01), after adjustment for age.Conclusion: The results of this study highlight the negative impact of corticosteroids on gonadal function in men with SLE. Furthermore, use of CYC during the year prior to study inclusion impaired bioactive testosterone levels in male patients with either SLE or SSc. Physicians should be more aware of the possibility of hypogonadism in male patients with autoimmune diseases. The need for hormonal supplementation remains to be formally evaluated in these patients.
|
|
| 6. |
- Badreddine, Ilham, et al.
(författare)
-
Cell Wall Chitosaccharides Are Essential Components and Exposed Patterns of the Phytopathogenic Oomycete Aphanomyces euteiches
- 2008
-
Ingår i: Eukaryotic Cell. - : American Society for Microbiology. - 1535-9778 .- 1535-9786. ; 7:11, s. 1980-1993
-
Tidskriftsartikel (refereegranskat)abstract
- Chitin is an essential component of fungal cell walls, where it forms a crystalline scaffold, and chitooligosaccharides derived from it are signaling molecules recognized by the hosts of pathogenic fungi. Oomycetes are cellulosic fungus-like microorganisms which most often lack chitin in their cell walls. Here we present the first study of the cell wall of the oomycete Aphanomyces euteiches, a major parasite of legume plants. Biochemical analyses demonstrated the presence of ca. 10% N-acetyl-D-glucosamine (GlcNAc) in the cell wall. Further characterization of the GlcNAc-containing material revealed that it corresponds to noncrystalline chitosaccharides associated with glucans, rather than to chitin per se. Two putative chitin synthase (CHS) genes were identified by data mining of an A. euteiches expressed sequence tag collection and Southern blot analysis, and full-length cDNA sequences of both genes were obtained. Phylogeny analysis indicated that oomycete CHS diversification occurred before the divergence of the major oomycete lineages. Remarkably, lectin labeling showed that the Aphanomyces euteiches chitosaccharides are exposed at the cell wall surface, and study of the effect of the CHS inhibitor nikkomycin Z demonstrated that they are involved in cell wall function. These data open new perspectives for the development of antioomycete drugs and further studies of the molecular mechanisms involved in the recognition of pathogenic oomycetes by the host plants.
|
|
| 7. |
- Beaumont, Mark A, et al.
(författare)
-
In defence of model-based inference in phylogeography.
- 2010
-
Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 19:3, s. 436-446
-
Tidskriftsartikel (refereegranskat)abstract
- Recent papers have promoted the view that model-based methods in general, and those based on Approximate Bayesian Computation (ABC) in particular, are flawed in a number of ways, and are therefore inappropriate for the analysis of phylogeographic data. These papers further argue that Nested Clade Phylogeographic Analysis (NCPA) offers the best approach in statistical phylogeography. In order to remove the confusion and misconceptions introduced by these papers, we justify and explain the reasoning behind model-based inference. We argue that ABC is a statistically valid approach, alongside other computational statistical techniques that have been successfully used to infer parameters and compare models in population genetics. We also examine the NCPA method and highlight numerous deficiencies, either when used with single or multiple loci. We further show that the ages of clades are carelessly used to infer ages of demographic events, that these ages are estimated under a simple model of panmixia and population stationarity but are then used under different and unspecified models to test hypotheses, a usage the invalidates these testing procedures. We conclude by encouraging researchers to study and use model-based inference in population genetics.
|
|
| 8. |
- Bécoulet, A., et al.
(författare)
-
Science and technology research and development in support to ITER and the Broader Approach at CEA
- 2013
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10
-
Tidskriftsartikel (refereegranskat)abstract
- In parallel to the direct contribution to the procurement phase of ITER and Broader Approach, CEA has initiated research & development programmes, accompanied by experiments together with a significant modelling effort, aimed at ensuring robust operation, plasma performance, as well as mitigating the risks of the procurement phase. This overview reports the latest progress in both fusion science and technology including many areas, namely the mitigation of superconducting magnet quenches, disruption-generated runaway electrons, edge-localized modes (ELMs), the development of imaging surveillance, and heating and current drive systems for steady-state operation. The WEST (W Environment for Steady-state Tokamaks) project, turning Tore Supra into an actively cooled W-divertor platform open to the ITER partners and industries, is presented.
|
|
| 9. |
- Blaess, Julien, et al.
(författare)
-
Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE) : consensus by an international task force
- 2024
-
Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 10:2
-
Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE.METHODS: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus.RESULTS: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals.CONCLUSION: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition.
|
|
| 10. |
|
|
| 11. |
- Fanouriakis, Antonis, et al.
(författare)
-
EULAR recommendations for the management of systemic lupus erythematosus : 2023 update
- 2024
-
Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83:1, s. 15-29
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
|
|
| 12. |
- Fragoulis, George E., et al.
(författare)
-
2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases
- 2023
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 742-753
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Methods: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. Results: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. Conclusions: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
|
|
| 13. |
- Graham, Emily B., et al.
(författare)
-
Microbes as Engines of Ecosystem Function : When Does Community Structure Enhance Predictions of Ecosystem Processes?
- 2016
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Microorganisms are vital in mediating the earth's biogeochemical cycles; yet, despite our rapidly increasing ability to explore complex environmental microbial communities, the relationship between microbial community structure and ecosystem processes remains poorly understood. Here, we address a fundamental and unanswered question in microbial ecology: 'When do we need to understand microbial community structure to accurately predict function?' We present a statistical analysis investigating the value of environmental data and microbial community structure independently and in combination for explaining rates of carbon and nitrogen cycling processes within 82 global datasets. Environmental variables were the strongest predictors of process rates but left 44% of variation unexplained on average, suggesting the potential for microbial data to increase model accuracy. Although only 29% of our datasets were significantly improved by adding information on microbial community structure, we observed improvement in models of processes mediated by narrow phylogenetic guilds via functional gene data, and conversely, improvement in models of facultative microbial processes via community diversity metrics. Our results also suggest that microbial diversity can strengthen predictions of respiration rates beyond microbial biomass parameters, as 53% of models were improved by incorporating both sets of predictors compared to 35% by microbial biomass alone. Our analysis represents the first comprehensive analysis of research examining links between microbial community structure and ecosystem function. Taken together, our results indicate that a greater understanding of microbial communities informed by ecological principles may enhance our ability to predict ecosystem process rates relative to assessments based on environmental variables and microbial physiology.
|
|
| 14. |
- Hamdi, Yosr, et al.
(författare)
-
Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
|
|
| 15. |
- He, Jia, et al.
(författare)
-
Socially Desirable Responding : Enhancement and Denial in 20 Countries
- 2015
-
Ingår i: Cross-cultural research. - : SAGE Publications. - 1069-3971 .- 1552-3578. ; 49:3, s. 227-249
-
Tidskriftsartikel (refereegranskat)abstract
- This article investigated the dimensionality, measurement invariance, and cross-cultural variations of social desirability. A total of 3,471 university students from 20 countries completed an adapted version of the Marlowe-Crowne scale. A two-dimensional structure was revealed in the pooled sample, distinguishing enhancement (endorsement of positive self-description) and denial (rejection of negative self-description). The factor structure was supported in most countries; medium-sized item bias was found in two denial items. In a multilevel analysis, we found that (a) there was more cross-cultural variation in denial than enhancement; (b) females tended to score higher on enhancement whereas males tended to score higher on denial; (c) the Human Development Index, an indicator of country socioeconomic development, was the best (negative) predictor of denial; and (d) both enhancement and denial seemed to be associated with country-level values and personality pertinent to fitting in. We conclude that social desirability has a positive and a negative impression management dimension that are meaningfully associated with country-level characteristics, and we argue that social desirability is better interpreted as culturally regulated response amplification.
|
|
| 16. |
|
|
| 17. |
- Jones, Geraint H., et al.
(författare)
-
The Comet Interceptor Mission
- 2024
-
Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
-
Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
|
|
| 18. |
- Lourdudoss, Cecilia, et al.
(författare)
-
Long-Term Dietary Changes after Diagnosis of Rheumatoid Arthritis in Swedish Women : Data from a Population-Based Cohort
- 2018
-
Ingår i: International Journal of Rheumatology. - : Hindawi Limited. - 1687-9260 .- 1687-9279. ; 2018
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate long-term dietary changes after rheumatoid arthritis (RA) diagnosis in Swedish women, compared to women without RA.Methods: This study included 21,602 women from the Swedish Mammography Cohort (SMC), who completed dietary questionnaires in 1997 and 2009. Between 1997 and 2009, 191 women were diagnosed with RA. Dietary changes after RA diagnosis were analyzed based on intake of 82 food items. Statistical analysis included linear mixed models.Results: Women with RA, compared to women without RA, had significantly lower intake (mean servings per week) of animal products such as black pudding, egg, kidney, and liver paste (2.94±2.73 versus 2.45±1.82, p=0.010) and dairy products (35.14±20.02 versus 28.42±16.10, p=0.040) in 1997 and of cereals and grains (31.01±15.54 versus 28.00±14.98, p=0.009) in 2009. However, multivariable adjusted changes in dietary intake from 1997 to 2009 did not show any significant difference in intake. Nevertheless, women without RA increased their intake of whole wheat bread, wheat/oat bran, and rice more than women with RA.Conclusion: Women who had been diagnosed with RA had similar dietary patterns over time as the general population; these women did not remarkably change their diet over time due to their disease. Dietary recommendations for RA patients are needed.
|
|
| 19. |
- Montagnat, Maurine, et al.
(författare)
-
Measurements and full-field predictions of deformation heterogeneities in ice
- 2011
-
Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 305:1-2, s. 153-160
-
Tidskriftsartikel (refereegranskat)abstract
- We have made creep experiments on columnar grained ice and characterised the microstructure and intragranular misorientations over a range of length scales. A FFT full-field model was used to predict the deformation behaviour, using the experimentally characterised microstructure as the starting material. This is the first time this combination of techniques has been used to study the deformation of ice. The microstructure was characterised at the cm scale using an optical technique, the automatic ice texture analyser AITA and at the micron scale using electron backscattered diffraction EBSD. The crystallographic texture and intragranular misorientations were fully characterised by EBSD (3 angles). The deformed microstructure frequently showed straight subgrain boundaries often originating at triple points. These were identified as kink bands, and for the first time we have measured the precise misorientation of the kink bands and deduced the nature of the dislocations responsible for them. These dislocations have a basal edge nature and align in contiguous prismatic planes enabling deformation along the c-axis. In addition, non-uniform grain boundaries and regions of recrystallization were seen. We present coupling between fine scale characterization of intragranular misorientations, from experiments, and prediction of internal stresses that cause it. The model predicts the morphology of the observed local misorientations within the grains, however it over predicts the misorientation values. This is because the annealing and recrystallization mechanisms are not taken into account in the model. Ice is excellent as a model material for measuring, predicting and understanding deformation behaviour for polycrystalline materials. Specifically for ice this knowledge is needed to improve models of ice sheet dynamics that are important for climatic signal interpretation.
|
|
| 20. |
|
|
| 21. |
- Mounier, Remi, et al.
(författare)
-
AMPK alpha 1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration
- 2013
-
Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 18:2, s. 251-264
-
Tidskriftsartikel (refereegranskat)abstract
- Macrophages control the resolution of inflammation through the transition from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype. Here, we present evidence for a role of AMPK alpha 1, a master regulator of energy homeostasis, in macrophage skewing that occurs during skeletal muscle regeneration. Muscle regeneration was impaired in AMPK alpha 1(-/-) mice. In vivo loss-of-function (LysM-Cre;AMPK alpha 1(fl/fl) mouse) and rescue (bone marrow transplantation) experiments showed that macrophagic AMPK alpha 1 was required for muscle regeneration. Cell-based experiments revealed that AMPK alpha 1(-/-) macrophages did not fully acquire the phenotype or the functions of M2 cells. In vivo, AMPK alpha 1(-/-) leukocytes did not acquire the expression of M2 markers during muscle regeneration. Skewing from M1 toward M2 phenotype upon phagocytosis of necrotic and apoptotic cells was impaired in AMPK alpha 1(-/-) macrophages and when AMPK activation was prevented by the inhibition of its upstream activator, CaMKK beta. In conclusion, AMPK alpha 1 is crucial for phagocytosis-induced macrophage skewing from a pro-to anti-inflammatory phenotype at the time of resolution of inflammation.
|
|
| 22. |
- Normand, Philippe, et al.
(författare)
-
Genome characteristics of facultatively symbiotic Frankia sp. strains reflect host range and host plant biogeography.
- 2007
-
Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 17:1, s. 7-15
-
Tidskriftsartikel (refereegranskat)abstract
- Soil bacteria that also form mutualistic symbioses in plants encounter two major levels of selection. One occurs during adaptation to and survival in soil, and the other occurs in concert with host plant speciation and adaptation. Actinobacteria from the genus Frankia are facultative symbionts that form N2-fixing root nodules on diverse and globally distributed angiosperms in the "actinorhizal" symbioses. Three closely related clades of Frankia sp. strains are recognized; members of each clade infect a subset of plants from among eight angiosperm families. We sequenced the genomes from three strains; their sizes varied from 5.43 Mbp for a narrow host range strain (Frankia sp. strain HFPCcI3) to 7.50 Mbp for a medium host range strain (Frankia alni strain ACN14a) to 9.04 Mbp for a broad host range strain (Frankia sp. strain EAN1pec.) This size divergence is the largest yet reported for such closely related soil bacteria (97.8%–98.9% identity of 16S rRNA genes). The extent of gene deletion, duplication, and acquisition is in concert with the biogeographic history of the symbioses and host plant speciation. Host plant isolation favored genome contraction, whereas host plant diversification favored genome expansion. The results support the idea that major genome expansions as well as reductions can occur in facultative symbiotic soil bacteria as they respond to new environments in the context of their symbioses.
|
|
| 23. |
- Pallier, Camille, et al.
(författare)
-
Thermal, electrical, and mechanical properties of hard nitrogen-alloyed Cr thin films deposited by magnetron sputtering
- 2022
-
Ingår i: Surface & Coatings Technology. - : Elsevier Science SA. - 0257-8972 .- 1879-3347. ; 441
-
Tidskriftsartikel (refereegranskat)abstract
- Cr-N based materials, including stoichiometric CrN and Cr:N with a wide range of nitrogen contents, are commonly used as hard and corrosion-resistant coatings. Cr-rich films in this materials system can retain the bcc structure of metallic Cr with few percent of dissolved nitrogen, which can be used for tailoring the mechanical, thermal, and electrical properties. Here, we investigated low nitrogen containing Cr thin films deposited by high ion assisted magnetron sputtering with a substrate temperature of 200 degrees C. With the gas flow ratio maintained at f(N2/Ar) = 0.02, the substrate bias and the target power allows for control of the film composition (0.03 < N/Cr < 0.34). The films comprise a mixture of bcc-Cr and hexagonal Cr2N1-delta phases. The mechanical properties studied by nanoindentation and Brillouin inelastic light scattering revealed a hardening effect due to the multiphase nanostructure. The mechanical properties of the Cr:N films depend on the residual stress, on the amount of h-Cr2N1-delta phase and on the nanostructuring nature of the coatings. A maximum hardness of 37 GPa was achieved for a dense film with a Youngs modulus of 340 GPa, a shear modulus of 118 GPa, and a relatively low thermal conductivity of 7 W/mK.
|
|
| 24. |
- Parodis, Ioannis, 1981-, et al.
(författare)
-
EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis
- 2024
-
Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83, s. 720-729
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc).METHODS: A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale A-D, A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0-10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting.RESULTS: Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc.CONCLUSIONS: The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician-patient communication and improved outcomes.
|
|
| 25. |
- Parodis, Ioannis, et al.
(författare)
-
Smoking and pre-existing organ damage reduce the efficacy of belimumab in systemic lupus erythematosus.
- 2017
-
Ingår i: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972 .- 1873-0183. ; 16:4, s. 343-351
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Belimumab is the first biologic drug approved for Systemic Lupus Erythematosus (SLE). Here, we aimed to investigate the effects of belimumab on clinical and serologic outcomes, and sought to identify predictors of treatment response in three Swedish real-life settings.METHODS: Fifty-eight patients were enrolled at initiation of belimumab and followed longitudinally for up to 53months. Surveillance outcomes included the SLE Disease Activity Index 2000 (SLEDAI-2K), 100mm Visual Analogue Scales for Physician's Global Assessment (PGA), fatigue, pain and general health, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Assessment of treatment response included the SLE responder index (SRI). B lymphocyte stimulator (BLyS) levels were determined using ELISA.RESULTS: SLEDAI-2K (median baseline score: 8.0; IQR: 4.0-13.8), PGA and corticosteroid use decreased during therapy, and patients reported improvements on fatigue, pain, and general health (p<0.0001 for all). SDI scores remained stable (p=0.08). Patients with baseline SDI scores >1 showed decreased probability and prolonged time to attain SRI response (HR: 0.449; 95% CI: 0.208-0.967), as did current smokers compared with non-smokers (HR: 0.103; 95% CI: 0.025-0.427). In contrast, baseline BLyS levels ≥1.2ng/mL predicted increased probability and shorter time to attain SRI response (HR: 2.566; 95% CI: 1.222-5.387).CONCLUSIONS: Disease activity and corticosteroid usage decreased, patient-reported outcomes improved, and no significant organ damage was accrued during follow-up. Smoking and organ damage predicted reduced treatment efficacy. These findings might contribute to a better selection of patients who are likely to benefit from belimumab.
|
|
| 26. |
- Platten, Michael, et al.
(författare)
-
Fully automated joint space width measurement and digital X-ray radiogrammetry in early RA
- 2017
-
Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To study fully automated digital joint space width (JSW) and bone mineral density (BMD) in relation to a conventional radiographic scoring method in early rheumatoid arthritis (eRA). Methods Radiographs scored by the modified Sharp van der Heijde score (SHS) in patients with eRA were acquired from the SWEdish FarmacOTherapy study. Fully automated JSW measurements of bilateral metacarpals 2, 3 and 4 were compared with the joint space narrowing (JSN) score in SHS. Multilevel mixed model statistics were applied to calculate the significance of the association between ΔJSW and ΔBMD over 1 year, and the JSW differences between damaged and undamaged joints as evaluated by the JSN. Results Based on 576 joints of 96 patients with eRA, a significant reduction from baseline to 1 year was observed in the JSW from 1.69 (±0.19) mm to 1.66 (±0.19) mm (p<0.01), and BMD from 0.583 (±0.068) g/cm 2 to 0.566 (±0.074) g/cm 2 (p<0.01). A significant positive association was observed between ΔJSW and ΔBMD over 1 year (p<0.0001). On an individual joint level, JSWs of undamaged (JSN=0) joints were wider than damaged (JSN>0) joints: 1.68 mm (95% CI 1.70 to 1.67) vs 1.54 mm (95% CI 1.63 to 1.46). Similarly the unadjusted multilevel model showed significant differences in JSW between undamaged (1.68 mm (95% CI 1.72 to 1.64)) and damaged joints (1.63 mm (95% CI 1.68 to 1.58)) (p=0.0048). This difference remained significant in the adjusted model: 1.66 mm (95% CI 1.70 to 1.61) vs 1.62 mm (95% CI 1.68 to 1.56) (p=0.042). Conclusions To measure the JSW with this fully automated digital tool may be useful as a quick and observer-independent application for evaluating cartilage damage in eRA. Trial registration number NCT00764725.
|
|
| 27. |
- Tsoi, Alexander, et al.
(författare)
-
Efficacy of lifestyle interventions in the management of systemic lupus erythematosus : a systematic review of the literature
- 2024
-
Ingår i: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 44:5, s. 765-778
-
Forskningsöversikt (refereegranskat)abstract
- We performed a systematic review to explore existing evidence regarding the efficacy of lifestyle interventions for the management of systemic lupus erythematosus (SLE). The search was conducted on the 22nd of June 2021 for publications between 1st of January 2000 and the date of search. Additional articles within the aforementioned timeframe and until December 2023 were added by hand searching. Databases utilized were Medline, Embase, Web of Science, and Cinahl. Lifestyle interventions were defined as any intervention encompassing one or more of the following: physical exercise, diet and nutrition, mental health, harmful exposures, sleep, and social relations. The Joanna Briggs Institute critical appraisal tools were used for risk of bias assessment. The search yielded 11,274 unique records, we assessed the full text of 199 records, and finally included 102 studies. Overall, the quality of the evidence is limited, and there were multiple sources of heterogeneity. The two domains most extensively researched were mental health (40 records) and physical exercise (39 records). Psychological interventions had a positive effect on depressive symptoms, anxiety, and health-related quality of life (HRQoL), whereas physical exercise improved fatigue, depressive symptoms, aerobic capacity, and physical functioning. Studies on diet and nutrition (15 records) support that low fat intake and Mediterranean diet may be beneficial for reducing cardiovascular risk, but large interventional studies are lacking. Studies on harmful exposures (7 records) support photoprotection and use of sunscreen. While studies imply benefits regarding disease burden and drug efficacy in non-smokers and regarding HRQoL in normal-weight patients, more survey is needed on tobacco smoking and alcohol consumption, as well as weight control strategies. Studies on social relations (1 record) and sleep (no records) were sparse or non-existent. In conclusion, psychosocial interventions are viable for managing depressive symptoms, and exercise appears essential for reducing fatigue and improving aerobic capacity and physical function. Photoprotection should be recommended to all patients. Lifestyle interventions should be considered a complement, not a substitute, to pharmacotherapy.
|
|
| 28. |
- Tureson, Nina, et al.
(författare)
-
Effect of ion-implantation-induced defects and Mg dopants on the thermoelectric properties of ScN
- 2018
-
Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 98:20
-
Tidskriftsartikel (refereegranskat)abstract
- For applications in energy harvesting and environmentally friendly cooling, and for power sources in remote or portable applications, it is desired to enhance the efficiency of thermoelectric materials. One strategy consists of reducing the thermal conductivity while increasing or retaining the thermoelectric power factor. An approach to achieve this is doping to enhance the Seebeck coefficient and electrical conductivity, while simultaneously introducing defects in the materials to increase phonon scattering. Here, we use Mg ion implantation to induce defects in epitaxial ScN (111) films. The films were implanted with Mg+ ions with different concentration profiles along the thickness of the film, incorporating 0.35 to 2.2 at. % of Mg in ScN. Implantation at high temperature (600 degrees C), with few defects due to the temperature, does not substantially affect the thermal conductivity compared to a reference ScN. Samples implanted at room temperature, in contrast, exhibited a reduction of the thermal conductivity by a factor of 3. The sample doped with 2.2 at. % of Mg also showed an increased power factor after implantation. This paper thus shows the effect of ion-induced defects on thermal conductivity of ScN films. High-temperature implantation allows the defects to be annealed out during implantation, while the defects are retained for room-temperature implanted samples, allowing for a drastic reduction in thermal conductivity.
|
|
| 29. |
- Tureson, Nina, et al.
(författare)
-
Reduction of the thermal conductivity of the thermoelectric material ScN by Nb alloying
- 2017
-
Ingår i: Journal of Applied Physics. - : AMER INST PHYSICS. - 0021-8979 .- 1089-7550. ; 122:2
-
Tidskriftsartikel (refereegranskat)abstract
- ScN-rich (Sc,Nb)N solid solution thin films have been studied, motivated by the promising thermoelectric properties of ScN-based materials. Cubic Sc1-xNbxN films for 0 amp;lt;= x amp;lt;= 0.25 were epitaxially grown by DC reactive magnetron sputtering on a c-plane sapphire substrate and oriented along the (111) orientation. The crystal structure, morphology, thermal conductivity, and thermoelectric and electrical properties were investigated. The ScN reference film exhibited a Seebeck coefficient of -45 mu V/K and a power factor of 6 x 10(-4) W/m K-2 at 750K. Estimated from room temperature Hall measurements, all samples exhibit a high carrier density of the order of 10(21) cm(-3). Inclusion of heavy transition metals into ScN enables the reduction in thermal conductivity by an increase in phonon scattering. The Nb inserted ScN thin films exhibited a thermal conductivity lower than the value of the ScN reference (10.5W m(-1) K-1) down to a minimum value of 2.2 Wm(-1) K-1. Insertion of Nb into ScN thus resulted in a reduction in thermal conductivity by a factor of similar to 5 due to the mass contrast in ScN, which increases the phonon scattering in the material. Published by AIP Publishing.
|
|
| 30. |
- Ugarte-Gil, Manuel Francisco, et al.
(författare)
-
Impact of glucocorticoids on the incidence of lupus-related major organ damage : A systematic literature review and meta-regression analysis of longitudinal observational studies
- 2021
-
Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 8:1
-
Forskningsöversikt (refereegranskat)abstract
- Objective In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. Methods We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. Results We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. Conclusions We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.
|
|
