| 1. |
- Ahluwalia, T. S., et al.
(författare)
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Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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| 2. |
- Bonomi, A, et al.
(författare)
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Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
- 2020
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Ingår i: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
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Tidskriftsartikel (refereegranskat)abstract
- The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–maxβ = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
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| 3. |
- Cabrera, C., et al.
(författare)
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Relationship between iron deficiency and expression of genes involved in iron metabolism in human myocardium and skeletal muscle
- 2023
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 379, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Iron deficiency (ID) is associated with adverse prognosis in patients with heart failure. This study aims to investigate the relationship between ID and expression of genes involved in iron metabolism in human myocardium and skeletal muscle, focusing on Transferrin 1 receptor (TfR1), the main pathway of cellular iron uptake.Methods: Patients undergoing elective CABG were assessed prior to surgery with echocardiography and serum iron parameters. Core needle biopsies were collected from the left and right ventricle (LV, RV), the right atrium and intercostal skeletal muscle (SM). Gene expression analyses were done by mRNA sequencing.Results: Of 69 patients (median age 69 years, 91% men), 28% had ID. 26% had HFrEF, 25% had HFpEF phys-iology according to echocardiographic findings and NT-proBNP levels, and 49% had normal LV function. The expression of TfR1 was increased in patients with ID compared to patients without ID in ventricular tissue (p = 0.04) and in intercostal SM (p = 0.01). The increase in TfR1 expression in LV and RV was more pronounced when analysing patients with absolute ID (S-Ferritin<100 mu g/L). Analysing the correlation between various iron pa-rameters, S-Ferritin levels showed the strongest correlation with TfR1 expression. There was no correlation with NT-proBNP levels and no difference in TfR1 expression between different HF phenotypes.Conclusions: In patients undergoing elective CABG we found an association between ID and increased TfR1 expression in myocardium regardless of LV function, indicating physiologically upregulated TfR1 expression in the presence of ID to restore intracellular iron needs.
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| 4. |
- Grieco, Francesco, 1992, et al.
(författare)
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Improvement of Odin/SMR water vapour and temperature measurements and validation of the obtained data sets
- 2021
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 14:8, s. 5823-5857
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Tidskriftsartikel (refereegranskat)abstract
- Its long photochemical lifetime makes H2O a good tracer for mesospheric dynamics. Temperature observations are also critical to study middle atmospheric dynamics. In this study, we present the reprocessing of 18 years of mesospheric H2O and temperature measurements from the Sub-Millimetre Radiometer (SMR) aboard the Odin satellite, resulting in a part of the SMR version 3.0 level 2 data set. The previous version of the data set showed poor accordance with measurements from other instruments, which suggested that the retrieved concentrations and temperature were subject to instrumental artefacts. Different hypotheses have been explored, and the idea of an underestimation of the singlesideband leakage turned out to be the most reasonable one. The value of the lowest transmission achievable has therefore been raised to account for greater sideband leakage, and new retrievals have been performed with the new settings. The retrieved profiles extend between 40-100 km altitude and cover the whole globe to reach 85° latitudes. A validation study has been carried out, revealing an overall better accordance with the compared instruments. In particular, relative differences in H2O mixing ratio are always in the ±20% range between 40 and 70 km and diverge at higher altitudes, while temperature absolute differences are within ±5K between 40-80 km and also diverge at higher altitudes.
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| 5. |
- Prata, Ilaria, et al.
(författare)
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Results of a diagnostic imaging audit in a randomised clinical trial in rectal cancer highlight the importance of careful planning and quality control
- 2023
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Ingår i: Insights into Imaging. - : Springer. - 1869-4101. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Background: Magnetic resonance (MR) imaging is the modality used for baseline assessment of locally advanced rectal cancer (LARC) and restaging after neoadjuvant treatment. The overall audited quality of MR imaging in large multicentre trials on rectal cancer is so far not routinely reported.Materials and methods: We collected MR images obtained within the Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation (RAPIDO) trial and performed an audit of the technical features of image acquisition. The required MR sequences and slice thickness stated in the RAPIDO protocol were used as a reference.Results: Out of 920 participants of the RAPIDO study, MR investigations of 668 and 623 patients in the baseline and restaging setting, respectively, were collected. Of these, 304/668 (45.5%) and 328/623 (52.6%) MR images, respectively, fulfilled the technical quality criteria. The main reason for non-compliance was exceeding slice thickness 238/668, 35.6% in the baseline setting and 162/623, 26.0% in the restaging setting. In 166/668, 24.9% and 168/623, 27.0% MR images in the baseline and restaging setting, respectively, one or more of the required pulse sequences were missing.Conclusion: Altogether, 49.0% of the MR images obtained within the RAPIDO trial fulfilled the image acquisition criteria required in the study protocol. High-quality MR imaging should be expected for the appropriate initial treatment and response evaluation of patients with LARC, and efforts should be made to maximise the quality of imaging in clinical trials and in clinical practice.
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| 6. |
- Rossignol, P, et al.
(författare)
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NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients
- 2022
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Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 2:6
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Tidskriftsartikel (refereegranskat)abstract
- Aimas: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine.Methods and Results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths.Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.
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| 7. |
- Strawbridge, Rona J., et al.
(författare)
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The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely
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| 8. |
- Bauer, Georg F., et al.
(författare)
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Future directions for the concept of salutogenesis : A position article
- 2020
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Ingår i: Health Promotion International. - : Oxford University Press. - 0957-4824 .- 1460-2245. ; 35:2, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- Aaron Antonovsky advanced the concept of salutogenesis almost four decades ago (Antonovsky, Health, Stress and Coping. Jossey-Bass, San Francisco, CA, 1979; Unravelling the Mystery of Health. Jossey-Bass,San Francisco, CA, 1987). Salutogenesis posits that life experiences shape the sense of coherence (SOC)VC that helps to mobilize resources to cope with stressors and manage tension successfully (determiningone's movement on the health Ease/Dis-ease continuum). Antonovsky considered the three-dimensionalSOC (i.e. comprehensibility, manageability, meaningfulness) as the key answer to his question about theorigin of health. The field of health promotion has adopted the concept of salutogenesis as reflected in theinternational Handbook of Salutogenesis (Mittelmark et al., The Handbook of Salutogenesis. Springer,New York, 2016). However, health promotion mostly builds on the more vague, general salutogenic orientation that implies the need to foster resources and capacities to promote health and wellbeing. Tostrengthen the knowledge base of salutogenesis, the Global Working Group on Salutogenesis (GWG-Sal)of the International Union of Health Promotion and Education produced the Handbook of Salutogenesis.During the creation of the handbook and the regular meetings of the GWG-Sal, the working group identified four key conceptual issues to be advanced: (i) the overall salutogenic model of health; (ii) the SOC concept; (iii) the design of salutogenic interventions and change processes in complex systems; (iv) the application of salutogenesis beyond health sector. For each of these areas, we first highlight Antonovsky'soriginal contribution and then present suggestions for future development. These ideas will help guideGWG-Sal's work to strengthen salutogenesis as a theory base for health promotion.
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| 9. |
- Danielson, Mattias, et al.
(författare)
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Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study
- 2020
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 87:3, s. 370-382
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Tidskriftsartikel (refereegranskat)abstract
- Objective Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of >= 1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. Methods Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. Results Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). Interpretation Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort.
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| 10. |
- Kumar Wagri, Naresh, 1988-
(författare)
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Assessment of bio-based fuel ash effects on magnesia refractory materials in quicklime production kilns
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Limestone is calcined into quicklime in lime kilns at temperatures above 1000°C. Heat is supplied through combustion inside the kilns, which are insulated with a lining of refractory bricks to mitigate heat loss and to protect the kiln from the hot, chemically aggressive, and mechanically abrasive environment. While magnesia bricks have proven to be effective lining materials, they are still susceptible to extensive wear in lime kilns, especially in the burn zone. Refractory corrosion, in particular, can occur when melted fuel ash infiltrates the refractory materials through pores and small cracks. This resultant wear can lead to high maintenance and operational costs, often due to unplanned kiln shutdowns.To reduce the release of fossil-based carbon dioxide into the atmosphere from lime production kilns, there is a growing interest in introducing bio-based fuels with only relatively minor modifications to the process. Biomass fuels can be sourced from bio-based waste streams from industries or be specifically cultivated for combustion. However, the ash content and properties of bio-based fuels tend to be problematic from an ash chemistry perspective. Therefore, before introducing a new fuel source, it is essential to investigate its potential effects on the kiln lining material. In this thesis work, the interactions between melted olive pomace ash and coal ash with commercially available magnesia refractory materials, primarily composed of periclase (MgO) with minor amounts of spinel (MgAl2O4), were studied. A procedure for quantifying the intrusion depths was described. Refractory samples were exposed to the fuel ashes under a simulated lime kiln atmosphere with high CO2 levels at 1200 and 1400°C for 15 and 60 minutes. Cold crushing strength tests were conducted on refractory samples exposed to coal and olive pomace ash, along with CaO powder, at 1400°C for 96 hours. Additionally, postmortem analyses of spent MgO-based refractory bricks were carried out to investigate their chemical characterization and resistance to slag attack after serving as part of the lining in a quick lime rotary kiln for six months.The morphology and elemental compositions of the exposed samples were examined using scanning electron microscopy and energy-dispersive X-ray spectroscopy. Crystalline phases were investigated with powder X-ray diffraction. Thermodynamic equilibrium calculations were performed to further investigate the ash’s melting behavior in contact with the refractories.The results indicated that the potassium-rich olive pomace ash exhibited a greater tendency to infiltrate compared to the silicon-rich coal ash, while the latter formed a glassy melt layer on top of the refractory samples. The ash slags primarily infiltrated through the porous matrix and grain boundaries of the refractory materials. Also, refractory phases were observed in both types of ashes, indicating migration of refractory constituents. K2MgSiO4 phase was found in the olive pomace ash residues on top of the samples, both for the 1200°C and 1400°C exposures. Similarly, Al6Si2O13 phase was dominant in the residual coal ash, in both the 1200°C and 1400°C exposed samples. None of these phases were present in the original ashes.The results of the postmortem analysis revealed that there was no potassium (K) from the fuel ash present on the hot side of the refractory bricks. However, some K was detected in the middle and back parts of the bricks. On the other hand, some phases, possibly connected to degradation, could be found on the hot side of the bricks, where most of the wear was observed.The crushing strengths increased after exposure for all samples, except for those exposed exclusively to coal ash. One possible explanation for this is that the refractory materials exhibited a sintered structure, as a result of their interaction with the ashes and CaO. However, in the samples exposed to coal ash, forsterite (Mg2SiO4) was identified, which can be considered a corrosion product.
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