| 1. |
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| 2. |
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 7. |
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| 8. |
- Hageman, S., et al.
(författare)
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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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| 9. |
- Juul-Dam, K. L., et al.
(författare)
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Measurable residual disease assessment by qPCR in peripheral blood is an informative tool for disease surveillance in childhood acute myeloid leukaemia
- 2020
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 190:2, s. 198-208
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Tidskriftsartikel (refereegranskat)abstract
- Serial assessments of measurable (or minimal) residual disease (MRD) by qPCR may identify nascent relapse in children with acute myeloid leukaemia (AML) and enable pre-emptive therapy. We investigated the kinetics and prognostic impact of recurrent fusion transcripts (RUNX1-RUNX1T1, CBFB-MYH11, KMT2A-MLLT3 or KMT2A-ELL) in 774 post-induction samples from bone marrow (BM, 347) and peripheral blood (PB, 427) from 75 children with AML. BM MRD persistence during consolidation did not increase the risk of relapse, and MRD at therapy completion did not correlate to outcome (HR=0·64/MRD log reduction (CI: 0·32–1·26), P=0·19). In contrast, 8/8 patients with detectable MRD in PB after first consolidation relapsed. Persistence (n=4) and shifting from negative to positive (n=10) in PB during follow-up predicted relapse in 14/14 patients. All 253PB samples collected during follow-up from 36 patients in continuous complete remission were MRD negative. In core-binding factor AML, persistent low-level MRD positivity in BM during follow-up was frequent but an increment to above 5×10−4 heralded subsequent haematological relapse in 12/12 patients. We demonstrate that MRD monitoring in PB after induction therapy is highly informative and propose an MRD increment above 5×10−4 in PB and BM as a definition of molecular relapse since it always leads to haematological relapse. © 2020 British Society for Haematology and John Wiley & Sons Ltd
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| 10. |
- Karlsson, Lene, et al.
(författare)
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Characteristics and outcome of primary resistant disease in paediatric acute myeloid leukaemia
- 2023
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 201:4, s. 757-765
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Tidskriftsartikel (refereegranskat)abstract
- A significant proportion of events in paediatric acute myeloid leukaemia (AML) are caused by resistant disease (RD). We investigated clinical and biological characteristics in 66 patients with RD from 1013 children with AML registered and treated according to the NOPHO-AML 93, NOPHO-AML 2004, DB AML-01 and NOPHO-DBH AML 2012 protocols. Risk factors for RD were age10 years or older and a white-blood-cell count (WBC) of 100 x 10(9)/L or more at diagnosis. The five-year overall survival (OS) was 38% (95% confidence interval [CI]: 28%-52%). Of the 63 children that received salvage therapy with chemotherapy, 59% (N = 37) achieved complete remission (CR) with OS 57% (95% CI: 42%-75%) compared to 12% (95% CI: 4%-35%) for children that did not achieve CR. Giving more than two salvage chemotherapy courses did not increase CR rates. OS for all 43 patients receiving allogeneic haematopoietic stem cell transplantation (HSCT) was 49% (95% CI: 36%-66%). Those achieving CR and proceeding to HSCT had an OS of 56% (95% CI: 41%-77%, N = 30). This study showed that almost 40% of children with primary resistant AML can be cured with salvage therapy followed by HSCT. Children that did not achieve CR after two salvage courses with chemotherapy did not benefit from additional chemotherapy.
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| 11. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Blasche, Sonja, et al.
(författare)
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Metabolic cooperation and spatiotemporal niche partitioning in a kefir microbial community
- 2021
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 6:2, s. 196-208
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Tidskriftsartikel (refereegranskat)abstract
- Microbial communities often undergo intricate compositional changes yet also maintain stable coexistence of diverse species. The mechanisms underlying long-term coexistence remain unclear as system-wide studies have been largely limited to engineered communities, ex situ adapted cultures or synthetic assemblies. Here, we show how kefir, a natural milk-fermenting community of prokaryotes (predominantly lactic and acetic acid bacteria) and yeasts (family Saccharomycetaceae), realizes stable coexistence through spatiotemporal orchestration of species and metabolite dynamics. During milk fermentation, kefir grains (a polysaccharide matrix synthesized by kefir microorganisms) grow in mass but remain unchanged in composition. In contrast, the milk is colonized in a sequential manner in which early members open the niche for the followers by making available metabolites such as amino acids and lactate. Through metabolomics, transcriptomics and large-scale mapping of inter-species interactions, we show how microorganisms poorly suited for milk survive in—and even dominate—the community, through metabolic cooperation and uneven partitioning between grain and milk. Overall, our findings reveal how inter-species interactions partitioned in space and time lead to stable coexistence.
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| 13. |
- Camen, Stephan, et al.
(författare)
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Risk Factors, Subsequent Disease Onset, and Prognostic Impact of Myocardial Infarction and Atrial Fibrillation
- 2022
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Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood.METHODS AND RESULTS: In pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all-cause mortality in 108 363 individuals (median age, 46.0 years; 48.2% men) free of MI and AF at baseline from 6 European population-based cohorts. During a maximum follow-up of 10.0 years, 3558 (3.3%) individuals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) individuals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was >70% for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68; 95% CI, 1.03–2.74) and subsequent AF after MI (HR, 1.75; 95% CI, 1.31–2.34) both significantly increased overall mortality risk.CONCLUSIONS: We observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.
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| 14. |
- Camen, Stephan, et al.
(författare)
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Temporal relations between atrial fibrillation and ischaemic stroke and their prognostic impact on mortality
- 2020
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 22:4, s. 522-529
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Tidskriftsartikel (refereegranskat)abstract
- Aims Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality. Methods and results Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001). Conclusion The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.
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| 15. |
- Csengeri, Dora, et al.
(författare)
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Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:12, s. 1170-1177
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts.METHODS AND RESULTS: In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11-1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF.CONCLUSIONS: In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention.
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| 16. |
- Krali, Olga, et al.
(författare)
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Dna methylation signatures predict cytogenetic subtype and outcome in pediatric acute myeloid leukemia (Aml)
- 2021
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 17. |
- Morseth, Bente, et al.
(författare)
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Age-specific atrial fibrillation incidence, attributable risk factors and risk of stroke and mortality : Results from the MORGAM Consortium
- 2021
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Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background The main aim was to examine age-specific risk factor associations with incident atrial fibrillation (AF) and their attributable fraction in a large European cohort. Additionally, we aimed to examine risk of stroke and mortality in relation to new-onset AF across age.Methods We used individual-level data (n=66 951, 49.1% men, age range 40-98 years at baseline) from five European cohorts of the MOnica Risk, Genetics, Archiving and Monograph Consortium. The participants were followed for incident AF for up to 10 years and the association with modifiable risk factors from the baseline examinations (body mass index (BMI), hypertension, diabetes, daily smoking, alcohol consumption and history of stroke and myocardial infarction (MI)) was examined. Additionally, the participants were followed up for incident stroke and all-cause mortality after new-onset AF.Results AF incidence increased from 0.9 per 1000 person-years at baseline age 40-49 years, to 17.7 at baseline age ≥70 years. Multivariable-adjusted Cox models showed that higher BMI, hypertension, high alcohol consumption and a history of stroke or MI were associated with increased risk of AF across age groups (p<0.05). Between 30% and 40% of the AF risk could be attributed to BMI, hypertension and a history of stroke or MI. New-onset AF was associated with a twofold increase in risk of stroke and death at ages≥70 years (p≤0.001).Conclusion In this large European cohort aged 40 years and above, risk of AF was largely attributed to BMI, high alcohol consumption and a history MI or stroke from middle age. Thus, preventive measures for AF should target risk factors such as obesity and hypertension from early age and continue throughout life.
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| 18. |
- Toprak, Betül, et al.
(författare)
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Exploring the incremental utility of circulating biomarkers for robust risk prediction of incident atrial fibrillation in European cohorts using regressions and modern machine learning methods
- 2023
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:3, s. 812-819
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables.Methods and results: In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82-2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13-1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10-1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02-1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index.Conclusion: Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively.
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| 19. |
- Zeller-Plumhoff, B., et al.
(författare)
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Analysis of the bone ultrastructure around biodegradable Mg-xGd implants using small angle X-ray scattering and X-ray diffraction
- 2020
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 101, s. 637-645
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Tidskriftsartikel (refereegranskat)abstract
- Magnesium alloys are increasingly researched as temporary biodegradable metal implants in bone applications due to their mechanical properties which are more similar to bone than conventional implant metals and the fact that Magnesium occurs naturally within the body. However, the degradation processes in vivo and in particular the interaction of the bone with the degrading material need to be further investigated. In this study we are presenting the first quantitative comparison of the bone ultrastructure formed at the interface of biodegradable Mg-5Gd and Mg-10Gd implants and titanium and PEEK implants after 4, 8 and 12 weeks healing time using two-dimensional small angle X-ray scattering and X-ray diffraction. Differences in mineralization, orientation and thickness of the hydroxyapatite are assessed. We find statistically significant (p < 0.05) differences for the lattice spacing of the (310)-reflex of hydroxyapatite between titanium and Mg-xGd materials, as well as for the (310) crystal size between titanium and Mg-5Gd, indicating a possible deposition of Mg within the bone matrix. The (310) lattice spacing and crystallite size further differ significantly between implant degradation layer and surrounding bone (p < 0.001 for Mg-10Gd), suggesting apatite formation with significant amounts of Gd and Mg within the degradation layer. Statement of significance Biodegradable Magnesium-based alloys are emerging as a viable alternative for temporary bone implant applications. However, in order to understand if the degradation of the implant material influences the bone ultrastructure, it is necessary to study the bone structure using high-resolution techniques. We have therefore employed 2D small angle X-ray scattering and X-ray diffraction to study the bone ultrastructure surrounding Magnesium-Gadolinium alloys as well as Titanium and PEEK alloys at three different healing times. This is the first time, that the bone ultrastructure around these materials is directly compared and that a statistical evaluation is performed. We found differences indicating a possible deposition of Mg within the bone matrix as well as a local deposition of Mg and/or Gd at the implant site. Data availability statement The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc.
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| 20. |
- Arnold, Natalie, et al.
(författare)
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C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease : the BiomarCaRE project
- 2024
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 45:12, s. 1043-1054
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L).Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024).Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.
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| 21. |
- Arnold, Natalie, et al.
(författare)
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Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease
- 2024
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 84:2, s. 165-177
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities.Objectives: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events.Methods: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as “LDL-C—Lp(a)-C,” where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile).Results: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49).Conclusions: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.
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| 22. |
- Bruns, S., et al.
(författare)
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On the material dependency of peri-implant morphology and stability in healing bone
- 2023
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Ingår i: Bioactive Materials. - : Elsevier. - 2452-199X. ; 28, s. 155-166
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Tidskriftsartikel (refereegranskat)abstract
- The microstructural architecture of remodeled bone in the peri-implant region of screw implants plays a vital role in the distribution of strain energy and implant stability. We present a study in which screw implants made from titanium, polyetheretherketone and biodegradable magnesium-gadolinium alloys were implanted into rat tibia and subjected to a push-out test four, eight and twelve weeks after implantation. Screws were 4 mm in length and with an M2 thread. The loading experiment was accompanied by simultaneous three-dimensional imaging using synchrotron-radiation microcomputed tomography at 5 mu m resolution. Bone deformation and strains were tracked by applying optical flow-based digital volume correlation to the recorded image sequences. Implant stabilities measured for screws of biodegradable alloys were comparable to pins whereas non-degradable biomaterials experienced additional mechanical stabilization. Peri-implant bone morphology and strain transfer from the loaded implant site depended heavily on the biomaterial utilized. Titanium implants stimulated rapid callus formation displaying a consistent monomodal strain profile whereas the bone volume fraction in the vicinity of magnesium-gadolinium alloys exhibited a minimum close to the interface of the implant and less ordered strain transfer. Correlations in our data suggest that implant stability benefits from disparate bone morphological properties depending on the biomaterial utilized. This leaves the choice of biomaterial as situational depending on local tissue properties.
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| 23. |
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| 24. |
- Börschel, Christin S., et al.
(författare)
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Risk prediction of atrial fibrillation and its complications in the community using hs troponin I
- 2023
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Ingår i: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 53:5
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Atrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood-based biomarkers reflecting cardiac injury such as high-sensitivity troponin I (hsTnI) may help close this gap.Methods: We investigated the predictive ability of hsTnI for incident AF in 45,298 participants (median age 51.4 years, 45.0% men) across European community cohorts in comparison to CVRF and established biomarkers (C-reactive protein, N-terminal pro B-type natriuretic peptide).Results: During a median follow-up of 7.7 years, 1734 (3.8%) participants developed AF. Those in the highest hsTnI quarter (≥4.2 ng/L) had a 3.91-fold (95% confidence interval (CI) 3.30, 4.63; p <.01) risk for developing AF compared to the lowest quarter (<1.4 ng/L). In multivariable-adjusted Cox proportional hazards models a statistically significant association was seen between hsTnI and AF (hazard ratio (HR) per 1 standard deviation (SD) increase in log10(hsTnI) 1.08; 95% CI 1.01, 1.16; p =.03). Inclusion of hsTnI did improve model discrimination (C-index CVRF 0.811 vs. C-index CVRF and hsTnI 0.813; p <.01). Higher hsTnI concentrations were associated with heart failure (HR per SD 1.37; 95% CI 1.12, 1.68; p <.01) and overall mortality (HR per SD 1.24; 95% CI 1.09, 1.41; p <.01).Conclusion: hsTnI as a biomarker of myocardial injury does not improve prediction of AF incidence beyond classical CVRF and NT-proBNP. However, it is associated with the AF-related disease heart failure and mortality likely reflecting underlying subclinical cardiovascular impairment.
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- Camen, Stephan, et al.
(författare)
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Cardiac Troponin I and Incident Stroke in European Cohorts : Insights From the BiomarCaRE Project
- 2020
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 51:9, s. 2770-2777
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce.Methods: High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82 881 individuals (median age, 50.7 years; 49.7% men) free of stroke or myocardial infarction at baseline from 9 prospective European community cohorts. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries.Results: Over a median follow-up of 12.7 years, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10-1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09-1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01-1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%-20%), the net reclassification improvement for overall stroke was 0.038 (P=0.021).Conclusions: Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort but might be of some value in individuals at an intermediate risk.
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