| 1. |
- Andraos, Rama, et al.
(författare)
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Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjogrens syndrome and systemic sclerosis
- 2022
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Ingår i: Lupus Science and Medicine. - : BMJ PUBLISHING GROUP. - 2053-8790. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveSLE, primary Sjogrens syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The diseases often show overlapping clinical manifestations, which may result in diagnostic challenges. We asked to which extent SSc-associated autoantibodies are present in SLE and pSS, and whether these link to serum IFN-alpha, clinical phenotypes and sex. Samples with clinical data from patients with SSc and healthy blood donors (HBDs) served as controls. Finally, the diagnostic performance of SSc-associated autoantibodies was evaluated.MethodsSamples from well-characterised subjects with SLE (n=510), pSS (n=116), SSc (n=57) and HBDs (n=236) were analysed using a commercially available immunoassay (EuroLine Systemic Sclerosis Profile (IgG)). IFN-alpha was quantified by ELISA. Self-reported data on Raynauds phenomenon (RP) were available.ResultsWith exceptions for anti-Ro52/SSA and anti-Th/To, SSc-associated autoantibodies were more frequent in SSc than in SLE, pSS and HBDs regardless of sex. IFN-alpha levels correlated with the number of positive SSc-associated autoantibodies (r=0.29, p<0.0001) and associated with Ro52/SSA positivity (p<0.0001). By using data from SLE, SSc and HBDs, RP was significantly associated with topoisomerase I, centromere protein (CENP)-B, RNA polymerase III 11 kDa, RNA polymerase III 155 kDa and PM-Scl100 whereas Ro52/SSA associated inversely with RP. In SLE, CENP-A was associated with immunological disorder, CENP-B with serositis and Ku with lupus nephritis. By combining analysis of ANA (immunofluorescence) with SSc-associated autoantibodies, the diagnostic sensitivity reached 98% and the specificity 33%.ConclusionsThe 13 specificities included in the EuroLine immunoassay are commonly detected in SSc, but they are also frequent among individuals with other diseases imprinted by type I IFNs. These findings are valuable when interpreting serological data on patients with suspected SSc, especially as patients may present with disease manifestations overlapping different rheumatological diseases. In SLE, we observed associations between manifestations and SSc-associated autoantibodies which have not previously been reported.
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| 2. |
- Frodlund, Martina, et al.
(författare)
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Glucocorticoid treatment in SLE is associated with infections, comorbidities and mortality-a national cohort study
- 2024
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Ingår i: Rheumatology. - : OXFORD UNIV PRESS. - 1462-0324 .- 1462-0332. ; 63:4, s. 1104-1112
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Patients with SLE have an increased risk of comorbidities and impaired survival. We aimed to assess whether various thresholds of oral CS (OCS) can predict development of infections, comorbidities, malignancies and survival in SLE using data from national health registries in Sweden. Methods All incident SLE cases, age >18 years, in Sweden (n = 5309) between 2005 and 2020 and matched population controls (n = 26 545) were included and followed until 2020, a total of 257 942 patient years. Data from national registers were retrieved including information from the National Prescribed Drug Register. Risk factors were analysed using time-dependent Cox regression models. Results Compared with no OCS, >0 to <5.0 mg/day, 5.0-7.5 mg/day as well as >7.5 mg/day OCS predicted development of infections (pneumonia, influenza, herpes zoster and urinary tract infection), osteoporosis, osteonecrosis, gastroduodenal ulcers, cataracts, hypertension and mortality (all P < 0.05). OCS >0 to <5.0 mg/day was associated with lower hazard ratios for these comorbidities than higher doses of OCS. Fifteen years after diagnosis, 48% of patients were taking OCS at a median dose of 5.7 mg/day. A small reduction of OCS treatment 5 years after diagnosis in patients diagnosed with SLE 2006-10 compared with 2011-15 was observed, 49% vs 46% respectively (P = 0.039). Conclusion Results highlight the potential harm associated with even low OCS dose treatment in SLE and the need to judiciously use OCS at the lowest possible dose to maximize efficacy and minimize harm.
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| 3. |
- Hanly, John G., et al.
(författare)
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Neuropsychiatric Events in Systemic Lupus Erythematosus : Predictors of Occurrence and Resolution in a Longitudinal Analysis of an International Inception Cohort
- 2021
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Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 73:12, s. 2293-2302
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE). Methods: Upon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure. Results: NP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE-associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P = 0.028), concurrent non-SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non-SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non-SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001). Conclusion: In a large and long-term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.
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| 4. |
- Hanly, John G., et al.
(författare)
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Peripheral Nervous System Disease in Systemic Lupus Erythematosus : Results From an International Inception Cohort Study
- 2020
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Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 72:1, s. 67-77
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. Conclusion: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.
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| 5. |
- Legge, Alexandra, et al.
(författare)
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Construction of a frailty index as a novel health measure in systemic lupus erythematosus
- 2020
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 47:1, s. 72-81
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods. The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values. Results. The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21. Conclusion. The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.
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| 6. |
- Legge, Alexandra, et al.
(författare)
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Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index
- 2020
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Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 72:4, s. 658-666
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. Methods: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. Results: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13–1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. Conclusion: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.
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| 7. |
- Legge, Alexandra, et al.
(författare)
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Prediction of Hospitalizations in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index
- 2022
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 74:4, s. 638-647
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort. Methods: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics. Results: The 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13–1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02–1.16]). Conclusion: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.
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| 8. |
- Svanberg, Andreas
(författare)
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Full-Scale Modelling and Simulation of Bucket Filling and Wear for Mining Rope Shovels
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Handling of granular material occurs all over the world for different reasons and under different conditions. In the mining industry, granular material handling is present in almost all processes. The machinery that deals with the granular material is typically subjected to significant wear. The loading process is a very crucial task in any mine. During the loading process, fragmented material is loaded with large rope- or hydraulic shovels. In open-pit mines, machines capable of loading more than 100 tonnes of fragmented rocks per bucket are often used. Maximizing the availability and increasing the productivity of these enormous machines are two challenges that are crucial in order to maintain the production.The work in this thesis is divided up into two parts, where the first part is to develop a numerical model to simulate granular material handling for full-scale applications, and the second part is to develop a wear model suitable for the prediction of abrasive sliding and impact wear for full-scale industrial use. A numerical model utilizing the discrete element method (DEM) in combination with rigid-finite element (FE) is used to obtain a realistic granular material model of copper ore. A multi rigid body dynamics model is utilized to model a realistic dynamic model of a rope shovel. Novel full-scale in-situ experiments are used for calibration and validation of the granular material model. A wear model, with the basis of the traditional Finnie's wear model is developed. The model enables the calculation of wear for different impact angles varying between sliding to vertical impacts. Calibration of the wear model is performed by measuring the wear on steel plates belonging to a vibratory feeder. A sensitivity analysis is performed to investigate how the particle size distribution (PSD) and the FE grid size influences the numerical wear. Furthermore, the model is validated by comparing predicted wear from simulations with experimentally measured wear on a rope shovel bucket.Validation of the granular material model from drone video recordings, and measurements of mass in the bucket confirms that the granular material model is able to capture the main phenomenon during the loading process. Validation of the wear simulation model agrees exceptionally well between the predicted wear when compared to the experimentally obtained wear data. In conclusion, numerical models including prediction of wear are developed and demonstrated for the loading process. Calibration and validation approaches for full-scale industrial use are also presented. The presented model can be used as a tool for industries to make better decisions regarding e.g. how to increase productivity and reduce wear.
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| 9. |
- Svanberg, Andreas, et al.
(författare)
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Full-scale simulation and validation of bucket filling for a mining rope shovel by using a combined rigid FE-DEM granular material model
- 2021
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Ingår i: Computational Particle Mechanics. - : Springer. - 2196-4386 .- 2196-4378. ; 8, s. 825-843
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Tidskriftsartikel (refereegranskat)abstract
- Rope shovels and other heavy mining equipment used for loading fragmented rocks to extract minerals from the earth are used in almost every open pit mine. The optimization of the loading process is of enormous value due to the extremely large amount of material turn over. In this work, a full-scale numerical model of the loading process is developed. Granular material of copper ore is modeled in a combination of rigid finite elements for larger particles with complex shapes, and the discrete element method for smaller particles. A multi rigid body dynamic model, discretized with finite elements are used to model the rope shovel. Calibration of the numerical model for the granular material is performed via a new and unique experimental full-scale approach of analyzing waste rock pile angles with a height of approximately 15 m. In situ experimental data acquisition is performed during the loading process for validation of the model. After model validation, the influence of several loading variables such as bucket rake angle, velocity, and position from the pile are investigated and evaluated. When comparing the numerical model results with experimental mass measurement an excellent agreement was observed. Also, drone camera video recordings of the mass flow behavior and the numerical mass flow behavior are in agreement. Small adjustments of dig variables show a significant effect on the average dig force as well as the bucket fill factor.
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| 10. |
- Svanberg, Andreas, et al.
(författare)
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Full-Scale Simulation and Validation of Wear for a Mining Rope Shovel Bucket
- 2021
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Ingår i: Minerals. - : MDPI. - 2075-163X. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Failure in industrial processes is often related to wear and can cause significant problems. It is estimated that approximately 1–4% of the gross national product for an industrialized nation is related to abrasive wear. This work aims to numerically predict development of wear for full-scale mining applications in harsh sub-arctic conditions. The purpose is to increase the understanding of wear development in industrial processes and optimize service life and minimize costs related to wear. In the present paper, a granular material model consisting of the discrete element method (DEM) and rigid finite element particles is utilized to study wear in full-scale mining applications where granular materials and steel structures are present. A wear model with the basis in Finnie’s wear model is developed to calculate wear from combined abrasive sliding and impact wear. Novel in situ full-scale experiments are presented for calibration of the wear model. A simulation model of the rope shovel loading process is set up where the bucket filling process is simulated several times, and the wear is calculated with the calibrated wear model. From the full-scale validation, it is shown that the simulated wear is in excellent agreement when compared to the experiments, both regarding wear locations and magnitudes. After validation, the model is utilized to study if wear can be minimized by making small changes to the bucket. One major conclusion from the work is that the presented wear simulator is a suitable tool that can be used for product development and optimization of the loading process.
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