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- Carlsson, Henrik, et al.
(författare)
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Measurement of hydroxychloroquine in blood from SLE patients using LC-HRMS : Evaluation of whole blood, plasma and serum as sample matrices
- 2020
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Hydroxychloroquine (HCQ) is the standard of care in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other inflammatory rheumatic diseases and potentially for the treatment in COVID-19 patients. Determination of HCQ for therapeutic drug monitoring (TDM) can be performed in whole blood (WB), serum, and plasma. Direct comparisons of WB, serum, and plasma levels of HCQ in patients with SLE have not previously been reported. We describe a method for the determination of HCQ in human blood using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and compare the suitability of the three sample matrices. Methods A method for the determination of HCQ in human blood using LC-HRMS was developed, validated, and applied for the determination of HCQ levels in WB, serum, and plasma from 26 SLE patients. The reproducibility of the method, in the three matrices, was evaluated using quality control samples and repeated preparations and measurements of patient samples. The performance of the developed method for HCQ measurement in serum was further evaluated by comparison with two previously reported extraction methods. Results The performance of the presented method demonstrated high accuracy and precision. A large range of HCQ concentrations was observed for the SLE patients in all three matrices (WB, serum, and plasma). The mean levels in WB were approximately two-fold the levels in serum and plasma (813 ng/mL compared to 436 ng/mL and 362 ng/mL, respectively). Spiked quality controls showed high reproducibility for all matrices (coefficient of variation, CV, approx. 5%), whereas in patient samples, equally high-precision was only found using WB as the matrix (CV 3%). The CV for serum and plasma was 14% and 39%, respectively. Two alternative methods applied to serum samples did not demonstrate improved precision. Conclusions A LC-HRMS method for the measurement of HCQ in human blood was developed and validated. Whole blood was found to be the superior sample matrix in terms of sample reproducibility. Thus, whole blood samples should be used for HCQ analysis when patients are monitored for HCQ treatment effects. The assay is in clinical use to monitor levels of HCQ in patients.
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- Carlsson, Henrik, et al.
(författare)
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Targeted metabolomics of CSF in healthy individuals and patients with secondary progressive multiple sclerosis using high-resolution mass spectrometry
- 2020
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Ingår i: Metabolomics. - : SPRINGER. - 1573-3882 .- 1573-3890. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Standardized commercial kits enable targeted metabolomics analysis and may thus provide an attractive complement to the more explorative approaches. The kits are typically developed for triple quadrupole mass spectrometers using serum and plasma.Objectives: Here we measure the concentrations of preselected metabolites in cerebrospinal fluid (CSF) using a kit developed for high-resolution mass spectrometry (HRMS). Secondarily, the study aimed to investigate metabolite alterations in patients with secondary progressive multiple sclerosis (SPMS) compared to controls.Methods: We performed targeted metabolomics in human CSF on twelve SPMS patients and twelve age and sex-matched healthy controls using the Absolute IDQ-p400 kit (Biocrates Life Sciences AG) developed for HRMS. The extracts were analysed using two methods; liquid chromatography-mass spectrometry (LC-HRMS) and flow injection analysis-MS (FIA-HRMS).Results: Out of 408 targeted metabolites, 196 (48%) were detected above limit of detection and 35 were absolutely quantified. Metabolites analyzed using LC-HRMS had a median coefficient of variation (CV) of 3% and 2.5% between reinjections the same day and after prolonged storage, respectively. The corresponding results for the FIA-HRMS were a median CV of 27% and 21%, respectively. We found significantly (p < 0.05) elevated levels of glycine, asymmetric dimethylarginine (ADMA), glycerophospholipid PC-O (34:0) and sum of hexoses in SPMS patients compared to controls.Conclusion: The Absolute IDQ-p400 kit could successfully be used for quantifying targeted metabolites in the CSF. Metabolites quantified using LC-HRMS showed superior reproducibility compared to FIA-HRMS.
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- Chistiakova, Tatiana, et al.
(författare)
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Combined L2-stable feedback and feedforward aeration control in a wastewater treatment plant
- 2020
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Ingår i: IEEE Transactions on Control Systems Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 1063-6536 .- 1558-0865. ; 28:3, s. 1017-1024
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Tidskriftsartikel (refereegranskat)abstract
- A nitrifying activated sludge process with ammonium feedback and inflow feedforward control is studied. The feedback and feedforward measurements are subject to time delay and the control loop includes a saturation. A Hammerstein-based model is therefore identified, including process delays and the nonlinearity. A Monod-type nonlinearity is used, as motivated by the oxygen injection efficiency reduction, with increasing dissolved oxygen concentration. The proposed feedback control strategy includes tuning of a linear lag compensator that has a limited low-frequency gain which allows global stability to be established with the Popov criterion. The feedforward controller attenuates the disturbance and provides an overall improvement of the control strategy. The performance of the combined feedback and feedforward aeration controller is evaluated with a benchmark model.
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- Dohlmar, Frida, et al.
(författare)
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An audit of high dose-rate prostate brachytherapy treatment planning at six Swedish clinics
- 2021
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Ingår i: Journal of Contemporary Brachytherapy. - : TERMEDIA PUBLISHING HOUSE LTD. - 1689-832X .- 2081-2841. ; 13:1, s. 59-71
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: High dose-rate prostate brachytherapy has been implemented in Sweden in the late 1980s and early 1990s in six clinics using the same schedule: 20 Gy in two fractions combined with 50 Gy in 25 fractions with external beam radiation therapy. Thirty years have passed and during these years, various aspects of the treatment process have developed, such as ultrasound-guided imaging and treatment planning system. An audit was conducted, including a questionnaire and treatment planning, which aimed to gather knowledge about treatment planning methods in Swedish clinics. Material and methods: A questionnaire and a treatment planning case (non-anatomical images) were sent to six Swedish clinics, in which high-dose-rate prostate brachytherapy is performed. Treatment plans were compared using dosimetric indices and equivalent 2 Gy doses (EQD(2)). Treatment planning system report was used to compare dwell positions and dwell times. Results: For all the clinics, the planning aim for the target was 10.0 Gy, but the volume to receive the dose differed from 95% to 100%. Dose constraints for organs at risk varied with up to 2 Gy. The dose to 90% of target volume ranged from 10.0 Gy to 11.1 Gy, equivalent to 26.0 Gy EQD(2) and 31.3 Gy EQD(2), respectively. Dose non-homogeneity ratio differed from 0.18 to 0.32 for clinical target volume (CTV) in treatment plans and conformity index ranged from 0.52 to 0.59 for CTV. Conclusions: Dose constraints for the organs at risk are showing a larger variation than that reflected in compared treatments plans. In all treatment plans in our audit, at least 10 Gy was administered giving a total treatment of 102 Gy EQD(2), which is in the upper part of the prescription doses published in the GEC/ESTRO recommendations.
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- Dohlmar, Frida, et al.
(författare)
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Validation of automated post-adjustments of HDR prostate brachytherapy treatment plans by quantitative measures and oncologist observer study
- 2023
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Ingår i: Brachytherapy. - : Elsevier BV. - 1538-4721 .- 1873-1449. ; 22:3, s. 407-415
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim was to evaluate a postprocessing optimization algorithm's ability to improve the spatial properties of a clinical treatment plan while preserving the target coverage and the dose to the organs at risk. The goal was to obtain a more homogenous treatment plan, minimizing the need for manual adjustments after inverse treatment planning. MATERIALS AND METHODS: The study included 25 previously treated prostate cancer pa-tients. The treatment plans were evaluated on dose-volume histogram parameters established clin-ical and quantitative measures of the high dose volumes. The volumes of the four largest hot spots were compared and complemented with a human observer study with visual grading by eight oncologists. Statistical analysis was done using ordinal logistic regression. Weighted kappa and Fleiss' kappa were used to evaluate intra-and interobserver reliability. RESULTS: The quantitative analysis showed that there was no change in planning target volume (PTV) coverage and dose to the rectum. There were significant improvements for the adjusted treatment plan in: V150% and V200% for PTV, dose to urethra, conformal index, and dose nonhomogeneity ratio. The three largest hot spots for the adjusted treatment plan were significantly smaller compared to the clinical treatment plan. The observers preferred the adjusted treatment plan in 132 cases and the clinical in 83 cases. The observers preferred the adjusted treatment plan on homogeneity and organs at risk but preferred the clinical plan on PTV coverage. CONCLUSIONS: Quantitative analysis showed that the postadjustment optimization tool could improve the spatial properties of the treatment plans while maintaining the target coverage.
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- Fureman, Anna-Lena, et al.
(författare)
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Partial clinical remission of Type 1 diabetes in Swedish children : A longitudinal study from the Swedish National Quality Register (SWEDIABKIDS) and the Better Diabetes Diagnosis (BDD) study
- 2024
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593.
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: To investigate the frequency and characteristics of partial remission in Swedish children with type 1 diabetes and whether insulin delivery method, i.e., continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) affect incidence and duration of this period 2007-2011. Factors that increase the proportion of subjects that enter partial remission and extend this period can improve long-term metabolic control and reduce the risk of severe hypoglycemia, improve quality of life and in the long run reduce late complications.METHODS: Longitudinal data from 2007-2020 were extracted from the Swedish National Quality Register (SWEDIABKIDS) with all reported newly diagnosed children. Data on C-peptide from the participants in the Better Diabetes Diagnosis study (BDD) from 2007-2010 were used. The definition of partial remission was Insulin Dose Adjusted HbA1c (IDAA1c): HbA1c (%)+(4 x total daily insulin dose (U/kg/day)) ≤9.RESULTS: Of the 3,887 patients, 56% were boys. More boys than girls were in partial remission throughout the follow-up period until 24 months after diabetes onset. Fewer children 0-6 years old had partial remission at 3 and 12 months but not at 24 months compared to older age groups. A larger proportion of patients using CSII at 12 and 24 months remained in partial remission compared to those with MDI (37% vs 33%, p=0.02 and 31% vs 27%, p<0.01 respectively). The level of C-peptide was higher in the group with partial remission and mean HbA1c was lower, both p<0.001. Partial remission at 12 months after diabetes onset was associated with CSII (OR:1.39 CI:1.13, 1.71), shorter diabetes duration (OR:0.80 CI:0.76, 0.84) and male sex (OR:1.23 CI:1.04, 1.46)Conclusions/interpretation: Insulin through MDI, longer duration of diabetes, and female sex were associated with lower frequency of partial remission. Use of CSII seem to contribute to longer partial remission among Swedish children with type 1 diabetes.
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- Häggström, Margaretha, 1962, et al.
(författare)
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Att undervisa i hållbar utveckling - Relationellt perspektiv
- 2022
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Hur kan lärare arbeta med hållbar utveckling i en tid då globala kriser och klimatförändringar väcker både rädsla och oro? Och hur kan elever samtidigt känna hopp inför sin framtid och sitt vuxna liv? Dessa frågor är utgångspunkt för det utvecklings- och forskningsprojekt som utgör basen i denna bok. Du får följa med i berättelser som lärare och elever skapat tillsammans för att utveckla kunskap om social, ekologisk och ekonomisk hållbarhet. Boken redogör för de pedagogiska utgångspunkterna, men ger också rikligt med praktiska exempel på metoder och former för undervisning i och genom demokratiska och relationella förhållningssätt. Du får konkreta tips på hur du kan integrera hållbar utveckling i undervisningen. Såväl kritiska aspekter som lärdomar och möjligheter lyfts fram. I centrum står eleven och läraren utifrån det relationspedagogiska perspektivet. Att undervisa i hållbar utveckling: Relationellt perspektiv vänder sig till lärarstudenter och verksamma lärare i årskurs F-6. Bokens syfte är att inspirera, stödja och utgöra diskussionsunderlag i skolans arbete med miljöperspektivet och hållbar utveckling.
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- Lagerqvist, Nina, et al.
(författare)
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Evaluation of 11 SARS-CoV-2 antibody tests by using samples from patients with defined IgG antibody titers
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the performance of 11 SARS-CoV-2 antibody tests using a reference set of heat-inactivated samples from 278 unexposed persons and 258 COVID-19 patients, some of whom contributed serial samples. The reference set included samples with a variation in SARS-CoV-2 IgG antibody titers, as determined by an in-house immunofluorescence assay (IFA). The five evaluated rapid diagnostic tests had a specificity of 99.0% and a sensitivity that ranged from 56.3 to 81.6% and decreased with low IFA IgG titers. The specificity was > 99% for five out of six platform-based tests, and when assessed using samples collected ≥ 22 days after symptom onset, two assays had a sensitivity of > 96%. These two assays also detected samples with low IFA titers more frequently than the other assays. In conclusion, the evaluated antibody tests showed a heterogeneity in their performances and only a few tests performed well with samples having low IFA IgG titers, an important aspect for diagnostics and epidemiological investigations.
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