| 1. |
- Beck, Astrid L, et al.
(författare)
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Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring : A prospective nested case-control study
- 2024
-
Ingår i: International Journal of Cancer. - 0020-7136. ; 154:1, s. 71-80
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Tidskriftsartikel (refereegranskat)abstract
- Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.
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| 2. |
- Bengtsson, Anders A., et al.
(författare)
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Neutrophil FcγRIIA availability is associated with disease activity in systemic lupus erythematosus
- 2020
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immune complexes (ICs) are detectable in a variety of inflammatory diseases, including systemic lupus erythematosus (SLE), reflecting autoantibody binding to antigens. Though ICs are the main contributors to disease pathogenesis through FcγR-mediated inflammation and organ damage, IC levels are not part of the clinical assessment of SLE. The aim of this study was to explore the clinical utility of analyzing levels of ICs in SLE patients using a novel technology, IC-FLOW. Methods: Paired serum samples, at the time point of high and low disease activity (n = 92), were analyzed using two assays: an IC ELISA from a commercial company and a novel in-house flow cytometry-based method, IC-FLOW. IC-FLOW measures FcγRIIA availability on the neutrophil cell surface by flow cytometry, whereas the commercial ELISA measures IC binding to C1q. Results: Using IC-FLOW, 90% of SLE patients with active disease had elevated levels of circulating ICs (p < 0.0001). Using the commercial assay, only 17% of SLE patients had elevated levels of circulating ICs. For both assays, levels of ICs reflected active disease as determined by SLEDAI (r = 0.45, p < 0.0001) and were associated with type I IFN activity (r = 0.37, p = 0.001), and complement consumption (p = 0.0002). Levels of ICs measured with IC-FLOW, but not with the commercial ELISA, were associated with active lupus nephritis (p = 0.004). Conclusions: This novel FcγRIIA-IC assay can detect levels of circulating ICs in patients with SLE. Analyzing IC levels may facilitate monitoring of disease activity, as well as identify patients at risk of lupus nephritis, allowing for early preventive interventions.
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| 3. |
- Bengtsson, Andreas, 1991, et al.
(författare)
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Improved Success Probability with Greater Circuit Depth for the Quantum Approximate Optimization Algorithm
- 2020
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Ingår i: Physical Review Applied. - 2331-7019. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Present-day, noisy, small or intermediate-scale quantum processors-although far from fault tolerant-support the execution of heuristic quantum algorithms, which might enable a quantum advantage, for example, when applied to combinatorial optimization problems. On small-scale quantum processors, validations of such algorithms serve as important technology demonstrators. We implement the quantum approximate optimization algorithm on our hardware platform, consisting of two superconducting transmon qubits and one parametrically modulated coupler. We solve small instances of the NP (nondeterministic polynomial time)-complete exact-cover problem, with 96.6% success probability, by iterating the algorithm up to level two.
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| 4. |
- Bengtsson, Christian, et al.
(författare)
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Association of genomically enhanced and parent average breeding values with cow performance in Nordic dairy cattle
- 2020
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Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 103, s. 6383-6391
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Tidskriftsartikel (refereegranskat)abstract
- This study compared the abilities of virgin heifer genomically enhanced breeding values (GEBV) and parent average breeding values (PA) to predict future cow performance. To increase confidence in genomic technology among farmers, a clear demonstration of the relationship between genomic predictions and future phenotypes is needed. We analyzed 12 different traits in first parity, including production, conformation, fer-tility, and other functional traits. Phenotype data were obtained from national milk recording schemes and breeding values from the Nordic Cattle Genetic Evalu-ation. Direct genomic breeding values were calculated using genomic BLUP and combined with traditional breeding values, using bivariate blending. The data covered 14,862 Red Dairy Cattle, 17,145 Holstein, and 7,330 Jersey genotyped virgin heifers born between 2013 and 2015 in Denmark, Finland, and Sweden. Phe-notypes adjusted for systematic environmental effects were used as measures of cow performance. Two meth-ods were used to compared virgin heifer GEBV and PA regarding their ability to predict future cow per-formance: (1) correlations between breeding values and adjusted phenotypes, (2) ranking cows into 4 quartiles for their virgin heifer GEBV or PA, and calculating actual cow performance for each quartile. We showed that virgin heifer GEBV predicted cow performance significantly better than PA for the vast majority of analyzed traits. The correlations with adjusted pheno-types were 38 to 136% higher for GEBV than for PA in Red Dairy Cattle, 42 to 194% higher for GEBV in Holstein, and 11 to 78% higher for GEBV in Jersey. The relative change between GEBV bottom and top quartiles compared with that between PA bottom and top quartiles ranged from 9 to 261% for RDC, 42 to 138% for Holstein, and 4 to 90% for Jersey. Hence, farmers in Denmark, Finland, and Sweden can have confidence in using genomic technology on their herds.
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| 5. |
- Bengtsson, Christian
(författare)
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Dairy cattle mating plans at herd level using genomic information
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Genotyping of dairy cattle can benefit farmers by increasing the accuracy of breeding values and improving mating plans at herd level. Validation studies on breeding values in this thesis revealed that for the vast majority of traits analysed in Holstein, Jersey and Nordic Red Dairy Cattle, genomically enhanced breeding values for virgin heifers were able to predict cow performance significantly more accurately than parent average breeding values. Linear programming was used to optimise matings based on economic scores for Red Dairy Cattle and Holstein, considering genetic level, semen cost, recessive genetic defects, and genetic relationship. For Holstein, we also studied polledness and beta-casein genotype. The mating results for Red Dairy Cattle showed that it was possible to reduce genetic relatedness between parents and eliminate expression of genetic defects with minimal effect on genetic level. Similar results were achieved for Holstein cattle, in which it was also possible to increase the frequency of polled and beta-casein genotype A2A2 offspring without negatively impacting other comparison criteria. Evaluation of the long-term impact of genomic mating allocations in a simulation study revealed that planning matings with genomic information at herd level involves important risk management decisions, e.g. a trade-off between using fewer bulls to increase the polled allele frequency more quickly and using more bulls to reduce the rate of inbreeding and the variation in carrier frequency for genetic defects.
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| 6. |
- Bengtsson, Christian, et al.
(författare)
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Mating allocations in Holstein combining genomic information and linear programming optimization at the herd level
- 2023
-
Ingår i: Journal of Dairy Science. - 0022-0302 .- 1525-3198. ; 106, s. 3359-3375
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we explored mating allocation in Hol-stein using genomic information for 24,333 Holstein fe-males born in Denmark, Finland, and Sweden. We used 2 data sets of bulls: the top 50 genotyped bulls and the top 25 polled genotyped bulls on the Nordic total merit scale. We used linear programming to optimize economic scores within each herd, considering genetic level, genetic relationship, semen cost, the economic impact of genetic defects, polledness, and 0-casein. We found that it was possible to reduce genetic relation-ships and eliminate expression of genetic defects with minimal effect on the genetic level in total merit index. Compared with maximizing only Nordic total merit in-dex, the relative frequency of polled offspring increased from 13.5 to 22.5%, and that of offspring homozygous for 0-casein (A2A2) from 66.7 to 75.0% in one genera-tion, without any substantial negative impact on other comparison criteria. Using only semen from polled bulls, which might become necessary if dehorning is banned, considerably reduced the genetic level. We also found that animals carrying the polled allele were less likely to be homozygous for 0-casein (A2A2) and more likely to be carriers of the genetic defect HH1. Hence, adding economic value to a monogenic trait in the economic score used for mating allocation sometimes negatively affected another monogenetic trait. We rec-ommend that the comparison criteria used in this study be monitored in a modern genomic mating program.
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| 7. |
- Bengtsson, Christian, et al.
(författare)
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Mating allocations in Nordic Red Dairy Cattle using genomic information
- 2022
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Konferensbidrag (refereegranskat)abstract
- In this study, we compared mating allocations in Nordic Red Dairy Cattle using genomic or pedigree information. We used linear programming to optimise different economic scores within each herd, considering genetic level, semen cost, the economic impact of recessive genetic defects, and genetic relationships. We found high correlations (≥0.83) between the pedigree and genomic relationship measures. The mating results showed that it was possible to reduce the different genetic relationships between parents with minimal effect on genetic level. Including the cost of known recessive genetic defects eliminated expression of genetic defects. It was possible to reduce genomic relationships between parents with pedigree information, but it was best done with genomic measures. Linear programming maximised the economic score for all herds studied within seconds, which means that it is suitable for implementation in mating software to be used by advisors and farmers.
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| 8. |
- Bengtsson, Christian, et al.
(författare)
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Mating allocations in Nordic Red Dairy Cattle using genomic information
- 2022
-
Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 105, s. 1281-1297
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we compared mating allocations in Nordic Red Dairy Cattle using genomic information. We used linear programming to optimize different economic scores within each herd, considering genetic level, semen cost, the economic impact of recessive genetic defects, and genetic relationships. We selected 9,841 genotyped females born in Denmark, Finland, or Sweden in 2019 for mating allocations. We used 2 different pedigree relationship coefficients, the first tracing the pedigree 3 generations back from the parents of the potential mating and the second based on all available pedigree information. We used 3 different genomic relationship coefficients, 1 SNP-by-SNP genomic relationship and 2 based on shared genomic segments. We found high correlations (≥0.83) between the pedigree and genomic relationship measures. The mating results showed that it was possible to reduce the different genetic relationships between parents with minimal effect on genetic level. Including the cost of known recessive genetic defects eliminated expression of genetic defects. It was possible to reduce genomic relationships between parents with pedigree measures, but it was best done with genomic measures. Linear programming maximized the economic score for all herds studied within seconds, which means that it is suitable for implementation in mating software to be used by advisors and farmers.
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| 9. |
- Carter, Victoria, et al.
(författare)
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High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus
- 2020
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Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 72:1, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Long interspersed nuclear element 1 (LINE-1) encodes 2 proteins, the RNA binding protein p40 and endonuclease and reverse transcriptase (open-reading frame 2p [ORF2p]), which are both required for LINE-1 to retrotranspose. In cells expressing LINE-1, these proteins assemble with LINE-1 RNA and additional RNA binding proteins, some of which are well-known autoantigens in patients with systemic lupus erythematosus (SLE). This study was undertaken to investigate whether SLE patients also produce autoantibodies against LINE-1 p40. Methods: Highly purified p40 protein was used to quantitate IgG autoantibodies in serum from 172 SLE patients and from disease controls and age-matched healthy subjects by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Preparations of p40 that also contained associated proteins were analyzed by immunoblotting with patient sera. Results: Antibodies reactive with p40 were detected in the majority of patients and many healthy controls. Their levels were higher in patients with SLE, but not those with systemic sclerosis, compared to healthy subjects (P = 0.01). Anti-p40 reactivity was higher in patients during a flare than in patients with disease in remission (P = 0.03); correlated with the SLE Disease Activity Index score (P = 0.0002), type I interferon score (P = 0.006), decrease in complement C3 level (P = 0.0001), the presence of anti-DNA antibodies (P < 0.0001) and anti-C1q antibodies (P = 0.004), and current or past history of nephritis (P = 0.02 and P = 0.003, respectively); and correlated inversely with age (r = −0.49, P < 0.0001). SLE patient sera also reacted with p40-associated proteins. Conclusion: Autoantibodies reacting with LINE-1 p40 characterize a population of SLE patients with severe and active disease. These autoantibodies may represent an early immune response against LINE-1 p40 that does not yet by itself imply clinically significant autoimmunity, but may represent an early, and still reversible, step toward SLE pathogenesis.
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| 10. |
- Clasen, Julie, et al.
(författare)
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Dairy cattle farmers' preferences for different breeding tools
- 2021
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Ingår i: Animal. - : Elsevier BV. - 1751-7311 .- 1751-732X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Breeding technologies play a significant role in improving dairy cattle production. Scientifically proven tools for improved management and genetic gain in dairy herds, such as sexed semen, beef semen, genomic testing, dairy crossbreeding, and multiple ovulation embryo transfer (MOET), are readily available to dairy farmers. However, despite good accessibility, decreasing costs, and continuous development of these tools, their use in Sweden is limited. This study investigated Swedish dairy farmers' preferences for breeding tools through a survey including a discrete choice experiment. The survey was distributed online to 1 521 Swedish farmers and by an open link published through a farming magazine. In total, the study included 204 completed responses. The discrete choice experiment consisted of 10 questions with two alternative combinations, which gave 48 combinations in total. Utility values and part-worth values were computed using a conditional logit model based on the responses in the discrete choice experiment for nine groups of respondents: one group with all respondents, two groups based on respondents using dairy crossbreeding or not within the past 12 months, two based on herd size, two based on respondent age, and two based on whether respondents had used breeding advisory services or not. The strongest preferences in all groups were for using sexed semen and beef semen. Genomic testing was also significantly preferred by all groups of respondents. Except in large herds, MOET on own animals was significantly and relatively strongly disfavoured by all groups. Buying embryos had no significant utility value to any group. Dairy crossbreeding had low and insignificant utility values in the group of all respondents, but it was strongly favoured by the group that had used dairy crossbreeding within the past 12 months, and it was disfavoured by the group that had not. Part-worth values of combined breeding tools showed that combinations of sexed and beef semen, alone or with genomic testing without dairy crossbreeding, were the most preferred tools. Compared with the most common combinations of breeding tools used in the past 12 months, the part-worth values indicated that Swedish dairy farmers may prefer to use breeding tools more than they do today. Statements on the different breeding tools indicated that the respondents agreed with the benefits attributed to the breeding tools, but these benefits may not be worth the cost of genomic testing and the time consumption of MOET. These valuable insights can be used for further development of breeding tools.
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| 11. |
- Compagno, Michele, et al.
(författare)
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Plasma levels of osteopontin in SLE
- 2022
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Ingår i: Lupus Science and Medicine. - : Lupus Foundation of America. - 2053-8790. ; 9:Suppl 2, s. 85-86
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Konferensbidrag (refereegranskat)
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| 12. |
- Dahl, Martin, 1984, et al.
(författare)
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Interactive formal specification for efficient preparation of intelligent automation systems
- 2022
-
Ingår i: CIRP Journal of Manufacturing Science and Technology. - : Elsevier BV. - 1755-5817 .- 1878-0016. ; 38, s. 129-138
-
Tidskriftsartikel (refereegranskat)abstract
- The automation system of the future will consist of an increasing amount of complex resources, such as collaborative robots and/or autonomously roaming robots for material handling. To control these devices in an environment shared with human operators require state of the art computer perception and motion planning algorithms to be used as part of the automation system. This new type of intelligent automation system, where intelligent machines and learning algorithms are replacing more traditional automation solutions, requires new methods and workflows to keep up with the increase in complexity. This paper presents an interactive and iterative framework for solving some of these new challenges. The framework supports model-based control system preparation performed simultaneously to preparation of 3D geometries, positioning of robots, and tool design. The workflow enables an interactive preparation process, where new resources and constraints can be added to a live (real or simulated) automation system and control system failures can be analyzed in familiar tools for virtual preparation. Additionally, the paper describes how the integrated preparation process was applied to reconfiguring an industrial use case that includes a collaborative robot working side by side with a human operator, smart tools, and a vision system for localizing both work objects and tools.
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| 13. |
- Egonsdotter, Gunilla
(författare)
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Datorbaserade simuleringar i socionomutbildningen : reflektion och social barnavård
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Socionomutbildningen i Sverige syftar till att ge blivande socialarbetare såväl vetenskaplig som praktisk professionell kunskap. En för utbildningen central fråga handlar dock om hur teori och praktik bäst kan integreras. Risken, menar kritiker, är att teori och praktik separeras: teori blir något som förmedlas i klassrummet och praktik något som studenterna ges tillgång till genom fältförlagda studier i olika professionella miljöer. Mot bakgrund av denna utmaning har olika didaktiska tillvägagångssätt prövats för att koppla samman teori med praktik. Ett sådant tillvägagångssätt är simuleringar, vilket innebär att professionella utmaningar i socialt arbete på olika sätt efterliknas i klassrummet, det vill säga i en miljö där sårbara klienter inte riskerar att komma till skada.Med denna avhandling fokuseras en specifik form av simuleringar, nämligen datorbaserade simuleringar.Avhandlingens syfte är att undersöka om en datorbaserad simulering som didaktiskt verktyg i undervisning av socionomstudenter främjar studenters reflektionsförmåga i sociala barnavårdsärenden. Vidare inbegriper syftet att ge en bild av den internationella omfattningen av liknande didaktiska utvecklingsarbeten samt diskutera möjligheterna av att använda datorbaserade simuleringar också i forskningssyfte.Avhandlingsarbetet bestod av två delar: dels en konstruktionsfas, dels en undersökningsfas.Under konstruktionsfasen utformades den datorbaserade simuleringen SimChild, vars avsikt är att utveckla svenska socionomstudenters förmåga att reflektera inom ett av det sociala arbetets viktigaste och svåraste verksamhetsfält, den sociala barnavården. Under övningar med SimChild antar studenter rollen som yrkesutövande socionomer och ställs inför uppgiften att individuellt göra bedömningar och fatta beslut i ett barnavårdsärende. Den skriftliga information som studenterna successivt får tillgång till är, som ofta är fallet i faktiska ärenden, knapphändig och motstridig. Deltagarna i simuleringen får tillgång till samma ärendebeskrivning men med den viktiga skillnaden att bakgrundsinformation om till exempel barnets etnicitet alternativt kön varieras slumpmässigt. Efter den individuella delen av övningen samlas deltagarna i lärarledda seminarier och får då tillgång till aggregerade data om hur skillnader i bakgrundsvariabler påverkat bedömningar och beslut. Från dessa utgångspunkter ges de möjligheter att reflektera över hur stereotypa uppfattningar om till exempel kön eller etnicitet kan påverka professionellt socialt arbete.Med undersökningsfasen fokuserades den betydelse etnicitet kan ha för bedömningar och beslut genom att barnets namn varierades på ett sätt som skulle kunna indikera olika etniciteter. Studier av sådana SimChild-övningar genomfördes vid tre lärosäten med totalt 176 socionomstudenter. Efter individuella bedömningar och beslut samlades undersökningens respondenter i fokusgrupper som för dem fick ersätta de seminarier som annars följer det individuella arbetet i SimChild. Aggregerade sammanställningar av individuella bedömningar och beslut för respektive lärosäte presenterades och låg till grund för fokusgruppsdiskussionerna. Tre fokusgrupper bestående av vardera åtta studenter, totalt 24 studenter, organiserades i direkt anslutning till de avslutade individuella bedömningen. Fokusgruppsdiskussionerna indikerade att denna typ av datorsimulering kan främja studenters reflektion och självinsikter (artikel I). Studie II illustrerar hur studenterna kunde bli medvetna om hur stereotypa föreställningar kan påverka bedömning i ett barnavårdsärende.Utöver de båda studierna av socionomstudenters upplevelser av SimChild ingår i avhandlingen ytterligare två studier som på olika sätt syftar till att fördjupa diskussionen om användningen av datorbaserade simuleringar i socialt arbete. En scoping review av internationell forskning, med 16 ingående publikationer, visar att datorbaserade simuleringar i utbildning av socialarbetare fortfarande är i en prövande, preliminär fas. Av översikten framgår att datorbaserade simuleringar främst används för att främja specifika färdigheter men också förmåga till reflektion eftersträvas. I den sista artikeln (IV) diskuteras huruvida utvecklingen av datorbaserade simuleringar för undervisningsbruk kan bidra till utvecklingen också av forskningsmetoder i socialt arbete. Diskussionen illustreras med data från en pilotstudie med 63 studenter och flera forskningsfördelar med simuleringar framhålls: studiers externa validitet främjas av realismen i simuleringen medan den interna validiteten främjas genom möjligheter till kontroll.Reflektion utgör en viktig teoretisk ram för avhandlingen och kan förstås som länken mellan socialarbetarens teoretiska kunskaper och praktiska färdigheter. För att förstå studenternas bedömningar och tolkningar i samband med den datorbaserade simuleringen utgår analysen från begreppen reflektion i handling, reflektion över handling och reflektion inför handling. Utöver dessa begrepp tar analysen även avstamp i kritisk reflektion, vilket bland annat innebär att synliggöra studenters förgivettagna föreställningar.En central slutsats i avhandlingen är att simuleringar av SimChilds typ gör det möjligt för socionomstudenter att se skillnader i beslut och bedömningar, reflektera över varför dessa skillnader uppstår och reflektera över den betydelse sådana skillnader kan få för klienter.
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| 14. |
- Eriksson, Sam, et al.
(författare)
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Changes in apparent diffusion coefficient and pathological response in colorectal liver metastases after preoperative chemotherapy
- 2023
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 64:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathological response to preoperative chemotherapy of colorectal liver metastases (CRLMs) is predictive of long-term prognosis after liver resection. Accurate preoperative assessment of chemotherapy response could enable treatment optimization. Purpose: To investigate whether changes in lesion-apparent diffusion coefficient (ADC) measured with diffusion-weighted magnetic resonance imaging (MRI) can be used to assess pathological treatment response in patients with CRLMs undergoing preoperative chemotherapy. Material and Methods: Patients who underwent liver resection for CRLMs after preoperative chemotherapy between January 2011 and December 2019 were retrospectively included if they had undergone MRI before and after preoperative chemotherapy on the same 1.5-T MRI scanner with diffusion-weighted imaging with b-values 50, 400, and 800 s/mm2. The pathological chemotherapy response was assessed using the tumor regression grade (TRG) by AJCC/CAP. Lesions were divided into two groups: pathological responding (TRG 0–2) and non-responding (TRG 3). The change in lesion ADC after preoperative chemotherapy was compared between responding and non-responding lesions. Results: A total of 27 patients with 49 CRLMs were included, and 24/49 lesions showed a pathological chemotherapy response. After chemotherapy, ADC increased in both pathological responding (pretreatment ADC: 1.26 [95% confidence interval (CI)=1.06–1.37] vs. post-treatment ADC: 1.33 [95% CI=1.13–1.56] × 10−3 mm2/s; P = 0.026) and non-responding lesions (1.12 [95% CI=0.980–1.21] vs. 1.20 [95% CI=1.09–1.43] × 10−3 mm2/s; P = 0.018). There was no difference in median relative difference in ADC after chemotherapy between pathological responding and non-responding lesions (15.8 [95% CI=1.42–26.3] vs. 7.17 [95% CI=−4.31 to 31.2]%; P = 0.795). Conclusion: Changes in CRLM ADCs did not differ between pathological responding and non-responding lesions.
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| 15. |
- Fooladgar, Ehsan, et al.
(författare)
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CFD modeling of pyrolysis oil combustion using finite rate chemistry
- 2021
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Ingår i: Fuel. - : Elsevier BV. - 0016-2361 .- 1873-7153. ; 299
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the first Computational Fluid Dynamics (CFD) model developed for biomass pyrolysis oil spray combustion using Finite-Rate Chemistry (FRC) approach. To make the CFD calculations feasible, a reduced mechanism for modeling the combustion of biomass Fast Pyrolysis Oil (FPO) based on the POLIMI 1412 mechanism and a model for eugenol oxidation was developed. The reduced mechanism consisted of 200 reactions and 71 species. This level of complexity was found to be a good tradeoff between predictive power and computational cost such that the reduced model could be used in CFD modeling. The predictive power of the reduced mechanism was demonstrated via 0D (adiabatic, premixed, constant pressure reactor), 1D (laminar counterflow flame) and 3D (CFD of a methane-air flat-flame piloted FPO spray flame) calculations. Results from CFD were compared against experimental data from non-intrusive optical diagnostics. The reduced model was successfully used in CFD calculations—the computational cost was approximately 2 orders of magnitude higher than that of a simplified model. Using the reduced mechanism, the concentration of pollutants, minor combustion products, and flame radicals could be predicted—this is added capability compared to already existing models. The CFD model using the reduced mechanism showed quantitative predictive power for major combustion products, flame temperature, some pollutants and temperature, and qualitative predictive power for flame radicals and soot.
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| 16. |
- Gorgisyan, Jenny, et al.
(författare)
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Evalutation of two commercial deep learning OAR segmentation models for prostate cancer treatment
- 2022
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Konferensbidrag (refereegranskat)abstract
- Purpose or ObjectiveTo evaluate two commercial, CE labeled deep learning-based models for automatic organs at risk segmentation on planning CT images for prostate cancer radiotherapy. Model evaluation was focused on assessing both geometrical metrics and evaluating a potential time saving.Material and MethodsThe evaluated models consisted of RayStation 10B Deep Learning Segmentation (RaySearch Laboratories AB, Stockholm, Sweden) and MVision AI Segmentation Service (MVision, Helsinki, Finland) and were applied to CT images for a dataset of 54 male pelvis patients. The RaySearch model was re-trained with 44 clinic specific patients (Skåne University Hospital, Lund, Sweden) for the femoral head structures to adjust the model to our specific delineation guidelines. The model was evaluated on 10 patients from the same clinic. Dice similarity coefficient (DSC) and Hausdorff distance (95th percentile) was computed for model evaluation, using an in-house developed Python script. The average time for manual and AI model delineations was recorded.ResultsAverage DSC scores and Hausdorff distances for all patients and both models are presented in Figure 1 and Table 1, respectively. The femoral head segmentations in the re-trained RaySearch model had increased overlap with our clinical data, with a DSC (mean±1 STD) for the right femoral head of 0.55±0.06 (n=53) increasing to 0.91±0.02 (n=10) and mean Hausdorff (mm) decreasing from 55±7 (n=53) to 4±1 (n=10) (similar results for the left femoral head). The deviation in femoral head compared to the RaySearch and MVision original models occurred due to a difference in the femoral head segmentation guideline in the clinic specific data, see Figure 2. Time recording of manual delineation was 13 minutes compared to 0.5 minutes (RaySearch) and 1.4 minutes (MVision) for the AI models, manual correction not included.ConclusionBoth AI models demonstrate good segmentation performance for bladder and rectum. Clinic specific training data (or data that complies to the clinic specific delineation guideline) might be necessary to achieve segmentation results in accordance to the clinical specific standard for some anatomical structures, such as the femoral heads in our case. The time saving was around 90%, not including manual correction.
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| 17. |
- Gustafsson, Anna, et al.
(författare)
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Subject-specific FE models of the human femur predict fracture path and bone strength under single-leg-stance loading
- 2021
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 113
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Tidskriftsartikel (refereegranskat)abstract
- Hip fractures are a major health problem with high socio-economic costs. Subject-specific finite element (FE) models have been suggested to improve the fracture risk assessment, as compared to clinical tools based on areal bone mineral density, by adding an estimate of bone strength. Typically, such FE models are limited to estimate bone strength and possibly the fracture onset, but do not model the fracture process itself. The aim of this study was to use a discrete damage approach to simulate the full fracture process in subject-specific femur models under stance loading conditions. A framework based on the partition of unity finite element method (PUFEM), also known as XFEM, was used. An existing PUFEM framework previously used on a homogeneous generic femur model was extended to include a heterogeneous material description together with a strain-based criterion for crack initiation. The model was tested on two femurs, previously mechanically tested in vitro. Our results illustrate the importance of implementing a subject-specific material distribution to capture the experimental fracture pattern under stance loading. Our models accurately predicted the fracture pattern and bone strength (1% and 5% error) in both investigated femurs. This is the first study to simulate complete fracture paths in subject-specific FE femur models and it demonstrated how discrete damage models can provide a more complete picture of fracture risk by considering both bone strength and fracture toughness in a subject-specific fashion.
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| 18. |
- Han, Bobby Kwanghoon, et al.
(författare)
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Neutrophil and lymphocyte counts are associated with different immunopathological mechanisms in systemic lupus erythematosus
- 2020
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Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Neutrophils contribute to the SLE pathogenesis. Neutrophil to lymphocyte ratio (NLR) is reported to correlate with disease activity in SLE. The aim of the study was to evaluate whether NLR reflects underlying immunopathogenic activity in SLE, as well as to determine the contribution of each component of NLR, neutrophil and lymphocyte count. Methods: Data were obtained from a cohort of patients with SLE (n=141) recruited at Lund University, Sweden. NLR levels were compared between patients with SLE and healthy controls (n=79). The relationship between NLR and clinical and immunological markers was examined using Mann-Whitney U test and logistic regression analysis. High NLR was defined as above the 90th percentile of healthy individuals. Results: Patients with SLE had elevated neutrophil count (p=0.04) and reduced lymphocyte count (p<0.0001), resulting in elevated NLR as compared with healthy controls (p<0.0001). Patients with high NLR had more active disease, and were more frequently on prednisone use and immunosuppressive medicines. High NLR was associated with immune complex (IC)-driven disease with presence of antidouble-stranded DNA antibodies (p=0.006), circulating ICs (p=0.02) and type I interferon (IFN) activity (p=0.009). Further, high NLR was associated with neutrophil abnormalities, including enrichment for low-density granulocytes (LDGs) (p=0.001), and increased levels of the serum neutrophil activation marker, calprotectin (p=0.02). Assessing the individual components within NLR, that is, neutrophil and lymphocyte count, high neutrophil count was associated with neutrophil activation markers (p<0.0001), whereas low lymphocyte count was associated with type I IFN activity and elevated numbers of LDGs (p=0.006 and p=0.001, respectively). Conclusions: NLR is elevated in patients with SLE as compared with healthy individuals, and is associated with key immunopathological events, including type I IFN activity and neutrophil activation. Neutrophil and lymphocyte count reflected different aspects of the pathogenesis of SLE. Further studies are needed to determine the causality of the associations.
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| 19. |
- Jordan, Stanley C., et al.
(författare)
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Imlifidase desensitization in crossmatch-positive, highly-sensitized kidney transplant recipients : Results of an international phase 2 trial (Highdes)
- 2021
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 105:8, s. 1808-1817
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Highly-HLA sensitized patients have limited access to life-saving kidney transplantation due to a paucity of immunologically suitable donors. Imlifidase is a cysteine protease that cleaves IgG leading to a rapid decrease in antibody level and inhibition of IgG-mediated injury. This study investigates the efficacy and safety of imlifidase in converting a positive crossmatch test to negative, allowing highly sensitized patients to be transplanted with a living or deceased donor kidney.METHODS: This open-label, single arm, phase 2 trial conducted at five transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 hours. Secondary endpoints included post-imlifidase DSA levels compared to pre-dose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile.RESULTS: 89.5% of the transplanted patients demonstrated conversion of baseline positive crossmatch to negative within 24 hours after imlifidase treatment. DSA most often rebounded 3-14 days post-imlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 months. 38.9% had early biopsy proven antibody mediated rejection with onset 2-19 days post-transplantation. Serum IgG levels began to normalize after ~3-7 days post-transplantation. Anti-drug antibody levels were consistent with previous studies. Seven adverse events in six patients were classified as possibly or probably related to treatment and were mild-moderate in severity.CONCLUSIONS: Imlifidase was well tolerated, converted positive crossmatches to negative, and enabled patients with a median cPRA of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 months.
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| 20. |
- Karason, Kristjan, 1962, et al.
(författare)
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Effect of growth hormone treatment on circulating levels of NT-proBNP in patients with ischemic heart failure.
- 2020
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1532-2238. ; 55
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) therapy in heart failure (HF) is controversial. We investigated the cardiovascular effects of GH in patients with chronic HF due to ischemic heart disease.In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66years; 95% male) with ischemic HF (ejection fraction [EF]<40%) to a 9-month treatment with either recombinant human GH (1.4mg every other day) or placebo, with subsequent 3-month treatment-free follow-up. The primary outcome was change in left ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes included changes in New York Heat Association (NYHA) functional class and quality of life (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP).No changes in cardiac structure or systolic function were identified in either treatment group; nor did GH treatment affect QoL or functional class. In the GH group, circulating levels of IGF-1 doubled from baseline (+105%; p<0.001) and NT-proBNP levels halved (-48%; p<0.001) during the treatment period, with subsequently a partial return of both towards baseline levels. No changes in IGF-1 or NT-proBNP were observed in the placebo group at any time during the study.In patients with chronic ischemic HF, nine months of GH treatment was associated with significant increases in levels of IGF-1 and reductions in levels of NT-proBNP, but did not affect cardiac structure, systolic function or functional capacity.
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| 21. |
- Krais, Annette M, et al.
(författare)
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Detection of the fungicide transformation product 4-hydroxychlorothalonil in serum of pregnant women from Sweden and Costa Rica
- 2024
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Ingår i: Journal of Exposure Science & Environmental Epidemiology. - 1559-064X. ; 34:2, s. 270-277
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 4-hydroxychlorothalonil (HCT, R182281), a transformation product of the fungicide chlorothalonil, was recently identified in human serum and breast milk. There are indications that HCT may be more toxic and environmentally persistent than chlorothalonil.OBJECTIVE: Our aim was to investigate serum concentrations of HCT in pregnant women in Sweden and Costa Rica.METHODS: We developed a quantitative analytical method for HCT using liquid chromatography tandem mass spectrometry. We measured HCT in 1808 serum samples from pregnant women from the general population in Sweden (1997-2015) and in 632 samples from 393 pregnant women from an agricultural population in Costa Rica (2010-2011). In Swedish samples, we assessed time trends and investigated seasonality. In the Costa Rican samples, we evaluated variability between and within women and explanatory variables of HCT concentrations.RESULTS: HCT was detected in all serum samples, and the limit of detection was 0.1 µg/L. The median HCT concentration in the Swedish samples was 4.1 µg/L (interquartile range [IQR] of 2.9 - 5.8 µg/L), and 3.9 times higher in the Costa Rican samples (median: 16.1 µg/L; IQR: 10.6 - 25.0 µg/L). We found clear seasonal variation with higher concentrations in the first half of each year among Swedish women. In the Costa Rican study, women working in agriculture and living near banana plantations had higher HCT concentrations, whilst higher parity and having a partner working in agriculture were associated with decreased HCT, and no clear seasonal pattern was observed.IMPACT STATEMENT: For the first time, this study quantifies human exposure to the fungicide chlorothalonil and/or its transformation product 4-hydroxychlorothalonil (HCT, R182281) and finds higher serum concentrations in women from a tropical agricultural setting as compared with women from the general population in Sweden.
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| 22. |
- Li, Zhongshan, et al.
(författare)
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Laser diagnostics in combustion and beyond dedicated to Prof. Marcus Aldén on his 70th birthday
- 2024
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Ingår i: Combustion and Flame. - 0010-2180. ; 263
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Forskningsöversikt (refereegranskat)abstract
- Laser diagnostics has been one of the most powerful tools in advancing state-of-the-art combustion research over the last five decades. Prof. Marcus Aldén, one of the most well-known pioneers in this field, has contributed many influential original publications over more than 40 years of his research career. In this paper, we will review some selected contributions, with emphasis on optical techniques developed and applied by Marcus and the group in Lund under his leadership, which are expected to play important roles in facing the challenge of the transition to a carbon-neutral energy system. A brief biography of Marcus is presented in the introduction section, including a summary of his academic services and achievements. The following sections are organized into chapters on different well-recognized techniques, i.e., laser-induced fluorescence, Raman and Rayleigh scattering, thermographic phosphors, coherent anti-Stokes Raman spectroscopy, resonant four-wave mixing, and additional novel technical developments and approaches. The description often follows different categories, including technique development, activities using relatively mature techniques for studies of combustion phenomena, and applications of the most mature techniques in practical devices. The last part of the paper includes a short interview with Marcus for his comments, suggestions, and thoughts on the future challenges and opportunities in this field. This article, on the one hand, is an acknowledgment of the outstanding contribution of Marcus to the field of combustion research and, on the other hand, intends to provide a valuable review of laser diagnostics in combustion research.
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| 23. |
- Liguori, Renato, et al.
(författare)
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Microbial retention and resistances in stormwater quality improvement devices treating road runoff
- 2021
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Ingår i: FEMS Microbes. - : Oxford University Press (OUP). - 2633-6685. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Current knowledge about the microbial communities that occur in urban road runoff is scarce. Road runoff of trafficked roads can be heavily polluted and is treated by stormwater quality improvement devices (SQIDs). However, microbes may influence the treatment process of these devices or could lead to stress resistant opportunistic microbial strains. In this study, the microbial community in the influent, effluent and the filter materials used to remove dissolved heavy metals from two different SQIDs were analyzed to determine microbial load, retention, composition, and mobile resistance genes. Although the microbes were replaced by new taxa in the effluent, there was no major retention of microbial genera. Further, the bacterial abundance of the SQIDs effluent was relatively stable over time. The heavy metal content correlated with intl1 and with microbial genera. The filter media itself was enriched with Intl1 gene cassettes, carrying several heavy metal and multidrug resistance genes (e.g. czrA, czcA, silP, mexW and mexI), indicating that this is a hot spot for horizontal gene transfer. Overall, the results shed light on road runoff microbial communities, and pointed to distinct bacterial communities within the SQIDs, which subsequently influence the microbial community and the genes released with the treated water.
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| 24. |
- Lindelöf, Linnea, et al.
(författare)
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A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile
- 2024
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.
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| 25. |
- Lundtoft, Christian, et al.
(författare)
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Combined genetic deficiencies of the classical complement pathway are strongly associated with both systemic lupus erythematosus and primary Sjögren's syndrome
- 2022
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5205 .- 2326-5191. ; 74:11, s. 1842-1850
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveComplete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjögren's syndrome (pSS) has not been studied systematically. Here we investigated heterozygous C2 deficiency and C4 copy number variation in relation to clinical manifestations in SLE and pSS.MethodsThe presence of the common 28-bp C2 deletion rs9332736 and C4 copy number variation was examined in Scandinavian patients diagnosed with SLE (n=958) or pSS (n=911), and 2,262 controls using DNA sequencing. Plasma concentration of complement proteins and classical complement function was analysed in a subgroup of patients.ResultsHeterozygous C2 deficiency – when present in combination with a low C4A copy number – substantially increased the risk of SLE (OR=10.2, CI95%: 3.5-37.0) and pSS (OR=13.0, CI95%: 4.5-48.4) when compared to individuals with two C4A copies and normal C2. For patients heterozygous for rs9332736 with one C4A copy, the median age of diagnosis was 7 years and 12 years earlier in SLE and pSS, respectively. Reduced plasma C2 (p=2x10-9) and impaired function of the classical complement pathway (p=0.03) was detected in SLE patients with heterozygous C2 deficiency. Finally, we describe a pSS patient with homozygous C2 deficiency.ConclusionWe demonstrate that the combination of partial deficiencies of C2 and C4A in the classical complement pathway is a strong risk factor for SLE and pSS. Our results emphasise the central role of the complement system in the pathogenesis of both diseases.
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