| 1. |
- Askling, Johan, et al.
(author)
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Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
- 2008
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
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Journal article (peer-reviewed)abstract
- Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365 026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998–2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
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| 2. |
- Askling, Johan, et al.
(author)
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Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas : relative risks and time trends in the Swedish Biologics Register
- 2009
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In: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
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Journal article (peer-reviewed)abstract
- BACKGROUND:Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.METHODS:Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67,743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471,024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.RESULTS:Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26,981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365,026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3,355,849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.CONCLUSION:Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
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| 3. |
- Askling, Johan, et al.
(author)
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Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden
- 2005
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:7, s. 1986-1992
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Journal article (peer-reviewed)abstract
- OBJECTIVE:Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA.METHODS:Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.RESULTS:During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.CONCLUSION:Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
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| 4. |
- Askling, Johan, et al.
(author)
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Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
- 2007
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344
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Journal article (peer-reviewed)abstract
- OBJECTIVES:The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.METHODS:First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.RESULTS:Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.CONCLUSION:Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
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| 8. |
- Jarvius, Jonas, et al.
(author)
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Digital Quantification using Amplified Single-Molecule Detection
- 2006
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In: Nature Methods. - 1548-7091 .- 1548-7105. ; 3:9, s. 725-727
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Journal article (peer-reviewed)abstract
- We describe a scheme for biomolecule enumeration by converting nanometer-scale specific molecular recognition events mediated by rolling-circle amplification to fluorescent micrometer-sized DNA molecules amenable to discrete optical detection. Our amplified single-molecule detection (SMD) approach preserves the discrete nature of the molecular population, allowing multiplex detection and highly precise quantification of molecules over a dynamic range of seven orders of magnitude. We apply the method for sensitive detection and quantification of the bacterial pathogen Vibrio cholerae.
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| 9. |
- Jonsson, Magnus, et al.
(author)
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Genetic divergence of climatically marginal populations of Vicia pisiformis on the Scandinavian Peninsula
- 2008
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In: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661 .- 1601-5223. ; 145:1, s. 1-8
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Journal article (peer-reviewed)abstract
- Vicia pisiformis L. is a perennial leguminous plant with a main distribution in broadleaved forest-steppes of eastern Europe. The species is classified as endangered (EN) according to the IUCN red-lists in both Norway and Sweden, due to severe fragmentation, small population sizes and continuing population decline. The populations on the Scandinavian Peninsula constitute the northern limit of the species distribution and are mostly restricted to warm stony slopes with predominantly southern aspects. In this study we used the AFLP method, which is a high-resolution genetic fingerprint method. Samples were collected from 22 Scandinavian populations. The overall genetic structure was analysed in an AMOVA, in a Mantel test and through constrained correspondence analysis (CCA). The ordination scores representing non-geographic genetic divergence were extracted from the CCA and analysed in a linear model using habitat variables and population size as explanatory variables. We found (i) a strong geographic structure, (ii) significant genetic divergence between populations, (iii) that this genetic divergence remained significant even after removing the effect of geography in a partial CCA and (iv) that the remaining non-geographic part of genetic divergence (distance from the ordination centre) was associated with aspect, populations with a northern aspect were more genetically divergent. Aspect explains more variation than population size and is the only variable retained in the minimal adequate model. We suggest that local adaptation has caused this divergence from an expected geographical pattern of genetic variation. This explanation is further supported by the association between aspect and specific AFLP fragments. Many plant populations are relics of a different climate (Aguirre-Planter et al. 2000; Despres et al. 2002; Pico and Riba 2002). In response to long-term climate change, populations can either migrate towards a more favourable climate or adapt to the new conditions (delaVega 1996; Jump et al. 2006). Species with limited dispersal ability are at risk of reaching isolated dead-ends of decreasingly suitable habitat, without any suitable habitat within dispersal distance (Colas et al. 1997). Isolated populations have to use their inherent evolutionary potential and adapt to changes in environmental conditions, or they will go extinct. As population fragments go extinct, those that remain will become increasingly isolated from each other both spatially and also genetically as the level of gene flow declines with increasing distance. Such correlation between genetic dissimilarities and geographic distances, known as isolation by distance (Slatkin 1993; Wright 1943), when found, suggests a history of geographically limited gene flow (Kimura and Weiss 1964). On top of an isolation by distance pattern there might be other genetic structures to be found. Occasional long-distance dispersal events for example may disturb geographic patterns with puzzling allele distributions as a result (Nichols and Hewitt 1994). Genetic drift is a process that will affect any pattern of genetic variation in a random fashion. Local adaptation through natural selection is a process that, if sufficiently strong in comparison with gene flow and genetic drift, will create patterns where genetic differentiation is associated with certain environmental conditions (Wright 1951). Several studies have shown the importance of local adaptation of populations (reviewed by Kawecki and Ebert 2004) (see also Bonin et al. 2006; Knight and Miller 2004; Kolseth and Lönn 2005; Lönn et al. 1998). Local adaptation can be strong also at small spatial scales (Snaydon and Davies 1976; Lönn 1993) even though it is sometimes very limited in terms of the number of genes involved (Kärkkainen et al. 2004) Environmental variability provides a base for biological variation by imposing differentiated selection pressures resulting in local adaptation. Topography provides large environmental variation within a relatively small area and thereby provides a basis for small-scale local adaptations. Depending on the local topographic possibilities populations can either migrate up and down slopes or along the same altitude to a different aspect to find a suitable microclimate. The dispersal distance will be much shorter per degree of temperature change during altitudinal migration (Hewitt 1996), than during simple latitudinal migration across a flat landscape. Slope and aspect are two important topographic parameters that determine the influx level of solar radiation, especially towards the poles where the total global radiation decreases (Larcher 2003). Vicia pisiformis is an endangered poorly-dispersed long-lived forest herb with its main distribution across the semi-open broadleaved forest steppes of eastern Europe. The Scandinavian populations are believed to be climate relict populations from warmer times. Earlier genetic studies of V. pisiformis using allozymes, RAPD:s and morhology, have found low to very low levels of genetic variation (Gustafsson and Gustafsson 1994; Black-Samuelsson et al. 1997; Black-Samuelsson and Lascoux 1999). Therefore we used AFLP (amplified fragment length polymorphism) markers, which detect even very small genetic differences between individuals. AFLP mainly analyse neutral variation, as the major fraction of most genomes is assumed to be neutral. However, since the AFLP-fragments are distributed randomly throughout the whole genome some fragments may be situated so close to regions under selection that they become more or less linked to them. This linkage disequilibrium between molecular markers and regions under selection, often referred to as quantitative trait loci (QTL), forms the basis for both QTL-mapping and marker assisted selection (MAS), reviewed by Dekkers and Hospital (2002). Gardner and Latta (2006) for example, found QTL under selection in both natural environments and in the greenhouse. Markers have been found to be connected to biomass production (Cavagnaro et al. 2006) and environmental variation (Bonin et al. 2006; Jump et al. 2006; Porcher et al. 2006). In this study we examine 22 Swedish and Norwegian populations of Vicia pisiformis and ask (i) if there is genetic differentiation between these populations, (ii) if there is can it be explained in its entirety by geographic location or (iii) can it partly be explained by habitat characteristics, suggesting local adaptation, or population size, suggesting genetic drift. We show that populations are differentiated geographically and that genetic variation in addition to the geographical pattern is associated with habitat.
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| 10. |
- Nygårds, Thomas, 1980, et al.
(author)
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Vibration Control of Washing Machine with Magnetorheological Dampers
- 2006
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In: Proc. The 8th International Conference on Motion and Vibration Control (MOVIC 2006), August 27-30, 2006, KAIST, Daejeon, Korea. ; , s. 480-485
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Conference paper (peer-reviewed)abstract
- The manufacturing of washing machines has lately been an important issue for the appliance industry. Current environmental awareness demands the improvement of machine efficiency and increasing of quality of washing processes. Developing of high efficient and high speed spinning washing machines raises the problem of designing smart suspension systems to control vibration and noise in real time. In the paper a horizontal-axis washing machine is under the study. The machine has a drum with perforated walls. In the water extraction process, the drum starts rotation and this gives rise to significant centrifugal imbalance forces and imbalanced rotation of the laundry mass. This results in vibration and shaking. By elimination of such vibrations it will be possible to design more silent washing machines for higher wash loads within the same outside dimensions. In the paper the results of modelling of dynamics of washing machine and designing of smart suspension system comprising magnetoreological dampers for semi-active vibration control are presented. The commercial software MSC.ADAMS/View and MATLAB/Simulink have been used for 3D-modelling of dynamics of washing machine. Both traditional suspension with passive dampers and suspension with magnetoreological dampers are implemented into the developing mathematical models. Identification of passive dampers and magnetoreological dampers dynamics was done based on experimental study. Full scale test rig of washing machine was used for validating the models. The validated model has been used for designing and optimization of smart suspension system with magnetoreological dampers of high speed spinning washing machines. Analysis of the obtained results has proved a big potential of utilization of magnetoreological dampers for developing of semi-active suspension systems for washing machines.
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