| 1641. |
- Larsson, Sara L., et al.
(författare)
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Psychometric properties of patient-reported outcome measures (PROMs) in wrist osteoarthritis: test-retest reliability and construct validity
- 2022
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Patient-reported outcome measures (PROMs) are frequently used to assess the effects of treatments in patients with wrist osteoarthritis (OA), but their psychometric properties have not been evaluated in this group of patients. Our aim was to evaluate the psychometric properties of the Numeric Rating Scale (NRS pain at rest, pain on motion without load, and pain on load), the Disabilities of the Arm, Shoulder and Hand (DASH) and the Patient Rated Wrist Evaluation (PRWE) questionnaires in patients with wrist OA regarding test-retest reliability and construct validity. Methods The NRS, DASH and PRWE were self-administered by 50 patients (40 men and 10 women, mean age 66 years) in a postal survey on two occasions, two weeks apart. Test-retest reliability was evaluated by Kappa statistics and the Spearman rank correlation coefficients (rho) were calculated to evaluate construct validity. Results The Kappa coefficients for DASH, PRWE and NRS pain on motion without load and NRS pain on load were > 0.90, 95% CI ranging from 0.84 to 0.98, while NRS pain at rest was 0.83, 95% CI 0.73-0.92. The construct validity of the PROMs was confirmed by three formulated hypotheses: a higher correlation between PRWE and NRS (rho 0.80-0.91, p < 0.001) was found, compared to DASH and NRS (rho 0.68-0.80, p < 0.001); the NRS pain on motion without load and NRS pain on load correlated more strongly to PRWE and DASH (rho 0.71-0.91, p < 0.001) compared to NRS pain at rest (rho 0.68-0.80) and a high correlation between PRWE and DASH was found (rho 0.86, p < 0.001). Conclusions The NRS, DASH and PRWE demonstrate excellent test-retest reliability and moderate to high construct validity in patients with wrist OA. These PROMs are highly related, but they also differ. Therefore, they complement each other in ensuring a comprehensive evaluation of perceived disability in wrist OA. As PRWE showed the highest test-retest reliability and the highest relation to the other PROMs, the sole use of the PRWE can be recommended in clinical practice.
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| 1642. |
- Larsson, Sofia L., 1971-
(författare)
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Structural and functional studies of the ribosomes : a closer look at expansion segments and translational dynamics in eukaryotes
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ribosome is the basic machinery for protein synthesis in all living cells. In the last decade, there has been an explosion of structural information on the ribosome. The eukaryotic ribosome is larger than the prokaryotic counterpart and contains several extra features, even though they have similar core structures. The major size and shape differences are due to added ribosomal proteins and the eukaryote specific expansion segments in ribosomal RNA. In this thesis, the secondary structure of several expansion segments was determined in an effort to explore the structural, and possibly functional, differences between prokaryotic and eukaryotic ribosomes. An experimental modeling method was chosen, since the exclusive use of phylogenetic covariation analysis results in inconclusive structures, due to the variability of the segments. A wide range of chemical and enzymatic modification reagents was used to probe the ribosomal RNA. The experimental data was combined with phylogenetic alignments, and applied in computer modeling based on energy minimization. Secondary structure models are presented for ES15 and ES39 in 28S rRNA from mouse, rat and rabbit, in addition to wheat in the latter case. Models are also proposed for V4 in 18S rRNA from mouse and wheat. Hopefully, these models can in time be fit into the three-dimensional ribosome structures and give us an indication of the role that expansion segments play in eukaryotic protein synthesis.Experimental probing of the rRNA and analysis of the three-dimensional models of the ribosome has made it clear that the ribosome exhibits inherent dynamic characteristics during translation. The flexibility is especially evident during the elongation cycle. Disruption of the ability of the ribosome to progress through different conformations during elongation destroys the ribosome's capacity to add new amino acids to the growing peptide chain. For instance, the function of elongation factors eEF2 and eEF1 is affected by the ribosome inactivating proteins ricin and -sarcin, respectively. Native ribosomes were treated with these inhibitors, which resulted in modification patterns that only partially overlap. This indicates that the different effects of the two inhibitors in ribosomal function are reflected in different effects on the conformation of ribosomal RNA. This is especially true at the GTPase activating center of the ribosome, i.e. the interaction site of the elongation factors.
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| 1643. |
- Larsson, S., et al.
(författare)
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On horizontal variability in lime-cement columns in deep mixing
- 2006
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Konferensbidrag (refereegranskat)abstract
- The variability with respect to results from hand-operated penetrometer tests on lime-cement column cross-sections is investigated by means of spatial correlation structures. Experimental directional semi-variograms are evaluated for a large number of column cross-sections from two field tests. Analyses of variance (ANOVA) are performed in order to investigate the influence of various factors in the installation process on the inherent variability. The paper also briefly discusses the concept of sufficient mixing: the link between the mixing process and the mechanical system. The results have been interpreted within the framework of variance reduction based on an averaging model for axially loaded columns. The results from the two field tests show that the radius is the dominating variable in the variability, and different types of correlation structure can be obtained in spite of the fact that they have been equally installed. The mechanical mixing work does not significantly influence the type of spatial correlation structure. Furthermore, a simple design consideration shows that the variance reduction has a major influence on the determination of the partial factor of safety.
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| 1644. |
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| 1645. |
- Larsson, Staffan, et al.
(författare)
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Serum ARGS-aggrecan in a phase 2 clinical trial targeting osteoarthritis
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Ingår i: Osteoarthritis and Cartilage. - 1063-4584. ; , s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- To monitor serum concentrations of the aggrecan alanine-arginine-glycine-serine (ARGS) neoepitope in a clinical trial of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 inhibition as disease-modifying therapy of knee osteoarthritis, and to investigate relationships between reduction in ARGS and change in cartilage thickness, knee-related pain and function.DesignROCCELLA trial participants received once-daily oral S201086 75, 150 or 300 mg, or placebo, for 52 weeks. Serum was collected at baseline, 4, 12, 28 and 52 weeks, and 2 weeks post-treatment with ARGS measured by an in-house immunoassay. Change from baseline to week 52 in central medial femorotibial compartment cartilage thickness was measured by magnetic resonance imaging, function and pain by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscores. Associations between cumulative change in ARGS and change in cartilage thickness or WOMAC subscores were evaluated by linear regression.ResultsS201086 reduced serum levels of ARGS in a dose-dependent manner throughout the treatment period. Maximal reduction was at 4 weeks with a 58.5% [95% CI 60.8%, 56.2%] reduction of ARGS compared to baseline for 300 mg S201086. Two weeks post-treatment, ARGS concentrations rebounded with a dose-dependent overshoot compared to baseline levels. Cumulative change of ARGS concentration from baseline to week 52 had no effect on change in cartilage thickness (slope −0.8×10−6 [−2.9×10−6, 1.3×10−6]) or change in WOMAC pain and function (slopes −30×10−6 [−64×10−6, 5.2×10−6] and −97×10−6 [−214×10−6, 20×10−6], respectively) at week 52.ConclusionSystemic inhibition of ADAMTS-5 resulted in markedly reduced serum ARGS, but change in serum ARGS concentrations showed no association with the progression of cartilage thinning, or patient reported pain and function.
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| 1646. |
- Larsson, S., et al.
(författare)
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Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid : An exploratory analysis in the KANON trial
- 2017
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 25:9, s. 1443-1451
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prospectively monitor how treatment of acutely ruptured anterior cruciate ligament (ACL) affects biomarkers of inflammation and proteolytic degradation over 5 years. Design: We studied 119 subjects with acute ACL injury from the randomized controlled knee anterior cruciate ligament, non-surgical versus surgical treatment (KANON)-trial (Clinical trial ISRCTN 84752559) who had synovial fluid, serum and urine samples available from at least two out of six visits over 5 years after acute ACL rupture. All subjects followed a similar rehabilitation protocol where, according to randomization, 60 also had early ACL reconstruction and 59 had the option to undergo a delayed ACL reconstruction if needed. Interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), tumor necrosis factor (TNF), amino acids alanine, arginine, glycine, serine (ARGS)-aggrecan, C-terminal crosslinking telopeptide type II collagen (CTX-II) and N-terminal crosslinking telopeptide type I collagen (NTX-I) were quantified by enzyme-linked immunosorbent assays (ELISA). Results: Subjects randomized to early ACL reconstruction had higher cytokine concentrations in index knee synovial fluid at 4 months (IL-6, IL-8, IL-10, TNF), 8 months (IL-6 and TNF) and at 5 years (IFNγ) compared to those randomized to optional delayed reconstruction. Those that underwent delayed ACL reconstruction within 5 years (30 subjects), had higher synovial fluid concentrations of IL-6 at 5 years compared to those treated with rehabilitation alone. No differences between groups were noted for ARGS-aggrecan in synovial fluid and serum or CTX-II and NTX-I in urine over 5 years, neither as randomized nor as treated. Conclusions: Surgical ACL reconstruction constitutes a second trauma to the acutely injured joint resulting in a prolonged elevation of already high synovial fluid levels of inflammatory cytokines.
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| 1647. |
- Larsson, S., et al.
(författare)
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The Background of the INTEGRAL SPI Anticoincidence Shield and the Observations of GRBs
- 2004
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Ingår i: PROCEEDINGS OF THE 5TH INTEGRAL WORKSHOP ON THE INTEGRAL UNIVERSE. - : European Space Agency. - 9290928638 ; , s. 649-652
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Konferensbidrag (refereegranskat)abstract
- The anti-coincidence shield, ACS, of the spectrometer, SPI (Vedrenne et al., 2003), on INTEGRAL provides the possibility to study temporal properties of gamma-ray bursts (GRBs) with high resolution (Rau et al. 2004). To correctly interpret the results of the analysis, a good understanding of the back,ground and noise levels of the instrument is required. The back-round noise of the ACS, oil timescales up to the length of a GRB, has a Gaussian distribution and its power is independent of frequency, that is, it is white noise. However, it does not follow a Poisson statistic since on average the variance is similar to 1.6 times larger than the mean, and varies significantly. We find a systematic relation between the mean count rate and its variance. The ratio, variance/mean, decreases as the mean count rate increases. As well as helping to understand the cause of this effect, this characterisation is useful when modelling the time variability of GRBs. To illustrate the discussion we present some GRB light curves detected by the SPI/ACS and shortly discuss the analysis that has been made of them.
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| 1648. |
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| 1649. |
- Larsson, Staffan, et al.
(författare)
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α1-microglobulin protects against bleeding-induced oxidative damage in knee arthropathies
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:NOV
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Tidskriftsartikel (refereegranskat)abstract
- Knee injury increases the risk of developing knee osteoarthritis (OA). Recent evidence suggests involvement of oxidative stress induced by inflammation and bleeding in the joint. This study investigates the role in this process of α1-microglobulin (A1M), a plasma and tissue antioxidant protein with reducing function, and heme- and radical-binding properties. We studied matched knee synovial fluid (sf) and serum (s) samples from 122 subjects (mean age 40 years, 31% females): 10 were knee healthy references, 13 had acute inflammatory arthritis (AIA), 79 knee injury 0-10 years prior to sampling, and 20 knee OA. Using immunoassays, we measured sf-A1M and s-A1M, sf-hemoglobin (sf-Hb), sf-total free heme (sf-Heme), and sf-carbonyl groups (sf-Carbonyl). We explored associations by partial correlation, or linear regression models with adjustments for age, sex and diagnosis, and evaluated diagnostic capacity by area under the receiver operator characteristics curve (AUC). The AIA group had 1.2- to 1.7-fold higher sf-A1M and s-A1M concentrations compared to the other diagnostic groups; other biomarkers showed no between-group differences. sf-A1M and s-A1M were with AUC of 0.76 and 0.78, respectively, diagnostic for AIA. In the injury group, the amount of bleeding in the joint was inversely correlated to time after injury when measured as sf-Heme (r = -0.41, p < 0.001), but not when measured as sf-Hb (r = - 0.19, p = 0.098). A similar inverse association with time after injury was noted for sf-A1M (r = -0.30, p = 0.007), but not for s-A1M and sf-Carbonyl. Linear regression models showed that sf-Heme was more strongly associated with sf-A1M and sf-Carbonyl than sf-Hb. Independent of diagnosis, sf-Heme explained 5.7% of the variability in sf-A1M and 3.0% in the variability in sf-Carbonyl, but appeared unrelated to s-A1M. High sf-A1M and low sf-Heme or sf-Hb were independently associated with low sf-Carbonyl. In conclusion, our results demonstrate that independent of disease, Hb and heme within a knee joint correlates with an increased sf-A1M concentration that appears to be protective of oxidative damage, i.e., a reduction in carbonyl groups. High concentrations of A1M in synovial fluid and serum was further diagnostic for AIA.
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| 1650. |
- Larsson Seim, Anna, et al.
(författare)
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Democracy as a Middle Ground : A Unified Theory of Development and Political Regimes
- 2013
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Ingår i: European Economic Review. - : Elsevier BV. - 0014-2921 .- 1873-572X. ; 64, s. 35-56
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Tidskriftsartikel (refereegranskat)abstract
- Although many of the worst performing countries over the post-World War II period were autocracies, many of the best were likewise autocratic. At the same time, no long-lived autocracy currently is rich whereas every long-lived democracy is. This paper proposes a theory to account for these observations that rests on the ideas that autocrats are heterogeneous and that elites experience lower land rents with industrialization. In a model calibrated to Britain's development, we show that elites democratize society only after the economy has accumulated enough wealth, and that the democratization date depends importantly on the history of rulers and distribution of land.
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