| 1. |
- Reza Felix, Mariana, et al.
(författare)
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Bone Scan Index as an Imaging Biomarker in Metastatic Castration-resistant Prostate Cancer : A Multicentre Study Based on Patients Treated with Abiraterone Acetate (Zytiga) in Clinical Practice
- 2016
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 2:5, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Background Abiraterone acetate (AA) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. To measure treatment response accurately in bone, quantitative methods are needed. The Bone Scan Index (BSI), a prognostic imaging biomarker, reflects the tumour burden in bone as a percentage of the total skeletal mass calculated from bone scintigraphy. Objective To evaluate the value of BSI as a biomarker for outcome evaluation in mCRPC patients on treatment with AA according to clinical routine. Design, setting, and participants We retrospectively studied 104 mCRPC patients who received AA following disease progression after chemotherapy. All patients underwent whole-body bone scintigraphy before and during AA treatment. Baseline and follow-up BSI data were obtained using EXINI BoneBSI software (EXINI Diagnostics AB, Lund, Sweden). Outcome measurements and statistical analysis Associations between change in BSI, clinical parameters at follow-up, and overall survival (OS) were evaluated using the Cox proportional hazards regression models and Kaplan-Meier estimates. Discrimination between variables was assessed using the concordance index (C-index). Results and limitations Patients with an increase in BSI at follow-up of at most 0.30 (n = 54) had a significantly longer median survival time than those with an increase of BSI >0.30 (n = 50) (median: 16 vs 10 mo; p = 0.001). BSI change was also associated with OS in a multivariate Cox analysis including commonly used clinical parameters for prognosis (C-index = 0.7; hazard ratio: 1.1; p = 0.03). The retrospective design was a limitation. Conclusions Change in BSI was significantly associated with OS in mCRPC patients undergoing AA treatment following disease progression in a postchemotherapy setting. BSI may be a useful imaging biomarker for outcome evaluation in this group of patients, and it could be a valuable complementary tool in monitoring patients with mCRPC on second-line therapies. Patient summary Bone Scan Index (BSI) change is related to survival time in metastatic castration-resistant prostate cancer (mCRPC) patients on abiraterone acetate. BSI may be a valuable complementary decision-making tool supporting physicians monitoring patients with mCRPC on second-line therapies.
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| 2. |
- Berglund, Torkel, et al.
(författare)
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Protection of spruce seedlings against pine weevil attacks by treatment of seeds or seedlings with nicotinamide, nicotinic acid and jasmonic acid
- 2016
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Ingår i: Forestry (London). - : Oxford University Press. - 0015-752X .- 1464-3626. ; 89:2, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- Sustainable methods are required to protect newly planted tree seedlings from insect herbivore attack. To this end, here Norway spruce (Picea abies (L.) Karst.) seeds were treated with 2.5 mM nicotinamide (NIC), 2.5 mM nicotinic acid (NIA), 3 mM jasmonic acid (JA) or 0.2 mM 5-azacytidine (5-Aza), and 6-month-old seedlings grown from these seeds were planted at a reforestation area in central Sweden. Attack by pine weevils (Hylobius abietis) was reduced by 50 per cent by NIC treatment, 62.5 per cent by JA treatment and 25 per cent by 5-Aza treatment, when compared with seedlings grown from untreated seeds. Watering 18-month-old spruce seedlings with 2 mM NIC or 2 mM NIA did reduce attack during the first season in the field by 40 and 53 per cent, respectively, compared with untreated plants. Girdling was also reduced by the different treatments. Analysis of conifer seedlings treated with 5-Aza points at a possible involvement of epigenetic mechanisms in this defensive capacity. This is supported by a reduced level of DNA methylation in the needles of young spruce seedlings grown in a greenhouse from NIC-treated seeds. Seed treatment for seedling defense potentiation is simple, inexpensive and also a new approach for forestry with many potential applications.
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| 3. |
- Frogner-Kockum, Paul, et al.
(författare)
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Metal contaminant fluxes across the sediment water interface
- 2016
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X. ; 111:1-2, s. 321-329
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Tidskriftsartikel (refereegranskat)abstract
- To date,most estimates of contaminant fluxes across the sediment/water interface in risk assessments have been done using diffusive flux models. However, the reliability of these is limited as the overall flux from the sediment may have contributions caused by advection and bioturbation. We found through a comparison of modelled fluxes versus measured fluxes, that the methods Benthic Flux Chamber and surface leaching tests in a risk assessment context showed similar magnitude while calculated fluxes deviated at least by a factor of 100 from measured fluxes. This may be explained by the flux contribution in connection with bioturbation. The chambermeasured fluxes of copper were low compared to those of zinc and cobalt, but this is consistent with leaching tests that indicated copper to be more strongly bound. Risk assessments based on total concentrations may be misleading.
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| 4. |
- Harvey, N. C., et al.
(författare)
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FRAX predicts incident falls in elderly men : findings from MrOs Sweden
- 2016
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 27:1, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- A Summary Falls and fractures share several common risk factors. Although past falls is not included as an input variable in the FRAX calculator, we demonstrate that FRAX probability predicts risk of incident falls in the MrOs Sweden cohort. Introduction Although not included in the FRAXA (R) algorithm, it is possible that increased falls risk is partly dependent on other risk factors that are incorporated into FRAX. The aim of the present study was to determine whether fracture probability generated by FRAX might also predict risk of incident falls and the extent that a falls history would add value to FRAX. Methods We studied the relationship between FRAX probabilities and risk of falls in 1836 elderly men recruited to the MrOS study, a population-based prospective cohort of men from Sweden. Baseline data included falls history, clinical risk factors, bone mineral density (BMD) at femoral neck, and calculated FRAX probabilities. Incident falls were captured during an average of 1.8 years of follow-up. An extension of Poisson regression was used to investigate the relationship between FRAX, other risk variables, and the time-to-event hazard function of falls. All associations were adjusted for age and time since baseline. Results At enrolment, 15.5 % of the men had fallen during the preceding 12 months (past falls) and 39 % experienced one or more falls during follow-up (incident falls). The risk of incident falls increased with increasing FRAX probabilities at baseline (hazard ratio (HR) per standard deviation (SD), 1.16; 95 % confidence interval (95%CI), 1.06 to 1.26). The association between incident falls and FRAX probability remained after adjustment for past falls (HR per SD, 1.12; 95%CI, 1.03 to 1.22). High compared with low baseline FRAX score (>15 vs <15 % probability of major osteoporotic fracture) was strongly predictive of increased falls risk (HR, 1.64; 95%CI, 1.36 to 1.97) and remained stable with time. Whereas past falls were a significant predictor of incident falls (HR, 2.75; 95%CI, 2.32 to 3.25), even after adjustment for FRAX, the hazard ratio decreased markedly with increasing follow-up time. Conclusions Although falls are not included as an input variable, FRAX captures a component of risk for future falls and outperforms falls history with an extended follow-up time.
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| 5. |
- Johansson, Åsa Cm, et al.
(författare)
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Impaired phagocytosis and reactive oxygen species production in phagocytes is associated with systemic vasculitis
- 2016
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anti-neutrophil cytoplasmic antibodies associated vasculitides (AAV) is a group of autoimmune diseases, characterized by small vessel inflammation. Phagocytes such as neutrophils and monocytes are the main effector cells found around the inflamed vessel wall. Therefore, we wanted to investigate aspects of function and activation of these cells in patients with AAV.METHODS: Flow cytometry was used to evaluate: the expression of activation markers (CD11c, CD62L, CD177 and C5aR); the number of recently released neutrophils from bone marrow, defined as CD10(-)D16(low) cells in peripheral blood; and the capacity of peripheral blood monocytes and polymorphonuclear leukocytes (PMN) to produce reactive oxygen species and to phagocytose opsonized bacteria.RESULTS: AAV patients (n = 104) showed an increase of CD10(-)CD16(low) neutrophils and total PMN in peripheral blood, suggesting a combination of increased bone marrow release and prolonged survival. An increased percentage of AAV PMN expressed CD177 but no other signs of activation were seen. A decreased production of reactive oxygen species was observed in AAV phagocytes, which was associated with disease activity. Moreover, granulocytes from patients with microscopic polyangiitis showed lower oxidative burst capacity compared to patients with granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis. In addition, decreased phagocytosis capacity was seen in PMN and monocytes.CONCLUSION: Our results indicate that phagocytes from AAV patients have impaired function, are easily mobilized from bone marrow but are not particularly activated. The association between low reactive oxygen species formation in PMN and disease severity is consistent with findings in other autoimmune diseases and might be considered as a risk factor.
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| 6. |
- McCloskey, Eugene V, et al.
(författare)
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A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:5, s. 940-948
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Tidskriftsartikel (refereegranskat)abstract
- Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.
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| 7. |
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| 8. |
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| 9. |
- Memedi, Mevludin, 1983-, et al.
(författare)
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Construction of levodopa-response index from wearable sensors for quantifying Parkinson's disease motor functions
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The goal of this study was to investigate the feasibility of wrist worn motion sensors to objectively measure motor functions in Parkinson’s disease (PD). More specifically, the aim was to construct a sensor-based levodopa-response index (SBLRI) and evaluate its clinimetric properties (convergent validity and internal consistency). Nineteen advanced PD patients and 22 healthy controls were recruited in a single center, open label, single dose clinical trial in Sweden. The subjects performed standardized motor tasks while wearing one sensor on each wrist and one on each ankle. Each sensor unit consisted of three-dimensional accelerometer and gyroscope. The patients were video recorded and the videos were blindly rated by three independent movement disorder specialists. The clinical scores were given using the Treatment Response Scale (TRS) on a scale from -3 = ‘Very Off’ to 0 = ‘On’ to +3 = ‘Very dyskinetic’. The clinical assessments were based on the overall motor function of the patients. A mean TRS was defined as the mean of the three specialists’ assessments per time point. The measurements were repeated over several time points following a single levodopa/carbidopa morning dose (50% over normal to induce dyskinesias). Sensor measurements during rapid alternating movements of hands were processed with time series analysis methods to calculate spatiotemporal parameters designed to measure bradykinesia and dyskinesia. For each hand, 96 spatiotemporal parameters were calculated and their average scores were then used in a principal component analysis to reduce the dimensionality by retaining 6 principal components. These components were then used as predictors to support vector machines and to be mapped to the mean TRS ratings of the three specialists and to calculate the SBLRI. For this analysis, a 10-fold stratified cross-validation was performed. The SBLRI was strongly correlated to mean TRS with a Pearson correlation coefficient of 0.79 (CI: 0.74-0.83, p<0.001). The 95% confidence interval for the mean squared error of SBLRI on patients data was ± 1.62 with a mean value of 0.57 whereas on healthy controls data was ± 1 with a mean value of 0.27. The sensor-based spatiotemporal parameters had good internal consistency with a Cronbach’s Alpha coefficient of 0.87 and significantly differed between patients and healthy controls. The results demonstrated that the SBLRI had good clinimetric properties for measuring motor functions (Off and dyskinesia) in PD patients. The method could also distinguish hand rotation movements exhibited by patients from those exhibited by healthy controls. The SBLRI provides effect-time profiles, which could be useful during therapy individualization of advanced PD patients.
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