| 1. |
- Chinga-Carrasco, Gary, et al.
(författare)
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A method for estimating the fibre length in fibre-PLA composites
- 2013
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 250:1, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- Wood pulp fibres are an important component of environmentally sound and renewable fibre-reinforced composite materials. The high aspect ratio of pulp fibres is an essential property with respect to the mechanical properties a given composite material can achieve. The length of pulp fibres is affected by composite processing operations. This thus emphasizes the importance of assessing the pulp fibre length and how this may be affected by a given process for manufacturing composites. In this work a new method for measuring the length distribution of fibres and fibre fragments has been developed. The method is based on; (i) dissolving the composites, (ii) preparing the fibres for image acquisition and (iii) image analysis of the resulting fibre structures. The image analysis part is relatively simple to implement and is based on images acquired with a desktop scanner and a new ImageJ plugin. The quantification of fibre length has demonstrated the fibre shortening effect because of an extrusion process and subsequent injection moulding. Fibres with original lengths of >1 mm where shortened to fibre fragments with length of <200 μm. The shortening seems to be affected by the number of times the fibres have passed through the extruder, the amount of chain extender and the fraction of fibres in the polymer matrix.
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| 2. |
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| 3. |
- Dalgard, Olav, et al.
(författare)
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In patients with HCV genotype 2 or 3 infection and RVR 14 weeks treatment is noninferior to 24 weeks. Pooled analysis of two Scandinavian trials.
- 2010
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Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 22, s. 552-556
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To compare 14 and 24 weeks treatment to patients with HCV genotype 2 or 3 infection and rapid virological response (RVR). MATERIALS AND METHODS: Patients included in two Scandinavian trials, one nonrandomized pilot trial (n=122) and one randomized controlled trial (RCT) (n=428) were entered into a pooled database. In both trials treatment naïve patients with genotype 2 or 3 were treated with pegylated interferon alpha 2b (1.5 mug/kg, subcutaneous) weekly and ribavirin (800-1400 mg, orally) daily. Primary endpoint was sustained virological response (SVR). RVR was defined as HCV RNA less than 50 IU/ml after 4 weeks of treatment. In the pilot trial all patients with RVR were treated for 14 weeks and in the RCT patients with RVR were randomised to either 14 or 24 weeks treatment. Patients treated per protocol were included in the primary analysis. The noninferiority margin was set to be 10% between the two groups with a one-sided 5% significance level. RESULTS: In patients with RVR and genotype 2 or 3 SVR was obtained in 181 of 199 (91.0%) and 93 of 98 (94.9%) after 14 and 24 weeks treatment, respectively. The observed difference in SVR rates was 3.9% (90% confidence interval: +1 to -8.8). The relapse rate was highest among those older than 40 years and those with genotype 3 and high viral load, but prolongation of treatment from 14 to 24 weeks did not reduce the relapse rate substantially in any of these groups. CONCLUSION: In patients with HCV genotype 2 or 3 infection and RVR 14 weeks treatment is noninferior to 24 weeks.
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| 4. |
- Eskesen, Arne Nørgaard, et al.
(författare)
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Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort.
- 2012
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Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 24:8, s. 890-896
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Two functional genetic variants in the inosine triphosphatase (ITPA) gene have been shown to be strongly associated with protection from ribavirin (RBV)-induced hemolysis. We aimed at evaluating this finding in a chronic hepatitis C genotype 2/3 cohort with a predominance of genotype 3 patients where available data are scarce. A second objective was to determine whether a protective association translated into the need for RBV reduction and hence a possible impact on treatment response. METHODS: Overall, 457 patients were recruited from two trials of genotype 2/3 patients treated with pegylated interferon α-2b and weight-based RBV. rs1127354 and rs7270101 were genotyped and a composite ITPAase deficiency variable was graded according to the two single nucleotide polymorphisms. The primary endpoints were hemoglobin (Hb) decline from baseline and Hb decline of more than 3 g/dl at week 4. RESULTS: Both single nucleotide polymorphisms and the composite ITPAase deficiency variable were strongly and independently associated with protection from a decline in Hb at week 4 in multivariate linear regression models (Prs1127354=7.0×10, Prs7270101=0.0036, PITPase deficiency variable =6.3×10). Patients with any degree of reduced ITPAase activity were less likely to have their RBV dose reduced (odds ratio 0.39, 95% confidence interval 0.16-0.96, P=0.040), although this did not translate into increased rapid viral response or sustained viral response (Prvr=0.93, Psvr=0.22). CONCLUSION: We have confirmed a strong association between functional ITPA variants and RBV-induced hemolysis and showed protection from RBV dose reduction, although this did not translate into increased rapid viral response or sustained viral response.
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| 5. |
- Grau, Tanja, et al.
(författare)
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Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:4, s. 719-730
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase (PDE6C) have been recently reported in patients with autosomal recessive inherited achromatopsia (ACHM) and early-onset cone photoreceptor dysfunction. Here we present the results of a comprehensive study on PDE6C mutations including the mutation spectrum, its prevalence in a large cohort of ACHM/cone dysfunction patients, the clinical phenotype and the functional characterization of mutant PDE6C proteins. Twelve affected patients from seven independent families segregating PDE6C mutations were identified in our total patient cohort of 492 independent families. Eleven different PDE6C mutations were found including two nonsense mutations, three mutations affecting transcript splicing as shown by minigene assays, one 1 bp-insertion and five missense mutations. We also performed a detailed functional characterization of six missense mutations applying the baculovirus system to express recombinant mutant and wildtype chimeric PDE6C/PDE5 proteins in Sf9 insect cells. Purified proteins were analyzed using Western blotting, phosphodiesterase (PDE) activity measurements as well as inhibition assays by zaprinast and P gamma. Four of the six PDE6C missense mutations led to baseline PDE activities and most likely represent functional null alleles. For two mutations, p.E790K and p.Y323N, we observed reduction in PDE activity of approximately 60% and 80%, respectively. We also observed differences for P gamma inhibition. The p.E790K mutant, with an IC50 value of 2.7 nM is 20.7-fold more sensitive for P gamma inhibition, whereas the p.Y323N mutant with an IC50 of 158 nM is 3-fold less sensitive when compared with the wildtype control.
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| 6. |
- Moghaddam, Amir, et al.
(författare)
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IL28B Genetic Variation and Treatment Response in Patients with Hepatitis C Virus Genotype 3 Infection
- 2011
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 53:3, s. 746-754
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms near the IL28B gene, which code for interferon (IFN)-lambda 3, predict response to pegylated interferon-alpha (PEG-IFN) and ribavirin treatment in hepatitis C virus (HCV) genotype 1 infected patients. Follow-up studies of the effect of IL28B gene in HCV non-genotype 1 infected patients have almost always used predominantly HCV genotype 2-infected or mixed genotype 2/3-infected cohorts with results partly conflicting with HCV genotype 1. We performed a retrospective analysis of 281 patients infected with HCV genotype 3 for association of response to therapy with IL28B polymorphisms. We found that the HCV genotype 1 responder genotypes at rs12979860 and rs8099917 did not associate with sustained virological response to PEG-IFN/ribavirin therapy. However, the responder genotypes of both SNPs showed association with rapid viral response measured at 4 weeks (rs12979860, P = 3 x 10(-5); rs8099917, P = 3 x 10(-4)). In multivariate analysis, age (< 40 years), baseline viral load (< 4 x 10(5) IU/mL) and the responder genotypes of SNPs rs12979860 or rs8099917 remained significant independent predictors of rapid viral response to therapy. Furthermore, we show that IL28B polymorphisms are associated with relapse in patients who achieve rapid viral response to PEG-IFN/ribavirin therapy. The responder genotypes also showed association with markers of stage and activity of liver disease, namely high aspartate aminotransferase platelet ratio index (APRI, rs12979860, P = 0.018; rs8099917, not significant) and high alanine aminotransferase (ALT, rs12979860, P = 0.002; rs8099917, P = 0.001), in addition to a high baseline viral load (rs12979860, P = 1.4 x 10(-5); rs8099917, P = 7.3 x 10(-6)). Conclusion: Polymorphisms near the IL28B gene show association with rapid viral response but not sustained viral response to PEG-IFN/ribavirin therapy in HCV genotype 3-infected patients. (HEPATOLOGY 2011;53:746-754)
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