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- 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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- 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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- Dalgard, Olav, et al.
(författare)
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Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response
- 2008
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 47:1, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA–positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon α-2b (1.5 μg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, −0.1 to +13.9). Conclusion: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks.
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| 7. |
- Dalgard, Olav, et al.
(författare)
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The Usefulness of Defining Rapid Virological Response by a Very Sensitive Assay (TMA) during Treatment of HCV Genotype 2/3 Infection.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine in patients with HCV genotype 2 or 3 the performance at week 4 of two assays with different sensitivities for HCV RNA detection, for the prediction of SVR and stratification for treatment duration (14 and 24 weeks). Recruitment was from two trials comparing 14 and 24 weeks treatment to patients with rapid virological response (RVR) (n = 550). RVR was originally defined as HCV RNA <50 IU/ml at week 4. Patients with an available frozen plasma sample drawn at week 4 and with follow-up data week 24 post-treatment were included (n = 429). HCV-RNA was prospectively measured with COBAS Amplicor V2, Roche (CA) (lower detection limit 50 IU/ml) and retrospectively assessed with VERSANT HCV-RNA Qualitative Assay, Siemens (TMA) (lower limit detection 10 IU/ml). Genotype 3 was present in 80% and genotype 2 in 20%. A SVR was achieved in 82%. At week 4 HCV-RNA was undetectable in 74.8% and 63% of serum samples tested with CA and TMA, respectively. CA undetectable/TMA positive was observed in 61/341 (18%) of the samples. In genotype 3 patients a relapse was seen in 9% of the patients with both CA and TMA undetectable and in 25% of the patients who were CA undetectable/TMA positive (p = 0.006). In patients allocated to 14 weeks treatment a relapse was observed in 11% of TMA undetectable patients and 26% of TMA positive (p = 0.031). In genotype 2 patients treated for 14 weeks relapse was observed in 6% of the patients with both CA and TMA undetectable week 4. Assays with high sensitivity for HCV RNA identifies patients at week 4 with high risk of virological relapse. We recommend that patients with genotype 3 and detectable HCV RNA at levels below 50 IU/ml do not receive truncated therapy with pegIFN and ribavirin.
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- 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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- 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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| 10. |
- Holm, Maja, et al.
(författare)
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Quality of life in men with metastatic prostate cancer in their final years before death : a retrospective analysis of prospective data
- 2018
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Ingår i: BMC Palliative Care. - : BMC. - 1472-684X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Quality of Life (QoL) is the most important outcome for patients in palliative care along with symptom alleviation. Metastatic prostate cancer (mPC) is a life-threatening illness, and hence, a palliative care approach may be beneficial to this group. Over time, new life-prolonging treatments have been developed for men with mPC, but the possibility to prolong life should also be balanced against the men’s QoL, particularly because there are side effects involved with these treatments. The aim of this study was to evaluate QoL, functioning and symptoms in men with mPC during their final years before death.Methods: This is a retrospective analysis of data from a long-term prospective study of men (n = 3885) with prostate cancer from two regions in Sweden. Validated questionnaires asking about participants’ QoL, functioning and symptoms were used to collect data. From the overall study, 190 men with mPC were identified. They were stratified into three groups, depending on the amount of time that had passed between the last questionnaire and their death; < 6 months, 6–18 months and > 18 months before death.Results: Men with mPC generally rated their QoL poorly compared to established clinically significant threshold values. The group of men that were < 6 months before death rated their QoL, functioning and several symptoms significantly worse than the two other groups. Men that died after the year 2006 reported lower QoL and functioning and more pain and fatigue than those who died before 2006.Conclusion: The results in this study indicate that men with mPC have unmet needs with regards to QoL and symptoms. A palliative care approach, alongside possible life-prolonging treatments, that focuses on QoL and symptom relief, may serve as an important frame to give the best support to these men in their final years of life.
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