| 1. |
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| 2. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 3. |
- Horne, B D, et al.
(författare)
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Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 232-240
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Tidskriftsartikel (refereegranskat)abstract
- By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6-11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that "effective" dose constituted a treatment response index . Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
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| 4. |
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| 6. |
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| 7. |
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| 8. |
- Sun, Chengjun, et al.
(författare)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
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Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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| 9. |
- Andersson, E. M., et al.
(författare)
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Comparison of the FilmArray assay and in-house real-time PCR for detection of respiratory infection
- 2014
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 46:12, s. 897-901
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Tidskriftsartikel (refereegranskat)abstract
- Recently, molecular methods capable of detecting almost all microbial agents that may cause acute respiratory infection have been introduced. The FilmArray Respiratory Panel assay, which integrates nucleic acid extraction, nested amplification and detection in a reaction pouch preloaded with all reagents required for detection of 17 viruses and 3 bacteria, was compared with an in-house real-time PCR that detects these agents in 8 parallel amplifications. When 128 clinical samples representing 18 of these agents were analysed by both assays the agreement was excellent, with kappa values ranging between 0.54 and 1.0. Discordances were mainly observed for adenovirus, but not when version 1.7 of FilmArray was used. The results show that these assays detect a wide range of pathogens with similar performance. FilmArray provides results after approximately 1 h, including approximate to 5 min hands-on time, and does not require advanced equipment or expertise in molecular diagnostics, making it a useful point-of-care-test for acute respiratory infections.
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| 10. |
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| 11. |
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| 12. |
- Ayukekbong, James A., et al.
(författare)
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Monitoring of seasonality of norovirus and other enteric viruses in Cameroon by real-time PCR : an exploratory study
- 2014
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Ingår i: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 142:7, s. 1393-1402
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Tidskriftsartikel (refereegranskat)abstract
- We studied the seasonal fluctuation of norovirus and other enteric viruses in Cameroon. Two hundred participants aged between 1 and 69 years were prospectively followed up. Each participant provided monthly faecal samples over a 12-month period. A total of 2484 samples were tested using multiplex real-time PCR assay for the detection of norovirus, rotavirus and enterovirus. The effect of weather variables and risk factors were analysed by Pearson correlation and bivariate analysis. Overall, enterovirus was the most commonly detected virus (216% of specimens), followed by norovirus (39%) and rotavirus (04%). Norovirus and enterovirus were detected throughout the year with a peak of norovirus detection at the beginning of the rainy season and a significant alternation of circulation of norovirus genogroups from one month to the next. Age <5 years and consumption of tap water were risk factors for norovirus infection. Better understanding of factors influencing transmission and seasonality may provide insights into the relationship between physical environment and risk of infection for these viruses.
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| 13. |
- Ayukekbong, James, et al.
(författare)
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Monitoring of seasonality of norovirus and other enteric viruses in Cameroon by real-time PCR: an exploratory study
- 2014
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Ingår i: Epidemiology and Infection. - : Cambridge University Press (CUP). - 0950-2688 .- 1469-4409. ; 142:7, s. 1393-1402
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Tidskriftsartikel (refereegranskat)abstract
- We studied the seasonal fluctuation of norovirus and other enteric viruses in Cameroon. Two hundred participants aged between 1 and 69 years were prospectively followed up. Each participant provided monthly faecal samples over a 12-month period. A total of 2484 samples were tested using multiplex real-time PCR assay for the detection of norovirus, rotavirus and enterovirus. The effect of weather variables and risk factors were analysed by Pearson correlation and bivariate analysis. Overall, enterovirus was the most commonly detected virus (216% of specimens), followed by norovirus (39%) and rotavirus (04%). Norovirus and enterovirus were detected throughout the year with a peak of norovirus detection at the beginning of the rainy season and a significant alternation of circulation of norovirus genogroups from one month to the next. Age <5 years and consumption of tap water were risk factors for norovirus infection. Better understanding of factors influencing transmission and seasonality may provide insights into the relationship between physical environment and risk of infection for these viruses.
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| 14. |
- Barregård, Lars, 1948, et al.
(författare)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 15. |
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| 16. |
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| 17. |
- Eliasson, E, et al.
(författare)
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Therapeutic drug monitoring for tomorrow
- 2013
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Ingår i: European journal of clinical pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 6969 Suppl 1, s. S25-S32
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Tidskriftsartikel (refereegranskat)
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| 18. |
- Eriksson, Leif E. B., et al.
(författare)
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Evaluation of new spaceborne SAR sensors for sea-ice monitoring in the Baltic Sea
- 2010
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Ingår i: Canadian journal of remote sensing. - : CANADIAN AERONAUTICS SPACE INST. - 0703-8992 .- 1712-7971. ; 36, s. S56-S73
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Tidskriftsartikel (refereegranskat)abstract
- In this study, synthetic aperture radar (SAR) data from the Advanced Land Observing Satellite (ALOS) and the Envisat, RADARSAT-2, and TerraSAR-X satellites were compared to evaluate their usefulness for sea-ice monitoring in the Baltic Sea. Radar signature characteristics at different frequencies, polarizations, and spatial resolutions are presented for three examples from 2009. C-band like-polarization data, which have been used for operational sea-ice mapping since the early 1990s, serve as a reference. Advantages and disadvantages were identified for the different SAR systems and imaging modes. One conclusion is that cross-polarized data improve the discrimination between sea ice and open water. Another observation is that it is easier to identify ice ridges in L-band data than in images from shorter wavelengths. The information content of X-and C-band images is largely equivalent, whereas L-band data provide complementary information. L-band SAR also seems to be less sensitive to wet snow cover on the ice.
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| 19. |
- Hatschek, T, et al.
(författare)
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Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial
- 2012
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Ingår i: Breast Cancer Research and Treatment. - New York, USA : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 131:3, s. 939-947
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Tidskriftsartikel (refereegranskat)abstract
- Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.
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| 20. |
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| 21. |
- Kippler, Maria, et al.
(författare)
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Early life low-level cadmium exposure is positively associated with increased oxidative stress
- 2012
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Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 112, s. 164-170
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Tidskriftsartikel (refereegranskat)abstract
- Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11-17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodG was 3.9 nmol/L, urinary Cd 0.30 mu g/L, and breast-milk Cd 0.13 mu g/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg: p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development. (C) 2011 Elsevier Inc. All rights reserved.
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| 22. |
- Lenzini, P., et al.
(författare)
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Integration of genetic, clinical, and INR data to refine warfarin dosing
- 2010
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 87:5, s. 572-578
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Tidskriftsartikel (refereegranskat)abstract
- Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.
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| 23. |
- Leter, Giorgio, et al.
(författare)
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Exposure to Perfluoroalkyl Substances and Sperm DNA Global Methylation in Arctic and European Populations
- 2014
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 55:7, s. 591-600
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFASs) are widely used in a variety of industrial processes and products, and have been detected globally in humans and wildlife. PFASs are suspected to interfere with endocrine signaling and to adversely affect human reproductive health. The aim of the present study was to investigate the associations between exposure to PFASs and sperm global methylation levels in a population of non-occupationally exposed fertile men. Measurements of PFASs in serum from 262 partners of pregnant women from Greenland, Poland and Ukraine, were also carried out by liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in 97% of the blood samples. Two surrogate markers were used to assess DNA global methylation levels in semen samples from the same men: (a) average DNA methylation level in repetitive DNA sequences (Alu, LINE-1, Sat alpha) quantified by PCR-pyrosequencing after bisulfite conversion; (b) flow cytometric immunodetection of 5-methyl-cytosines. After multivariate linear regression analysis, no major consistent associations between PFASs exposure and sperm DNA global methylation endpoints could be detected. However, since weak but statistically significant associations of different PFASs with DNA hypo- and hypermethylation were found in some of the studied populations, effects of PFASs on sperm epigenetic processes cannot be completely excluded, and this issue warrants further investigation. (C) 2014 Wiley Periodicals, Inc.
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| 24. |
- Lindh, E. Mattias, 1986-, et al.
(författare)
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Inkjet Printed Bilayer Light-Emitting Electrochemical Cells for Display and Lighting Applications
- 2014
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Ingår i: Small. - : John Wiley & Sons. - 1613-6810 .- 1613-6829. ; 10:20, s. 4148-4153
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Tidskriftsartikel (refereegranskat)abstract
- A new bilayer light-emitting electrochemical cell (LEC) device, which allows well-defined patterned light emission through an easily adjustable, mask-free, and additive fabrication process, is reported. The bilayer stack comprises an inkjet-printed lattice of micrometer-sized electrolyte droplets, in a filled or patterned lattice configuration. On top of this, a thin layer of light-emitting compound is deposited from solution. The light emission is demonstrated to originate from regions proximate to the interfaces between the inkjetted electrolyte, the light-emitting compound, and one electrode, where bipolar electron/hole injection and electrochemical doping are facilitated by ion motion. By employing KCF3SO3 in poly(ethylene glycol) as the electrolyte, Super Yellow as the light-emitting compound, and two air-stabile electrodes, it is possible to realize filled lattice devices that feature uniform yellow-green light emission to the naked eye, and patterned lattice devices that deliver well-defined and high-contrast static messages with a pixel density of 170 PPI.
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| 25. |
- Lindh, Jenny M., et al.
(författare)
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Optimizing the Colour and Fabric of Targets for the Control of the Tsetse Fly Glossina fuscipes fuscipes
- 2012
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Ingår i: PLOS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2735. ; 6:5, s. e1661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most cases of human African trypanosomiasis (HAT) start with a bite from one of the subspecies of Glossina fuscipes. Tsetse use a range of olfactory and visual stimuli to locate their hosts and this response can be exploited to lure tsetse to insecticide-treated targets thereby reducing transmission. To provide a rational basis for cost-effective designs of target, we undertook studies to identify the optimal target colour. Methodology/Principal Findings: On the Chamaunga islands of Lake Victoria, Kenya, studies were made of the numbers of G. fuscipes fuscipes attracted to targets consisting of a panel (25 cm square) of various coloured fabrics flanked by a panel (also 25 cm square) of fine black netting. Both panels were covered with an electrocuting grid to catch tsetse as they contacted the target. The reflectances of the 37 different-coloured cloth panels utilised in the study were measured spectrophotometrically. Catch was positively correlated with percentage reflectance at the blue (460 nm) wavelength and negatively correlated with reflectance at UV (360 nm) and green (520 nm) wavelengths. The best target was subjectively blue, with percentage reflectances of 3%, 29%, and 20% at 360 nm, 460 nm and 520 nm respectively. The worst target was also, subjectively, blue, but with high reflectances at UV (35% reflectance at 360 nm) wavelengths as well as blue (36% reflectance at 460 nm); the best low UV-reflecting blue caught 3x more tsetse than the high UV-reflecting blue. Conclusions/Significance: Insecticide-treated targets to control G. f. fuscipes should be blue with low reflectance in both the UV and green bands of the spectrum. Targets that are subjectively blue will perform poorly if they also reflect UV strongly. The selection of fabrics for targets should be guided by spectral analysis of the cloth across both the spectrum visible to humans and the UV region.
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| 26. |
- Lindh, JD, et al.
(författare)
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Vitamin D and drug-metabolising enzymes
- 2012
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Ingår i: Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology. - : Springer Science and Business Media LLC. - 1474-9092. ; 11:12, s. 1797-1801
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Tidskriftsartikel (refereegranskat)
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| 27. |
- Lindh, Magnus, 1960, et al.
(författare)
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Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin
- 2013
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24–72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
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| 28. |
- Ljunggren, Östen, et al.
(författare)
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Study description and baseline characteristics of the population enrolled in a multinational observational study of extended teriparatide use (ExFOS)
- 2014
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Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 0300-7995 .- 1473-4877. ; 30:8, s. 1607-1616
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To better characterize patients who are currently being prescribed teriparatide in Europe, this article describes the study design and baseline characteristics of participants of the Extended Forsteo* Observational Study (ExFOS). Research design and methods: ExFOS is a noninterventional, multicenter, prospective, observational study in men and women with osteoporosis treated with teriparatide during the course of normal clinical practice for up to 24 months and with a post-treatment follow-up of at least 18 months. Main outcome measures: Baseline characteristics, including history of fracture and back pain, and health-related quality of life (HRQoL, assessed using the EuroQol-5 Dimension [EQ-5D]). Results: Of 1607 patients enrolled, 90.9% were women. At baseline, mean (standard deviation [SD]) age was 70.3 (9.8) years, and 85.8% of patients had a history of fracture (64.7% with >= 2 fragility fractures). Of those with historic fractures, 90.8% had vertebral fractures (67.8% had thoracic fractures). The mean (SD) of reported bone mineral density T-scores were -3.0 (1.2), -2.4 (1.0), and -2.5 (0.9) for lumbar spine, total hip (left), and femoral neck (left), respectively. Overall, 39.3% of patients had experienced >= 1 fall during the 12 months before enrollment. At baseline, 11.4% of patients were osteoporosis-treatment naive and 15% were currently using glucocorticoids. The mean (SD) visual analog scale score for back pain during the last month was 50.7 (26.9), and 62.1% of patients experienced daily or almost daily back pain. The median EQ-5D health state value at baseline was 0.62 (first and third quartiles: 0.19, 0.74). Conclusions: Baseline characteristics of the ExFOS study cohort indicate that patients prescribed teriparatide in Europe have severe osteoporosis with highly prevalent vertebral fractures, frequent and disabling back pain, and a poor HRQoL, despite previous pharmacotherapy for osteoporosis. Limitations include non-randomization, lack of a comparator group, and patient self-report for data on prior medication and fracture history.
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| 29. |
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| 30. |
- Lütgendorf-Caucig, C, et al.
(författare)
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Multicenter evaluation of different target volume delineation concepts in pediatric Hodgkin's lymphoma : a case study
- 2012
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Ingår i: Strahlentherapie und Onkologie (Print). - : Springer Science and Business Media LLC. - 0179-7158 .- 1439-099X. ; 188:11, s. 1025-1030
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: In pediatric Hodgkin's lymphoma (PHL) improvements in imaging and multiagent chemotherapy have allowed for a reduction in target volume. The involved-node (IN) concept is being tested in several treatment regimens for adult Hodgkin's lymphoma. So far there is no consensus on the definition of the IN. To improve the reproducibility of the IN, we tested a new involved-node-level (INL) concept, using defined anatomical boundaries as basis for target delineation. The aim was to evaluate the feasibility of IN and INL concepts for PHL in terms of interobserver variability. PATIENTS AND METHODS: The INL concept was defined for the neck and mediastinum by the PHL Radiotherapy Group based on accepted concepts for solid tumors. Seven radiation oncologists from six European centers contoured neck and mediastinal clinical target volumes (CTVs) of 2 patients according to the IN and the new INL concepts. The median CTVs, coefficient of variation (COV), and general conformity index (CI) were assessed. The intraclass correlation coefficient (ICC) for reliability of delineations was calculated. RESULTS: All observers agreed that INL is a feasible and practicable delineation concept resulting in stronger interobserver concordance than the IN (mediastinum CI(INL) = 0.39 vs. CI(IN) = 0.28, neck left CI(INL) = 0.33; CI(IN) = 0.18; neck right CI(INL) = 0.24, CI(IN) = 0.14). The COV showed less dispersion and the ICC indicated higher reliability of contouring for INL (ICC(INL) = 0.62, p < 0.05) as for IN (ICC(IN) = 0.40, p < 0.05). CONCLUSION: INL is a practical and feasible alternative to IN resulting in more homogeneous target delineation, and it should be therefore considered as a future target volume concept in PHL.
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| 33. |
- Margolin, S, et al.
(författare)
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CYP2D6 and adjuvant tamoxifen: possible differences of outcome in pre- and post-menopausal patients
- 2013
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Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 14:6, s. 613-622
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Previous studies on CYP2D6 activity and the effect of adjuvant tamoxifen in breast cancer are inconsistent. We analyzed the impact of the CYP2D6 polymorphism in pre- and post-menopausal patients that were adherent to tamoxifen treatment for at least a year. Materials & methods: A total of 382 breast cancer patients prescribed adjuvant tamoxifen for 5 years constituted the study-base. Clinical information, including compliance and outcome, was retrieved from medical records. Comprehensive CYP2D6 genotyping was performed and translated into predicted metabolic activity. Results & conclusion: In patients adherent to tamoxifen for at least one year (n = 313) there was an association between reduced CYP2D6 activity (≤50% of normal) and recurrence (p = 0.025) and breast cancer-specific mortality (p = 0.034). In a multivariable analysis, CYP2D6 remained an independent predictor of outcome. In a subgroup analysis, the effect of CYP2D6 seemed to derive mainly from premenopausal patients, which represents a new finding that needs validation in a larger study sample. Original submitted 13 November 2012; Revision submitted 1 March 2013
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| 34. |
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| 35. |
- Opstal-van Winden, Annemieke W. J., et al.
(författare)
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Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
- 2011
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort. Methods: In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS). Results: Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3a(desArg)), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3a(desArg) and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer. Conclusions: We show that serum protein profiles are already altered up to three years before breast cancer detection.
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| 36. |
- Rondahl, E., et al.
(författare)
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The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer
- 2014
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 60:2, s. 172-173
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination. Objectives: The aim of this study was to evaluate the risk of such contamination in a proposed clinical setting. Study design: In the present study, known HCV RNA positive (n= 149) and negative (n= 149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination. Results: In subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33. IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low. Conclusions: We conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000. IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity. © 2014 The Authors.
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| 37. |
- Santos, Olga, et al.
(författare)
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Adsorption of HSA, IgG and laminin-1 on model titania surfaces : effects of glow discharge treatment on competitively adsorbed film composition
- 2011
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Ingår i: Biofouling (Print). - : Taylor & Francis. - 0892-7014 .- 1029-2454. ; 27:9, s. 1003-1015
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effect of glow discharge treatment of titania surfaces on plasma protein adsorption, by means of ellipsometry and mechanically assisted SDS elution. The adsorption and film elution of three plasma proteins, viz. human serum albumin (HSA), human immunoglobulin G (IgG) and laminin-1, as well as competitive adsorption from a mixture of the three proteins, showed that the adsorbed amount of the individual proteins after 1 h increased in the order HSA
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| 38. |
- Skovbjerg, Susann, 1973, et al.
(författare)
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High cytokine levels in perforated acute otitis media exudates containing live bacteria
- 2010
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Ingår i: Clinical microbiology and infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 16:9, s. 1382-1388
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Tidskriftsartikel (refereegranskat)abstract
- Acute otitis media (AOM) is an inflammatory response to microbes in the middle ear, sometimes associated with rupture of the tympanic membrane. Human leukocytes produce different patterns of inflammatory mediators in vitro when stimulated with Gram-positive and Gram-negative bacteria, respectively. Here, we investigated the cytokine and prostaglandin E(2) (PGE(2)) responses in middle ear fluids (MEFs) from children with spontaneous perforated AOM and related the levels to the presence of pathogens detected by culture (live) or PCR (live or dead). Furthermore, in vivo cytokine pattern was compared with that induced in leukocytes stimulated by dead bacteria in vitro. MEFs with culturable pathogenic bacteria contained more IL-1beta (median 110 vs <7.5 ng/ml), TNF (6.3 vs <2.5 ng/ml), IL-8 (410 vs 38 ng/ml), and IL-10 (0.48 vs <0.30 ng/ml), than culture negative fluids, irrespective of PCR findings. IL-6 and PGE(2) were equally abundant (69-110 ng/ml) in effusions with live, dead or undetectable bacteria. Cytokine levels were unrelated to bacterial species and to the presence or absence of virus. Similar levels of TNF and IL-6 as found in the MEFs were obtained by in vitro stimulation of leukocytes, while 11x more IL-1beta and 3.5x more IL-8 was produced in vivo, and 22x more IL-10 was produced in vitro. A vigorous production of pro-inflammatory cytokines accompany AOM with membrane rupture regardless of causative agent, but the production seems to cease rapidly once the bacteria are killed and fragmented. IL-6 and PGE(2), however, remain after bacterial disintegration and may play a role in the resolution phase.
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| 39. |
- Song Van, Nguyen, et al.
(författare)
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Gene Polymorphism of Matrix Metalloproteinase-12 and-13 and Association with Colorectal Cancer in Swedish Patients
- 2013
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33, s. 3247-3250
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been widely reported that matrix metalloproteinases (MMPs) have fundamental roles in pathological processes in cancer through degradation of basal membranes and extracellular matrix. For MMP12 and MMP13, a functional single nucleotide polymorphism (SNP) has been detected -82A -> G (rs2276109) and -77A -> G (rs2252070), respectively. These SNPs are suggested to have an influence on different diseases. The present study evaluated the association between these SNPs in patients with colorectal cancer (CRC) patients and healthy controls. Patients and Methods: Using the TaqMan system, these SNPs were screened in 385 patients with CRC and 619 controls. Results: No significant difference in genotype distribution or in allelic frequencies was found between the two groups. However, we showed that the AA MMP-12 genotype is connected with a higher risk of disseminated CRC (Odds Ratio=1.77; 95% Confidence Interval=1.11-2.81, p=0.018). Conclusion: The results of this study suggest that the -82A -> G (rs2276109) polymorphism of the MMP12 gene reflects clinical outcome of patients with CRC.
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| 40. |
- Specht, Ina Olmer, et al.
(författare)
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Associations between serum phthalates and biomarkers of reproductive function in 589 adult men.
- 2014
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Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 66:Feb 26, s. 146-156
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level. Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in serum are associated with serum concentrations of male reproductive hormones and semen quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP on semen quality and reproductive hormones. A cross-sectional sample of 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men gave semen and blood samples and were interviewed. Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography tandem mass spectrometry in serum. The metabolites were summed according to their molar weight. We observed significant inverse associations between serum levels of the metabolites, the proxies and serum testosterone. Negative associations were also discovered between some metabolites and sex hormone-binding globulin, semen volume and total sperm count. Findings are compatible with a weak anti-androgenic action of DEHP metabolites, but less so for DiNP metabolites. Metabolic pathways differed significantly between the three study sites, but without major effect on semen quality or reproductive hormones.
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| 41. |
- Specht, Ina Olmer, et al.
(författare)
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Sperm DNA integrity in relation to exposure to environmental perfluoroalkyl substances - A study of spouses of pregnant women in three geographical regions
- 2012
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 33:4, s. 577-583
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFASs) can interfere with male reproductive function, but evidence in humans is limited. Six hundred four fertile men (199 from Greenland, 197 from Poland and 208 from Ukraine) were enrolled in the study. We measured four PFASs in serum (PFOS, PFOA, PFNA and PFHxS) and concurrent DNA damage in spermatozoa by sperm chromatin structure assay (SCSA) and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, apoptotic markers in semen (Fas-receptor and Bcl-xL), and reproductive hormones in serum. No association between PFASs and SCSA, apoptotic markers or reproductive hormones emerged. We observed a slight increase in SHBG and TUNEL-positivity with increased PFOA exposure in men from Greenland. Thus, consistent evidence that PFAS exposure interferes with sperm DNA fragmentation, apoptosis or reproductive hormones was not found. (C) 2012 Elsevier Inc. All rights reserved.
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