| 1. |
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| 2. |
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| 3. |
- 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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| 4. |
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| 5. |
- Sanjeevi, Carani B., et al.
(författare)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Tidskriftsartikel (refereegranskat)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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| 6. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 7. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 8. |
- 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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| 9. |
- 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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| 10. |
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| 11. |
- Lindehammer, Sabina, et al.
(författare)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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| 12. |
- Lindh, Christina, et al.
(författare)
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Mandibular cortical index for osteoporosis diagnosis : the OSTEODENT project
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: to determine the diagnostic validity of the mandibular cortical index (MCI) for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Five observers, all oral radiologists but of different experience, made an assessment of porosity of the cortex of the lower border of the mandible using MCI. Results: Data of 661 subjects (mean age 54.8y; sd = 6.19y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. MCI data for each observer were dichotomosed so that MCI grade 3 indicated a positive test result and grades 1 and 2 a negative test result. The sensitivities and specificties of MCI for osteoporosis diagnosis were determined: Osteoporosis at any site Osteoporosis at femoral neck Observer Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%) 1 24.8 93.3 27.3 91.3 2 23.4 93.2 24.2 91.3 3 23.4 91.5 24.2 89.8 4 20.6 99.8 22.7 91.8 5 19.1 91.1 22.7 90.3 Interobserver repeatability (using weighted Kappa) showed a range of 0.183 to 0.780, with a median value of 0.467. This median indicated moderate agreement. Conclusions: MCI had low sensitivity but high specificity for diagnosis of osteoporosis. This high specificity might prove to be more appropriate for use in primary dental care than using a different diagnostic threshold. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 13. |
- Lindh, Christina, et al.
(författare)
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Tooth loss and osteoporosis
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: To test the relationship between the number of existing teeth (3rd molars and impacted teeth excluded) and the Bone Mineral Density (BMD). Methods: The study entailed perimenopausal and postmenopausal subjects (age 45-70 years). The BMD at three different sites (standardized total hip t-score, standardized femoral neck t-score and standardized lumbar spine t-score) was measured using DXA. The subjects received a panoramic radiograph and their medical history was evaluated. The number of existing teeth was calculated using the panoramic radiographs and the relation between the BMD and the number of existing teeth in different age groups of the subjects was examined.The equation introduced by Taguchi et al (1995) for calculating the probability of osteoporosis using two variables (age and number of existing teeth) Pv =1/(1+e-z) was also applied and assessed. Results: Data of 178 subjects (mean age 54,38 y; sd =6,32y) were available for analysis. Patients with a standardized t-score value less than -2.5 at any of the three sites were classified as osteoporotic. Those with a score above this were classified as normal or osteopenic. When osteoporosis was diagnosed at any of the three sites, there were fewer existing teeth (mean 18,47 ,95% CI;15,89 to 21,05) compared with normal (mean 21,24, 95% CI; 19.96 to 22,53) and osteopenic subjects (mean 19,97 95% CI;18,58 to 21,37). The results approaches statistical significance. Conclusions: It seems that there is a relationship between the number of remaining teeth and BMD.This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 14. |
- Ringbom, A, et al.
(författare)
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The B-10,B-11(n, p)Be-10,Be-11 reactions at E-n=96 MeV
- 2001
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Ingår i: NUCLEAR PHYSICS A. - : ELSEVIER SCIENCE BV. - 0375-9474. ; 679:3-4, s. 231-250
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Tidskriftsartikel (refereegranskat)abstract
- Double-differential cross sections of the B-10,B-11(n,p)Be-10,Be-11 reactions have been measured at 96 MeV in the angular range 0 degrees -30 degrees for excitation energies up to 35 MeV. The spectra have been decomposed into different multipolarities usi
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| 15. |
- Andersson, M, et al.
(författare)
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Isospin resolved double pion production at Celsius
- 1998
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Ingår i: ACTA PHYSICA POLONICA B. - : ACTA PHYSICA POLONICA B, JAGELLONIAN UNIV, INST PHYSICS. - 0587-4254. ; 29:11, s. 2963-2968
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Two-pion production close to threshold has been measured in dfd and p+d reactions at CELSIUS. The results are compared to results at higher energies.
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| 16. |
- Andersson, M, et al.
(författare)
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Isospin resolved double pion production in the reaction p+d -> He-3+2 pi
- 2000
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Ingår i: PHYSICS LETTERS B. - : ELSEVIER SCIENCE BV. - 0370-2693. ; 485:4, s. 327-333
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Tidskriftsartikel (refereegranskat)abstract
- Neutral and charged two-pion production in p + d --> He-3 + 2 pi reactions has been studied at CELSIUS at a proton beam energy of 477 MeV. The total cross section for double pion production is 0.22 +/- 0.03 mu b. The ratio of the cross sections for the pr
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| 17. |
- Andersson, M, et al.
(författare)
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Pionic fusion close to threshold: d+alpha -> Li-6*+pi(0) at CELSIUS
- 2000
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Ingår i: ACTA PHYSICA POLONICA B. - : ACTA PHYSICA POLONICA B, JAGELLONIAN UNIV, INST PHYSICS. - 0587-4254. ; 31:10-11, s. 2343-2347
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Tidskriftsartikel (refereegranskat)abstract
- The isobaric analogue state of the ground state of the halo nucleus He-6 in Li-6 has been studied in a pionic fusion experiment at the CELSIUS storage ring facility in Uppsala, Sweden. The Li-6 ions were detected in a zero-degree spectrometer situated in
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| 18. |
- Andersson, M, et al.
(författare)
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Pionic fusion to a halo state, the d(alpha, Li-6*)pi(0) reaction studied close to threshold
- 2000
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Ingår i: PHYSICS LETTERS B. - : ELSEVIER SCIENCE BV. - 0370-2693. ; 481:2-4, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- The d(alpha,Li-6(3.56)*)pi(0) reaction has been studied at E-c.m. = 1.2 and 1.9 MeV above threshold with an alpha-particle beam incident on a deuterium cluster-jet target in CELSIUS. Complete differential cross sections were measured at both energies, int
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| 19. |
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| 20. |
- Andersson, M, et al.
(författare)
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Study of the p+d -> He-3+2 pi reaction at Celsius
- 1998
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Ingår i: ACTA PHYSICA POLONICA B. - : ACTA PHYSICA POLONICA B, JAGELLONIAN UNIV, INST PHYSICS. - 0587-4254. ; 29:11, s. 2969-2971
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The exclusive p + d -->(3) He + 2 pi reaction has been studied at CELSIUS at a beam energy of 477 MeV. Preliminary results indicate that the two pions are created mainly in an isospin T = 1 state.
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| 21. |
- Andersson, M, et al.
(författare)
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The exclusive p plus d -> He-3+2 pi reaction at CELSIUS
- 2000
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Ingår i: ACTA PHYSICA POLONICA B. - : ACTA PHYSICA POLONICA B, JAGELLONIAN UNIV, INST PHYSICS. ; , s. 2123-2126
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Konferensbidrag (refereegranskat)abstract
- Neutral and charged two-pion production in p + d --> He-3 --> 2 pi reactions has been studied at a proton beam energy of 477 MeV. The total cross section for double pion production is 0.22 +/- 0.03 mub. The ratio of the cross sections for the production o
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Eek, Meta Nyström, et al.
(författare)
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Objective measurement of sitting-Application in children with cerebral palsy
- 2022
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Ingår i: Gait & Posture. - : Elsevier BV. - 0966-6362. ; 96, s. 210-215
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with cerebral palsy (CP) and a severe motor impairment, have limited ability to perform volitional movements due to spasticity, involuntary postures and movements and reduced ability to maintain antigravity head and trunk control. A stable sitting position is a prerequisite for participation in daily life, but there is a lack of objective measurement methods for this population. Research question: Is it feasible to measure a stable sitting position with pressure mapping and 2D motion analysis, and can it detect differences to a) a reference group, b) between subgroups of CP and c) before and after treatment with intrathecal baclofen (ITB)? Methods: Pressure mapping, and a 2D motion analysis system, were used to capture movements of centre of pressure (CoP), and movements of head, hand and leg, sitting on a bench for 90 s. Twenty-two children with dyskinetic or bilateral spastic CP, GMFCS III-V, mean age 9.0, and 30 children with typical development (TD) mean age 10.7, were recruited between 2010 and 2019. Seventeen children were treated with ITB. Parents were interviewed regarding aspect of sitting. Non-parametric methods were used for statistical analysis. Results: Differences in CoP and kinematics were detected with more movements in children with CP compared to children with TD (p < 0.001). There were more movements in children with dyskinetic CP compared to children with bilateral spastic CP as captured with the pressure mapping system (CoP distance p = .005 and AnterioPosterior sway p = .014). After treatment with ITB, involuntary movements had decreased (CoP p = 0.006-0.035, kinematics p = 0.002-0.020). Parents reported improvement in sitting. The two measurement systems showed consistent results (rho 0.500-0.771, p = < 0.001-0.049). Significance: It was feasible to objectively measure sitting position in children with a moderate-to-severe motor impairment with differences to a reference group and after an intervention. CoP and head movements were the variables that were easiest to capture.
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| 26. |
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| 27. |
- Hognert, Helena, 1973, et al.
(författare)
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Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial
- 2016
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 31:11, s. 2484-2490
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Tidskriftsartikel (refereegranskat)abstract
- Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the +/- 5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018. For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis. Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days. This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare.
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| 28. |
- 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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| 29. |
- Johanson, G., et al.
(författare)
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Quantitative relationships of perfluoroalkyl acids in drinking water associated with serum concentrations above background in adults living near contamination hotspots in Sweden
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 219
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Tidskriftsartikel (refereegranskat)abstract
- Contaminated drinking water (DW) is a major source of exposure to per- and polyfluoroalkyl substances (PFAS) at locations around PFAS production/use facilities and military airports. This study aimed to investigate quantitative relationships between concentrations in DW and serum of nine perfluoroalkyl acids (PFAAs) in Swedish adult populations living near contamination hotspots. Short-chained (PFPeA, PFHxA, PFHpA, and PFBS) and long-chained PFAAs (PFOA, PFNA, PFDA, PFHxS and PFOS) were measured in DW and serum. We matched DW and serum concentrations for a total of 398 subjects living or working in areas receiving contaminated DW and in one non-contaminated area. Thereafter, linear regression analysis with and without adjustments for co-variates was conducted. This enabled to derive (i) serum concentrations at background exposure (CB) from sources other than local DW exposure (i.e. food, dust and textiles) at 0 ng/L DW concentration, (ii) population-mean PFAA serum:water ratios (SWR) and (iii) PFAA concentrations in DW causing observable elevated serum PFAA concentrations above background variability. Median concentrations of the sum of nine PFAAs ranged between 2.8 and 1790 ng/L in DW and between 7.6 and 96.9 ng/mL in serum. DW concentration was the strongest predictor, resulting in similar unadjusted and adjusted regression coefficients. Mean CB ranged from <0.1 (PFPeA, PFHpA, PFBS) to 5.1 ng/mL (PFOS). Serum concentrations increased significantly with increasing DW concentrations for all PFAAs except for PFPeA with SWRs ranging from <10 (PFHxA, PFHpA and PFBS) to 111 (PFHxS). Observed elevated serum concentrations above background variability were reached at DW concentrations between 24 (PFOA) and 357 ng/L (PFHxA). The unadjusted linear regression predictions agreed well with serum concentrations previously reported in various populations exposed to low and high DW levels of PFOA, PFHxS and PFOS. The quantitative relationships derived herein should be helpful to translate PFAA concentrations in DW to concentrations in serum at the population level.
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| 30. |
- Johnstone, Erik V., et al.
(författare)
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Molecular and Electronic Structure of Re2Br4(PMe3)(4)
- 2016
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 55:14, s. 7111-7116
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Tidskriftsartikel (refereegranskat)abstract
- The dinuclear rhenium(II) complex Re2Br4(PMe3)(4) was prepared from the reduction of [Re2Br8](2-) with (n-Bu4N)BH4 in the presence of PMe3 in propanol. The complex was characterized by single-crystal X-ray diffraction (SCXRD) and UV-visible spectroscopy. It crystallizes in the monoclinic C2/c space group and is isostructural with its molybdenum and technetium analogues. The Re-Re distance (2.2521(3) angstrom) is slightly longer than the one in Re2Cl4(PMe3)(4) (2.247(1) angstrom). The molecular and electronic structure of Re2X4(PMe3)(4) (X = Cl, Br) were studied by multiconfigurational quantum chemical methods. The computed ground-state geometry is in excellent agreement with the experimental structure determined by SCXRD. The calculated total bond order (2.75) is consistent with the presence of an electron-rich triple bond and is similar to the one found for Re2Cl4(PMe3)(4). The electronic absorption spectrum of Re2Br4(PMe3)(4) was recorded in benzene and shows a series of low-intensity bands in the range 10 000-26 000 cm(-1). The absorption bands were assigned based on calculations of the excitation energies with the multireference wave functions followed by second-order perturbation theory using the CASSCF/CASPT2 method. Calculations predict that the lowest energy band corresponds to the delta* -> sigma* transition, while the next higher energy bands were attributed to the delta* -> pi*, delta -> sigma*, and delta -> pi* transitions.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Lindh, Christina, et al.
(författare)
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Combination of radiographic measurement of cortical width and clinical risk index for diagnosis of osteoporosis : the OSTEDENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured by an Active Shape Model (ASM) method in combination with a clinical risk index, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry (DXA) of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. A questionnaire was completed for each subject to identify factors related to osteoporosis risk and calculate a clinical risk index (OSIRIS). A manually initialised ASM method was used to derive cortical width measurements from each radiograph. ROC analysis was used to identify the most effective clinical index. Logistic regression analysis was used to build a model, with the presence or absence of osteoporosis as the dichotomous dependent variable and OSIRIS and the radiographic data as independent variables. Results: ROC analysis gave an Az value for OSIRIS of 0.841 (95% CI: 0.811 to 0.868). The sensitivity and specificity of the combined radiographic-clinical risk assessment were 38.6% and 97.9% respectively. Conclusions: Combining the cortical width measurement and the clinical risk index provided a high specificity method for detection of subjects with osteoporosis, although sensitivity was modest. This model would be most suitable for use in the context of restricted availability of DXA. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 36. |
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| 37. |
- Lindh, Christina, et al.
(författare)
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OSTEODENT: Using model-base image analysis of dental panoramic radiographs to identify sujects with osteopenia
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: To develop image analysis software that can robustly and accurately measure the width of the inferior mandibular cortex on dental panoramic radiographs as an indicator of reduced bone mineral density (BMD). Methods: An Active Shape Model of the cortex was trained by expert annotation of 132 radiographs and used to locate the superior and inferior boundaries of the cortex automatically in a leave-one-out cross-validation test. Anatomical accuracy of the search is increased by employing a straightforward user interaction. Width was measured at 50 locations bilaterally between the antegonion and the mental foramen and averaged. Correlation between width and BMD (determined by DXA at the hip and spine) was measured and found to be highest in a region slightly medial to the antegonion – the “optimal” region. Taking osteopenia (T≤-1.0) as the categorical variable, we conducted ROC analysis using average width for both automatic and interactive search (tests 1 and 2) and “optimal” width (interactive search only – test 3). Results: Significant correlation (R=0.24, p<0.01) was found between BMD and average cortical width. ROC analysis gave Az values of 0.64, 0.66 and 0.71 in tests 1 2 and 3 respectively. Conclusions: We have developed an automatic image analysis method for measuring width of the inferior mandibular cortex. The average width between the antegonion and mental foramen correlates significantly with BMD. ROC analysis indicates that this method can contribute towards identification of osteopenia. The sensitivity and specificity of the measurement can be increased by the use of a straightforward user interaction. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 38. |
- Lindh, Christina, et al.
(författare)
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Quantitative analysis of the tradigraphic trabecular pattern as a predictor for BMD-values : the OSTEODENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of computer aided analysis of the radiographic trabecular pattern as a predictor of BMD-values of peri- and post-menopausal women to support the diagnosis of osteoporosis. Methods: Panoramic and intra-oral radiographs were obtained from volunteer female subjects in the 45 to 70 year age band, recruited from four European centres. These volunteers also underwent dual x-ray energy absorptiometry (DXA) of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis. A computer aided analysis of the radiographic trabecular pattern was performed on the radiographs in relevant regions of interest, and used to predict the BMD values of hip and spine by multiple regression techniques. Results: Data of 525 subjects (mean age 54.6 y; sd = 6.0 y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. The most suitable ROIs for the panoramic images were in the mandibular premolar region and in the ramus. For the intra-oral radiographs (upper- and lower jaw) an area in between the first and second premolar was chosen. Including age as a parameter improved the results. Az values are given below: ROI BMD-hip BMD-spine panoramic radiograph 0.65 0.71 panoramic radiograph + age 0.77 0.79 intra-oral radiograph 0.71 0.73 intra-oral radiograph + age 0.79 0.82 panoramic + intraoral radiographs 0.72 0.75 panoramic + intraoral radiographs + age 0.80 0.84 Conclusions: Quantitative analysis of the radiographic trabecular pattern together with the age of the patient is a promising parameter for the prediction of BMD values as an indicator of osteoporosis. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 39. |
- Lindh, Christina, et al.
(författare)
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ROC analysis of automatically measured mandibular cortical width from panoramic radiographs for diagnosis of osteoporosis : the OSTEDENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- 1School of Dentistry and 2Imaging Science and Biomedical Engineering, The University of Manchester, United Kingdom 3School of Dentistry, Oral Pathology and Maxillofacial Surgery, Oral Imaging Centre, Katholieke Universiteit Leuven, Belgium 4Oral Diagnosis and Radiology, The National and Kapodistrian University of Athens, Greece 5Oral Radiology, Malmö University, Sweden 6Oral Radiology, ACTA, Amsterdam, The Netherlands Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured by Active Shape Model (ASM) methods, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Two ASM methods, one entirely automatic and one manually initialised, were used to derive measurements of mandibular cortical width. ROC analysis was used to determine the diagnostic ability of manual and ASM methods. Results: 652 subjects were examined (mean age 54.9y; sd=6.10), with 140 (21.5%) being classified as having osteoporosis. Using the manually initialized ASM method, Az values for the diagnosis of osteoporosis at any site and at femoral neck alone were 0.816 (95% CI: 0.784 to 0.845) and 0.835, (95% CI: 0.805-0.863), respectively. Using the automatically initialized ASM method, the Az values for the diagnosis of osteoporosis at any site and at the femoral neck alone were 0.759 (95% CI: 0.724-0.791) and 0.805 (95% CI: 0.773 -0.835), respectively. The difference in Az of the two methods for the diagnosis of osteoporosis at either the hip or spine was significant (p<0.001), but not significant at the femoral neck alone. Conclusions: ASM-based methods ofmandibular cortical width measurement were effective in the diagnosis of osteoporosis. The manually initialized method, involving a small amount of user interaction, performed best. Further analysis is necessary to establish the appropriate diagnostic threshold for clinical use. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 40. |
- Lindh, Christina, et al.
(författare)
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ROC analysis of densitometric measurements on intraoral radiographs for detection of osteoporosis as part of the OSTEDENT study
- 2006
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To determine the diagnostic validity of mandibular and maxillary bone density, measured between the premolars (mm Aleq) in detecting osteoporosis at the hip or lumbar spine. Methods: Female subjects between 45 and 70 years of age, were recruited from 4 European centres. They underwent dual x-ray energy absorptiometry of the hip and lumber spine, to provide a gold standard diagnosis of osteoporosis. In addition, intra-oral radiography of upper and lower right premolar region was performed, using an aluminum wedge as a densitometric reference. Jaw bone density in 4 selected regions of interest (ROI) was determined using dedicated software Osteop (Nackaerts et al 2005**). Two ROIs were determined between the upper premolar teeth and another 2 between the lower premolars. 5 observers performed the analysis. Intra- and inter-observer differences and ROC curves were analyzed. Results: Results from 660 subjects (mean age 54.8y; sd 6.19) were suitable for analysis. 136 of these subjects were classified as having osteoporosis. For ROC analysis, measurement data from all observers were averaged, since there was no significant inter-observer difference. Az values as well as 95% confidence intervals are shown in the table: Detecting osteoporosis at any site (spine, hip, femoral neck): ROI1 upper jaw Az 0.691 (0.653 to 0.726) ROI2 upper jaw Az 0.708 (0.671 to 0.743) ROI1 lower jaw Az 0.709 (0.672 o 0.745) ROI2 lower jaw Az 0.702 (0.655 to 0.738) None of the differences in Az between sites was statistically significant (p always > >0.05). Conclusions: Density of the premolar region expressed in mm Aleq is a fair indication for the presence of osteoporosis. More extensive analysis of the OSTEODENT results might reveal an even better predictive tool for osteoporosis screening. **Nackaerts O, Jacobs R, Pillen M, Engelen L, Gijbels F, Devlin H, Lindh C, Nicopolou-Karayianni K, van der Stelt P, Horner K. Accuracy and precision of a densitometric tool for jaw bone. DentoMaxilloFacial Radiology. In press This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 41. |
- Lindh, Christina, et al.
(författare)
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ROC analysis of directly measured mandibular cortical width from panoramic radiogarphs for diagnosis of osteoporosis : the OSTEODENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured directly by observers, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Five observers, all oral radiologists but of different experience, made manual measurements of width of the mandibular lower border cortex below the mental foramina bilaterally. Results: Data of 661 subjects (mean age 54.8y; sd = 6.19y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. Az values are given below: Osteoporosis at any site Osteoporosis at femoral neck Observer Az (se) 95% CI Az (se) 95% CI 1 0.782 0.748-0.813 0.804 0.771-0.833 2 0.766 0.731-0.799 0.757 0.722-0.791 3 0.756 0.721-0.788 0.790 0.757-0.821 4 0.746 0.711-0.779 0.762 0.727-0.794 5 0.710 0.673-0.744 0.752 0.718-0.785 A diagnostic threshold of 3mm resulted in a sensitivity of 50.7% and a specificity of 80.4% (data for median observer, 2). Mean within-subject variance for the five observers was 0.126mm (sd = 0.355mm). Repeatability is the difference between two measurements made by any pair of observers for the same subject and was expected to be less than 0.983 mm for 95% of pairs of observations. Conclusions: Direct measurement of mandibular cortical width was diagnostically effective in diagnosis of osteoporosis. However, repeatability may be a problem in clinical use. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 42. |
- Lindh, Christina, et al.
(författare)
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Trabecular pattern in intraoral radiographs as a sign of osteoporosis : the OSTEODENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: The aim of this study was to investigate if the trabecular pattern in intraoral radiographs, assessed by five observers, could serve as an indicator of osteoporosis. Methods: Six hundred and seventy one women (45 - 70 yrs) from four European centers were included in the study and examined with intraoral radiographs in the right upper and lower premolar region. The patients also underwent examinations with central dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine. Five observers assessed the trabecular pattern in the intraoral radiographs into one of three classes: dense, heterogeneous or sparse trabecular pattern. The assessments were made with the aid of reference images and the observers underwent a calibration procedure before starting their assessments. The classifications were compared with the true diagnosis of osteoporosis measured using DXA. Results: The sensitivity and specificity for five observers’ assessments of the intraoral radiographs with sparse trabecular pattern as indicative of osteoporosis at either hip or spine are given in the table below. The values are calculated for patients diagnosed as having osteoporosis at any of the examined sites. Upper jaw Lower jaw Observer Sensitivity Specificity Sensitivity Specificity 1 22.2 90.2 13.2 94.5 2 22.6 94.8 15.8 94.2 3 26.5 91.6 28.1 86.7 4 36.3 87.4 30.2 82.4 5 35.3 93.7 39.1 95.6 If the cut-off included either “heterogeneous” or “sparse” trabeculation then a higher sensitivity was achieved (90.6 – 73.7) but a lower specificity (49.4 – 26.2). Conclusion: Assessment of sparse trabecular pattern on intraoral radiographs offered a combination of low sensitivity but high specificity for osteoporosis diagnosis. If it is assumed that high specificity is preferred for osteoporosis assessment by dentists, then this method may have potential for clinical use, although inter-observer variability may be a problem. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 43. |
- Manni, Giovanni Li, et al.
(författare)
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The OpenMolcas Web : A Community-Driven Approach to Advancing Computational Chemistry
- 2023
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 19:20, s. 6933-6991
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Tidskriftsartikel (refereegranskat)abstract
- The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.
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| 44. |
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| 45. |
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| 46. |
- Rylander, L, et al.
(författare)
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Per- and Polyfluoroalkyl Substances in Early Pregnancy and Risk for Preeclampsia: A Case-Control Study in Southern Sweden
- 2020
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is one of the most common causes of perinatal and maternal morbidity/mortality. One suggested environmental risk factor is exposure to endocrine-disrupting pollutants such as per- and polyfluoroalkyl substances (PFAS). The present case-control study in southern Sweden aims to investigate the hypothesized association between serum concentrations of PFAS in early pregnancy and the risk of developing preeclampsia. The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Maternal serum samples were obtained from a biobank of samples collected in early pregnancy in connection with screening for infections. Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were analyzed using liquid chromatography-tandem-mass-spectrometry (LC/MS/MS). Among primiparous women, there were no differences in PFAS concentrations in early pregnancy between the cases and the controls whereas among multipara women, the cases had significantly higher concentrations of PFNA (median concentrations were 0.44 and 0.38 ng/mL, p = 0.04). When individual PFAS were categorized into quartiles and adjustment for potential confounders was performed, the women in the highest quartiles had no significant increased risks of developing preeclampsia as compared with women in the lowest category. In conclusion, the present study provides limited support for the hypothesized association between PFAS and preeclampsia in a population with relatively low exposure levels.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Wahlberg, K., et al.
(författare)
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Filaggrin variations are associated with PAH metabolites in urine and DNA alterations in blood
- 2019
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- Dermal chemical exposure is common in many professions. The filaggrin protein is important for the skin barrier and variations in the filaggrin gene (FLG) may influence the uptake of chemicals via the skin, and consequently, the degree of systemic effects. The aim of this study was to investigate, in chimney sweeps with occupational exposure to polycyclic aromatic hydrocarbons (PAH) from soot, the influence of variation in FLG on internal PAH dose and DNA alterations, including epigenetic, previously linked to cancer and cardiovascular disease. We used TaqMan PCR to genotype 151 chimney sweeps and 152 controls for four FLG null variants (R501X, R2447X, S3247X and 2282del4) which cause impaired skin barrier, and FLG copy number variation (12th repeat, CNV12) which potentially is beneficial for the skin barrier. The internal dose of PAH was represented by urinary PAH metabolites (e.g. 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene) that we measured by LC-MS/MS. We measured epigenetic alterations (methylation of AHRR and F2RL3) in blood by pyrosequencing; and DNA alterations (telomere length and mitochondrial DNA copy number) by real-time PCR. Hypomethylation of AHRR or F2RL3 is a risk factor for lung cancer and shorter telomere length a risk factor for cardiovascular disease. The frequencies of FLG null were 8.6 and 11.8% (p = 0.35), and CNV12 27.8 and 19.7% (p = 0.09) in chimney sweeps and controls, respectively. We found that among chimney sweeps working predominately with soot sweeping (high PAH exposure), CNV12 carriers had lower concentrations of PAH metabolites in urine compared with non-carriers (median 1-hydroxypyrene = 0.37 vs 0.86 μg/g creatinine respectively; p = 0.025 by linear regression models adjusted for age, BMI and smoking) compared to sweeps not carrying CNV12. Further, FLG null was associated with approximately 2.5% higher methylation of F2RL3 (cg03636183, p = 0.019 after adjustment for exposure group, age, BMI and smoking). FLG null was associated with approximately 7% shorter telomere length (p = 0.015, adjusted model). Our results suggest that FLG variations may influence the dose of PAH in highly exposed workers, possibly via dermal uptake. It also suggests that FLG variation may influence the degree of (epi)genotoxicity in the body. FLG variation is common in the working population and should be considered in risk assessment. © 2019
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