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- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 2. |
- Bjerg, Anders, et al.
(författare)
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Shorter time to clinical decision in work-related asthma using a digital tool
- 2020
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Ingår i: ERJ open research. - Lausanne, Switzerland : European Respiratory Society (ERS). - 2312-0541. ; 6:3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- PEF curves are a useful but cumbersome tool in diagnosing work-related asthma. Using a digital spirometer and smartphone app, time to clinical decision could be shortened by 6-7 weeks. Physician's time spent analysing PEF data is also shortened.
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| 3. |
- Dierschke, Katrin, et al.
(författare)
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Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates
- 2017
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 90:5, s. 451-463
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Tidskriftsartikel (refereegranskat)abstract
- Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).
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| 7. |
- Isaxon, Christina, et al.
(författare)
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Realistic indoor nano-aerosols for a human exposure facility
- 2013
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Ingår i: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502. ; 60, s. 55-66
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to achieve realistic levels of two different types of aerosols commonly abundant in indoor environments in an experimental chamber intended for human exposure studies and aerosol characterization. The aerosols chosen were particles from candle lights (in particle number dominated by inorganic water soluble particles) and from ozone-terpene reactions (organic particles). The aerosol generation and characterization system consisted of a controlled air tight stainless steel 22 m(3) chamber, to which the generation set-ups were connected. No air could enter or leave the chamber except through a conditioning system by which temperature, relative humidity and air exchange rate could be controlled. Candle smoke aerosol was generated from ten candles burning in a 1.33 m(3) glass and stainless steel chamber. The aerosol was diluted by clean air from the conditioning system before entering the chamber. Terpene vapor was generated by passing pure nitrogen through a glass bottle containing limonene oil. Ozone was generated by a spark discharge using pure O-2, and was added to the ventilation air flow downstream the inlet for terpene vapors and upstream the inlet to the chamber. Both aerosols were characterized with respect to number and mass concentrations, size distribution and chemical composition. Particle number concentration in the size range 10-650 nm could be varied from <10 cm(-3) to more than 900,000 cm(-3) (for candle smoke) or to more than 30,000 cm(-3) (for particles formed in a 160 ppb terpene/40 ppb ozone mixture). Furthermore, the set-ups were evaluated by, for each source, repeating the generation at six three-hour long events. For both aerosols repeatable generations at pre-determined concentration levels, that were stable over time, could be achieved. The results show that realistic concentrations of aerosols from real-world environments could be reproduced in a well-controlled manner and that this set-up could be used both for aerosol characterization and for human exposures. (C) 2013 Elsevier Ltd. All rights reserved.
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